Sample records for particle disease induced

  1. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  2. Proton ion-microbeam elemental analysis for inhaled particle-induced pulmonary diseases: application for diagnosis and assessment of progression.

    PubMed

    Shimizu, Y; Dobashi, K

    2013-02-01

    Elemental analysis can be applied in the medical field to investigate the causes of disease. In patients with some pulmonary diseases, elements can be found in the exogenous dust deposited in the lungs and are also accumulated through the loss of cell homeostasis. Diseases induced by inhalation of dust typically affect the lungs. Although there are many pulmonary diseases induced by dust inhalation, it is often difficult to clarify the exact cause. In-air microparticle induced X-ray emission (in-air micro-PIXE) analysis is a method of elemental analysis that employs a proton ion-beam to directly measure the content of elements and their distribution in frozen sections or paraffin sections of tissue. We constantly inhale particles while breathing, but most of us do not develop pulmonary disease. Because in-air micro-PIXE analysis can determine the two-dimensional localization and content of particles in tissue, we can clarify the relationship between inhaled particles and diseases based on such analysis and the immunohistochemical expression of disease-related proteins. Elemental analysis methods like in-air micro-PIXE analysis may be useful for making precise diagnosis amd assesing disease progression to overcome threat such as occupational or environmental exposure. PMID:23244523

  3. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made. Images FIGURE 1. PMID:6376114

  4. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  5. Toxicity of Mineral Dusts and a Proposed Mechanism for the Pathogenesis of Particle-Induced Lung Diseases

    NASA Technical Reports Server (NTRS)

    Lam, C.-W.; Zeidler-Erdely, P.; Scully, R.R.; Meyers, V.; Wallace, W.; Hunter, R.; Renne, R.; McCluskey, R.; Castranova, V.; Barger, M.; Meighan, T.; James, J.T.

    2015-01-01

    Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. To investigate the impact of surface reactivity (SR) on the toxicity of particles, and in particular, lunar dust (LD), we ground 2 Apollo 14 LD samples to increase their SR and compare their toxicity with those of unground LD, TiO2 and quartz. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all dusts caused dose-dependent increases in pulmonary lesions, and enhancement of biomarkers of toxicity assessed in bronchoalveolar lavage fluids (BALF). The toxicity of LD was greater than that of TiO2 but less than that of quartz. Three LDs differed 14-fold in SR but were equally toxic; quartz had the lowest SR but was most toxic. These results show no correlation between particle SR and toxicity. Often pulmonary toxicity of a dust can be attributed to oxidative stress (OS). We further observed dose-dependent and dustcytotoxicity- dependent increases in neutrophils. The oxidative content per BALF cell was also directly proportional to both the dose and cytotoxicity of the dusts. Because neutrophils are short-lived and release of oxidative contents after they die could initiate and promote a spectrum of lesions, we postulate a general mechanism for the pathogenesis of particle-induced diseases in the lung that involves chiefly neutrophils, the source of persistent endogenous OS. This mechanism explains why one dust (e.g., quartz or nanoparticles) is more toxic than another (e.g., micrometer-sized TiO2), why dust-induced lesions progress with time, and why lung cancer occurs in rats but not in mice and hamsters exposed to the same duration and concentration of dust.

  6. Newcastle Disease Virus Vector Producing Human Norovirus-Like Particles Induces Serum, Cellular, and Mucosal Immune Responses in Mice

    PubMed Central

    Kim, Shin-Hee; Chen, Shun; Jiang, Xi; Green, Kim Y.

    2014-01-01

    ABSTRACT Human norovirus infection is the most common cause of viral gastroenteritis worldwide. Development of an effective vaccine is required for reducing norovirus outbreaks. The inability to grow human norovirus in cell culture has hindered the development of live-attenuated vaccines. To overcome this obstacle, we generated a recombinant Newcastle disease virus (rNDV)-vectored experimental norovirus vaccine by expressing the capsid protein (VP1) of norovirus strain VA387. We compared two different NDV vectors, a conventional rNDV vector and a modified rNDV vector, for their efficiencies in expressing VP1 protein. Our results showed that the modified vector replicated to higher titers and expressed higher levels of VP1 protein in DF1 cells and in allantoic fluid of embryonated chicken eggs than did the conventional vector. We further demonstrated that the VP1 protein produced by rNDVs was able to self-assemble into virus-like particles (VLPs) that are morphologically similar to baculovirus-expressed VLPs. Evaluation of their immunogenicity in mice showed that the modified rNDV vector induced a higher level of IgG response than those induced by the conventional vector and by the baculovirus-expressed VLPs. The rNDV vectors predominantly induced IgG2a subclass antibody for the Th1 response, and specifically, high levels of gamma interferon (IFN-?), tumor necrosis factor alpha (TNF-?), and interleukin-2 (IL-2) were detected in splenocytes. In addition, the modified rNDV vector induced a higher level of fecal IgA response in mice than did baculovirus-expressed VLPs. Our findings suggest that the rNDV vector is an efficient system to produce cost-effective VLPs in embryonated chicken eggs and has the potential to be used as a live-attenuated vaccine in humans. IMPORTANCE Noroviruses are the major cause of viral gastroenteritis worldwide. Currently, effective vaccines against norovirus infection are not available. In this study, we have evaluated Newcastle disease virus (NDV) as a vaccine vector for norovirus. Our results suggest that NDV can be used not only as a cost-effective method for large-scale production of norovirus-like particle vaccines but also as a live-attenuated vectored vaccine. PMID:24920815

  7. Total revision of the hip using allograft to correct particle disease induced osteolysis: a case study.

    PubMed

    Taylor, Drew W; Taylor, Jennifer E; Raizman, Igal; Gross, Allan E

    2009-01-01

    Total hip replacement is considered to be a highly successful and routine surgery; however, the internal components produce particles through friction and wear in the device. These particles are identified as one of the main reasons for total hip revisions. The generated, biologically active, particles provoke the formation of osteolytic areas through the inhibition of bone formation and increased fluid production. The resulting bone loss can be managed through the use of allograft bone in combination with bone chips and cement. In addition, implants constructed with highly porous trabecular metal can be used to further facilitate rapid and extensive tissue infiltration resulting in strong implant attachment. In this case study we show the use of a tibial allograft coupled with bone chips and cement to cover and support a lytic cyst in the proximal femur, distal to the greater trochanter. Additionally, we detail the use of a trabecular metal cup to halt the migration of the component into the acetabulum and promote greater fixation and bone ingrowth. PMID:19753282

  8. Particle therapy for noncancer diseases

    SciTech Connect

    Bert, Christoph; Engenhart-Cabillic, Rita; Durante, Marco [GSI Helmholtzzentrum fuer Schwerionenforschung, Biophysics Department, Planckstrasse 1, 64291 Darmstadt (Germany); Philipps-University Marburg, Center for Radiology, Department of Radiation Therapy, Baldinger Strasse, 35043 Marburg (Germany); GSI Helmholtzzentrum fuer Schwerionenforschung, Biophysics Department, Planckstrasse 1, 64291 Darmstadt (Germany); Technische Universitaet Darmstadt, Institut fuer Festkoerperphysik, Hochschulstrasse 3, 64289 Darmstadt (Germany) and Frankfurt Institute for Advanced Studies, Johann Wolfgang Goethe University, Ruth-Moufang-Str. 1, 60438 Frankfurt am Main (Germany)

    2012-04-15

    Radiation therapy using high-energy charged particles is generally acknowledged as a powerful new technique in cancer treatment. However, particle therapy in oncology is still controversial, specifically because it is unclear whether the putative clinical advantages justify the high additional costs. However, particle therapy can find important applications in the management of noncancer diseases, especially in radiosurgery. Extension to other diseases and targets (both cranial and extracranial) may widen the applications of the technique and decrease the cost/benefit ratio of the accelerator facilities. Future challenges in this field include the use of different particles and energies, motion management in particle body radiotherapy and extension to new targets currently treated by catheter ablation (atrial fibrillation and renal denervation) or stereotactic radiation therapy (trigeminal neuralgia, epilepsy, and macular degeneration). Particle body radiosurgery could be a future key application of accelerator-based particle therapy facilities in 10 years from today.

  9. Venezuelan Equine Encephalitis Virus replicon particles can induce rapid protection against Foot-and-Mouth Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously shown that swine pretreated with a replication-defective human adenovirus vector (Ad5) containing the porcine type I interferon gene (poIFN-alpha/Beta) are sterilely protected when challenged one day later with Foot-and-Mouth Disease Virus (FMDV), but the dose required is relativ...

  10. Drug induced pulmonary parenchymal disease.

    PubMed

    Prasad, Rajendra; Gupta, Pawan; Singh, Abhijeet; Goel, Nitin

    2014-12-01

    Drug-induced pulmonary parenchymal disease (DIPPD) can be caused by a variety of agents, including antibiotics, chemotherapeutic drugs, antiarrhythmic agents and non-steroidal anti-inflammatory drugs (NSAIDs). DIPPD includes acute bronchospasm, organizing pneumonia, alveolar hypoventilation and hypersensitivity reactions. History, physical examination and investigations are required mainly to exclude other causes of lung diseases. Investigations may include chest radiography, pulmonary function testing and bronchoscopy with bronchoalveolar lavage (BAL). Recognition of DIPPD is difficult because the clinical, radiologic, and histologic findings are nonspecific. Management includes drug withdrawal and in some cases corticosteroid therapy. In this article we reviewed the various drugs known to cause pulmonary parenchymal diseases, various patterns of parenchymal diseases observed and their management. PMID:25639301

  11. Energetic Particle-induced Geodesic Acoustic Mode

    SciTech Connect

    Fu, G.Y.

    2008-09-12

    A new energetic particle-induced Geodesic Acoustic Mode (EGAM) is shown to exist. The mode frequency, mode structure, and mode destabilization are determined non-perturbatively by energetic particle kinetic effects. In particular the EGAM frequency is found to be substantially lower than the standard GAM frequency. The radial mode width is determined by the energetic particle drift orbit width and can be fairly large for high energetic particle pressure and large safety factor. These results are consistent with the recent experimental observation of the beam- driven n=0 mode in DIII-D. The new mode is important since it can degrade energetic particle confinement as shown in the DIII-D experiments. The new mode may also affect the thermal plasma confinement via its interaction with plasma micro-turbulence.

  12. Diphenylhydantoin (phenytoin)-induced chronic pulmonary disease

    PubMed Central

    Dixit, Ramakant; Dixit, Kalpana; Nuwal, Paras; Banerjee, Arunima; Sharma, Sidharth; Dave, Lokendra

    2009-01-01

    Drug-induced respiratory diseases are difficult to diagnose and therefore usually not identified, probably underestimated and under-reported. We report a case of diphenylhydantoin/phenytoin-induced chronic pulmonary disease in a 62-year-old male patient presenting with progressive dyspnea, eosinophilia, and pulmonary abnormalities. The importance of drug history in clinical history-taking and early diagnosis of drug-induced respiratory diseases is emphasized so as to prevent permanent pulmonary damage. PMID:20532004

  13. Induced Disease Resistance in Plants by Chemicals

    Microsoft Academic Search

    Michael Oostendorp; Walter Kunz; Bob Dietrich; Theodor Staub

    2001-01-01

    Plants can be induced locally and systemically to become more resistant to diseases through various biotic or abiotic stresses. The biological inducers include necrotizing pathogens, non- pathogens or root colonizing bacteria. Through at network of signal pathways they induce resistance spectra and marker proteins that are characteristic for the different plant species and activation systems. The best characterized signal pathway

  14. Metal-induced diffuse lung disease.

    PubMed

    Fontenot, Andrew P; Amicosante, Massimo

    2008-12-01

    The number of metals that are associated with the development of diffuse parenchymal lung disease continues to expand. In addition to lung fibrosis, inhalation of metal particulates can induce a wide range of lung pathology, including reactive airways disease and cancer. This article focuses on diffuse parenchymal diseases resulting from the inhalation of beryllium and cobalt. More is known regarding the immunopathogenesis of beryllium-induced disease than is known for disease induced by any other metal. Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium exposure in the workplace and is characterized by the accumulation of beryllium-specific CD4 (+) T cells in the bronchoalveolar lavage. Genetic susceptibility markers associated with increased risk have been identified for both CBD and hard metal lung disease. The mechanism for the genetic susceptibility of CBD lies in the ability of certain human leukocyte antigen (HLA)-DP molecules to bind and present beryllium to pathogenic CD4 (+) T cells. Whether the same is true for hard metal lung disease is unknown. In contrast, no HLA allelic association has been identified in nickel allergic subjects. The study of metal-induced lung disease allows the investigation of the relationship between environmental exposure and genetic susceptibility. These studies will enhance our understanding of the immunopathogenesis of metal-induced disease and how exposure to these metals results in irreversible lung fibrosis. PMID:19221964

  15. Particle production in antiproton induced nuclear reactions

    E-print Network

    Zhao-Qing Feng; Horst Lenske

    2014-05-07

    The quantum molecular dynamics model has been improved to investigate the reaction dynamics induced by antiprotons. The reaction channels of elastic scattering, annihilation, charge exchange and inelastic collisions have been included in the model. Dynamics on particle production, in particular pions, kaons, antikaons and hyperons, is investigated in collisions of $\\overline{p}$ on $^{12}$C, $^{20}$Ne, $^{40}$Ca, $^{112}$Sn, $^{181}$Ta, $^{197}$Au and $^{238}$U from a low to high incident momentum. The rapidity and momentum distributions of $\\pi^{+}$ and protons from the LEAR measurements can be well reproduced. The impacts of system size and incident momentum on particle emissions are investigated from the inclusive spectra, transverse momentum and rapidity distributions. It is found that the annihilations of $\\overline{p}$ on nucleons are of importance on the particle production. Hyperons are mainly produced via meson induced reactions on nucleons and strangeness exchange collisions when the incident momentum is below the threshold value of annihilation reaction. A higher nuclear temperature is obtained from the kaon emission, but it has a lower value for hyperon production.

  16. Alpha-particle-induced cancer in humans.

    PubMed

    Mays, C W

    1988-10-01

    Updated information is given on alpha-particle-induced cancer in persons internally exposed to 222Rn progeny, Thorotrast, long-lived 226Ra and 228Ra, and short-lived 224Ra. The lung cancer risk to persons breathing 222Rn progeny in the indoor air of offices, schools, and homes is of increasing concern. About half of the recent deaths among the German Thorotrast patients have been from liver cancer. Animal studies indicate that the liver cancer risk from Thorotrast is mainly from its radioactivity and that the risk coefficient for the Thorotrast patients can be used provisionally for other alpha emitters in the human liver. Six skeletal cancers have occurred in persons with average skeletal doses between 0.85 and 11.8 Gy from 226Ra and 228Ra. In the low-dose German 224Ra patients, two skeletal sarcomas have occurred at about 0.7 Gy compared to about six cases predicted by results from 224Ra patients at higher doses. The minimal appearance time for radiation-induced bone sarcomas in humans is about 4 y. Following brief irradiation, the vast majority of induced bone sarcomas are expressed by about 30 y. Recent evidence against the "practical threshold" hypothesis is given. With the downward revision of neutron doses to the atomic-bomb survivors, the follow-up of persons exposed to alpha particles may be the best opportunity to evaluate directly the effects of high LET radiation on humans. PMID:2844697

  17. Disease-specific induced pluripotent stem cells.

    PubMed

    Park, In-Hyun; Arora, Natasha; Huo, Hongguang; Maherali, Nimet; Ahfeldt, Tim; Shimamura, Akiko; Lensch, M William; Cowan, Chad; Hochedlinger, Konrad; Daley, George Q

    2008-09-01

    Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development. PMID:18691744

  18. Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

    PubMed Central

    Saber, Anne Thoustrup; Lamson, Jacob Stuart; Jacobsen, Nicklas Raun; Ravn-Haren, Gitte; Hougaard, Karin Sørig; Nyendi, Allen Njimeri; Wahlberg, Pia; Madsen, Anne Mette; Jackson, Petra; Wallin, Håkan; Vogel, Ulla

    2013-01-01

    Background Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk. Methods We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes. Results Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points. Conclusions Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease. PMID:23894396

  19. Neuroinflammation in Overnutrition-induced Diseases

    PubMed Central

    Cai, Dongsheng

    2015-01-01

    Inflammation is a biological response mounted by the immune system against dangerous assaults that threaten the integrity and normal physiology of an organism. During the past decades, cross-disciplinary research from immunology and endocrinology has much broadened this knowledge by demonstrating that chronic conditions of nutritional excess constitute an independent category of inflammatory activators, and the resulting chronic and low-grade inflammation is an important characteristic of overnutrition-induced diseases. A large body of research has demonstrated that these diseases are pathogenically associated with the local, negative actions of inflammation in peripheral tissues predominantly including the liver, muscle and fat. In this research background, more recent research has advanced to a new level, with the important discoveries showing that overnutrition-induced inflammation occurs in the brain and thus plays a broad and leadership role in overnutrition-induced diseases. While much more research establishments are expected in this emerging and quickly expanding research, the appreciated understandings have been mainly based on proinflammatory IKK?/NF-?B pathway and related molecules in the hypothalamus. In this chapter, the author focuses on describing IKK?/NF-?B-induced neural inflammation in the context of overnutrition-induced metabolic inflammation and especially the central roles of this neural inflammation in the development of a spectrum of overnutrition-related diseases. PMID:23374717

  20. Rasagiline induced hypersexuality in Parkinson's disease.

    PubMed

    Reyes, Dennys; Kurako, Kateryna; Galvez-Jimenez, Nestor

    2014-03-01

    Impulse control disorders (ICD) are increasingly recognized in patients with Parkinson's disease (PD), particularly when treated with commonly used dopamine agonists such as pramipexole and ropinirole. Less evident is the possible association between monoamine oxidase inhibitors type B (MAO-B) and the development of ICD. Rasagiline is a second generation MAO-B I inducing moderate symptomatic and possibly disease modifying benefits with apparently good tolerability and safety profile in PD patients. Rasagiline is effective and well tolerated in PD as a monotherapy or in combination with levodopa. Here, we report a patient with PD who developed ICD when treated de novo with MAO-B inhibitors. PMID:24055209

  1. Neurobiology of Disease Alzheimer's Disease-Like Pathology Induced by Amyloid-

    E-print Network

    Munoz, Douglas Perry

    for AD. Key words: Alzheimer's disease; amyloid- oligomers; nonhuman primate; synapse loss; tau pathologyNeurobiology of Disease Alzheimer's Disease-Like Pathology Induced by Amyloid- Oligomers of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208 Alzheimer's disease (AD

  2. Suppression of nanosilica particle-induced inflammation by surface modification of the particles.

    PubMed

    Morishige, Tomohiro; Yoshioka, Yasuo; Inakura, Hiroshi; Tanabe, Aya; Narimatsu, Shogo; Yao, Xinglei; Monobe, Youko; Imazawa, Takayoshi; Tsunoda, Shin-ichi; Tsutsumi, Yasuo; Mukai, Yohei; Okada, Naoki; Nakagawa, Shinsaku

    2012-08-01

    It has gradually become evident that nanomaterials, which are widely used in cosmetics, foods, and medicinal products, could induce substantial inflammation. However, the roles played by the physical characteristics of nanomaterials in inflammatory responses have not been elucidated. Here, we examined how particle size and surface modification influenced the inflammatory effects of nanosilica particles, and we investigated the mechanisms by which the particles induced inflammation. We compared the inflammatory effects of silica particles with diameters of 30-1,000 nm in vitro and in vivo. In macrophages in vitro, 30- and 70-nm nanosilica particles (nSP30 and nSP70) induced higher production of tumor necrosis factor-? (TNF?) than did larger particles. In addition, intraperitoneal injection of nSP30 and nSP70 induced stronger inflammatory responses involving cytokine production than did larger particles in mice. nSP70-induced TNF? production in macrophage depended on the production of reactive oxygen species and the activation of mitogen-activated protein kinases (MAPKs). Furthermore, nSP70-induced inflammatory responses were dramatically suppressed by surface modification of the particles with carboxyl groups in vitro and in vivo; the mechanism of the suppression involved reduction in MAPK activation. These results provide basic information that will be useful for the development of safe nanomaterials. PMID:22418595

  3. SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

    Microsoft Academic Search

    Diaz-Sanchez

    2000-01-01

    Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies.

  4. Environmentally induced autoimmune diseases: potential mechanisms.

    PubMed Central

    Rao, T; Richardson, B

    1999-01-01

    Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists. PMID:10502539

  5. Ultrasound-inducible fluorescent particles for internal tattooing

    Microsoft Academic Search

    O. Couture; N. Pannacci; A. Babataheri; P. Tabeling; M. Fink; M. Tanter; V. Servois

    2009-01-01

    Our objective is to selectively and non-invasively deposits markers under image guidance for internal tattooing. This study describes the production of ultrasound-inducible particles carrying large payloads of fluorescent markers and the in vivo proof of concept of their remote deposit via focused ultrasound. The particles are double emulsions produced in a microfluidic system, consisting of aqueous fluorescein in perfluorocarbon in

  6. Optics of spin-1 particles from gravity-induced phases

    E-print Network

    G. Papini; G. Scarpetta; A. Feoli; G. Lambiase

    2007-11-19

    The Maxwell and Maxwell-de Rham equations can be solved exactly to first order in an external gravitational field. The gravitational background induces phases in the wave functions of spin-1 particles. These phases yield the optics of the particles without requiring any thin lens approximation.

  7. Case Report: Subdural Hematoma in Grave's Disease Induced Thrombocytopenia.

    E-print Network

    Carr, Leslie

    1 Case Report: Subdural Hematoma in Grave's Disease Induced Thrombocytopenia. Authors Sunil Kumar. Subdural Hematoma in Grave's Disease Induced Thrombocytopenia. Online J Health Allied Scs.2012 and menorrhagia and later diagnosed to be a case of Grave's disease with thrombocytopenia with sub dural hematoma

  8. Method for ion implantation induced embedded particle formation via reduction

    DOEpatents

    Hampikian, Janet M (Decatur, GA); Hunt, Eden M (Atlanta, GA)

    2001-01-01

    A method for ion implantation induced embedded particle formation via reduction with the steps of ion implantation with an ion/element that will chemically reduce the chosen substrate material, implantation of the ion/element to a sufficient concentration and at a sufficient energy for particle formation, and control of the temperature of the substrate during implantation. A preferred embodiment includes the formation of particles which are nano-dimensional (<100 m-n in size). The phase of the particles may be affected by control of the substrate temperature during and/or after the ion implantation process.

  9. Aeolian Induced Erosion and Particle Entrainment

    NASA Technical Reports Server (NTRS)

    Saint, Brandon

    2007-01-01

    The Granular Physics Department at The Kennedy Space Center is addressing the problem of erosion on the lunar surface. The early stages of research required an instrument that would produce erosion at a specific rate with a specific sample variation. This paper focuses on the development and experimental procedures to measure and record erosion rates. This was done with the construction of an open air wind tunnel, and examining the relationship between airflow and particle motion.

  10. Asbestos-induced lung diseases: an update

    PubMed Central

    KAMP, DAVID W.

    2009-01-01

    Asbestos causes asbestosis (pulmonary fibrosis caused by asbestos inhalation) and malignancies (bronchogenic carcinoma and mesothelioma) by mechanisms that are not fully elucidated. Despite a dramatic reduction in asbestos use worldwide, asbestos-induced lung diseases remain a substantial health concern primarily because of the vast amounts of fibers that have been mined, processed, and used during the 20th century combined with the long latency period of up to 40 years between exposure and disease presentation. This review summarizes the important new epidemiologic and pathogenic information that has emerged over the past several years. Whereas the development of asbestosis is directly associated with the magnitude and duration of asbestos exposure, the development of a malignant clone of cells can occur in the setting of low-level asbestos exposure. Emphasis is placed on the recent epidemiologic investigations that explore the malignancy risk that occurs from nonoccupational, environmental asbestos exposure. Accumulating studies are shedding light on novel mechanistic pathways by which asbestos damages the lung. Attention is focused on the importance of alveolar epithelial cell (AEC) injury and repair, the role of iron-derived reactive oxygen species (ROS), and apoptosis by the p53- and mitochondria-regulated death pathways. Furthermore, recent evidence underscores crucial roles for specific cellular signaling pathways that regulate the production of cytokines and growth factors. An evolving role for epithelial-mesenchymal transition (EMT) is also reviewed. The translational significance of these studies is evident in providing the molecular basis for developing novel therapeutic strategies for asbestos-related lung diseases and, importantly, other pulmonary diseases, such as interstitial pulmonary fibrosis and lung cancer. PMID:19304273

  11. Gyrokinetic particle simulation of beta-induced Alfven eigenmode

    SciTech Connect

    Zhang, H. S. [Fusion Simulation Center and State Key Laboratory of Nuclear Physics and Technology, Peking University, Beijing 100871 (China); Department of Physics and Astronomy, University of California, Irvine, Irvine, California 92697 (United States); Lin, Z.; Holod, I.; Xiao, Y. [Department of Physics and Astronomy, University of California, Irvine, Irvine, California 92697 (United States); Wang, X. [Institute for Fusion Theory and Simulation, Zhejiang University, Hangzhou 310027 (China); Department of Physics and Astronomy, University of California, Irvine, Irvine, California 92697 (United States); Zhang, W. L. [CAS Key Laboratory of Plasma Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Department of Physics and Astronomy, University of California, Irvine, Irvine, California 92697 (United States)

    2010-11-15

    The beta-induced Alfven eigenmode (BAE) in toroidal plasmas is studied using global gyrokinetic particle simulations. The BAE real frequency and damping rate measured in the initial perturbation simulation and in the antenna excitation simulation agree well with each other. The real frequency is slightly higher than the ideal magnetohydrodynamic (MHD) accumulation point frequency due to the kinetic effects of thermal ions. Simulations with energetic particle density gradient show exponential growth of BAE with a growth rate sensitive to the energetic particle temperature and density. The nonperturbative contributions by energetic particles modify the mode structure and reduce the frequency relative to the MHD theory. The finite Larmor radius effects of energetic particles reduce the BAE growth rate. Benchmarks between gyrokinetic particle simulation and hybrid MHD-gyrokinetic simulation show good agreement in BAE real frequency and mode structure.

  12. Nanoceria Particles Prevent ROI-Induced Blindness

    Microsoft Academic Search

    Junping Chen; Swanand Patil; Sudipta Seal; James F. McGinnis

    Retinal degeneration caused blindness, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis\\u000a pigmentosa (RP) and retinal detachment, is a major problem in clinical ophthalmology.Although genetic modifications are responsible\\u000a for most retinal degenerative diseases, there is increasing evidence showing that reactive oxygen intermediates (ROIs), the\\u000a byproducts of the oxidative metabolic reactions, are closely involved in the process of photoreceptor

  13. Hormetic Effect Induced by Alpha-Particle-Induced Stress Communicated In Vivo between Zebrafish Embryos

    E-print Network

    Yu, K.N.

    Hormetic Effect Induced by Alpha-Particle-Induced Stress Communicated In Vivo between Zebrafish data showing that embryos of the zebrafish, Danio rerio, at 1.5 h post fertilization (hpf) subjected be communicated to unirradiated bystander zebrafish embryos sharing the same water medium to induce a hormetic

  14. Interaction-induced connectivity of disordered two-particle states

    NASA Astrophysics Data System (ADS)

    Krimer, D. O.; Flach, S.

    2015-03-01

    We study the interaction-induced connectivity in the Fock space of two particles in a disordered one-dimensional potential. Recent computational studies showed that the largest localization length ?2 of two interacting particles in a weakly random tight-binding chain is increasing unexpectedly slow relative to the single-particle localization length ?1, questioning previous scaling estimates. We show this to be a consequence of the approximate restoring of momentum conservation of weakly localized single-particle eigenstates, and disorder-induced phase shifts for partially overlapping states. The leading resonant links appear among states which share the same energy and momentum. We substantiate our analytical approach by computational studies for up to ?1=1000 . A potential nontrivial scaling regime sets in for ?1?400 .

  15. Infectious particles, stress, and induced prion amyloids

    PubMed Central

    2013-01-01

    Transmissible encephalopathies (TSEs) are believed by many to arise by spontaneous conversion of host prion protein (PrP) into an infectious amyloid (PrP-res, PrPSc) without nucleic acid. Many TSE agents reside in the environment, with infection controlled by public health measures. These include the disappearance of kuru with the cessation of ritual cannibalism, the dramatic reduction of epidemic bovine encephalopathy (BSE) by removal of contaminated feed, and the lack of endemic scrapie in geographically isolated Australian sheep with susceptible PrP genotypes. While prion protein modeling has engendered an intense focus on common types of protein misfolding and amyloid formation in diverse organisms and diseases, the biological characteristics of infectious TSE agents, and their recognition by the host as foreign entities, raises several fundamental new directions for fruitful investigation such as: (1) unrecognized microbial agents in the environmental metagenome that may cause latent neurodegenerative disease, (2) the evolutionary social and protective functions of different amyloid proteins in diverse organisms from bacteria to mammals, and (3) amyloid formation as a beneficial innate immune response to stress (infectious and non-infectious). This innate process however, once initiated, can become unstoppable in accelerated neuronal aging. PMID:23633671

  16. Radiation induces turbulence in particle-laden fluids

    SciTech Connect

    Zamansky, Rémi [Centre for Turbulence Research, Stanford University, Stanford, California 94305-3035 (United States); Coletti, Filippo [Mechanical Engineering, Stanford University, California 94305-3035 (United States); Massot, Marc [Centre for Turbulence Research, Stanford University, Stanford, California 94305-3035 (United States); Ecole Centrale Paris, Laboratoire EM2C - UPR CNRS 288 et Fédération de Mathématiques - FR CNRS 3487, Grande Voie des Vignes, 92295 Chatenay-Malabry Cedex (France); Mani, Ali [Centre for Turbulence Research, Stanford University, Stanford, California 94305-3035 (United States); Mechanical Engineering, Stanford University, California 94305-3035 (United States)

    2014-07-15

    When a transparent fluid laden with solid particles is subject to radiative heating, non-uniformities in particle distribution result in local fluid temperature fluctuations. Under the influence of gravity, buoyancy induces vortical fluid motion which can lead to strong preferential concentration, enhancing the local heating and more non-uniformities in particle distribution. By employing direct numerical simulations this study shows that the described feedback loop can create and sustain turbulence. The velocity and length scale of the resulting turbulence is not known a priori, and is set by balance between viscous forces and buoyancy effects. When the particle response time is comparable to a viscous time scale, introduced in our analysis, the system exhibits intense fluctuations of turbulent kinetic energy and strong preferential concentration of particles.

  17. Particle-induced amorphization complex ceramic

    SciTech Connect

    Ewing, R.C.; Wang, Lu-Min

    1996-02-16

    The presently funded three-year research program, supported by the Division of Materials Sciences of the Office of Basic Energy Sciences, was initiated on August 1, 1993; during the period in which the grant will have been active, $249,561 of support have been provided to date with an additional $79,723 to be spent during the third, final year (ending July 30, 1996). The primary purpose of the program is to develop an understanding of heavy-particle radiation effects -- {alpha}-recoil nuclei, fission fragments, ion-irradiations -- on ceramic materials and the thermal annealing mechanisms by which crystallinity might be restored. During the past two years, we have completed major studies on zircon (ZrSiO{sub 4}), olivine (Mg{sub 2}SiO{sub 4} and ten other compositions), spinel (MgAl{sub 2}O{sub 4} and four other compositions), and silica polymorphs (quartz, coesite and stishovite), as well as berlinite (AlPO{sub 4}) which is isomorphous with quartz. In addition, based on the above research, we propose the use of zircon as a host phase for the immobilization of plutonium resulting from weapons dismantlement.

  18. Channel flow induced by wall injection of fluid and particles

    NASA Astrophysics Data System (ADS)

    Féraille, Thierry; Casalis, Grégoire

    2003-02-01

    The Taylor flow is the laminar single-phase flow induced by gas injection through porous walls, and is assumed to represent the flow inside solid propellant motors. Such a flow is intrinsically unstable, and the generated instabilities are probably responsible for the thrust oscillations observed in the aforesaid motors. However particles are embedded in the propellants usually used, and are released in the fluid by the lateral walls during the combustion, so that there are two heterogeneous phases in the flow. The purpose of this paper is to study the influence of these particles on stability by comparison with stability results from the single-phase studies, in a plane two-dimensional configuration. The particles are supposed to be chemically inert and of a uniform size. In order to carry out a linear stability study for this flow modified by the presence of particles, the mean particle velocity field is first determined, assuming that only the gas exerts forces on the particles. This field is sought in a self-similar form, which imposes a limit on the size of the particles. However, the particle mass concentration cannot be obtained in a self-similar form, but can only be described by a partial differential equation. The mean flow characteristics being determined, the spectrum of the discretized linear stability operator shows first that particle addition does not trigger any new "dangerous" modes compared with the single-phase flow case. It also shows that the most amplified mode in the case of the single-phase flow remains the most amplified mode in the case of the two-phase flow. Moreover, the addition of particles acts continuously upon stability results, behaving linearly with respect to the particle mass concentration when the latter is small. The linear correction to the monophasic mode, as well as the evolution of the modes with weak values of the particle mass concentration at the wall, are shown to be proportional to the ejection velocity of the particles. Then, the evolution of the eigenmodes from a given injection speed of the particles to another one is deduced by affinity, all other parameters being fixed. With a fixed Stokes number, stability results for a finite Reynolds number and results for the inviscid flow bring together when augmenting the particle mass concentration at the wall. Therefore, by knowing single-phase flow results and the evolution of stability characteristics of the two-phase flow in the inviscid case, it is easy to determine whether particle-laden Taylor flow is more or less stable than the monophasic Taylor flow for large particle mass concentration.

  19. CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES

    EPA Science Inventory

    Abstract Submitted to the American Thoracic Society 98th International Conference, May 17 - 22, 2002, Atlanta, GA CARDIAC MOLECULAR EFFECTS INDUCED BY AIR POLLUTION PARTICLES K. Dreher1, R. Jaskot1, J. Richards1, and T. Knuckles2. 1U. S. Environmental Protection Agency,...

  20. A compilation of charged-particle induced thermonuclear reaction rates

    Microsoft Academic Search

    C. Angulo; M. Arnould; M. Rayet; P. Descouvemont; D. Baye; C. Leclercq-Willain; A. Coc; S. Barhoumi; P. Aguer; C. Rolfs; R. Kunz; J. W. Hammer; A. Mayer; T. Paradellis; S. Kossionides; C. Chronidou; K. Spyrou; S. Degl'Innocenti; G. Fiorentini; B. Ricci; S. Zavatarelli; C. Providencia; H. Wolters; J. Soares; C. Grama; J. Rahighi; A. Shotter; M. Lamehi Rachti

    1999-01-01

    Low-energy cross section data for 86 charged-particle induced reactions involving light (1 ? Z ? 14), mostly stable, nuclei are compiled. The corresponding Maxwellian-averaged thermonuclear reaction rates of relevance in astrophysical plasmas at temperatures in the range from 106 K to 1010 K are calculated. These evaluations assume either that the target nuclei are in their ground state, or that

  1. External front instabilities induced by a shocked particle ring

    NASA Astrophysics Data System (ADS)

    Rodriguez, V.; Saurel, R.; Jourdan, G.; Houas, L.

    2014-10-01

    The dispersion of a cylindrical particle ring by a blast or shock wave induces the formation of coherent structures which take the form of particle jets. A blast wave, issuing from the discharge of a planar shock wave at the exit of a conventional shock tube, is generated in the center of a granular medium ring initially confined inside a Hele-Shaw cell. With the present experimental setup, under impulsive acceleration, a solid particle-jet formation is observed in a quasi-two-dimensional configuration. The aim of the present investigation is to observe in detail the formation of very thin perturbations created around the external surface of the dispersed particle layer. By means of fast flow visualization with an appropriate recording window, we focus solely on the first instants during which the external particle ring becomes unstable. We find that the critical area of the destabilization of the external ring surface is constant regardless of the acceleration of the initial layer. Moreover, we observe in detail the external front perturbation wavelength, rendered dimensionless by the initial ring perimeter, and follow its evolution with the initial particle layer acceleration. We report this quantity to be constant regardless of the evolution of the initial particle layer acceleration. Finally, we can reasonably assert that external front perturbations depend solely on the material of the particles.

  2. Macrophage Polarization and Activation in Response to Implant Debris: Influence by “Particle Disease” and “Ion Disease

    PubMed Central

    Konttinen, Yrjö T.; Pajarinen, Jukka; Takakubo, Yuja; Gallo, Jiri; Nich, Christophe; Takagi, Michiaki; Goodman, Stuart B.

    2015-01-01

    Macrophages derive from human embryonic and fetal stem cells and from human bone marrow-derived blood monocytes. They play a major homeostatic role in tissue remodeling and maintenance facilitated by apoptotic “eat me” opsonins like CRP, serum amyloid P, C1q, C3b, IgM, ficolin, and surfactant proteins. Three subsets of monocytes, classic, intermediate, and nonclassic, are mobilized and transmigrate to tissues. Implant-derived wear particles opsonized by danger signals regulate macrophage priming, polarization (M1, M2, M17, and Mreg), and activation. CD14+ monocytes in healthy controls and CD16+ monocytes in inflammation differentiate/polarize to foreign body giant cells/osteoclasts or inflammatory dendritic cells (infDC). These danger signal opsonins can be pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), but in aseptic loosening, usually are damage-associated molecular patterns (DAMPs). Danger signal-opsonized particles elicit “particle disease” and aseptic loosening. They provide soluble and cell membrane-bound co-stimulatory signals that can lead to cell-mediated immune reactions to metal ions. Metal-on-metal implant failure has disclosed that quite like Ni2+, its neighbor in the periodic table Co2+ can directly activate toll-like receptor 4 (TLR4) as a lipopolysaccharide-mimic. “Ion disease” concept needs to be incorporated into the “particle disease” concept, due to the toxic, immune, and inflammatory potential of metal ions. PMID:25747030

  3. Macrophage polarization and activation in response to implant debris: influence by "particle disease" and "ion disease".

    PubMed

    Konttinen, Yrjo T; Pajarinen, Jukka; Takakubo, Yuya; Gallo, Jiri; Nich, Christophe; Takagi, Michiaki; Goodman, Stuart B

    2014-01-01

    Macrophages derive from human embryonic and fetal stem cells and from human bone marrow-derived blood monocytes. They play a major homeostatic role in tissue remodeling and maintenance facilitated by apoptotic "eat me" opsonins like CRP, serum amyloid P, C1q, C3b, IgM, ficolin, and surfactant proteins. Three subsets of monocytes, classic, intermediate, and nonclassic, are mobilized and transmigrate to tissues. Implant-derived wear particles opsonized by danger signals regulate macrophage priming, polarization (M1, M2, M17, and Mreg), and activation. CD14+ monocytes in healthy controls and CD16+ monocytes in inflammation differentiate/polarize to foreign body giant cells/osteoclasts or inflammatory dendritic cells (infDC). These danger signal opsonins can be pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), but in aseptic loosening, usually are damage-associated molecular patterns (DAMPs). Danger signal-opsonized particles elicit "particle disease" and aseptic loosening. They provide soluble and cell membrane-bound co-stimulatory signals that can lead to cell-mediated immune reactions to metal ions. Metal-on-metal implant failure has disclosed that quite like Ni2+, its neighbor in the periodic table Co2+ can directly activate toll-like receptor 4 (TLR4) as a lipopolysaccharide-mimic. "Ion disease" concept needs to be incorporated into the "particle disease" concept, due to the toxic, immune, and inflammatory potential of metal ions. PMID:25747030

  4. Radiation-induced coronary artery disease

    SciTech Connect

    Dunsmore, L.D.; LoPonte, M.A.; Dunsmore, R.A.

    1986-07-01

    This report describes three patients who developed myocardial infarction at an untimely age, 4 to 12 years after radiation therapy for Hodgkin's disease. These cases lend credence to the cause and effect relation of such therapy to coronary artery disease.

  5. Histone hyperacetylation can induce unfolding of the nucleosome core particle.

    PubMed Central

    Oliva, R; Bazett-Jones, D P; Locklear, L; Dixon, G H

    1990-01-01

    A direct correlation exists between the level of histone H4 hyperacetylation induced by sodium butyrate and the extent to which nucleosomes lose their compact shape and become elongated (62.0% of the particles have a length/width ratio over 1.6; overall mean in the length/width ratio = 1.83 +/- 0.48) when bound to electron microscope specimen grids at low ionic strength (1mM EDTA, 10mM Tris, pH 8.0). A marked proportion of elongated core particles is also observed in the naturally occurring hyperacetylated chicken testis chromatin undergoing spermatogenesis when analyzed at low ionic strength (36.8% of the particles have a length/width ratio over 1.6). Core particles of elongated shape (length/width ratio over 1.6) generated under low ionic strength conditions are absent in the hypoacetylated chicken erythrocyte chromatin and represent only 2.3% of the untreated Hela S3 cell core particles containing a low proportion of hyperacetylated histones. The marked differences between control and hyperacetylated core particles are absent if the particles are bound to the carbon support film in the presence of 0.2 M NaCl, 6mM MgCl2 and 10mM Tris pH 8.0, conditions known to stabilize nucleosomes. A survey of the published work on histone hyperacetylation together with the present results indicate that histone hyperacetylation does not produce any marked disruption of the core particle 'per se', but that it decreases intranucleosomal stabilizing forces as judged by the lowered stability of the hyperacetylated core particle under conditions of shearing stress such as cationic competition by the carbon support film of the EM grid for DNA binding. Images PMID:2339060

  6. Dual neutral particle induced transmutation in CINDER2008

    NASA Astrophysics Data System (ADS)

    Martin, W. J.; de Oliveira, C. R. E.; Hecht, A. A.

    2014-12-01

    Although nuclear transmutation methods for fission have existed for decades, the focus has been on neutron-induced reactions. Recent novel concepts have sought to use both neutrons and photons for purposes such as active interrogation of cargo to detect the smuggling of highly enriched uranium, a concept that would require modeling the transmutation caused by both incident particles. As photonuclear transmutation has yet to be modeled alongside neutron-induced transmutation in a production code, new methods need to be developed. The CINDER2008 nuclear transmutation code from Los Alamos National Laboratory is extended from neutron applications to dual neutral particle applications, allowing both neutron- and photon-induced reactions for this modeling with a focus on fission. Following standard reaction modeling, the induced fission reaction is understood as a two-part reaction, with an entrance channel to the excited compound nucleus, and an exit channel from the excited compound nucleus to the fission fragmentation. Because photofission yield data-the exit channel from the compound nucleus-are sparse, neutron fission yield data are used in this work. With a different compound nucleus and excitation, the translation to the excited compound state is modified, as appropriate. A verification and validation of these methods and data has been performed. This has shown that the translation of neutron-induced fission product yield sets, and their use in photonuclear applications, is appropriate, and that the code has been extended correctly.

  7. Nuclear reactions induced by high-energy alpha particles

    NASA Technical Reports Server (NTRS)

    Shen, B. S. P.

    1974-01-01

    Experimental and theoretical studies of nuclear reactions induced by high energy protons and heavier ions are included. Fundamental data needed in the shielding, dosimetry, and radiobiology of high energy particles produced by accelerators were generated, along with data on cosmic ray interaction with matter. The mechanism of high energy nucleon-nucleus reactions is also examined, especially for light target nuclei of mass number comparable to that of biological tissue.

  8. Induced pluripotent stem cells and neurodegenerative diseases

    Microsoft Academic Search

    Chao Chen; Shi-Fu Xiao

    2011-01-01

    Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Amyotrophic Lateral Sclerosis, are characterized\\u000a by idiopathic neuron loss in different regions of the central nervous system, which contributes to the relevant dysfunctions\\u000a in the patients. The application of cell replacement therapy using human embryonic stem (hES) cells, though having attracted\\u000a much attention, has been hampered by the intrinsic ethical problems. It

  9. Alpha Particles Induce Apoptosis through the Sphingomyelin Pathway

    PubMed Central

    Seideman, Jonathan H.; Stancevic, Branka; Rotolo, Jimmy A.; McDevitt, Michael R.; Howell, Roger W.; Kolesnick, Richard N.; Scheinberg, David A.

    2011-01-01

    The sphingomyelin pathway involves the enzymatic cleavage of sphingomyelin to produce ceramide, a second messenger that serves as a key mediator in the rapid apoptotic response to various cell stressors. Low-linear energy transfer (LET) ? radiation can initiate this pathway, independent of DNA damage, via the cell membrane. Whether short-ranged, high-LET a particles, which are of interest as potent environmental carcinogens, radiotherapies and potential components of dirty bombs, can act through this mechanism to signal apoptosis is unknown. Here we show that irradiation of Jurkat cells with a particles emitted by the 225Ac-DOTA-anti-CD3 IgG antibody construct results in dose-dependent apoptosis. This apoptosis was significantly reduced by pretreating cells with cholesterol-depleting nystatin, a reagent known to inhibit ceramide signaling by interfering with membrane raft coalescence and ceramide-rich platform generation. The effects of nystatin on ?-particle-induced apoptosis were related to disruption of the ceramide pathway and not to microdosimetry alterations, because similar results were obtained after external irradiation of the cells with a broad beam of collimated a particles using a planar 241Am source. External irradiation allowed for more precise control of the dosimetry and geometry of the irradiation, independent of antibody binding or cell internalization kinetics. Mechanistically consistent with these findings, Jurkat cells rapidly increased membrane concentrations of ceramide after external irradiation with an average of five ?-particle traversals per cell. These data indicate that a particles can activate the sphingomyelin pathway to induce apoptosis. PMID:21631289

  10. APOPTOTIC AND INFLAMMATORY EFFECTS INDUCED BY DIFFERENT PARTICLES IN HUMAN ALVEOLAR MACROPHAGES

    EPA Science Inventory

    Pollutant particles induce apoptosis and inflammation, but the relationship between these two biological processes is not entirely clear. In this study, we compared the proapoptotic and proinflammatory effects of four particles: residual oil fly ash (ROFA), St. Louis particles SR...

  11. Overview of Virus-induced Airway Disease

    Microsoft Academic Search

    Sebastian L. Johnston

    2005-01-01

    Acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are the major cause of morbidity, mortality, and health costs of both diseases. Currently available treatments are poorly effective in both acute treatment of and prevention of acute exacerbations. New treatments for intervention and prophylaxis are therefore required; to facilitate their development, we must understand the causes and mechanisms of

  12. SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

    SciTech Connect

    Diaz-Sanchez, David

    2000-08-20

    Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies. A link between industrialization and allergic disease has long been presumed. Indeed, only 50 years after the first recorded reported case of allergy in 1819, Charles Blackely wrote that the ''hay-fever epidemic'' was associated with the movement of people from the country into the cities. Ishizaki et al. (1987) found that people in Japan living on busy roads lined with cedar trees have more allergies to cedar than residents living on similar streets with much less traffic. Since that time other epidemiological studies have reported similar findings. Kramer, et al., showed that hay fever is greater in residential areas with heavy truck traffic, while Weiland, et al., reported that allergic symptoms correlate with the distance of residences to roads with heavy traffic.

  13. Comparison of toroidicity-induced Alfvén eigenmodes and energetic particle modes by gyrokinetic particle simulations

    SciTech Connect

    Zhang, Chenxi; Li, Ding [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China) [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Zhang, Wenlu [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China) [Department of Modern Physics, University of Science and Technology of China, Hefei 230026 (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Department of Physics and Astronomy, University of California, Irvine, California 92697 (United States); Lin, Zhihong [Department of Physics and Astronomy, University of California, Irvine, California 92697 (United States) [Department of Physics and Astronomy, University of California, Irvine, California 92697 (United States); Fusion Simulation Center, Peking University, Beijing 100871 (China)

    2013-05-15

    This work reports on linear global gyrokinetic particle simulations of the excitation of toroidicity-induced Alfvén eigenmodes (TAE) and energetic particle modes (EPM), and the comparison between these two modes. The TAE excitation by antenna clarifies the magnetohydrodynamic (MHD) mode structure and the discrete eigenmode exists in the gap between the upper and lower accumulation points. The TAE excitation by fast ions modifies the MHD mode structure because of radial symmetry breaking and the eigenmode frequency moves towards the lower accumulation point. The phase space structure of fast ions shows that both passing and trapped particles contribute to the TAE excitation and that trapped particles dominate the wave-particle resonance in our simulations. The growth rate of TAE is sensitive to the fast ion energy, density, and density gradient, which are also important factors contributing to the transition of the TAE to the EPM. The gyrokinetic particle simulations also confirm the excitation of EPM when the drive is stronger. The frequency of the EPM is determined by the characteristic frequencies of fast ion motion in toroidal geometry.

  14. Original article Lentivirus-induced interstitial lung disease

    E-print Network

    Boyer, Edmond

    Original article Lentivirus-induced interstitial lung disease: pulmonary pathology in sheep a chronic disease in sheep affecting, among other organs, the lungs. Interstitial pneumonitis is similar the pathological features of lungs of sheep naturally infected with visna-maedi virus with the results obtained

  15. Drug-Induced Nephrotoxicity in Inflammatory Bowel Disease

    Microsoft Academic Search

    Konstantinos A. Oikonomou; Andreas N. Kapsoritakis; Ioannis Stefanidis; Spyros P. Potamianos

    2011-01-01

    Conservative management of inflammatory bowel disease (IBD) is based on a combination of drugs, including aminosalicylates (ASAs), steroids, antibiotics, immunosuppressives and biologic agents. Although various side effects have been related to treatment regimens, drug-induced nephrotoxicity is rather uncommon. Furthermore, it is often underestimated since renal function deterioration may be attributed to the underlying disease. The nephrotoxicity of ASAs and cyclosporine

  16. Food-Induced Immune Responses as Origin of Bowel Disease?

    Microsoft Academic Search

    Frank Seibold

    2005-01-01

    Food-induced immune responses cause or influence a number of intestinal diseases. Food antigens may either directly affect the mucosal immune system, or food modulate the intestinal flora, which may alter the immune response. The system preventing food-induced immune responses is complex: The mucosal barrier is the primary mechanism of host defense. Secondly, the innate immune system can neutralize some of

  17. The EPIC-MOS Particle-Induced Background Spectrum

    NASA Technical Reports Server (NTRS)

    Kuntz, K. D.; Snowden, S. L.

    2006-01-01

    We have developed a method for constructing a spectrum of the particle-induced instrumental background of the XMM-Newton EPIC MOS detectors that can be used for observations of the diffuse background and extended sources that fill a significant fraction of the instrument field of view. The strength and spectrum of the particle-induced background, that is, the background due to the interaction of particles with the detector and the detector surroundings, is temporally variable as well as spatially variable over individual chips. Our method uses a combination of the filter-wheel-closed data and a database of unexposed-region data to construct a spectrum of the "quiescent" background. We show that, using this method of background subtraction, the differences between independent observations of the same region of "blank sky" are consistent with the statistical uncertainties except when there is clear evidence of solar wind charge exchange emission. We use the blank sky observations to show that contamination by SWCX emission is a strong function of the solar wind proton flux, and that observations through the flanks of the magnetosheath appear to be contaminated only at much higher solar wind fluxes. We have also developed a spectral model of the residual soft proton flares, which allows their effects to be removed to a substantial degree during spectral fitting.

  18. Anchanling reduces pathology in a lactacystin- induced Parkinson's disease model?

    PubMed Central

    Li, Yinghong; Wu, Zhengzhi; Gao, Xiaowei; Zhu, Qingwei; Jin, Yu; Wu, Anmin; Huang, Andrew C. J.

    2012-01-01

    A rat model of Parkinson's disease was induced by injecting lactacystin stereotaxically into the left mesencephalic ventral tegmental area and substantia nigra pars compacta. After rats were intragastrically perfused with Anchanling, a Chinese medicine, mainly composed of magnolol, for 5 weeks, when compared with Parkinson's disease model rats, tyrosine hydroxylase expression was increased, ?-synuclein and ubiquitin expression was decreased, substantia nigra cell apoptosis was reduced, and apomorphine-induced rotational behavior was improved. Results suggested that Anchanling can ameliorate Parkinson's disease pathology possibly by enhancing degradation activity of the ubiquitin-proteasome system.

  19. Solar radiation induced rotational bursting of interplanetary particles

    NASA Technical Reports Server (NTRS)

    Sparrow, J. G.

    1975-01-01

    It is suggested that the magnitudes of the two radiation-induced rotational bursting mechanisms (Radzieskii effect and windmill effect) have been overestimated and that they do not work significantly faster than the Poynting-Robertson effect in removing interplanetary particles. These two mechanisms are described, and serious doubts are raised regarding the derivation of their radiation pressure-torque proportionality constants, which are required for calculating their magnitudes. It is shown that both mechanisms will cause the alignment of elongated particles and, consequently, the polarization of zodiacal light. Since no positive polarization has been measured at the antisolar point, it is concluded that the magnitudes of the rotational bursting mechanisms are smaller than that of the Poynting-Robertson effect.

  20. Light induced by charged particles in optical fibers

    NASA Astrophysics Data System (ADS)

    Artru, Xavier; Ray, Cédric

    2013-08-01

    The field of a charged particle passing through or near an optical fiber polarizes the fiber atoms transiently. This produces a particle-induced guided light (PIGL). PIGL can also be assisted by a metallic object stuck to the fiber, via plasmon excitation. Type-I PIGL is produced in a translation-invariant part of the fiber, type-II PIGL is produced at a fiber end, an indentation or a metallic object. Properties of type-I PIGL in a single-mode fiber (spectrum, polarization) are reviewed. Order of magnitudes are given for type-II PIGL from a fiber end or a metallic ball. Interference effects are outlined, in particular the guided Smith-Purcell radiation. Applications of PIGL to beam diagnostics are discussed.

  1. Asian Dust Particles Induce Macrophage Inflammatory Responses via Mitogen-Activated Protein Kinase Activation and Reactive Oxygen Species Production

    PubMed Central

    Higashisaka, Kazuma; Fujimura, Maho; Taira, Mayu; Yoshida, Tokuyuki; Tsunoda, Shin-ichi; Baba, Takashi; Yamaguchi, Nobuyasu; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Nasu, Masao; Tsutsumi, Yasuo

    2014-01-01

    Asian dust is a springtime meteorological phenomenon that originates in the deserts of China and Mongolia. The dust is carried by prevailing winds across East Asia where it causes serious health problems. Most of the information available on the impact of Asian dust on human health is based on epidemiological investigations, so from a biological standpoint little is known of its effects. To clarify the effects of Asian dust on human health, it is essential to assess inflammatory responses to the dust and to evaluate the involvement of these responses in the pathogenesis or aggravation of disease. Here, we investigated the induction of inflammatory responses by Asian dust particles in macrophages. Treatment with Asian dust particles induced greater production of inflammatory cytokines interleukin-6 and tumor necrosis factor-? (TNF-?) compared with treatment with soil dust. Furthermore, a soil dust sample containing only particles ?10??m in diameter provoked a greater inflammatory response than soil dust samples containing particles >10??m. In addition, Asian dust particles-induced TNF-? production was dependent on endocytosis, the production of reactive oxygen species, and the activation of nuclear factor-?B and mitogen-activated protein kinases. Together, these results suggest that Asian dust particles induce inflammatory disease through the activation of macrophages. PMID:24987712

  2. Inhaled particles in human disease and animal models: use of electron beam instrumentation.

    PubMed Central

    Brody, A R

    1984-01-01

    The mineral pneumoconioses (lung disease caused by inhalation of inorganic dust) have been an important disease entity for centuries. In the last several decades, the electron microscope has been used to elucidate the distribution and identification of inhaled minerals, to aid in establishing etiologic factors, and less commonly, to determine the basic biologic mechanisms through which inhaled minerals cause lung disease. In this section, I review the instrumentation and tissue preparation currently used to address some modern problems in particle-induced lung disease. For example, human pneumoconioses of undetermined etiology can be clarified by electron microscopy and X-ray energy spectrometry. In addition, the initial deposition patterns of asbestos and silica are demonstrated in animal models, and the contributions of electron microscopy in establishing the initial lesions of asbestosis are described. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. FIGURE 13. FIGURE 14. PMID:6090114

  3. Using human induced pluripotent stem cells to treat retinal disease?

    PubMed Central

    Borooah, S.; Phillips, M.J.; Bilican, B.; Wright, A.F.; Wilmut, I.; Chandran, S.; Gamm, D.; Dhillon, B.

    2013-01-01

    The eye is an ideal target for exploiting the potential of human induced pluripotent stem cell (hiPSC) technology in order to understand disease pathways and explore novel therapeutic strategies for inherited retinal disease. The aim of this article is to map the pathway from state-of-the art laboratory-based discoveries to realising the translational potential of this emerging technique. We describe the relevance and routes to establishing hiPSCs in selected models of human retinal disease. Additionally, we define pathways for applying hiPSC technology in treating currently incurable, progressive and blinding retinal disease. PMID:24104210

  4. Diesel exhaust particles induce the over expression of tumor necrosis factor-alpha (TNF-alpha) gene in alvelor machrophage and failed to induce apoptosis through activation of nuclear factor-kappaB (NF-kappaB)

    EPA Science Inventory

    Exposure to particulate matter (PM2.5-10), including diesel exhaust particles (DEP) has been reported to induce lung injury and exacerbation of asthma and chronic obstructive pulmonary disease. Alveolar macrophages play a major role in the lung's response to inhaled particles and...

  5. Heavy charged-particle induced lesions in rabbit cerebral cortex

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Fabrikant, J.I.

    1988-02-01

    Fourteen male rabbits received single doses of 20, 40, and 80 Gy of neon irradiation with an extended Bragg peak. They were sacrificed at 1 day, 1 week, and 6 months post-irradiation. The tissue changes which showed a significant time-dose relationship were leakage of carbon particles from blood vessels, focal arachnoiditis, hemorrhage, cystic necrosis, and a total histopathologic score using a point system of grading. The focal nature of the lesions was clearly demonstrated with 2 mm thick macrotome sections. The transition zone between damaged brain and microscopically normal appearing brain was less than 1 mm and the tissue damage induced was morphologically similar to that of other radiation modalities. These findings may have important therapeutic implications for patients. The sharply demarcated boundaries of heavy charged-particle induced lesions suggest these beams will be useful for obliterating tissue in areas where it is critical that a transition from undamaged to severely damaged tissue must occur over a short distance, such as in the central nervous system.

  6. Induced radioactivity in and around high-energy particle accelerators.

    PubMed

    Vincke, Helmut; Theis, Chris; Roesler, Stefan

    2011-07-01

    Particle accelerators and their surroundings are locations of residual radioactivity production that is induced by the interaction of high-energy particles with matter. This paper gives an overview of the principles of activation caused at proton accelerators, which are the main machines operated at Conseil Européen pour la Recherche Nucléaire. It describes the parameters defining radio-nuclide production caused by beam losses. The second part of the paper concentrates on the analytic calculation of activation and the Monte Carlo approach as it is implemented in the FLUKA code. Techniques used to obtain, on the one hand, estimates of radioactivity in Becquerel and, on the other hand, residual dose rates caused by the activated material are discussed. The last part of the paper focuses on experiments that allow for benchmarking FLUKA activation calculations and on simulations used to predict activation in and around high-energy proton machines. In that respect, the paper addresses the residual dose rate that will be induced by proton-proton collisions at an energy of two times 7 TeV in and around the Compact Muon Solenoid (CMS) detector. Besides activation of solid materials, the air activation expected in the CMS cavern caused by this beam operation is also discussed. PMID:21697180

  7. Management of drug-induced liver disease

    Microsoft Academic Search

    Gustavo Marino; Hyman J. Zimmerman; James H. Lewis

    2001-01-01

    The treatment and prevention of drug-induced liver injury starts with the recognition of hepatotoxicity at the earliest possible\\u000a time so that the suspected drug can be discontinued expeditiously. Both liver enzyme monitoring and vigilance for signs of\\u000a hypersensitivity involving the liver are useful strategies for many agents known to cause hepatocellular necrosis leading\\u000a to liver failure. Specific antidotes to prevent

  8. The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway.

    PubMed

    Liu, Xuqiang; Qu, Xinhua; Wu, Chuanlong; Zhai, Zanjing; Tian, Bo; Li, Haowei; Ouyang, Zhengxiao; Xu, Xinchen; Wang, Wengang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

    2014-07-01

    The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function. PMID:24767789

  9. Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

    PubMed Central

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I.; Skinner, Michael K.

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology. PMID:22570695

  10. Human Induced Pluripotent Stem Cell Models of Inherited Cardiovascular Diseases.

    PubMed

    Jiang, Wenjian; Lan, Feng; Zhang, Hongjia

    2014-10-16

    Cardiovascular cells derived from patient specific induced Pluripotent Stem Cell (iPSC) harbor gene mutations associated with the pathogenesis of inherited cardiac diseases and congenital heart diseases (CHD). Numerous reports have demonstrated the utilization of human induced Pluripotent Stem Cell (hiPSC) to model cardiac diseases as a means of investigating their underlying mechanisms. So far, they have been shown to investigate the molecular mechanisms of many cardiac disorders, such as long-QT syndrome (LQT), catecholaminergic polymorphic ventricular tachycardia (CPVT), dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), LEOPARD syndrome (LS), arrhythmogenic cardiomyopathy (ACM), Friedreich ataxia (FRDA), Barth syndrome (BTHS), hypoplastic left heart syndrome (HLHS), Marfan syndrome (MFS) and other CHD. This article summarizes the growing body of research related to modeling various cardiac diseases using hiPSCs. Moreover, by reviewing the methods used in previous studies, we propose multiple novel applications of hiPSCs to investigate comprehensive cardiovascular disorders and facilitate drug discovery. PMID:25322695

  11. Sintered Indium-Tin Oxide Particles Induce Pro-Inflammatory Responses In Vitro, in Part through Inflammasome Activation

    PubMed Central

    Badding, Melissa A.; Schwegler-Berry, Diane; Park, Ju-Hyeong; Fix, Natalie R.; Cummings, Kristin J.; Leonard, Stephen S.

    2015-01-01

    Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO), and ventilation dust particles activated nuclear factor kappa B (NF?B) within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1?, IL-6, TNF?, and IL-8) within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1? release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue. PMID:25874458

  12. Chronic Subclinical Prion Disease Induced by Low-Dose Inoculum

    Microsoft Academic Search

    Alana M. Thackray; Michael A. Klein; Adriano Aguzzi; Raymond Bujdoso

    2002-01-01

    We have compared the transmission characteristics of the two mouse-adapted scrapie isolates, ME7 and Rocky Mountain Laboratory (RML), in tga20 mice. These mice express elevated levels of PrP protein compared to wild-type mice and display a relatively short disease incubation period following intracerebral prion inoculation. Terminal prion disease in tga20 mice induced by ME7 or RML was characterized by a

  13. Diesel exhaust particles induce endothelial dysfunction in apoE{sup -/-} mice

    SciTech Connect

    Hansen, Christian S. [Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Oster Farimagsgade 5, Building 5B, 2nd Floor, 1014 Copenhagen K (Denmark); Sheykhzade, Majid [Department of Pharmacology and Pharmacotherapy, Danish University of Pharmaceutical Sciences (Denmark); Moller, Peter [Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Oster Farimagsgade 5, Building 5B, 2nd Floor, 1014 Copenhagen K (Denmark); Folkmann, Janne Kjaergaard [Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Oster Farimagsgade 5, Building 5B, 2nd Floor, 1014 Copenhagen K (Denmark); Amtorp, Ole [Department of Pharmacology, University of Copenhagen (Denmark); Jonassen, Thomas [Department of Pharmacology, University of Copenhagen (Denmark); Loft, Steffen [Department of Environmental and Occupational Health, Institute of Public Health, University of Copenhagen, Oster Farimagsgade 5, Building 5B, 2nd Floor, 1014 Copenhagen K (Denmark)]. E-mail: s.loft@pubhealth.ku.dk

    2007-02-15

    Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve translocation of particles to the bloodstream and impairment of endothelial function, possibly dependent on present atherosclerosis. Aim: We investigated the effects of exposure to diesel exhaust particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE{sup -/-} mice with slight atherosclerosis and from normal apoE{sup +/+} mice. Methods: DEP 0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were sacrificed 1 h later and aorta ring segments were mounted on wire myographs. Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100 {mu}g DEP/ml before measurement of vasomotor functions. Results: Exposure to 0.5 mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine elicited vasorelaxation in apoE{sup -/-} mice, whereas the response was enhanced in apoE{sup +/+} mice. No significant change was observed after administration of 5 mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K{sup +} or phenylephrine. In vitro exposure to 100 {mu}g DEP/ml enhanced acetylcholine-induced relaxation and attenuated phenylephrine-induced constriction. Vasodilation induced by sodium nitroprusside was not affected by any DEP exposure. Conclusion: Exposure to DEP has acute effect on vascular functions. Endothelial dysfunction possibly due to decreased NO production as suggested by decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside response can be induced by DEP in vivo only in vessels of mice with some atherosclerosis.

  14. The Inhibition of RANKL-Induced Osteoclastogenesis through the Suppression of p38 Signaling Pathway by Naringenin and Attenuation of Titanium-Particle-Induced Osteolysis

    PubMed Central

    Wang, Wengang; Wu, Chuanlong; Tian, Bo; Liu, Xuqiang; Zhai, Zanjing; Qu, Xinhua; Jiang, Chuan; Ouyang, Zhengxiao; Mao, Yuanqing; Tang, Tingting; Qin, An; Zhu, Zhenan

    2014-01-01

    The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor-?B (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies, we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity. PMID:25464380

  15. The inhibition of RANKL-induced osteoclastogenesis through the suppression of p38 signaling pathway by naringenin and attenuation of titanium-particle-induced osteolysis.

    PubMed

    Wang, Wengang; Wu, Chuanlong; Tian, Bo; Liu, Xuqiang; Zhai, Zanjing; Qu, Xinhua; Jiang, Chuan; Ouyang, Zhengxiao; Mao, Yuanqing; Tang, Tingting; Qin, An; Zhu, Zhenan

    2014-01-01

    The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor-?B (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies, we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity. PMID:25464380

  16. Rotavirus virus-like particles administered mucosally induce protective immunity.

    PubMed Central

    O'Neal, C M; Crawford, S E; Estes, M K; Conner, M E

    1997-01-01

    We have evaluated the immunogenicity and protective efficacy of rotavirus subunit vaccines administered by mucosal routes. Virus-like particles (VLPs) produced by self-assembly of individual rotavirus structural proteins coexpressed by baculovirus recombinants in insect cells were the subunit vaccine tested. We first compared the immunogenicities and protective efficacies of VLPs containing VP2 and VP6 (2/6-VLPs) and G3 2/6/7-VLPs mixed with cholera toxin and administered by oral and intranasal routes in the adult mouse model of rotavirus infection. VLPs administered orally induced serum antibody and intestinal immunoglobulin A (IgA) and IgG. The highest oral dose (100 microg) of VLPs induced protection from rotavirus challenge (> or = 50% reduction in virus shedding) in 50% of the mice. VLPs administered intranasally induced higher serum and intestinal antibody responses than VLPs administered orally. All mice receiving VLPs intranasally were protected from challenge; no virus was shed after challenge. Since there was no difference in immunogenicity or protective efficacy between 2/6- and 2/6/7-VLPs, protection was achieved without inclusion of the neutralization antigens VP7 and VP4. We also tested the immunogenicities and protective efficacies of 2/6-VLPs administered intranasally without the addition of cholera toxin. 2/6-VLPs administered intranasally without cholera toxin induced lower serum and intestinal antibody titers than 2/6-VLPs administered with cholera toxin. The highest dose (100 microg) of 2/6-VLPs administered intranasally without cholera toxin resulted in a mean reduction in shedding of 38%. When cholera toxin was added, higher levels of protection were achieved with 10-fold less immunogen. VLPs administered mucosally offer a promising, safe, nonreplicating vaccine for rotavirus. PMID:9343229

  17. Geraniin suppresses RANKL-induced osteoclastogenesis in vitro and ameliorates wear particle-induced osteolysis in mouse model.

    PubMed

    Xiao, Fei; Zhai, Zanjing; Jiang, Chuan; Liu, Xuqiang; Li, Haowei; Qu, Xinhua; Ouyang, Zhengxiao; Fan, Qiming; Tang, Tingting; Qin, An; Gu, Dongyun

    2015-01-01

    Wear particle-induced osteolysis and subsequent aseptic loosening remains the most common complication that limits the longevity of prostheses. Wear particle-induced osteoclastogenesis is known to be responsible for extensive bone erosion that leads to prosthesis failure. Thus, inhibition of osteoclastic bone resorption may serve as a therapeutic strategy for the treatment of wear particle induced osteolysis. In this study, we demonstrated for the first time that geraniin, an active natural compound derived from Geranium thunbergii, ameliorated particle-induced osteolysis in a Ti particle-induced mouse calvaria model in vivo. We also investigated the mechanism by which geraniin exerts inhibitory effects on osteoclasts. Geraniin inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner, evidenced by reduced osteoclast formation and suppressed osteoclast specific gene expression. Specially, geraniin inhibited actin ring formation and bone resorption in vitro. Further molecular investigation demonstrated geraniin impaired osteoclast differentiation via the inhibition of the RANKL-induced NF-?B and ERK signaling pathways, as well as suppressed the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Collectively, our data suggested that geraniin exerts inhibitory effects on osteoclast differentiation in vitro and suppresses Ti particle-induced osteolysis in vivo. Geraniin is therefore a potential natural compound for the treatment of wear particle induced osteolysis in prostheses failure. PMID:25016282

  18. Radiation-Induced Heart Disease: Pathologic Abnormalities and Putative Mechanisms

    PubMed Central

    Taunk, Neil K.; Haffty, Bruce G.; Kostis, John B.; Goyal, Sharad

    2015-01-01

    Breast cancer is a common diagnosis in women. Breast radiation has become critical in managing patients who receive breast conserving surgery, or have certain high-risk features after mastectomy. Most patients have an excellent prognosis, therefore understanding the late effects of radiation to the chest is important. Radiation-induced heart disease (RIHD) comprises a spectrum of cardiac pathology including myocardial fibrosis and cardiomyopathy, coronary artery disease, valvular disease, pericardial disease, and arrhythmias. Tissue fibrosis is a common mediator in RIHD. Multiple pathways converge with both acute and chronic cellular, molecular, and genetic changes to result in fibrosis. In this article, we review the pathophysiology of cardiac disease related to radiation therapy to the chest. Our understanding of these mechanisms has improved substantially, but much work remains to further refine radiation delivery techniques and develop therapeutics to battle late effects of radiation. PMID:25741474

  19. Visual phenomena induced by cosmic rays and accelerated particles

    NASA Technical Reports Server (NTRS)

    Tobias, C. A.; Budinger, T. F.; Leith, J. T.; Mamoon, A.; Chapman, P. K.

    1972-01-01

    Experiments, conducted at cyclotrons together with observations by Apollo astronauts, suggest with little doubt that cosmic nuclei interacting with the visual apparatus cause the phenomenon of light flashes seen on translunar and transearth coast over the past four Apollo missions. Other experiments with high and low energy neutrons and a helium ion beam suggest that slow protons and helium ions with a stopping power greater than 10 to the 8th power eV/gram sq cm can cause the phenomenon in the dark adapted eye. It was demonstrated that charged particles induced by neutrons and helium ions can stimulate the visual apparatus. Some approaches to understanding the long term mission effects of galactic cosmic nuclei interacting with man and his nervous system are outlined.

  20. Energetic particle induced desorption of water vapor cryo-condensate

    SciTech Connect

    Menon, M.M.; Owen, L.W.; Simpkins, J.E.; Uckan, T.; Mioduszewski, P.K.

    1990-01-01

    An in-vessel cryo-condensation pump is being designed for the Advanced Divertor configuration of the DIII-D tokamak. To assess the importance of possible desorption of water vapor from the cryogenic surfaces of the pump due to impingement of energetic particles from the plasma, a 77 K surface on which a thin layer of water vapor was condensed was exposed to a tenuous plasma (density = 2 {times} 10{sup 10} cm{sup {minus}3}, electron temperature = 3 eV). Significant desorption of the condensate occurred, suggesting that impingement of energeticparticles (10 eV) at flux levels of {approximately}10{sup 16} cm{sup 2}s{sup {minus}1} on cryogenic surfaces could potentially induce impurity problems in the tokamak plasma. A pumping configuration is presented in which this problem is minimized without sacrificing the pumping speed.

  1. Dielectric response of particles in flowing media: The effect of shear-induced rotation on the variation in particle polarizability

    NASA Astrophysics Data System (ADS)

    Nikolic-Jaric, Marija; Ferrier, Graham A.; Thomson, Douglas J.; Bridges, Greg E.; Freeman, Mark R.

    2011-07-01

    When particles in liquid suspensions flow through channels and pipes in a laminar fashion, the resulting parabolic velocity profile gives rise to shear, which induces the particles to rotate. If flowing suspensions containing dielectric particles are immersed in an external electric field, the anisotropic polarization induced in rotating nonspherical particles will vary with the orientation of the particle with respect to the external field; what results is an uncertainty in experimental measurements that involve particle polarization. The present study establishes the limits of this uncertainty and shows that departure from spherical symmetry in individual particles can lead to a significant overlap in measurements attempting to discriminate between particle subpopulations in suspensions. For example, the uncertainty in signal amplitude for a population of activated T-lymphocytes can be as high as 20%. Such concerns arise in applications like field-flow fractionation, dielectrophoretic sorting of particles, flow impedance measurements and cytometry, and, most recently, isodielectric separation, all of which are used to separate particles in a flow based on their dielectric response. This paper considers axisymmetric particles as the first departure from the approximation of spherical symmetry, shows how to calculate an estimate of the size of the population overlap, and suggests possible strategies to minimize it.

  2. Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

    Microsoft Academic Search

    Lot de Witte; Younes Zoughlami; Birgit Aengeneyndt; Guido David; Yvette van Kooyk; Lutz Gissmann; Teunis B. H. Geijtenbeek

    2008-01-01

    Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during

  3. Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases

    PubMed Central

    Nath, Bharath; Szabo, Gyongyi

    2011-01-01

    Hypoxia has been shown to have a role in the pathogenesis of several forms of liver disease. The Hypoxia Inducible Factors (HIFs) are a family of evolutionarily conserved transcriptional regulators that affect a homeostatic response to low oxygen tension and have been identified as key mediators of angiogenesis, inflammation, and metabolism. In this review, we summarize the evidence for a role of HIFs across a range of hepatic pathophysiology. We describe regulation of the hypoxia inducible factors and review investigations that demonstrate a role for HIFs in the development of liver fibrosis, activation of innate immune pathways, hepatocellular carcinoma, as well as other liver diseases in both human disease as well as murine models. PMID:22120903

  4. Contact nucleation of ice induced by biological aerosol particles

    NASA Astrophysics Data System (ADS)

    Kiselev, Alexei; Hoffmann, Nadine; Schaefer, Manfred; Duft, Denis; Leisner, Thomas

    2014-05-01

    The contact freezing of supercooled water droplets is one of the potentially important and the least understood heterogeneous mechanism of ice formation in tropospheric clouds. On the time scales of cloud lifetime the freezing of supercooled water droplets via contact mechanism may occur at higher temperature compared to the same IN immersed in the droplet. Recently we have developed an experimental method allowing for quantification of the freezing probability on a single droplet-particle collision event [1]. In the previous experimental studies with mineral dust (kaolinite, illite, feldspar, and hematite) we have been able to show that the rate of freezing at a given temperature is governed by the rate of droplet - particle collisions, and by the properties of the contact ice nuclei: its size, morphology and composition [1, 2]. In this contribution, we focus on the contact freezing efficiency of biological ice nuclei. We demonstrate that the contact freezing efficiency of Snomax (freeze-dried fragments of Pseudomonas syringae bacteria) follows very similar pattern observed in immersion freezing experiments, indicating that the INA-protein identified as the ice nucleation agent in the immersion freezing mode is also responsible for initiation of contact freezing. The same similarity is observed for contact freezing induced by semi-dry residual particles of birch pollen washing water, providing an evidence for the importance of organic macromolecules of biological origin for nucleation of atmospheric ice. Finally, our experiments show that mixing the birch pollen washing water with mineral dust (illite) significantly increases the IN efficiency of mineral dust and extends the temperature range of its IN activity. These findings suggest a possible route of multiplication of the effect of biological IN beyond observed atmospheric concentrations of pollen grains. [1] - Hoffmann, N., Kiselev, A., Rzesanke, D., Duft, D., and Leisner, T.: Experimental quantification of contact freezing in an electrodynamic balance Atmos. Meas. Tech., 6, 2373-2382, 2013. [2] - Hoffmann, N., Duft, D., Kiselev, A., and Leisner, T.: Contact freezing efficiency of mineral dust aerosols studied in an electrodynamic balance: quantitative size and temperature dependence for illite particles, Faraday Discuss., 2013.

  5. Development of disease-resistant rice using regulatory components of induced disease resistance

    PubMed Central

    Takatsuji, Hiroshi

    2014-01-01

    Infectious diseases cause huge crop losses annually. In response to pathogen attacks, plants activate defense systems that are mediated through various signaling pathways. The salicylic acid (SA) signaling pathway is the most powerful of these pathways. Several regulatory components of the SA signaling pathway have been identified, and are potential targets for genetic manipulation of plants’ disease resistance. However, the resistance associated with these regulatory components is often accompanied by fitness costs; that is, negative effects on plant growth and crop yield. Chemical defense inducers, such as benzothiadiazole and probenazole, act on the SA pathway and induce strong resistance to various pathogens without major fitness costs, owing to their ‘priming effect.’ Studies on how benzothiadiazole induces disease resistance in rice have identified WRKY45, a key transcription factor in the branched SA pathway, and OsNPR1/NH1. Rice plants overexpressing WRKY45 were extremely resistant to rice blast disease caused by the fungus Magnaporthe oryzae and bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo), the two major rice diseases. Disease resistance is often accompanied by fitness costs; however, WRKY45 overexpression imposed relatively small fitness costs on rice because of its priming effect. This priming effect was similar to that of chemical defense inducers, although the fitness costs were amplified by some environmental factors. WRKY45 is degraded by the ubiquitin–proteasome system, and the dual role of this degradation partly explains the priming effect. The synergistic interaction between SA and cytokinin signaling that activates WRKY45 also likely contributes to the priming effect. With a main focus on these studies, I review the current knowledge of SA-pathway-dependent defense in rice by comparing it with that in Arabidopsis, and discuss potential strategies to develop disease-resistant rice using signaling components. PMID:25431577

  6. Development of disease-resistant rice using regulatory components of induced disease resistance.

    PubMed

    Takatsuji, Hiroshi

    2014-01-01

    Infectious diseases cause huge crop losses annually. In response to pathogen attacks, plants activate defense systems that are mediated through various signaling pathways. The salicylic acid (SA) signaling pathway is the most powerful of these pathways. Several regulatory components of the SA signaling pathway have been identified, and are potential targets for genetic manipulation of plants' disease resistance. However, the resistance associated with these regulatory components is often accompanied by fitness costs; that is, negative effects on plant growth and crop yield. Chemical defense inducers, such as benzothiadiazole and probenazole, act on the SA pathway and induce strong resistance to various pathogens without major fitness costs, owing to their 'priming effect.' Studies on how benzothiadiazole induces disease resistance in rice have identified WRKY45, a key transcription factor in the branched SA pathway, and OsNPR1/NH1. Rice plants overexpressing WRKY45 were extremely resistant to rice blast disease caused by the fungus Magnaporthe oryzae and bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo), the two major rice diseases. Disease resistance is often accompanied by fitness costs; however, WRKY45 overexpression imposed relatively small fitness costs on rice because of its priming effect. This priming effect was similar to that of chemical defense inducers, although the fitness costs were amplified by some environmental factors. WRKY45 is degraded by the ubiquitin-proteasome system, and the dual role of this degradation partly explains the priming effect. The synergistic interaction between SA and cytokinin signaling that activates WRKY45 also likely contributes to the priming effect. With a main focus on these studies, I review the current knowledge of SA-pathway-dependent defense in rice by comparing it with that in Arabidopsis, and discuss potential strategies to develop disease-resistant rice using signaling components. PMID:25431577

  7. Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease

    EPA Science Inventory

    Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air p...

  8. Role of intracellular tyrosines in activating KIT induced myeloproliferative disease

    PubMed Central

    Ramdas, Baskar; Sims, Emily; Kapur, Reuben

    2015-01-01

    Gain-of-function mutations in KIT receptor in humans are associated with gastrointestinal stromal tumors (GIST), systemic mastocytosis (SM), and acute myelogenous leukemia (AML). The intracellular signals that contribute to oncogenic KIT induced myeloproliferative disease (MPD) are poorly understood. Here, we show that oncogenic KITD814V induced MPD occurs in the absence of ligand stimulation. The intracellular tyrosine residues are important for KITD814V induced MPD, albeit to varying degrees. Among the seven intracellular tyrosines examined, tyrosine 719 alone plays a unique role in regulating KITD814V induced proliferation and survival in vitro, and MPD in vivo. Importantly, the extent to which AKT, ERK and Stat5 signaling pathways are activated via the seven intracellular tyrosines in KITD814V impacts the latency of MPD and severity of the disease. Our results identify critical signaling molecules involved in regulating KITD814V induced MPD, which might be useful for developing novel therapeutic targets for hematologic malignancies involving this mutation. PMID:22297723

  9. ccsd00000796 Electric-eld induced capillary interaction of charged particles at a polar interface

    E-print Network

    induced capillary interaction of charged particles at a polar interface. The algebraic tailsccsd­00000796 (version 1) : 28 Oct 2003 Electric-#12;eld induced capillary interaction of charged particles at a polar interface Lionel Foret and Alois Wurger CPMOH #3; , Universit#19;e Bordeaux 1, 351

  10. Anomalous field-induced particle orientation in dilute mixtures of charged

    E-print Network

    Loss, Daniel

    . The dependence of the perpendicular orientation on frequency and particle charge, size and concentration indicates the presence of field-induced asymmetric crowding of spherical particles around each rod, which gives rise to asymmetric electro-osmotic flows that induce a negative torque. Rod-like colloids made

  11. Piribedil-induced sleep attacks in Parkinson's disease.

    PubMed

    Tan, E K

    2003-02-01

    'Sleep attacks', episodes of sudden onset of sleep without any prodromal symptoms, were initially described in patients with Parkinson's disease (PD) taking the newer dopamine agonists pramipexole and ropinirole. Piribedil, a nonergot agonist with both D2 and D3 agonist action, is an effective antiparkinsonian medication. However, there are very few reports of Piribedil-induced sleep attacks in PD. Among 50 PD patients seen at our Movement Disorder Clinic who had recently taken Piribedil, we identified three (6%) who satisfied the clinical description of sleep attacks. Here we provide details of the clinical characteristics of Piribedil-induced sleep attacks in these PD patients. PMID:12588638

  12. Induced-charge electroosmotic flow around dielectric particles in uniform electric field.

    PubMed

    Zhang, Fang; Li, Dongqing

    2013-11-15

    The current research of induced-charge electroosmotic flow (ICEOF) is mostly confined to systems with ideally or fully polarizable surfaces (e.g., metal). However, most materials in nature have various degrees of polarizability, which directly affects the induced charges and subsequently the induced-charge electroosmotic flow. This paper studied the effect of the polarizability of the materials on the ICEOF. An analytical expression of the induced potential on the surface of a dielectric particle in a uniform electrical field was derived. Three-dimensional transient numerical simulations of the ICEOF and the motion of dielectric particles were performed to study the effect of the polarizability. Simulation results show that the transportation of the dielectric particle in a microchannel is not affected by the polarizability of the particle; however, the interaction of two dielectric particles is sensitive to the polarizability of the particles. PMID:24034219

  13. Recombinant Adeno-Vaccine Expressing Enterovirus 71-Like Particles against Hand, Foot, and Mouth Disease

    PubMed Central

    Tsou, Yueh-Liang; Lin, Yi-Wen; Shao, Hsiao-Yun; Yu, Shu-Ling; Wu, Shang-Rung; Lin, Hsiao-Yu; Liu, Chia-Chyi; Huang, Chieh; Chong, Pele; Chow, Yen-Hung

    2015-01-01

    Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth disease (HFMD). There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71) vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs) formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-? T cells associated with Th1/Th2-balanced IFN-?, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-? T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and cellular immune responses against CV infection. PMID:25855976

  14. Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

    Microsoft Academic Search

    Christopher J. Johnson; Joel A. Pedersen; Rick J. Chappell; Debbie McKenzie; Judd M. Aiken

    2007-01-01

    Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies (TSEs)) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral

  15. Thiopurine-induced pancreatitis in inflammatory bowel diseases.

    PubMed

    Ledder, Oren; Lemberg, Daniel A; Day, Andrew S

    2015-04-01

    Crohn's disease and ulcerative colitis are chronic inflammatory conditions affecting the gut and can present at any age with increased numbers of diagnoses seen in many countries in recent years. The thiopurine drugs, azathioprine and 6-mercaptopurine, are commonly used to maintain remission in Crohn's disease and ulcerative colitis; however, the use of these drugs may be limited by the development of pancreatitis in some individuals. Recent data indicate a genetic risk factor and provides a potential immune-mediated mechanism for thiopurine-induced pancreatitis. Management of thiopurine-induced pancreatitis requires exclusion of the triggering drug, which leads to prompt resolution of symptoms. This thiopurine side-effect may limit therapeutic options for future management of patients. PMID:25494551

  16. Single Particle Fluorescence Burst Analysis of Epsin Induced Membrane Fission

    PubMed Central

    Kustigian, Lauren; Puchalla, Jason; Carr, Chavela M.; Rye, Hays S.

    2015-01-01

    Vital cellular processes, from cell growth to synaptic transmission, rely on membrane-bounded carriers and vesicles to transport molecular cargo to and from specific intracellular compartments throughout the cell. Compartment-specific proteins are required for the final step, membrane fission, which releases the transport carrier from the intracellular compartment. The role of fission proteins, especially at intracellular locations and in non-neuronal cells, while informed by the dynamin-1 paradigm, remains to be resolved. In this study, we introduce a highly sensitive approach for the identification and analysis of membrane fission machinery, called burst analysis spectroscopy (BAS). BAS is a single particle, free-solution approach, well suited for quantitative measurements of membrane dynamics. Here, we use BAS to analyze membrane fission induced by the potent, fission-active ENTH domain of epsin. Using this method, we obtained temperature-dependent, time-resolved measurements of liposome size and concentration changes, even at sub-micromolar concentration of the epsin ENTH domain. We also uncovered, at 37°C, fission activity for the full-length epsin protein, supporting the argument that the membrane-fission activity observed with the ENTH domain represents a native function of the full-length epsin protein. PMID:25799353

  17. Interstitial Lung Disease Induced by Drugs and Radiation

    Microsoft Academic Search

    Philippe Camus; Annlyse Fanton; Philippe Bonniaud; Clio Camus; Pascal Foucher

    2004-01-01

    An ever-increasing number of drugs can reproduce variegated patterns of naturally occurring interstitial lung disease (ILD), including most forms of interstitial pneumonias, alveolar involvement and, rarely, vasculitis. Drugs in one therapeutic class may collectively produce the same pattern of involvement. A few drugs can produce more than one pattern of ILD. The diagnosis of drug-induced ILD (DI-ILD) essentially rests on

  18. Electric-field induced capillary interaction of charged particles at a polar interface

    E-print Network

    Lionel Foret; Alois Würger

    2014-02-07

    We study the electric-field induced capillary interaction of charged particles at a polar interface. The algebraic tails of the electrostatic pressure of each charge results in a deformation of the interface $u\\sim \\rho ^{-4}$. The resulting capillary interaction is repulsive and varies as $\\rho ^{-6}$ with the particle distance. As a consequence, electric-field induced capillary forces cannot be at the origin of the secondary minimum observed recently for charged PMMA particles at on oil-water interface.

  19. A bipolar mechanism for alpha-particle-induced soft errors in GaAs integrated circuits

    Microsoft Academic Search

    Yasunari Umemoto; Nobutoshi Matsunaga; Kazumichi Mitsusada

    1989-01-01

    The alpha-particle-induced collected charge in undoped LEC semi-insulating GaAs is measured in n+-i-n+ and n+-p-n+ isolation structures and is compared with the results of an analytical model based on a bipolar mechnism. In n+-i-n+ isolation structures, a collected-storage multiplication phenomenon induced by alpha-particle incidence is observed. The measured collected charge is about three times the alpha-particle-generated charge. This phenomenon can

  20. Thermodynamics Inducing Massive Particles' Tunneling and Cosmic Censorship

    E-print Network

    Baocheng Zhang; Qing-yu Cai; Ming-sheng Zhan

    2010-08-13

    By calculating the change of entropy, we prove that the first law of black hole thermodynamics leads to the tunneling probability of massive particles through the horizon, including the tunneling probability of massive charged particles from the Reissner-Nordstr\\"om black hole and the Kerr-Newman black hole. Novelly, we find the trajectories of massive particles are close to that of massless particles near the horizon, although the trajectories of massive charged particles may be affected by electromagnetic forces. We show that Hawking radiation as massive particles tunneling does not lead to violation of the weak cosmic-censorship conjecture.

  1. Autoimmune and virus-induced demyelinating diseases. A review.

    PubMed Central

    Lampert, P. W.

    1978-01-01

    Patterns of demyelination are described in several autoimmune and virus-induced demyelinating diseases of the peripheral and central nervous system. Myelin can be destroyed by injuries that affect either the myelin-supporting cells and/or the myelin lamellae. After destruction of the supporting cells, the related disintegrating sheaths are stripped off axons by invading phagocytes. Virus-induced cytolysis can occur with or without participation of immune responses, as demonstrated in subacute sclerosing panencephalitis and progressive mutlifocal leukoencephalopathy, respectively. Autoimmune demyelination is characterized by disintegration of myelin sheaths in periventular, mononuclear cell infiltrates. Myelin lamellae rather than the myelin-supporting cells are the target of the allergic reaction. The lamellae are lysed in focal areas when in contact with presumably sensitized mononuclear cells. The damaged sheaths are then removed in a nonspecific manner by invading macrophages that strip the myelin remnant off the axons. This sequence of changes is best revealed in experimental and human autoimmune demyelination of peripheral nerves, ie, allergic neuritis and idiopathic polyneutris (the Guillain-Barré syndrome). Autoimmune demyelination triggered by virus infection is described in Marek's disease and postinfectious Theiler's virus myelitis. Changes in canine distemper are discussed with reference to both autoimmune and virus-induced demyelination. The observations are compared with lesions in multiple sclerosis, the most common human demyelinating disease of unknown etiology. Images Figure 7 Figure 8 Figure 9 Figure 10 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 1 PMID:417631

  2. Particle dispersion and mixing induced by breaking internal gravity waves

    NASA Astrophysics Data System (ADS)

    Bouruet-Aubertot, Pascale; Koudella, C.; Staquet, C.; Winters, K. B.

    2001-01-01

    The purpose of this paper is to analyze diapycnal mixing induced by the breaking of an internal gravity wave — the primary wave — either standing or propagating. To achieve this aim we apply two different methods. The first method consists of a direct estimate of vertical eddy diffusion from particle dispersion while the second method relies upon potential energy budgets [Winters, K.B., Lombard, P.N., Riley, J.J., D'Asaro, E.A., 1995. J. Fluid Mech. 289, 115-128; Winters, K.B., D'Asaro, E.A., 1996. J. Fluid Mech. 317, 179-193]. The primary wave we consider is of small amplitude and is statically stable, a case for which the breaking process involves two-dimensional instabilities. The dynamics of the waves have been previously analyzed by means of two-dimensional direct numerical simulations [Bouruet-Aubertot, P., Sommeria, J., Staquet, C., 1995. J. Fluid Mech. 285, 265-301; Bouruet-Aubertot, P., Sommeria, J., Staquet, C., 1996. Dyn. Atmos. Oceans 29, 41-63; Koudella, C., Staquet, C., 1998. In: Davis, P. (Ed.), Proceedings of the IMA Conference on Mixing and Dispersion on Stably-stratified Flows, Dundee, September 1996. IMA Publication]. High resolution three-dimensional calculations of the same wave are also reported here [Koudella, C., 1999]. A local estimate of mixing is first inferred from the time evolution of sets of particles released in the flow during the breaking regime. We show that, after an early evolution dominated by shear effects, a diffusion law is reached and the dispersion coefficient is fairly independent of the initial seeding location of the particles in the flow. The eddy diffusion coefficient, K, is then estimated from the diapycnal diffusive flux. A good agreement with the value inferred from particle dispersion is obtained. This finding is of particular interest regarding the interpretation of in situ estimates of K inferred either from tracer dispersion or from microstructure measurements. Computation of the Cox number, equal to the ratio of eddy diffusivity to molecular diffusivity, shows that the Cox number varies within the interval [9, 262], which corresponds to the range of vertical eddy diffusivity measured in the interior of the ocean. The Cox number is found to depend on the turbulent Froude number squared. We show eventually that mixing results in a weak distortion of the initial density profile and we relate this result to observations made at small scale in the ocean. Comparisons between the analysis of the two-dimensional and high resolution (256 3) three-dimensional direct numerical simulations of the primary wave were also conducted. We show that the energetics and the amount of mixing are very close when the primary wave is of small amplitude. This results from the fact that, for a statically stable wave, the dynamics of the initially two-dimensional primary wave remains mostly two-dimensional even after the onset of wavebreaking.

  3. High-density lipoprotein particles, coronary heart disease, and niacin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In clinical trials, the use of statins in patients with high risk for cardiovascular disease (CVD) has resulted in a 25% to 40% decrease in major clinical events. However, despite a marked reduction (up to 60%) in LDL-C, approximately 50% (or more) of patients continue to have CVD events. This high ...

  4. Dynamics of magnetic particles near a surface: Model and experiments on field-induced disaggregation

    NASA Astrophysics Data System (ADS)

    van Reenen, A.; Gao, Y.; de Jong, A. M.; Hulsen, M. A.; den Toonder, J. M. J.; Prins, M. W. J.

    2014-04-01

    Magnetic particles are widely used in biological research and bioanalytical applications. As the corresponding tools are progressively being miniaturized and integrated, the understanding of particle dynamics and the control of particles down to the level of single particles become important. Here, we describe a numerical model to simulate the dynamic behavior of ensembles of magnetic particles, taking account of magnetic interparticle interactions, interactions with the liquid medium and solid surfaces, as well as thermal diffusive motion of the particles. The model is verified using experimental data of magnetic field-induced disaggregation of magnetic particle clusters near a physical surface, wherein the magnetic field properties, particle size, cluster size, and cluster geometry were varied. Furthermore, the model clarifies how the cluster configuration, cluster alignment, magnitude of the field gradient, and the field repetition rate play a role in the particle disaggregation process. The simulation model will be very useful for further in silico studies on magnetic particle dynamics in biotechnological tools.

  5. Treg Inducing Adjuvants for Therapeutic Vaccination Against Chronic Inflammatory Diseases

    PubMed Central

    Keijzer, Chantal; van der Zee, Ruurd; van Eden, Willem; Broere, Femke

    2013-01-01

    Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation and the observed side effects of these therapies illustrate the pressing need for more specific interventions. Regulatory T-cells (Treg) are pivotal controllers of (auto-aggressive) immune responses and inflammation, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Therefore, Treg became frequently studied targets for more specific immunotherapy. Especially antigen-specific targeting of Treg would enable local and tailor made interventions, while obviating the negative side effect of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for antigen-specific interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory-site. In this perspective heat shock proteins (Hsp) have several characteristics that make them highly attractive targets for antigen-specific Treg inducing therapy. The development of an antigen-specific Treg inducing vaccine is a major novel goal in the field of immunotherapy in autoimmune diseases. However, progress is hampered not only by the lack of effective antigens, but also by the fact that other factors such as dose, route, and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to the effective induction of Treg. In addition, the use of a Treg inducing adjuvant might be required to achieve an effective regulatory response, in the case of ongoing inflammation. Future goals in clinical trials will be the optimization of natural Treg expansion (or the induction of adaptive Treg) without loss of their suppressive function or the concomitant induction of non-regulatory T-cells. Here, we will discuss the potential use of protein/peptide-based vaccines combined with Treg inducing adjuvants for the development of therapeutic vaccines against chronic inflammatory conditions. PMID:23970886

  6. Different particle determinants induce apoptosis and cytokine release in primary alveolar macrophage cultures

    PubMed Central

    Refsnes, Magne; Hetland, Ragna B; Øvrevik, Johan; Sundfør, Idunn; Schwarze, Per E; Låg, Marit

    2006-01-01

    Background Particles are known to induce both cytokine release (MIP-2, TNF-?), a reduction in cell viability and an increased apoptosis in alveolar macrophages. To examine whether these responses are triggered by the same particle determinants, alveolar macrophages were exposed in vitro to mineral particles of different physical-chemical properties. Results The crystalline particles of the different stone types mylonite, gabbro, basalt, feldspar, quartz, hornfels and fine grain syenite porphyr (porphyr), with a relatively equal size distribution (? 10 ?m), but different chemical/mineral composition, all induced low and relatively similar levels of apoptosis. In contrast, mylonite and gabbro induced a marked MIP-2 response compared to the other particles. For particles of smaller size, quartz (? 2 ?m) seemed to induce a somewhat stronger apoptotic response than even smaller quartz (? 0.5 ?m) and larger quartz (? 10 ?m) in relation to surface area, and was more potent than hornfels and porphyr (? 2 ?m). The reduction in cell viability induced by quartz of the different sizes was roughly similar when adjusted to surface area. With respect to cytokines, the release was more marked after exposure to quartz ? 0.5 ?m than to quartz ? 2 ?m and ? 10 ?m. Furthermore, hornfels (? 2 ?m) was more potent than the corresponding hornfels (? 10 ?m) and quartz (? 2 ?m) to induce cytokine responses. Pre-treatment of hornfels and quartz particles ? 2 ?m with aluminium lactate, to diminish the surface reactivity, did significantly reduce the MIP-2 response to hornfels. In contrast, the apoptotic responses to the particles were not affected. Conclusion These results indicate that different determinants of mineral/stone particles are critical for inducing cytokine responses, reduction in cell viability and apoptosis in alveolar macrophages. The data suggest that the particle surface reactivity was critical for cytokine responses, but contributed less to cell death for the types of particles tested. The size-dependent variations, specially in cytokine release, seem not to be explained only by particle surface area. PMID:16774673

  7. Seamless Correction of the Sickle Cell Disease Mutation of the HBB Gene in Human Induced

    E-print Network

    Zhao, Huimin

    Seamless Correction of the Sickle Cell Disease Mutation of the HBB Gene in Human Induced ABSTRACT: Sickle cell disease (SCD) is the most common human genetic disease which is caused by a single effector nucleases; induced pluripotent stem cells; piggyBac transposon; sickle cell disease; gene therapy

  8. Numerical Simulation of Intercalation-Induced Stress in Li-Ion Battery Electrode Particles

    E-print Network

    Sastry, Ann Marie

    with smaller sizes and larger aspect ratios to reduce intercalation-induced stress during cycling of lithiumNumerical Simulation of Intercalation-Induced Stress in Li-Ion Battery Electrode Particles induced stresses in Li cells, this correlation is critical in determining optimal materials

  9. Adenovirus particles that display the Plasmodium falciparum circumsporozoite protein NANP repeat induce sporozoite-neutralizing antibodies in mice.

    PubMed

    Palma, Christopher; Overstreet, Michael G; Guedon, Jean-Marc; Hoiczyk, Egbert; Ward, Cameron; Karen, Kasey A; Zavala, Fidel; Ketner, Gary

    2011-02-11

    Adenovirus particles can be engineered to display exogenous peptides on their surfaces by modification of viral capsid proteins, and particles that display pathogen-derived peptides can induce protective immunity. We constructed viable recombinant adenoviruses that display B-cell epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) in the major adenovirus capsid protein, hexon. Recombinants induced high-titer antibodies against CSP when injected intraperitoneally into mice. Serum obtained from immunized mice recognized both recombinant PfCSP protein and P. falciparum sporozoites, and neutralized P. falciparum sporozoites in vitro. Replicating adenovirus vaccines have provided economical protection against adenovirus disease for over three decades. The recombinants described here may provide a path to an affordable malaria vaccine in the developing world. PMID:21199707

  10. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells

    PubMed Central

    Xu, Xiao-hong; Zhong, Zhong

    2013-01-01

    With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors. PMID:23685955

  11. ULTRAFINE CARBON PARTICLES INDUCE IL-8 EXPRESSION IN HUMAN AIRWAY EPITHELIAL CELLS THROUGH A POST-TRANSCRIPTIONAL MECHANISM

    EPA Science Inventory

    Ultrafine carbon particles induce IL-8 expression in human airway epithelial cells through a post-transcritpional mechanism Epidemiological studies suggest that ultrafine particles contribute to particulate matter (PM) - induced adverse health effects. IL-8 is an i...

  12. Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles-induced toxicity in mice

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoyan; Jin, Tingting; Jin, Yachao; Wu, Leihong; Hu, Bin; Tian, Yu; Fan, Xiaohui

    2013-01-01

    This study investigated the relationship between particle size and toxicity of silica particles (SP) with diameters of 30, 70, and 300 nm, which is essential to the safe design and application of SP. Data obtained from histopathological examinations suggested that SP of these sizes can all induce acute inflammation in the liver. In vivo imaging showed that intravenously administrated SP are mainly present in the liver, spleen and intestinal tract. Interestingly, in gene expression analysis, the cellular response pathways activated in the liver are predominantly conserved independently of particle dose when the same size SP are administered or are conserved independently of particle size, surface area and particle number when nano- or submicro-sized SP are administered at their toxic doses. Meanwhile, integrated analysis of transcriptomics, previous metabonomics and conventional toxicological results support the view that SP can result in inflammatory and oxidative stress, generate mitochondrial dysfunction, and eventually cause hepatocyte necrosis by neutrophil-mediated liver injury.

  13. Passing particle toroidal precession induced by electric field in a tokamak

    SciTech Connect

    Andreev, V. V. [Peoples' Friendship University of Russia, Ordzhonikidze St. 3, Moscow 117198 (Russian Federation)] [Peoples' Friendship University of Russia, Ordzhonikidze St. 3, Moscow 117198 (Russian Federation); Ilgisonis, V. I.; Sorokina, E. A. [Peoples' Friendship University of Russia, Ordzhonikidze St. 3, Moscow 117198 (Russian Federation) [Peoples' Friendship University of Russia, Ordzhonikidze St. 3, Moscow 117198 (Russian Federation); NRC “Kurchatov Institute”, Kurchatov Sq. 1, Moscow 123182 (Russian Federation)

    2013-12-15

    Characteristics of a rotation of passing particles in a tokamak with radial electric field are calculated. The expression for time-averaged toroidal velocity of the passing particle induced by the electric field is derived. The electric-field-induced additive to the toroidal velocity of the passing particle appears to be much smaller than the velocity of the electric drift calculated for the poloidal magnetic field typical for the trapped particle. This quantity can even have the different sign depending on the azimuthal position of the particle starting point. The unified approach for the calculation of the bounce period and of the time-averaged toroidal velocity of both trapped and passing particles in the whole volume of plasma column is presented. The results are obtained analytically and are confirmed by 3D numerical calculations of the trajectories of charged particles.

  14. Influence of interactions on particle production induced by time-varying mass terms

    E-print Network

    Seishi Enomoto; Olga Fuksi?ska; Zygmunt Lalak

    2014-12-30

    We have investigated effects of interaction terms on non-perturbative particle production. It is well known that time-varying masses induce abundant particle production. In this paper we have shown that it is possible to induce particle production even if the mass term of a particle species is not varying in time. Such particles are produced through the interactions with other fields, whose mass terms are varying due to a time-dependent background. The necessary formalism has been introduced and analytic and numerical calculations have been performed in a simple but illustrative model. The rather general result is that the amount of produced particles without time-dependent masses can be comparable with the particle density produced directly by the varying background if the strength of interaction terms is reasonably large.

  15. Separation of dielectric Janus particles based on polarizability-dependent induced-charge electroosmotic flow.

    PubMed

    Zhang, Fang; Li, Dongqing

    2015-06-15

    A new method of sorting dielectric Janus particle is proposed and studied numerically in this paper. The Janus particles are composed of two hemispheres of two different dielectric materials. When the particle is placed in a microchannel under uniform DC electric field along the channel, vortices are induced near the particle. The strengths of the four vortices are determined by the dielectric permittivity of the particle surface, the size of the particle, the external electric field and the orientation of the Janus particle in the electric field. The numerical simulation results show that the dividing line of the Janus particle will align with the channel walls in the uniform electric field. The equilibrium distance between the wall and a particle is determined by the relative polarizability ratio and the size of the Janus particle. Thus Janus particles of the same polarizability ratio and the same size will follow the same streamline; Janus particles of different polarizability ratio and different sizes will have different trajectories. Consequently, by inducing different streamlines into different branch channels, Janus particles can be separated and collected by their polarizability ratios and their sizes. PMID:25746182

  16. Newcastle Disease Virus-Like Particles: Preparation, Purification, Quantification, and Incorporation of Foreign Glycoproteins

    PubMed Central

    McGinnes, Lori W.; Morrison, Trudy G.

    2014-01-01

    Virus-like particles (VLPs) are large particles, the size of viruses, composed of repeating structures that mimic those of infectious virus. Since their structures are similar to that of viruses, they have been used to study the mechanisms of virus assembly. They are also in development for delivery of molecules to cells and they are used in studies of the immunogenicity of particle-associated antigens. However, they have been most widely used for development of vaccines and vaccine candidates. VLPs can form upon the expression of the structural proteins of many different viruses. This chapter describes the generation and purification of VLPs formed with the structural proteins, M, NP, F and HN proteins, of Newcastle disease virus (NDV). Newcastle disease virus-like particles (ND VLPs) have also been developed as a platform for assembly into VLPs of glycoproteins from other viruses. This chapter describes the methods for this use of ND VLPs. PMID:24510891

  17. The natural history of histologically proved drug induced liver disease

    PubMed Central

    Aithal, P; Day, C

    1999-01-01

    BACKGROUND—The long term outcome of drug related liver disease is unknown. ?AIMS—To study the natural history of histologically proved drug induced hepatotoxicity. ?METHODS—110 patients with liver biopsies coded either as drug induced liver disease or hepatitis/cholestasis of unknown aetiology were identified from hospital records 1978-1996. Review of case notes and histology identified 44 patients with definite drug induced hepatotoxicity. Forty surviving patients were invited to attend a follow up clinic. History, examination, full liver screen, and isotope and ultrasound liver scans were repeated in all patients. Repeat liver biopsies were offered to patients with abnormal liver tests. ?RESULTS—Presentation at index biopsy was jaundice in 24 patients, abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and non-steroidal anti-inflammatory drugs (n=11) were the most common drugs implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in 20, and cholestasis in 18. At 1-19 years (median 5 years) follow up, 13/33 (39%) patients had persistent significant abnormalities in their liver blood tests and/or scans. Three of the five repeat liver biopsies performed showed significant abnormalities. Factors predicting persistence or development of chronic liver disease were fibrosis and continued exposure to the drug. ?CONCLUSIONS—Drugs should be considered in the differential diagnosis of abnormal liver function and/or histology, as failure to withdraw the offending drug is associated with a high risk of persistent liver damage. ?? Keywords: drugs; chronic active hepatitis; toxic hepatitis; diclofenac PMID:10205214

  18. Mineralogical and geochemical aspects of mineral-induced disease

    SciTech Connect

    Guthrie, G.; Raymond, R.; Saffiotti, U.; Aust, A. [Los Alamos National Lab., NM (United States); Mossman, B. [Univ. of Vermont, Burlington, VT (United States)

    1996-04-01

    Many minerals are known to cause disease following inhalation, including asbestos, silica, zeolites, and clays. The mineralogical properties that determine toxicity are not known, hindering effective risk assessment. Consequently, many minerals that do not pose risks are controlled excessively and many minerals that do pose risk remain uncontrolled. The authors are integrating mineralogy and biology in an interdisciplinary scientific investigation of the mechanisms of mineral-induced disease. The biological endpoints include the formation of ferruginous bodies and chemical signaling (e.g., production of cytokines or active oxygen species) by cells; the mineralogical variables include structure, composition, and surface properties. The authors are also determining what information about the biological reaction is preserved in the mineral surface.

  19. Hypoxia Inducible Factor-1 as a Target for Neurodegenerative Diseases

    PubMed Central

    Zhang, Ziyan; Yan, Jingqi; Chang, Yanzhong; Yan, Shirley ShiDu; Shi, Honglian

    2011-01-01

    Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. HIF-1, a heterodimer consisting of a constitutively expressed ? subunit and an oxygen-regulated ? subunit, regulates a series of genes that participate in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. The activity of HIF-1 is controlled by post-translational modifications on different amino acid residues of its subunits, mainly the alpha subunit. Besides in ischemic stroke (see review [1]), emerging evidence has revealed that HIF-1 activity and expression of its down-stream genes, such as vascular endothelial growth factor and erythropoietin, are altered in a range of neurodegenerative diseases. At the same time, experimental and clinical evidence has demonstrated that regulating HIF-1 might ameliorate the cellular and tissue damage in the neurodegenerative diseases. These new findings suggest HIF-1 as a potential medicinal target for the neurodegenerative diseases. This review focuses on HIF-1? protein modifications and HIF-1’s potential neuroprotective roles in Alzheimer’s (AD), Parkinson’s (PD), Huntington’s diseases (HD), and amyotrophic lateral sclerosis (ALS). PMID:21861815

  20. Levodopa-induced dyskinesias in Parkinson's disease: emerging treatments.

    PubMed

    Bargiotas, Panagiotis; Konitsiotis, Spyridon

    2013-01-01

    Parkinson's disease therapy is still focused on the use of L-3,4-dihydroxyphenylalanine (levodopa or L-dopa) for the symptomatic treatment of the main clinical features of the disease, despite intensive pharmacological research in the last few decades. However, regardless of its effectiveness, the long-term use of levodopa causes, in combination with disease progression, the development of motor complications termed levodopa-induced dyskinesias (LIDs). LIDs are the result of profound modifications in the functional organization of the basal ganglia circuitry, possibly related to the chronic and pulsatile stimulation of striatal dopaminergic receptors by levodopa. Hence, for decades the key feature of a potentially effective agent against LIDs has been its ability to ensure more continuous dopaminergic stimulation in the brain. The growing knowledge regarding the pathophysiology of LIDs and the increasing evidence on involvement of nondopaminergic systems raises the possibility of more promising therapeutic approaches in the future. In the current review, we focus on novel therapies for LIDs in Parkinson's disease, based mainly on agents that interfere with glutamatergic, serotonergic, adenosine, adrenergic, and cholinergic neurotransmission that are currently in testing or clinical development. PMID:24174877

  1. Apomorphine-induced penile erections in Parkinson's disease.

    PubMed

    O'Sullivan, J D; Hughes, A J

    1998-05-01

    Penile erections were regularly induced by intermittent subcutaneous injections of apomorphine in five patients with Parkinson's disease (PD) complicated by motor fluctuations. Four of the patients reported erectile dysfunction before beginning apomorphine and two of these report a significant improvement in their sexual function resulting from apomorphine use. Animal studies suggest central D2-type dopamine receptor stimulation and oxytocin release from the paraventricular nucleus of the hypothalamus mediate the effect. Erections reported with other dopamine agonists and levodopa are probably mediated by the same mechanism. Apomorphine-induced erections in PD are probably more common than previously thought. The benefit of apomorphine on sexual function in some patients suggests a possible role in the treatment of impotence in PD. PMID:9613749

  2. [Diagnosing and expertizing asbestos-induced occupational diseases].

    PubMed

    Baur, X; Schneider, J; Woitowitz, H-J

    2011-11-01

    Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non-uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information. PMID:22048939

  3. Particle-induced oscillations in inductively coupled plasmas

    Microsoft Academic Search

    Achim von Keudell; Martin Bauer

    2004-01-01

    The feedback between particles and the heating of an inductively coupled plasma (ICP) from argon is investigated. The ICP is heated by a pancake coil antenna, which is coupled to the plasma via a dielectric window. Particles are generated by injecting a pulse of acetylene for a few seconds into an argon plasma. Afterwards, the emission of the ICP starts

  4. DIESEL EXHAUST PARTICLES INDUCE ABERRANT ALVEOLAR EPITHELIAL DIRECTED CELL MOVEMENT BY DISRUPTION OF POLARITY MECHANISMS

    EPA Science Inventory

    Disruption of the respiratory epithelium contributes to the progression of a variety of respiratory diseases that are aggravated by exposure to air pollutants, specifically traffic-based pollutants such as diesel exhaust particles (DEP). Recognizing that lung repair following inj...

  5. Animal models of beryllium-induced lung disease

    SciTech Connect

    Finch, G.L.; Hoover, M.D.; Hahn, F.F. [Inhalation Toxicology Research Institute, Albuquerque, NM (United States)] [and others

    1996-10-01

    The Inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000{degrees}C. At similar lung burdens, the 500{degrees}C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000{degrees}C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/HeJ mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 pg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving {ge}1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 {mu}g ({approximately}300 {mu}g Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models. 47 refs., 1 fig., 3 tabs.

  6. Oligomeric A?-induced synaptic dysfunction in Alzheimer's disease.

    PubMed

    Tu, Shichun; Okamoto, Shu-ichi; Lipton, Stuart A; Xu, Huaxi

    2014-01-01

    Alzheimer's disease (AD) is a devastating disease characterized by synaptic and neuronal loss in the elderly. Compelling evidence suggests that soluble amyloid-? peptide (A?) oligomers induce synaptic loss in AD. A?-induced synaptic dysfunction is dependent on overstimulation of N-methyl-D-aspartate receptors (NMDARs) resulting in aberrant activation of redox-mediated events as well as elevation of cytoplasmic Ca2+, which in turn triggers downstream pathways involving phospho-tau (p-tau), caspases, Cdk5/dynamin-related protein 1 (Drp1), calcineurin/PP2B, PP2A, Gsk-3?, Fyn, cofilin, and CaMKII and causes endocytosis of AMPA receptors (AMPARs) as well as NMDARs. Dysfunction in these pathways leads to mitochondrial dysfunction, bioenergetic compromise and consequent synaptic dysfunction and loss, impaired long-term potentiation (LTP), and cognitive decline. Evidence also suggests that A? may, at least in part, mediate these events by causing an aberrant rise in extrasynaptic glutamate levels by inhibiting glutamate uptake or triggering glutamate release from glial cells. Consequent extrasynaptic NMDAR (eNMDAR) overstimulation then results in synaptic dysfunction via the aforementioned pathways. Consistent with this model of A?-induced synaptic loss, A? synaptic toxicity can be partially ameliorated by the NMDAR antagonists (such as memantine and NitroMemantine). PSD-95, an important scaffolding protein that regulates synaptic distribution and activity of both NMDA and AMPA receptors, is also functionally disrupted by A?. PSD-95 dysregulation is likely an important intermediate step in the pathological cascade of events caused by A?. In summary, A?-induced synaptic dysfunction is a complicated process involving multiple pathways, components and biological events, and their underlying mechanisms, albeit as yet incompletely understood, may offer hope for new therapeutic avenues. PMID:25394486

  7. Investigation on the thermophoretic tension force induced by particle rotation

    NASA Astrophysics Data System (ADS)

    Dong, Shuangling; Cao, Bingyang; Lin, Ping

    2015-04-01

    Considering the rotational movement of particles in fluid with temperature gradient, the viewpoint that particles in the fluid will experience thermophoretic tension force is proposed. The force is related to the particle motion in thermophoresis but different from the thermophoretic force. The procedure to obtain the thermophoretic tension force is introduced. In analogy with the lift force on a rotating particle in uniform fluid flow, the expression for thermophoretic tension force exerted on a particle is given under the influence of temperature gradient. It is suggested that the thermophoretic tension force is perpendicular to the rotational axis and the direction of temperature gradient. The role of thermophoretic tension force is analysed for thermophoresis in microchannel and laboratory experiment related with the evolution of protoplanetary discs.

  8. Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

    PubMed

    He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

    2015-03-01

    Curcumin is known to possess anti?inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+?ATPase activity, the mechanism underlying the curcumin?induced inhibition of the transcription of the H+, K+?ATPase ? subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+?ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress?induced gastric ulcers was produced, in which the anti?ulcer effects of curcumin were examined. Curcumin?induced inhibition of the H+, K+?ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress?induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+?ATPase promoter and in the expression of the gastric H+,K+?ATPase ? subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+?ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+?ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease. PMID:25405899

  9. Angular distribution in two-particle emission induced by neutrinos and electrons

    E-print Network

    Simo, I. Ruiz

    The angular distribution of the phase space arising in two-particle emission reactions induced by electrons and neutrinos is computed in the laboratory (Lab) system by boosting the isotropic distribution in the center of ...

  10. Corporation-induced Diseases, Upstream Epidemiologic Surveillance, and Urban Health

    PubMed Central

    2008-01-01

    Corporation-induced diseases are defined as diseases of consumers, workers, or community residents who have been exposed to disease agents contained in corporate products. To study the epidemiology and to guide expanded surveillance of these diseases, a new analytical framework is proposed. This framework is based on the agent–host–environment model and the upstream multilevel epidemiologic approach and posits an epidemiologic cascade starting with government-sanctioned corporate profit making and ending in a social cost, i.e., harm to population health. Each of the framework’s levels addresses a specific level of analysis, including government, corporations, corporate conduits, the environment of the host, and the host. The explained variable at one level is also the explanatory variable at the next lower level. In this way, a causal chain can be followed along the epidemiologic cascade from the site of societal power down to the host. The framework thus describes the pathways by which corporate decisions filter down to disease production in the host and identifies opportunities for epidemiologic surveillance. Since the environment of city dwellers is strongly shaped by corporations that are far upstream and several levels away, the framework has relevance for the study of urban health. Corporations that influence the health of urban populations include developers and financial corporations that determine growth or decay of urban neighborhoods, as well as companies that use strategies based on neighborhood characteristics to sell products that harm consumer health. Epidemiological inquiry and surveillance are necessary at all levels to provide the knowledge needed for action to protect the health of the population. To achieve optimal inquiry and surveillance at the uppermost levels, epidemiologists will have to work with political scientists and other social scientists and to utilize novel sources of information. PMID:18437580

  11. The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics.

    PubMed

    Shafagati, Nazly; Patanarut, Alexis; Luchini, Alessandra; Lundberg, Lindsay; Bailey, Charles; Petricoin, Emanuel; Liotta, Lance; Narayanan, Aarthi; Lepene, Benjamin; Kehn-Hall, Kylene

    2014-07-01

    Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays. PMID:24449537

  12. Turbulence-induced Relative Velocity of Dust Particles. I. Identical Particles

    NASA Astrophysics Data System (ADS)

    Pan, Liubin; Padoan, Paolo

    2013-10-01

    We study the relative velocity of inertial particles suspended in turbulent flows and discuss implications for dust particle collisions in protoplanetary disks. We simulate a weakly compressible turbulent flow, evolving 14 particle species with friction timescale, ?p, covering the entire range of scales in the flow. The particle Stokes numbers, St, measuring the ratio of ?p to the Kolmogorov timescale, are in the range 0.1 <~ St <~ 800. Using simulation results, we show that the model by Pan & Padoan gives satisfactory predictions for the rms relative velocity between identical particles. The probability distribution function (PDF) of the relative velocity is found to be highly non-Gaussian. The PDF tails are well described by a 4/3 stretched exponential function for particles with ?p ~= 1-2 T L, where T L is the Lagrangian correlation timescale, consistent with a prediction based on PP10. The PDF approaches Gaussian only for very large particles with ?p >~ 54 T L. We split particle pairs at given distances into two types with low and high relative speeds, referred to as continuous and caustic types, respectively, and compute their contributions to the collision kernel. Although amplified by the effect of clustering, the continuous contribution vanishes in the limit of infinitesimal particle distance, where the caustic contribution dominates. The caustic kernel per unit cross section rises rapidly as St increases toward ~= 1, reaches a maximum at ?p ~= 2 T L, and decreases as \\tau _p^{-1/2} for ?p Gt T L.

  13. Placental Induced Growth Factor (PIGf) in Coronary Artery Disease

    NASA Technical Reports Server (NTRS)

    Sundaresan, Alamelu; Carabello, Blaise; Mehta, Satish; Schlegel, Todd; Pellis, Neal; Ott, Mark; Pierson, Duane

    2010-01-01

    Our previous studies on normal human lymphocytes have shown a five-fold increase (p less than 0.001) in angiogenic inducers such as Placental Induced Growth Factor (PIGf) in physiologically stressful environments such as modeled microgravity, a space analog. This suggests de-regulation of cardiovascular signalling pathways indicated by upregulation of PIGf. In the current study, we measured PIGf in the plasma of 33 patients with and without coronary artery disease (CAD) to investigate whether such disease is associated with increased levels of PIGf. A control consisting of 31 sex matched apparently healthy subjects was also included in the study. We observed that the levels of PIGf in CAD patients were significantly increased compared to those in healthy control subjects (p less than 0.001) and usually increased beyond the clinical threshold level (greater than 27ng/L). The mechanisms leading to up-regulation of angiogenic factors and the adaptation of organisms to stressful environments such as isolation, high altitude, hypoxia, ischemia, microgravity, increased radiation, etc are presently unknown and require further investigation in spaceflight and these other physiologically stressed environments.

  14. Applying Particle Image Velocimetry to Map Fire Ant Alate Wing Beat Induced Flows Lichuan Gui1

    E-print Network

    Gui, Lichuan

    Applying Particle Image Velocimetry to Map Fire Ant Alate Wing Beat Induced Flows Lichuan Gui1, Mississippi A particle image velocimetry (PIV) system was built at the University of Mississippi's National alate is tethered on a fine metal wire so that its body does not move during the flight. It is also

  15. Incipient motion of spherical particles induced by a vortex ring disturbance

    Microsoft Academic Search

    Maria-Laura Beninati; Michael McErlean; Michael Krane; Arnold Fontaine

    2009-01-01

    Experiments to characterize the ability of a vortical disturbance to induce incipent motion of a stationary particle resting on a horizontal planar surface are described. The ultimate goal of this study is to assess the role of turbulent boundary layer coherent structures in particle suspension. In this study, a vortex ring plays the role of a model flow disturbance because

  16. Human-Induced Particle ReSuspension in a Room

    Microsoft Academic Search

    Roshan C. Oberoi; Jung-Il Choi; Jack R. Edwards; Jacky A. Rosati; Jonathan Thornburg; Charles E. Rodes

    2010-01-01

    A large-eddy simulation\\/immersed boundary method for particulate flows in an Eulerian framework is utilized to investigate short-term particle re-suspension due to human motion. The simulations involve a human walking through a room, stopping, and then walking in place, causing particles to be re-suspended from a carpet. The carpet layer is modeled as the porous medium and a classical adhesive force

  17. The prevention of titanium-particle-induced osteolysis by OA-14 through the suppression of the p38 signaling pathway and inhibition of osteoclastogenesis.

    PubMed

    Tian, Bo; Jiang, Tao; Shao, Zhanying; Zhai, Zanjing; Li, Haowei; Fan, Qiming; Liu, Xuqiang; Ouyang, Zhengxiao; Tang, Tingting; Jiang, Qing; Zheng, Minghao; Dai, Kerong; Qin, An; Yu, Yongping; Zhu, Zhenan

    2014-10-01

    Wear-particle-induced osteolysis leads to prosthesis loosening, which is one of the most common causes of joint-implant failure, a problem that must be fixed using revision surgery. Thus, a potential treatment for prosthetic loosening is focused on inhibiting osteoclastic bone resorption, which prevents wear-particle-induced osteolysis. In this study, we synthesized a compound named OA-14 (N-(3- (dodecylcarbamoyl)phenyl)-1H-indole-2-carboxamide) and examined how OA-14 affects titanium (Ti)-particle-induced osteolysis and osteoclastogenesis. We report that OA-14 treatment protected against Ti-particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of tartrate-resistant acid phosphatase-positive osteoclasts decreased after treatment with OA-14 in vivo, which suggested that OA-14 inhibits osteoclast formation. To test this hypothesis, we conducted in vitro studies, and our results revealed that OA-14 markedly diminished osteoclast differentiation and osteoclast-specific gene expression in a dose- and time-dependent manner. Moreover, OA-14 suppressed osteoclastic bone resorption and F-actin ring formation. Furthermore, we determined that OA-14 inhibited osteoclastogenesis by specifically blocking the p38-Mitf-c-fos-NFATc1 signaling cascade induced by RANKL (ligand of receptor activator of nuclear factor ?B). Collectively, our results suggest that the compound OA-14 can be safely used for treating particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function. PMID:25086794

  18. The measurement and modeling of alpha-particle-induced charge collection in dynamic memories

    Microsoft Academic Search

    Oldiges

    1989-01-01

    This thesis addresses the problem of α-particle-induced charge collection in high-density dynamic random access memories. A novel technique for the measurement of charge collection in high-density memory cells and bit lines due to α-particle strikes was developed. The technique involves D.C. tests on simple test structures with an α-particle source on the device package as a lid. The advantages of

  19. PIV Measurements of Particle and Fluid Motion Induced by AC Electric Fields

    Microsoft Academic Search

    Dazhi Wang; Carl Meinhart; Marin Sigurdson

    2003-01-01

    The techniques to induce particle and fluid motion inside microsystems using ac electric fields have important applications in sensing and manipulating bioparticles. Micron-Resolution Particle Image Velocimetry (m-PIV) is a powerful tool to measure the spatially resolved motion with resolution approaching 1mm. In the presence of nonuniform ac electric fields, the particles experience dielectrophoretic (DEP) forces due to polarization and drag

  20. Particle-induced damage and subsequent healing of materials: Erosion, corrosion and self-healing coatings

    Microsoft Academic Search

    Akihiro Yabuki

    2011-01-01

    This review summarizes research on particle-induced damage and the subsequent repair of metallic materials. Metallic materials are damaged by solid particle impact via two damage processes: repeated plastic deformation and cutting. At a certain low-impact velocity, the particle does not skid, resulting in only plastic deformation with no damage by cutting. The critical impact velocity has been theoretically derived. Self-healing

  1. In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

    1993-04-01

    The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

  2. Hypericin suppresses osteoclast formation and wear particle-induced osteolysis via modulating ERK signalling pathway.

    PubMed

    Ouyang, Zhengxiao; Zhai, Zanjing; Li, Haowei; Liu, Xuqiang; Qu, Xinhua; Li, Xianan; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

    2014-08-01

    Osteoclast-induced bone resorption and wear-particle-induced osteolysis leads to prosthetic loosening, one of the most common causes of joint implant failure, resulting in revision surgery. Thus, inhibition of osteoclastic bone resorption, which further prevents wear particle-induced osteolysis, is a potential treatment strategy for prosthetic loosening. Here, we examined the therapeutic effect of hypericin (HP), which was photosensitive, on osteoclastogenesis and wear particle-induced osteolysis in the absence of visible light. HP inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) and RAW264.7 cell line without any evidence of cytotoxicity. The bone-resorbing activity of mature osteoclasts was significantly inhibited by HP. As HP has been previously reported to inhibit signalling pathway such as ERK and NF-?B in other cells, which is also important in osteoclast differentiation. We thus examined the molecular mechanism and showed that HP significantly inhibited the ERK/mitogen-activated protein kinase (MAPK) signalling pathway without affecting nuclear factor kappaB (NF-?B), c-Jun N-terminal kinase (JNK) and p38 signalling in RANKL-stimulated BMMs. Further in vivo studies revealed HP attenuated osteoclast formation and subsequently prevented wear particle-induced bone erosion. Taken together, the results suggest that HP inhibits RANKL-mediated osteoclastogenesis via affecting ERK signalling in vitro and suppresses wear particle-induced osteolysis in vivo. We therefore conclude that HP may be an innovative and safe alternative treatment for osteoclast-related prosthetic loosening. PMID:24950468

  3. Derivation of Induced Pluripotent Stem Cells for Human Disease Modeling

    PubMed Central

    Narsinh, Kamileh; Narsinh, Kazim H.; Wu, Joseph C.

    2011-01-01

    The successful derivation of human induced pluripotent stem cells (hiPSCs) by de-differentiation of somatic cells offers significant potential to overcome obstacles in the field of cardiovascular disease. hiPSC derivatives offer incredible potential for new disease models and regenerative medicine therapies. However, many questions remain regarding the optimal starting materials and methods to enable safe, efficient derivation of hiPSCs suitable for clinical applications. Initial reprogramming experiments were carried out using lentiviral or retroviral gene delivery methods. More recently, various non-viral methods that avoid permanent and random transgene insertion have emerged as alternatives. These include transient DNA transfection approaches using transposons or minicircle plasmids, protein transduction approaches, and RNA transfection approaches. In addition, several small molecules have been found to significantly augment iPSC derivation efficiency, allowing the use of a fewer number of genes during pluripotency induction. Here, we review these various methods for the derivation of hiPSCs, focusing on their ultimate clinical applicability, with an emphasis on their potential for use as cardiovascular therapies and disease modeling platforms. PMID:21527744

  4. Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice

    PubMed Central

    Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; Castro-Faria-Neto, Hugo Caire; Pereira, Mirian Claudia de Souza; Tibiriçá, Eduardo; Garzoni, Luciana Ribeiro

    2014-01-01

    Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD. PMID:25010691

  5. Adjuvant effects of chitosan and calcium phosphate particles in an inactivated Newcastle disease vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The adjuvant activity of chitosan and calcium phosphate-particles (CAP) was studied following intranasal coadministration of commercial chickens with inactivated Newcastle disease virus (NDV) vaccine. After three vaccinations with inactivated NDV in combination with chitosan or CAP an increase in an...

  6. FACTORS THAT INFLUENCE THE RELATIVE POTENCY OF DIESEL EXHAUST PARTICLES AS ADJUVANTS IN ALLERGIC AIRWAY DISEASE

    EPA Science Inventory

    Description: Studies have shown that diesel exhaust particles (DEP) worsen respiratory diseases including allergic asthma. The adjuvant effects of DEP in the airways have been widely reported; however, the precise determinants and mechanisms of these effects are ill-defined. S...

  7. Wave-induced particle precipitation from the magnetosphere and the associated ionospheric perturbations

    SciTech Connect

    Inan, U.S.

    1987-01-01

    A brief review of the gyroresonant wave-induced precipitation of energetic radiation belt particles is presented, using the particular case of interactions involving lightning-generated whistler waves as an example. The interaction physics is first discussed in the context of results from a recently developed theoretical model of the whistler-particle scattering process occurring in the magnetosphere. This is followed by a discussion of the Trimpi effect, a particularly sensitive ground-based technique that has recently been increasingly used for detecting ionospheric perturbations produced by whistler-induced energetic particle precipitation from the magnetosphere on L-shells of 2-5.

  8. The preferential targeting of the diseased microvasculature by disk-like particles

    PubMed Central

    Adriani, Giulia; de Tullio, Marco D.; Ferrari, Mauro; Hussain, Fazle; Pascazio, Giuseppe; Liu, Xuewu; Decuzzi, Paolo

    2012-01-01

    Different classes of nanoparticles (NPs) have been developed for controlling and improving the systemic administration of therapeutic and contrast agents. Particle shape has been shown to be crucial in the vascular transport and adhesion of NPs. Here, we use mesoporous silicon non-spherical particles, of disk and rod shapes, ranging in size from 200 nm to 1800 nm. The fabrication process of the mesoporous particles is described in detail, and their transport and adhesion properties under flow are studied using a parallel plate flow chamber. Numerical simulations predict the hydrodynamic forces on the particles and help in interpreting their distinctive behaviors. Under microvascular flow conditions, for disk-like shape, 1000×400 nm particles show maximum adhesion, whereas smaller (600×200 nm) and larger (1800×600 nm) particles adhere less by a factor of about two. Larger rods (1800×400 nm) are observed to adhere at least 3 times more than smaller ones (1500×200 nm). For particles of equal volumes, disks adhere about 2 times more than rods. Maximum adhesion for intermediate sized disks reflects the balance between adhesive interfacial interactions and hydrodynamic dislodging forces. In view of the growing evidence on vascular molecular heterogeneity, the present data suggest that thin disk-like particles could more effectively target the diseased microvasculature as compared to spheres and slender rods. PMID:22579236

  9. TURBULENCE-INDUCED RELATIVE VELOCITY OF DUST PARTICLES. I. IDENTICAL PARTICLES

    SciTech Connect

    Pan, Liubin [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Padoan, Paolo, E-mail: lpan@cfa.harvard.edu, E-mail: ppadoan@icc.ub.edu [ICREA and ICC, University of Barcelona, Marti i Franquès 1, E-08028 Barcelona (Spain)

    2013-10-10

    We study the relative velocity of inertial particles suspended in turbulent flows and discuss implications for dust particle collisions in protoplanetary disks. We simulate a weakly compressible turbulent flow, evolving 14 particle species with friction timescale, ?{sub p}, covering the entire range of scales in the flow. The particle Stokes numbers, St, measuring the ratio of ?{sub p} to the Kolmogorov timescale, are in the range 0.1 ?< St ?< 800. Using simulation results, we show that the model by Pan and Padoan gives satisfactory predictions for the rms relative velocity between identical particles. The probability distribution function (PDF) of the relative velocity is found to be highly non-Gaussian. The PDF tails are well described by a 4/3 stretched exponential function for particles with ?{sub p} ? 1-2 T{sub L}, where T{sub L} is the Lagrangian correlation timescale, consistent with a prediction based on PP10. The PDF approaches Gaussian only for very large particles with ?{sub p} ?> 54 T{sub L}. We split particle pairs at given distances into two types with low and high relative speeds, referred to as continuous and caustic types, respectively, and compute their contributions to the collision kernel. Although amplified by the effect of clustering, the continuous contribution vanishes in the limit of infinitesimal particle distance, where the caustic contribution dominates. The caustic kernel per unit cross section rises rapidly as St increases toward ? 1, reaches a maximum at ?{sub p} ? 2 T{sub L}, and decreases as ?{sub p}{sup -1/2} for ?{sub p} >> T{sub L}.

  10. Chromatin core particle unfolding induced by tryptic cleavage of histones.

    PubMed Central

    Lilley, D M; Tatchell, K

    1977-01-01

    Chromatin 'core particles' have been digested with trypsin to varying extents. The resulting particles are homogeneous by the criterion of ultracentrifuge boundary analysis. Sedimentation coefficients are lowered as cleavages are introduced into the histones, showing that an unfolding of the core particle occurs. This unfolding is further characterised by a lower melting temperature together with a premelting phase, higher molar ellipticity in the circular dichroism spectra at 280 nm and increased kinetics of digestion by both micrococcal nuclease and DNase I. Differences are also observed in the products of nuclease digestion. The most consistent interpretation of the data involves an unfolding process whereby free rods of DNA are released to extend from a nucleoprotein core. Images PMID:896484

  11. Gross Cystic Disease Fluid Protein-15/Prolactin-Inducible Protein as a Biomarker for Keratoconus Disease

    PubMed Central

    Priyadarsini, Shrestha; Hjortdal, Jesper; Sarker-Nag, Akhee; Sejersen, Henrik; Asara, John M.; Karamichos, Dimitrios

    2014-01-01

    Keratoconus (KC) is a bilateral degenerative disease of the cornea characterized by corneal bulging, stromal thinning, and scarring. The etiology of the disease is unknown. In this study, we identified a new biomarker for KC that is present in vivo and in vitro. In vivo, tear samples were collected from age-matched controls with no eye disease (n?=?36) and KC diagnosed subjects (n?=?17). Samples were processed for proteomics using LC-MS/MS. In vitro, cells were isolated from controls (Human Corneal Fibroblasts-HCF) and KC subjects (Human Keratoconus Cells-HKC) and stimulated with a Vitamin C (VitC) derivative for 4 weeks, and with one of the three transforming growth factor-beta (TGF-?) isoforms. Samples were analyzed using real-time PCR and Western Blots. By using proteomics analysis, the Gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP) was found to be the best independent biomarker able to discriminate between KC and controls. The intensity of GCDFP-15/PIP was significantly higher in healthy subjects compared to KC-diagnosed. Similar findings were seen in vitro, using a 3D culture model. All three TGF-? isoforms significantly down-regulated the expression of GCDFP-15/PIP. Zinc-alpha-2-glycoprotein (AZGP1), a protein that binds to PIP, was identified by proteomics and cell culture to be highly regulated. In this study by different complementary techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for KC disease. It is likely that exploring the GCDFP-15/PIP-AZGP1 interactions will help better understand the mechanism of KC disease. PMID:25405607

  12. Role of direct estrogen receptor signaling in wear particle-induced osteolysis

    PubMed Central

    Nich, Christophe; Rao, Allison J.; Valladares, Roberto D.; Li, Chenguang; Christman, Jane E.; Antonios, Joseph K.; Yao, Zhenyu; Zwingenberger, Stefan; Petite, Hervé; Hamadouche, Moussa; Goodman, Stuart B.

    2014-01-01

    Estrogen withdrawal following surgical ovariectomy was recently shown to mitigate particle-induced osteolysis in the murine calvarial model. Currently, we hypothesize that estrogen receptors (ERs) were involved in this paradoxical phenomenon. To test this hypothesis, we first evaluated polyethylene (PE) particle-induced osteolysis in the murine calvarial model, using wild type (WT) C57BL6J female mice, ER? deficient (ER?KO) mice, and WT mice either treated with 17?-estradiol (E2) or with the ER pan-antagonist ICI 182,780. According to micro-CT and histomorphometry, we showed that bone resorption was consistently altered in both ER?KO and ICI 182,780 treated mice as compared to WT and E2 groups. Then, we demonstrated that ER disruption consistently decreased both PE and polymethylmethacrylate (PMMA) particle-induced production of TNF-? by murine macrophages in vitro. Similar results were obtained following ER blockade using ICI 182,780 in RAW 264.7 and WT macrophages. ER disruption and pre treatment with ICI 182,780 resulted in a consistent down-regulation of particle-induced TNF-? mRNA expression relative to WT macrophages or untreated RAW cells. These results indicate that the response to wear particles involves estrogen receptors in female mice, as part of macrophage activation. Estrogen receptors may be considered as a future therapeutic target for particle-induced osteolysis. PMID:23113918

  13. Cross sections and spectra for charged-particle induced reactions

    SciTech Connect

    Hale, G.M.; Talley, T.L.

    1994-06-01

    Using calculational methods based on R-matrix theory, we have obtained cross sections and spectra for a number of charged-particle reactions, including those initiated by d+t, t+t, and t+{sup 6}Li. The three-body resonance model used to calculate the spectra resembles the sequential-decay model, but it sometimes gives different results. Contributions from resonances involving the detected particle can produce the broad structure underlying the narrow peaks in the spectra that is often attributed to ``three-body phase space.`` We will show examples of calculated cross sections and spectra, compared to the measured data.

  14. Monitoring process induced attrition of drug substance particles within formulated blends.

    PubMed

    Gamble, John F; Hoffmann, Magnus; Hughes, Helen; Hutchins, Paul; Tobyn, Mike

    2014-08-15

    The aim of the study was to investigate the impact of unit processing steps such as blending, cone milling and powder feeding systems on the particle size of a formulated API. The particle properties of a single component (API) within formulated samples were tracked using an image based particle characterisation system with an integrated Raman probe. In addition to the primary aim, the impact of excipient selection was also assessed. The study demonstrated the ability to track the size and shape of particles of a single component within a blended system. Process induced attrition can affect significant changes in the size and shape characteristics of the API particles. Whilst blending and cone milling were found to have minimal impact on the API properties, significant particle attrition was induced through transmission of the formulations through a powder feeding system. The impact of excipients within the formulated blends on API attrition propensity was observed to be low. The findings suggest that the propensity for particles to undergo process induced attrition should be taken into consideration when designing a manufacturing process and/or relating initial particle properties to the performance of intermediate or final dosage forms. PMID:24793838

  15. Induced-Charge Electrophoresis of Metallodielectric Particles Sumit Gangwal,1

    E-print Network

    Bazant, Martin Z.

    Martin Z. Bazant,2 and Orlin D. Velev1,* 1 Department of Chemical and Biomolecular Engineering, North to a glass wall. This phenomenon may find applications in microactuators, microsensors, and microfluidic. The liquid and particle velocities typically depend on the strength of the applied field squared and are com

  16. Disease-corrected hepatocyte-like cells from familial hypercholesterolemia-induced pluripotent stem cells.

    PubMed

    Fattahi, Faranak; Asgari, Samira; Pournasr, Behshad; Seifinejad, Ali; Totonchi, Mehdi; Taei, Adeleh; Aghdami, Nasser; Salekdeh, Ghasem Hosseini; Baharvand, Hossein

    2013-07-01

    The generation of human induced pluripotent stem cells (hiPSCs) from an individual patient provides a unique tool for disease modeling, drug discovery, and cell replacement therapies. Patient-specific pluripotent stem cells can be expanded in vitro and are thus suitable for genetic manipulations. To date, several genetic liver disorders have been modeled using patient-specific hiPSCs. Here, we present the generation of corrected hepatocyte-like cells (HLCs) from hiPSCs of a familial hypercholesterolemia (FH) patient with a homozygous mutation in the low-density lipoprotein receptor (LDLR) gene. We generated hiPSCs from a patient with FH with the mutated gene encoding a truncated non-functional receptor. In order to deliver normal LDLR to the defective cells, we used a plasmid vector carrying the normal receptor ORF to genetically transform the hiPSCs. The transformed cells were expanded and directed toward HLCs. Undifferentiated defective hiPSCs and HLCs differentiated from the defective hiPSCs did not have the ability to uptake labeled low-density lipoprotein (LDL) particles. The differentiated transformed hiPSCs showed LDL-uptake ability and the correction of disease phenotype as well as expressions of hepatocyte-specific markers. The functionality of differentiated cells was also confirmed by indo-cyanine green (ICG) uptake assay, PAS staining, inducible cyp450 activity, and oil red staining. These data suggest that hiPSC technology can be used for generation of disease-corrected, patient-specific HLCs with potential value for disease modeling and drug discovery as well as cell therapy applications in future. PMID:23247991

  17. Immune-mediated drug-induced liver disease.

    PubMed

    Liu, Zhang-Xu; Kaplowitz, Neil

    2002-08-01

    Drug-induced immune-mediated hepatic injury is an adverse immune response against the liver that results in a disease with hepatitic, cholestatic, or mixed clinical features. Drugs such as halothane, tienilic acid, dihydralazine, and anticonvulsants trigger a hepatitic reaction, and drugs such as chlorpromazine, erythromycins, amoxicillin-calvulanic acid, sulfonamides and sulindac trigger a cholestatic or mixed reaction. Unstable metabolites derived from the metabolism of the drug may bind to cellular proteins or macromolecules, leading to a direct toxic effect on hepatocytes. Protein adducts formed in the metabolism of the drug may be recognized by the immune system as neoantigens. Immunocyte activation may then generate autoantibodies and cell-mediated immune responses, which in turn damage the hepatocytes. Cytochromes 450 are the major oxidative catalysts in drug metabolism, and they can form a neoantigen by covalently binding with the drug metabolite that they produce. Autoantibodies that develop are selectively directed against the particular cytochrome isoenzyme that metabolized the parent drug. The hapten hypothesis proposes that the drug metabolite can act as a hapten and can modify the self of the individual by covalently binding to proteins. The danger hypothesis proposes that the immune system only responds to a foreign antigen if the antigen is associated with a danger signal, such as cell stress or cell death. Most clinically overt adverse hepatic events associated with drugs are unpredictable, and they have intermediate (1 to 8 weeks) or long latency (up to 12 months) periods characteristic of hypersensitivity reactions. Immune-mediated drug-induced liver disease nearly always disappears or becomes quiescent when the drug is removed. Methyldopa, minocycline, and nitrofurantoin can produce a chronic hepatitis resembling AIH if the drug is continued. PMID:12362579

  18. Molecular Basis of Asbestos-Induced Lung Disease

    PubMed Central

    Liu, Gang; Cheresh, Paul; Kamp, David W.

    2013-01-01

    Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking. PMID:23347351

  19. Transgenic models for cytokine-induced neurological disease

    PubMed Central

    Campbell, Iain L.; Hofer, Markus J.; Pagenstecher, Axel

    2009-01-01

    Considerable evidence supports the idea that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in a variety of neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. One approach to address this problem that has been used widely employs transgenic mice with CNS-targeted production of different cytokines. Transgenic production of cytokines in the CNS of mice allows not only for the investigation of complex cellular responses at a localized level in the intact brain, but also more closely recapitulates the expression of these mediators as found in disease states. As discussed in this review, the findings show that these transgenic animals exhibit wide-ranging structural and functional deficits that are linked to the development of distinct neuroinflammatory responses which are relatively specific for each cytokine. These cytokine-induced alterations often recapitulate those found in various human neurological disorders not only underscoring the relevance of these models but also reinforcing the clinicopathogenetic significance of cytokines in diseases of the CNS. PMID:19835956

  20. Experimental background due to particle induced gas desorption in RHIC

    SciTech Connect

    Zhang,S.Y.; Trbojevic, D.

    2008-08-10

    Beam-gas collision created experimental background, i.e., singles, has affected heavy ion and polarized proton operations in Relativistic Heavy Ion Collider at Brookhaven National Laboratory. The gas molecules in interaction region are mainly caused by the electron induced gas desorption. and the electrons are produced from the beam induced electron multipacting, or called electron cloud. The background has a dependence on the usual electron cloud related parameters, such as the bunch intensity, bunch spacing, and the solenoid field. With the RHIC upgrade plan, the experimental background may become a luminosity limiting factor. Mitigations are discussed.

  1. Energetic particle-induced enhancements of stratospheric nitric acid

    NASA Technical Reports Server (NTRS)

    Aikin, Arthur C.

    1994-01-01

    Inclusion of complete ion chemistry in the calculation of minor species production during energetic particle deposition events leads to significant enhancement in the calculated nitric acid concentration during precipitation. An ionization rate of 1.2 x 10(exp 3)/cu cm/s imposed for 1 day increases HNO3 from 3 x 10(exp 5) to 6 x 10(exp 7)/cu cm at 50 km. With an ionization rate of 600 cu cm/s, the maximum HNO3 is 3 x 10(exp 7)/cu cm. Calculations which neglect negative ions predict the nitric acid will fall during precipitation events. The decay time for converting HNO3 into odd nitrogen and hydrogen is more than 1 day for equinoctial periods at 70 deg latitude. Examination of nitric acid data should yield important information on the magnitude and frequency of charged particle events.

  2. Crater-ray formation by impact-induced ejecta particles

    NASA Astrophysics Data System (ADS)

    Kadono, T.; Suzuki, A. I.; Wada, K.; Mitani, N. K.; Yamamoto, S.; Arakawa, M.; Sugita, S.; Haruyama, J.; Nakamura, A. M.

    2015-04-01

    We performed impact experiments with granular targets to reveal the formation process of crater "rays", the non-uniform ejecta distributions around some fresh craters on the Moon and planets. We found mesh patterns, loosely woven with spaces like a net, as ejecta. A characteristic length of spaces between meshes was evaluated, and an angle, defined as the ratio of the characteristic length to the distance from the ejection point, was obtained as ?a few degrees. These features are similar to the results of the analyses of the ray patterns around two lunar craters, Glushko and Kepler. Numerical simulations of granular material showed that clear mesh pattern appeared at lower coefficients of restitution between particles but was less clear at larger one, suggesting that the inelastic collisions between particles cause the clear mesh-pattern formation of impact ejecta.

  3. Particle roughness in magnetorheology: effect on the strength of the field-induced structures

    NASA Astrophysics Data System (ADS)

    Vereda, F.; Segovia-Gutiérrez, J. P.; de Vicente, J.; Hidalgo-Alvarez, R.

    2015-01-01

    We report a study on the effect of particle roughness on the strength of the field-induced structures of magnetorheological (MR) fluids in the quasi-static regime. We prepared one set of MR fluids with carbonyl iron particles and another set with magnetite particles, and in both sets we had particles with different degrees of surface roughness. Small amplitude oscillatory shear (SAOS) magnetosweeps and steady shear (SS) tests were carried out on the suspensions to measure their elastic modulus (G?) and static yield stress (?static). Results for both the iron and the magnetite sets of suspensions were consistent: for the MR fluids prepared with rougher particles, G? increased at smaller fields and ?static was ca. 20% larger than for the suspensions prepared with relatively smooth particles. In addition to the experimental study, we carried out finite element method calculations to assess the effect of particle roughness on the magnetic interaction between particles. These calculations showed that roughness can facilitate the magnetization of the particles, thus increasing the magnetic energy of the system for a given field, but that this effect depends on the concrete morphology of the surface. For our real systems, no major differences were observed between the magnetization cycles of the MR fluids prepared with particles with different degree of roughness, which implied that the effect of roughness on the measured G? and ?static was due mainly to friction between the solid surfaces of adjacent particles.

  4. Disorder-induced breakdown of soliton and polaron particles

    SciTech Connect

    Bishop, A.R.; Cai, D.; Gronbech-Jensen, N.; Salkola, M.I.

    1995-12-31

    Using examples of the perturbed (1+1) dimensional sine-Gordon, the continuous and discrete nonlinear Schroedinger systems, and a three-site quantum polaron problem, the authors briefly review some phenomena related to the fascinating interplays between nonlinearity, disorder, noise, nonadiabaticity, and lattice discreteness. The concept of competing length-scales and time-scales is emphasized as they pertain to the common concept of solitons and polarons behaving as {open_quotes}particles.{close_quotes}

  5. Simultaneous measurement of electron and heavy particle temperatures in He laser-induced plasma by Thomson and Rayleigh scattering

    E-print Network

    .1063/1.4801467] Laser-induced plasmas (LIP) have found numerous appli- cations, including laser ablation, shortSimultaneous measurement of electron and heavy particle temperatures in He laser-induced plasma particle temperatures in He laser-induced plasma by Thomson and Rayleigh scattering K. Dzier_zeRga,1 A

  6. Binding of (-)-epigallocatechin-3-gallate with thermally-induced bovine serum albumin/?-carrageenan particles.

    PubMed

    Li, Jinbing; Wang, Xiaoyong

    2015-02-01

    Novel thermally-induced BSA/?-carrageenan particles are used as a protective carrier for (-)-epigallocatechin-3-gallate (EGCG). The addition of EGCG to BSA/?-carrageenan particles can highly quench the intrinsic fluorescence of BSA, which is explained in terms of the binding of EGCG to the hydrophobic pockets of BSA mainly through the hydrophobic force. According to the double logarithm equation, the binding constant is determined as 1.1×10(8)M(-1) for the binding of EGCG with BSA/?-carrageenan particles. The high binding affinity is ascribed to both the molecular structure of EGCG and the partial unfolding state of BSA in BSA/?-carrageenan particles. The circular dichroism spectra and calculated ?-helix of BSA suggest that the bound EGCG leads to a more random secondary structure of BSA. Furthermore, BSA/?-carrageenan particles are found to be superior to native BSA and pure BSA particles for improving the stability and radical scavenging activity of EGCG. PMID:25172749

  7. Oxidative stress as a mechanism of added sugar-induced cardiovascular disease.

    PubMed

    Prasad, Kailash; Dhar, Indu

    2014-12-01

    Added sugars comprising of table sugar, brown sugar, corn syrup, maple syrup, honey, molasses, and other sweeteners in the prepared processed foods and beverages have been implicated in the pathophysiology of cardiovascular diseases. This article deals with the reactive oxygen species (ROS) as a mechanism of sugar-induced cardiovascular diseases. There is an association between the consumption of high levels of serum glucose with cardiovascular diseases. Various sources of sugar-induced generation of ROS, including mitochondria, nicotinamide adenine dinucleotide phosphate-oxidase, advanced glycation end products, insulin, and uric acid have been discussed. The mechanism by which ROS induce the development of atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias have been discussed in detail. In conclusion, the data suggest that added sugars induce atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias and that these effects of added sugars are mediated through ROS. PMID:25484552

  8. Induced pluripotent stem cell technology for disease modeling and drug screening with emphasis on lysosomal storage diseases

    PubMed Central

    2012-01-01

    The recent derivation of disease-specific induced pluripotent stem cells (iPSCs) from somatic cells of patients with familial and sporadic forms of diseases and the demonstration of their ability to give rise to disease-relevant cell types provide an excellent opportunity to gain further insights into the mechanisms responsible for the pathophysiology of these diseases and develop novel therapeutic drugs. Here, we review the recent advances in iPSC technology for modeling of various lysosomal storage diseases (LSDs) and discuss possible strategies through which LSD-iPSCs can be exploited to identify novel drugs and improve future clinical treatment of LSDs. PMID:22925465

  9. Solar Particle Induced Upsets in the TDRS-1 Attitude Control System RAM During the October 1989 Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Croley, D. R.; Garrett, H. B.; Murphy, G. B.; Garrard,T. L.

    1995-01-01

    The three large solar particle events, beginning on October 19, 1989 and lasting approximately six days, were characterized by high fluences of solar protons and heavy ions at 1 AU. During these events, an abnormally large number of upsets (243) were observed in the random access memory of the attitude control system (ACS) control processing electronics (CPE) on-board the geosynchronous TDRS-1 (Telemetry and Data Relay Satellite). The RAM unit affected was composed of eight Fairchild 93L422 memory chips. The Galileo spacecraft, launched on October 18, 1989 (one day prior to the solar particle events) observed the fluxes of heavy ions experienced by TDRS-1. Two solid-state detector telescopes on-board Galileo, designed to measure heavy ion species and energy, were turned on during time periods within each of the three separate events. The heavy ion data have been modeled and the time history of the events reconstructed to estimate heavy ion fluences. These fluences were converted to effective LET spectra after transport through the estimated shielding distribution around the TDRS-1 ACS system. The number of single event upsets (SEU) expected was calculated by integrating the measured cross section for the Fairchild 93L422 memory chip with average effective LET spectrum. The expected number of heavy ion induced SEU's calculated was 176. GOES-7 proton data, observed during the solar particle events, were used to estimate the number of proton-induced SEU's by integrating the proton fluence spectrum incident on the memory chips, with the two-parameter Bendel cross section for proton SEU'S. The proton fluence spectrum at the device level was gotten by transporting the protons through the estimated shielding distribution. The number of calculated proton-induced SEU's was 72, yielding a total of 248 predicted SEU'S, very dose to the 243 observed SEU'S. These calculations uniquely demonstrate the roles that solar heavy ions and protons played in the production of SEU's during the October 1989 solar particle events.

  10. Cobalt nano-particles modulate cytokine in vitro release by human mononuclear cells mimicking autoimmune disease.

    PubMed

    Petrarca, C; Perrone, A; Verna, N; Verginelli, F; Ponti, J; Sabbioni, E; Di Giampaolo, L; Dadorante, V; Schiavone, C; Boscolo, P; Mariani Costantini, R; Di Gioacchino, M

    2006-01-01

    The use of particles from micro to nanoscale provides benefits to diverse scientific fields, but because a large percentage of their atoms lie on the surface, nanomaterials could be highly reactive and pose potential risks to humans. Due to their wide range of application, Cobalt nano-particles are of great interest both in industry and in life-science. To date, there are few studies on Co nano-particle toxicology. In this respect, this study aims at evaluating in vitro the potential interference of Co nano-particles on the production of several cytokines (IL-2, IL-4, IL-6, IL-10, IFNgamma and TNFalpha) by PBMCs, comparing their effects to those of Co micro-particles and Co solution (CoCl2). Cells were cultured in Opticell flasks with escalating concentrations (10-5, 10-6 and 10-7 M), of Co nano and micro-particles and CoCl2 or without metal. Cytokines were quantified in the supernatants using a human Th1/Th2 cytokine cytometric bead array. Co micro-particles showed a greater inhibitory effect compared to other Co forms. Its inhibitory activity was detected at all concentrations and towards all cytokines, whereas Co solutions selectively inhibited IL-2, IL-10 and TNF-alpha at maximal concentration. Co nano-particles induced an increase of TNF-alpha and IFN-gamma release and an inhibition of IL-10 and IL-2: a cytokine pattern similar to that detected in the experimental and clinical autoimmunity. On the basis of the obtained data, immune endpoints should be sought in the next series of studies both in vitro and in vivo in subjects exposed to cobalt nano-particles. PMID:17291400

  11. Wave induced transport and mixing of buoyant particles

    NASA Astrophysics Data System (ADS)

    Drivdal, Magnus; Broström, Göran; Christensen, Kai H.

    2014-05-01

    The modeling of wave-current and wave-turbulence interactions have received much attention during recent years. Both the breaking of surface waves and the inclusion of the Stokes shear production have been shown to increase the upper ocean turbulence. Furthermore the Coriolis force acting on the Stokes drift redistributes the momentum in the upper ocean, leading to a deflection of the currents. An important application affected by these processes that still needs to be studied is the mixing and drift of particles. Using an ocean column model, modified to take surface wave effects into account, we investigate how the increased mixing by wave breaking and Stokes shear production as well as the stronger veering by the Coriolis-Stokes force effects the drift of suspended particles. Here the suspended particles are buoyant tracers that can represent oil droplets or plankton, for example fish eggs and larvae. The energy and momentum fluxes as well as the Stokes drift depend on the directional wave spectrum that can be obtained from a wave model or from observations. Comparing with classical Ekman theory some physical effects on the system are studied, and as a realistic test case we use the model to study the oil drift after an offshore oil spill that took place outside the western coast of Norway in 2007. During this accident the average net drift of oil was observed to be approximately 0.1% of the wind speed at an angle of about 90-120 degrees to the right, far slower and more deflected away from the wind direction than predicted by both numerical and empirical models. With wind and wave forcing from ECMWF reanalysis data, it is shown that the wave effects are important for the resultant drift in this case, and has the potential to improve drift forecasting.

  12. Collective two-particle resonances induced by photon entanglement

    SciTech Connect

    Richter, Marten [Department of Chemistry, University of California, Irvine, California 92697-2025 (United States); Institut fuer Theoretische Physik, Nichtlineare Optik und Quantenelektronik, Technische Universitaet Berlin, Hardenbergstr. 36, 10623 Berlin (Germany); Mukamel, Shaul [Department of Chemistry, University of California, Irvine, California 92697-2025 (United States)

    2011-06-15

    An assembly of noninteracting atoms may become correlated upon interaction with entangled photons, and certain elements of their joint density matrix can then show collective resonances. We explore experimental signatures of these resonances in the nonlinear response of a pair of two-level atoms. We find that these resonances are canceled out in stimulated signals such as pump-probe and two-photon absorption due to the destructive interference of two-photon-absorption and emission pathways in the joint two-particle space. However, they may be observed in photon statistics (Hanbury-Brown-Twiss) measurements through the attenuation of two-time intensity correlations.

  13. Persistence and extinction of disease in non-autonomous SIRS epidemic models with disease-induced mortality

    Microsoft Academic Search

    Zhidong Teng; Yanping Liu; Long Zhang

    2008-01-01

    In this paper, non-autonomous SIRS epidemic models with bilinear incidence and disease-induced mortality are studied. Under the quite weak assumptions, the sufficient and necessary conditions on the permanence and strong persistence of the disease and the sufficient condition on the extinction of the disease are established. Some new threshold values of the integral form R0?, R1? and R2? are obtained.

  14. The characterization of latex particles prepared by pulsed electron beam induced emulsion polymerization

    NASA Astrophysics Data System (ADS)

    Xu, Yongfei; Wang, Mozhen; Ge, Xuewu

    2012-10-01

    The emulsion polymerization of styrene (St) and methyl methacrylate (MMA) induced by 10 MeV pulsed electron beams (PEB) was investigated. The monomer conversion of MMA and St was found to be very low so that the final prepared poly(methyl methacrylate) (P(MMA)) and polystyrene (PS) latex particles exhibit porous structures, as verified by TEM and SEM observations. The results of dynamic light scattering (DLS) and gel permeation chromatography (GPC) showed that both the particle size and the molecular weight of PS and PMMA latexes decrease with the increase of the absorbed dose. However, the molecular weights and the particle sizes of the PS and PMMA latexes change differently with the irradiation time. This work indicated that emulsion polymerization induced by high energy electron beam has an advantage over that induced by ?-ray or chemical initiators in the preparation of latex with a low molecular weight and porous structure.

  15. Self-induced polar order of active Brownian particles in a harmonic trap

    E-print Network

    Marc Hennes; Katrin Wolff; Holger Stark

    2014-02-06

    Hydrodynamically interacting active particles in an external harmonic potential form a self-assembled fluid pump at large enough P\\'eclet numbers. Here, we give a quantitative criterion for the formation of the pump and show that particle orientations align in the self-induced flow field in surprising analogy to ferromagnetic order where the active P\\'eclet number plays the role of inverse temperature. The particle orientations follow a Boltzmann distribution $\\Phi(\\mathbf{p}) \\sim \\exp(A p_z)$ where the ordering mean field $A$ scales with active P\\'eclet number and polar order parameter. The mean flow field in which the particles' swimming directions align corresponds to a regularized stokeslet with strength proportional to swimming speed. Analytic mean-field results are compared with results from Brownian dynamics simulations with hydrodynamic interactions included and are found to capture the self-induced alignment very well.

  16. Stopping power and polarization induced in a plasma by a fast charged particle in circular motion

    NASA Astrophysics Data System (ADS)

    Villó-Pérez, Isidro; Arista, Néstor R.; Garcia-Molina, Rafael

    2002-03-01

    We describe the perturbation induced in a plasma by a charged particle in circular motion, analysing in detail the evolution of the induced charge, the electrostatic potential and the energy loss of the particle. We describe the initial transitory behaviour and the different ways in which convergence to final stationary solutions may be obtained depending on the basic parameters of the problem. The results for the stopping power show a resonant behaviour which may give place to large stopping enhancement values as compared with the case of particles in straight-line motion with the same linear velocity. The results also explain a resonant effect recently obtained for particles in circular motion in magnetized plasmas.

  17. Requirements for the assembly and release of Newcastle disease virus-like particles

    Microsoft Academic Search

    Homer Dadios Pantua; Lori W. McGinnes; Mark E. Peeples; Trudy G. Morrison

    2006-01-01

    Paramyxoviruses, such as Newcastle disease virus (NDV), assemble in and bud from plasma membranes of infected cells. To explore the role of each of the NDV structural proteins in virion assembly and release, virus-like particles (VLPs) released from avian cells expressing all possible combinations of the nucleoprotein (NP), membrane or matrix protein (M), an uncleaved fusion protein (F-K115Q), and hemagglutinin-neuraminidase

  18. Determining aerosol particle size distributions using time-resolved laser-induced incandescence

    Microsoft Academic Search

    K. J. Daun; B. J. Stagg; F. Liu; G. J. Smallwood; D. R. Snelling

    2007-01-01

    The particle size distribution within an aerosol containing refractory nanoparticles can be inferred using time-resolved laser-induced\\u000a incandescence (TR-LII). In this procedure, a small volume of aerosol is heated to incandescent temperatures by a short laser\\u000a pulse, and the incandescence of the aerosol particles is then measured as they return to the ambient gas temperature by conduction\\u000a heat transfer. Although the

  19. Determining aerosol particle size distributions using time-resolved laser-induced incandescence

    Microsoft Academic Search

    K. J. Daun; B. J. Stagg; F. Liu; G. J. Smallwood; D. R. Snelling

    2007-01-01

    The particle size distribution within an aerosol containing refractory nanoparticles can be inferred using time-resolved laser-induced incandescence (TR-LII). In this procedure, a small volume of aerosol is heated to incandescent temperatures by a short laser pulse, and the incandescence of the aerosol particles is then measured as they return to the ambient gas temperature by conduction heat transfer. Although the

  20. The effect of induced charges on low-energy particle trajectories near conducting and semiconducting plates

    NASA Technical Reports Server (NTRS)

    Coffey, Victoria N.; Moore, Thomas E.

    1992-01-01

    The effect of the induced charge was found on particles less than 1 eV as they passed through simulated parallel, grounded channels that are comparable in dimension to those that are presently in space plasma instruments which measure the flux of low-energy ions. Applications were made to both conducting and semiconducting channels that ranged in length from 0.1 to 50 mm and in aspect ratio from 1 to 100. The effect of the induced charge on particle trajectories from simple straight lines. Several configurations of channel aspect ratio and detector locations are considered. The effect is important only at very low energies with small dimensions.

  1. A disease marker for aspirin-induced chronic urticaria.

    PubMed

    Hsieh, Chia-Wei; Lee, Jeen-Wei; Liao, En-Chih; Tsai, Jaw-Ji

    2014-01-01

    There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (Fc?RI?) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (-344C/T) and rs2251746 (-66T/C) gene polymorphisms of Fc?RI? in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (-344C>T, -66C>T) were similar to the normal controls. The allele frequency of -344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p=0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5±5.2 vs. 103.3±3.3 respectively, (p<0.05), and the percentages of histamine release were 31.3%±7.4% vs. -24.0%±17.5%, (p<0.05) respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of Fc?RI? (-344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU. PMID:25029546

  2. Particle-induced amorphization of complex ceramics. Final report

    SciTech Connect

    Ewing, R.C.; Wang, L.M.

    1998-08-01

    The crystalline-to-amorphous (c-a) phase transition is of fundamental importance. Particle irradiations provide an important, highly controlled means of investigating this phase transformation and the structure of the amorphous state. The interaction of heavy-particles with ceramics is complex because these materials have a wide range of structure types, complex compositions, and because chemical bonding is variable. Radiation damage and annealing can produce diverse results, but most commonly, single crystals become aperiodic or break down into a polycrystalline aggregate. The authors continued the studies of the transition from the periodic-to-aperiodic state in natural materials that have been damaged by {alpha}-recoil nuclei in the uranium and thorium decay series and in synthetic, analogous structures. The transition from the periodic to aperiodic state was followed by detailed x-ray diffraction analysis, in-situ irradiation/transmission electron microscopy, high resolution transmission electron microscopy, extended x-ray absorption fine structure spectroscopy/x-ray absorption near edge spectroscopy and other spectroscopic techniques. These studies were completed in conjunction with bulk irradiations that can be completed at Los Alamos National Laboratory or Sandia National Laboratories. Principal questions addressed in this research program included: (1) What is the process at the atomic level by which a ceramic material is transformed into a disordered or aperiodic state? (2) What are the controlling effects of structural topology, bond-type, dose rate, and irradiation temperature on the final state of the irradiated material? (3) What is the structure of the damaged material? (4) What are the mechanisms and kinetics for the annealing of interstitial and aggregate defects in these irradiated ceramic materials? (5) What general criteria may be applied to the prediction of amorphization in complex ceramics?

  3. Preparation of polystyrene latex particles by ?-rays-induced emulsifier-free emulsion polymerization

    NASA Astrophysics Data System (ADS)

    Wang, Xinbo; Zhang, Zhicheng

    2006-09-01

    Monodisperse polystyrene latex particles were prepared by 60Co- ?-ray radiation-induced emulsifier-free emulsion polymerization with the use of surfactant monomer at room temperature. The surfactant monomer 10(9)-hydroxyl-9(10)-allyl ether octadecanoic acid (HAEOA) was synthesized and characterized by FT-IR and 1H-NMR spectra. TEM was used to characterize the polystyrene latex particles. HAEOA acted as not only a comonomer but also a stabilizer to copolymerize with styrene and stabilize the polystyrene latex particles. Kinetics analysis shows that there is no constant rate stage which seems to indicate a droplet nucleation mechanism.

  4. Further study on mechanism of production of light complex particles in nucleon-induced reactions

    NASA Astrophysics Data System (ADS)

    Wei, Dexian; Mao, Lihua; Wang, Ning; Liu, Min; Ou, Li

    2015-01-01

    The Improved Quantum Molecular Dynamics model incorporated with the statistical decay model is used to investigate the intermediate energy nucleon-induced reactions. In our last work, by introducing a phenomenological mechanism called surface coalescence and emission into ImQMD model, the description on the light complex particle emission has been great improved. In this work, taking account of different specific binding energies and separation energies for various light complex particles, the phase space parameters in surface coalescence model are readjusted. By using the new phase space parameters set with better physical fundament, the double differential cross sections of light complex particles are found to be in better agreement with experimental data.

  5. ULTRAFINE CARBON PARTICLES INDUCE INTERLEUKIN-8 GENE TRANSCRIPTION AND P38 MAPK ACTIVATION IN NORMAL BRONCHIAL EPITHELIAL CELLS

    EPA Science Inventory

    Epidemiological studies suggest that ultrafine particles contribute to particulate matter-induced adverse health effects. Interleukin (IL)-8 is an important proinflammatory cytokine in the human lung that is induced in respiratory cells exposed to a variety of environmental insul...

  6. Marek's disease virus induced transient paralysis--a closer look

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s Disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, crippling, weight loss, and transient paralysis (TP). TP is a disease of the central nervous system...

  7. Particle-induced spatial dark current fluctuations in focal plane arrays

    Microsoft Academic Search

    Cheryl J. Dale; P. W. Marshall; E. A. Burke

    1990-01-01

    An analytic calculation which describes the pixel-to-pixel variation in the particle-induced dark current distribution of a focal plane array is developed. The most important contributions to the dark current variance are shown to be the variations in the number of primary interactions, the energies of the primary recoils produced, and the charge emission from radiation-induced defects due to that electric

  8. The mechanism of particles transport induced by electrostatic perturbation in tokamak

    SciTech Connect

    Feng, Zhichen; Qiu, Zhiyong; Sheng, Zhengmao [Department of Physics, Institute for Fusion Theory and Simulation, Zhejiang University, Hangzhou 310027 (China)] [Department of Physics, Institute for Fusion Theory and Simulation, Zhejiang University, Hangzhou 310027 (China)

    2013-12-15

    Particle transport in tokamak devices due to wave-particle resonance induced diffusion is studied. The diffusion coefficient is derived both analytically using quasilinear theory, and numerically using a test particle code, and the obtained diffusion coefficient agrees with each other in its validity regime. Dependence of the diffusion coefficient on turbulence intensity, turbulence radial mode structures, and particle energy is investigated. It is found that the diffusion coefficient is proportional to the turbulence intensity, and the diffusion is maximized for E{sub t}?T{sub i}, and k{sub r}?{sub 0}?1. Here, E{sub t} is the test particle energy, T{sub i} is the thermal ion temperature, ?{sub 0} is the distance between neighboring mode rational surfaces, and 1/k{sub r} is the half width of the fine radial mode structure on each rational surface.

  9. Experimentally induced Vogt–Koyanagi–Harada disease in two Akita dogs

    Microsoft Academic Search

    Kunihiko Yamaki; Naoaki Takiyama; Norihiko Itho; Nobuhisa Mizuki; Maehara Seiya; Wakaiki Sinsuke; Kouichi Hayakawa; Tadao Kotani

    2005-01-01

    We have investigated whether a Vogt–Koyanagi–Harada (VKH)-like disease can be induced in Akita dogs by immunizing them with tyrosinase related protein 1 (TRP1), and compared the alterations induced to those of Akita dogs with a spontaneously occurring disease that resembles human VKH disease. Two Akita dogs were immunized with a peptide mixture of human TRP1. The changes in the eyes

  10. Therapies for dopaminergic-induced dyskinesias in Parkinson disease.

    PubMed

    Gottwald, Mildred D; Aminoff, Michael J

    2011-06-01

    Existing and emerging strategies for managing L-dopa-induced dyskinesias (LIDs) in patients with Parkinson disease have involved either delaying the introduction of L-dopa therapy, treatment with an antidyskinetic agent, using a therapy or delivery system that can provide continuous dopaminergic stimulation, or using novel agents that target receptors implicated in the mechanisms underlying LIDs. Treatment with dopamine agonists such as pramipexole or ropinirole allows levodopa to be delayed, but once levodopa is added to the drug regimen the usual course of onset of dyskinesias is observed. Amantadine, an N-methyl-D-aspartate antagonist, is so far the only approved compound with evidence of providing a sustained antidyskinetic benefit in the absence of unacceptable side effects. These findings support the hypothesis of glutamate overactivity in the development of dyskinesias. More continuous delivery of dopaminergic medication, such as through intraintestinal or subcutaneous routes, is promising but invasive and associated with injection site reactions. As a result of molecular research and elucidation of the role of a variety of neurotransmitters in the mechanism of LIDs, new compounds have been identified, including those that modulate the direct and indirect striatal output pathways; some of these new agents are in the early stages of development or undergoing proof-of-concept evaluation as antidyskinetic agents. PMID:21681795

  11. DISEASE-SPECIFIC SUSCEPTIBILITY TO ACUTE OZONE-INDUCED INJURY AND INFLAMMATION IN EIGHT RAT STRAINS

    EPA Science Inventory

    Susceptibility to environmental pollutant-induced injuries may be influenced by presence of disease and genetic make-up. To identify disease-specific susceptibility phenotype, we used eight rat strains with or without genetic cardiovascular disease. Male 12-15 wk old Sprague Dawl...

  12. Marek's Disease Virus-Induced Immunosuppression: Array Analysis of Chicken Immune Response Gene Expression Profiling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease of chickens induced by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latency infection within CD4+ T cells. Host-virus interaction, immune responses to...

  13. Purification and some properties of reovirus-like particles from leafhoppers and their possible involvement in wallaby ear disease of maize.

    PubMed

    Boccardo, G; Hatta, T; Francki, R I; Grivell, C J

    1980-01-30

    Reovirus-like particles, occurring in association with viroplasms, crystalline arrays and tubules, in the cytoplasm of Cicadulina bimaculata capable of inducing wallaby ear disease in maize, were purified from the insects by differential centrifugation, treatment with the nonionic detergent, Nonidet P-40, and sucrose density gradient centrifugation. The purified particles have a double-shelled icosahedral structure about 70 nm in diameter with external projections (A spikes) about 10 nm long located at the 12 vertices. These intact particles (IPs) are morphologically similar to those of Fiji disease virus (FDV), but are more stable. Cores were produced by enzymatic digestion of IPs with alpha-chymotrypsin. The cores are icosahedra about 57 nm in diameter with projections (B spikes) located at the 12 vertices, resembling those of FDV and cytoplasmic polyhedrosis virus. Immunization of a rabbit with purified IPs resulted in the production of antibodies specific to IPs, cores, and dsRNA. Immunoelectron microscopic investigations revealed that there is no relationship between this virus and FDV, maize rough dwarf, oat sterile dwarf, pangola stunt, and rice ragged stunt viruses, all members of the genus Fijivirus in the family Reoviridae. The nucleic acid extracted from partially purified virus was resolved into 10 segments by polyacrylamide gel electrophoresis. Reovirus-like particles or viroplasms could not be detected in thin sections of maize seedlings colonized by C. bimaculata showing wallaby ear symptoms. In the light of these data the possible etiology of wallaby ear disease is discussed. PMID:18631635

  14. Sheath-induced distortions in particle distributions near enhanced polar outflow probe particle sensors

    NASA Astrophysics Data System (ADS)

    Hussain, S.; Marchand, R.

    2014-07-01

    We discuss sheath and kinetic effects on ion and electron distribution functions at the aperture of enhanced Polar Outflow Probe particle sensors. For this purpose, the interaction between the CASSIOPE spacecraft and space environment is simulated fully kinetically using the electrostatic Particle In Cell code PTetra. The simulations account for the geometry of the main features of the spacecraft body, the booms, and the sensors. In addition to the background plasma, the model also accounts for Earth magnetic field. The plasma parameters assumed in the simulations are obtained from the latest version of the International Reference Ionosphere (IRI) model and the value of magnetic field is obtained from the International Geophysical Reference Field model. Our analysis shows significant distortions in the ion distribution function in the plane of the sensor aperture, as well as in the direction along the boom holding the sensor. We argue that significant distortions and asymmetries should also occur at the aperture of the suprathermal electron imager when suprathermal electrons are detected, with energies of 5 eV or more.

  15. Sheath-induced distortions in particle distributions near enhanced polar outflow probe particle sensors

    SciTech Connect

    Hussain, S. [Department of Physics, University of Alberta, Edmonton, Alberta, T6G 2E1 (Canada); Theoretical Physics Division, PINSTECH, Nilore, Islamabad (Pakistan); Department of Physics and Applied Mathematics, PIEAS, Nilore, Islamabad (Pakistan); Marchand, R. [Department of Physics, University of Alberta, Edmonton, T6G 2E1 Alberta (Canada)

    2014-07-15

    We discuss sheath and kinetic effects on ion and electron distribution functions at the aperture of enhanced Polar Outflow Probe particle sensors. For this purpose, the interaction between the CASSIOPE spacecraft and space environment is simulated fully kinetically using the electrostatic Particle In Cell code PTetra. The simulations account for the geometry of the main features of the spacecraft body, the booms, and the sensors. In addition to the background plasma, the model also accounts for Earth magnetic field. The plasma parameters assumed in the simulations are obtained from the latest version of the International Reference Ionosphere (IRI) model and the value of magnetic field is obtained from the International Geophysical Reference Field model. Our analysis shows significant distortions in the ion distribution function in the plane of the sensor aperture, as well as in the direction along the boom holding the sensor. We argue that significant distortions and asymmetries should also occur at the aperture of the suprathermal electron imager when suprathermal electrons are detected, with energies of 5?eV or more.

  16. DIESEL EXHAUST PARTICLE INDUCED GENE EXPRESSION CHANGES IN A MURINE MUCOSAL SENSITIZATION MODEL

    EPA Science Inventory

    Studies in humans and animals have shown diesel exhaust particles (DEP) can act as an immunological adjuvant to enhance the development of allergic lung disease and this effect is influenced by the chemical composition of the DEP. The adjuvancy of NIST SRM 2975 (NDEP) generated...

  17. Light flash phenomena induced by HzE particles

    NASA Technical Reports Server (NTRS)

    Mcnulty, P. J.; Pease, V. P.

    1980-01-01

    Astronauts and Apollo and Skylab missions have reported observing a variety of visual phenomena when their eyes are closed and adapted to darkness. These phenomena have been collectively labelled as light flashes. Visual phenomena which are similar in appearance to those observed in space have been demonstrated at the number of accelerator facilities by expressing the eyes of human subjects to beams of various types of radiation. In some laboratory experiments Cerenkov radiation was found to be the basis for the flashes observed while in other experiments Cerenkov radiation could apparently be ruled out. Experiments that differentiate between Cerenkov radiation and other possible mechanisms for inducing visual phenomena was then compared. The phenomena obtained in the presence and absence of Cerenkov radiation were designed and conducted. A new mechanism proposed to explain the visual phenomena observed by Skylab astronauts as they passed through the South Atlantic Anomaly, namely nuclear interactions in and near the sensitive layer of the retina, is covered. Also some studies to search for similar transient effects of space radiation on sensors and microcomputer memories are described.

  18. Particle image velocimetry and planar laser-induced fluorescence measurements on lobed jet mixing flows

    E-print Network

    Hu, Hui

    Particle image velocimetry and planar laser-induced fluorescence measurements on lobed jet mixing have been used to reduce take-off jet noise and speci®c fuel consumption (SFC) (Tillman and Presz 1993 of the vortical and turbulent structures in lobed jet mixing ¯ows was con- ducted. The techniques of planar laser

  19. Alpha particle induced charge collection measurements and the effectiveness of reflecting barriers on VLSI memories

    Microsoft Academic Search

    Sai-Wai Fu; Amr M. Mohsen; Tim C. May

    1982-01-01

    This paper presents experimental results of analog charge collection measurement of alpha particle induced carriers in memory arrays. Measurements with high intensity foils and variable angle collimated sources on various memory arrays with different reflecting structures are reported. A P-well reflecting barrier is shown to reduce charge collection by a factor 2 and SER by about two orders of magnitude.

  20. DIESEL AND CARBON PARTICLES ENHANCE HOUSE DUST MITE-INDUCED PULMONARY HYPERSENSITIVITY IN BROWN NORWAY RATS

    EPA Science Inventory

    Diesel and Carbon Particles Enhance House Dust Mite-Induced Pulmonary Hypersensitivity in Brown Norway Rats. P. Singh1, M.J. Daniels2, D. Winsett2, J. Richards2, K. Crissman2, M. Madden2 and M.I. Gilmour2. 1NCSU, Raleigh, NC and 2 USEPA, Research Triangle Park, NC. Ep...

  1. URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRUCTION IS MEDIATED BY SUPEROXIDE PRODUCTION

    EPA Science Inventory

    URBAN PARTICLE-INDUCED PULMONARY ARTERY CONSTRICTION IS MEDIATED BY SUPEROXIDE PRODUCTION.Jacqueline D. Carter, Zhuowei Li, Lisa A. Dailey, Yuh-Chin T. Huang. CEMALB, University of North Carolina, and ORD, US EPA, Chapel Hill, North Carolina. Exposure to particulate matter...

  2. Characterization of colloidal particles by laser-induced plasma spectroscopy (LIPS)

    Microsoft Academic Search

    C. Haisch; J. Liermann; U. Panne; R. Niessner

    1997-01-01

    To study the nature and abundance of colloids in aquifer systems Laser-Induced Plasma Spectroscopy (LIPS) was used for elemental analysis of heavy metal colloids with particle diameters between 0.1 and 1 ?m. Different experimental approaches to the qualitative and quantitative characterization of inorganic colloids are examined. Some of the inherent problems associated with a direct detection are discussed. A direct

  3. The role of adsorbed endotoxin in particle-induced stimulation of cytokine release

    Microsoft Academic Search

    David R. Cho; Arun S. Shanbhag; Chi-Yuan Hong; George R. Baran; Steven R. Goldring

    2002-01-01

    Numerous in vitro models have demonstrated the capacity of wear particles to stimulate the release of soluble pro-inflammatory products with the ability to induce local bone resorption. Recent observations have demonstrated that binding of lipopolysaccharide (LPS) to particulate wear debris can significantly modulate the pattern of cell response in the in vitro models. These findings raise concerns over the possible

  4. A charged-particle spectrometer for measuring neutron-induced reaction products

    NASA Astrophysics Data System (ADS)

    Stiehler, Thomas; Mösner, Jürgen; Schmidt, Günter; Pilz, Wolfgang; Hutsch, Jochen

    1985-05-01

    We describe a spectrometer consisting of plastic scintillators and multiwire proportional counters which is suitable to measure light charged particles from neutron-induced reactions at forward angles. The performance of the spectrometer is demonstrated in the case of a measurement of the n-p capture cross section at En = 25 MeV.

  5. Fluid-Induced Propulsion of Rigid Particles in Wormlike Micellar Solutions

    E-print Network

    David A. Gagnon; Nathan C. Keim; Xiaoning Shen; Paulo E. Arratia

    2014-09-13

    In the absence of inertia, a reciprocal swimmer achieves no net motion in a viscous Newtonian fluid. Here, we investigate the ability of a reciprocally actuated particle to translate through a complex fluid that possesses a network using tracking methods and birefringence imaging. A geometrically polar particle, a rod with a bead on one end, is reciprocally rotated using magnetic fields. The particle is immersed in a wormlike micellar (WLM) solution that is known to be susceptible to the formation of shear bands and other localized structures due to shear-induced remodeling of its microstructure. Results show that the nonlinearities present in this WLM solution break time-reversal symmetry under certain conditions, and enable propulsion of an artificial "swimmer." We find three regimes dependent on the Deborah number (De): net motion towards the bead-end of the particle at low De, net motion towards the rod-end of the particle at intermediate De, and no appreciable propulsion at high De. At low De, where the particle time-scale is longer then the fluid relaxation time, we believe that propulsion is caused by an imbalance in the fluid first normal stress differences between the two ends of the particle (bead and rod). At De~1, however, we observe the emergence of a region of network anisotropy near the rod using birefringence imaging. This anisotropy suggests alignment of the micellar network, which is "locked in" due to the shorter time-scale of the particle relative to the fluid.

  6. Fluctuation-induced transport of two coupled particles: Effect of the interparticle interaction

    NASA Astrophysics Data System (ADS)

    Makhnovskii, Yurii A.; Rozenbaum, Viktor M.; Sheu, Sheh-Yi; Yang, Dah-Yen; Trakhtenberg, Leonid I.; Lin, Sheng Hsien

    2014-06-01

    We consider a system of two coupled particles fluctuating between two states, with different interparticle interaction potentials and particle friction coefficients. An external action drives the interstate transitions that induces reciprocating motion along the internal coordinate x (the interparticle distance). The system moves unidirectionally due to rectification of the internal motion by asymmetric friction fluctuations and thus operates as a dimeric motor that converts input energy into net movement. We focus on how the law of interaction between the particles affects the dimer transport and, in particular, the role of thermal noise in the motion inducing mechanism. It is argued that if the interaction potential behaves at large distances as x?, depending on the value of the exponent ?, the thermal noise plays a constructive (? > 2), neutral (? = 2), or destructive (? < 2) role. In the case of ? = 1, corresponding piecewise linear potential profiles, an exact solution is obtained and discussed in detail.

  7. A Disease Marker for Aspirin-Induced Chronic Urticaria

    PubMed Central

    Hsieh, Chia-Wei; Lee, Jeen-Wei; Liao, En-Chih; Tsai, Jaw-Ji

    2014-01-01

    There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (Fc?RI?) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T) and rs2251746 (–66T/C) gene polymorphisms of Fc?RI? in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T) were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p < 0.05), and the percentages of histamine release were 31.3% ± 7.4% vs. ?24.0% ± 17.5%, (p < 0.05) respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of Fc?RI? (–344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU. PMID:25029546

  8. Particle irradiation induces FGF2 expression in normal human lens cells

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Bjornstad K, A.; Chang, E.; McNamara, M.; Barcellos-Hoff, M. H.; Lin, S. P.; Aragon, G.; Polansky, J. R.; Lui, G. M.; Blakely, E. A.

    2000-01-01

    Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

  9. Exercise-induced myokines and their role in chronic diseases

    Microsoft Academic Search

    Bente K. Pedersen

    2011-01-01

    Physical inactivity has recently been identified as a major and independent risk factor for the development of dementia and cognitive decline. In addition to the effect of exercise with regard to protection against neurodegenerative diseases, it is well-established that physical inactivity increases the risk of type 2 diabetes, cardiovascular diseases (CVD), colon cancer and postmenopausal breast cancer. These diseases constitute

  10. Methamphetamine-induced neurotoxicity: the road to Parkinson's disease

    Microsoft Academic Search

    Bessy Thrash; Kariharan Thiruchelvan; Manuj Ahuja; Vishnu Suppiramaniam; Muralikrishnan Dhanasekaran

    Studies have implicated methamphetamine exposure as a contributor to the development of Parkinson's disease. There is a signifi- cant degree of striatal dopamine depletion produced by methamphetamine, which makes the toxin useful in the creation of an animal model of Parkinson's disease. Parkinson's disease is a progressive neurodegenerative disorder associated with selective degenera- tion of nigrostriatal dopaminergic neurons. The immediate

  11. Adalimumab-induced interstitial pneumonia in a patient with Crohn’s disease

    PubMed Central

    Casanova, María José; Chaparro, María; Valenzuela, Claudia; Cisneros, Carolina; Gisbert, Javier P

    2015-01-01

    There are several reports of anti-tumor necrosis factor (TNF)-induced lung disease, especially in patients with rheumatologic diseases. Adalimumab is an anti-TNF drug used to induce and maintain remission in patients with immune-mediated diseases, such as Crohn’s disease. Although pulmonary disorders could be an extra-intestinal manifestation of inflammatory bowel disease, biologic therapy could also be a cause of lung injury. Only few cases of adalimumab-induced lung toxicity have been reported, and the majority of them were in patients with rheumatologic diseases. Lung injury secondary to anti-TNF therapy should, after ruling out other etiologies, be considered in patients who have a temporal association between the onset of respiratory symptoms and the exposure to these drugs. A compatible pattern in the biopsy and the clinical improvement after discontinuation of the anti-TNF drug would strongly support the diagnosis. PMID:25717268

  12. Frequency-dependent behaviors of individual microscopic particles in an optically induced dielectrophoresis device

    PubMed Central

    Zhu, Xiaolu; Yi, Hong; Ni, Zhonghua

    2010-01-01

    An optoelectronic microdevice is set up to drive single microparticles and a maximum synchronous velocity (MS-velocity) spectrum method is proposed for quantifying the frequency-dependent behaviors of individual neutral microparticles from 40 kHz to 10 MHz. Dielectrophoretic behaviors of three types of microparticles are investigated under the optically induced nonuniform electric field. Different MS-velocity spectra for the three different particles are experimentally found. Numerical calculations for the MS-velocity spectra of polystyrene microparticles are performed. The spectrum of the MS-velocities for a specific particle is mainly determined by the particle inherent property and the electric characteristics of the device. Moreover the experimental and the numerical MS-velocity spectra are compared to be accordant. Based on the dielectrophoretic (DEP) behaviors of the particles under a nonuniform electric field, microparticles can be finely characterized or distinguished according to their distinct MS-velocity spectra. PMID:20644665

  13. Mechanism of the production of light complex particles in nucleon-induced reactions

    NASA Astrophysics Data System (ADS)

    Wei, Dexian; Wang, Ning; Ou, Li

    2014-03-01

    The improved quantum molecular dynamics (ImQMD) model incorporated with the statistical decay model is successful in describing emission of the nucleons in the intermediate energy spallation reactions, but not good enough in describing productions of the light complex particles, i.e. d, t, 3He and 4He. To improve the description on emission of light complex particles, a phenomenological mechanism called surface coalescence and emission is introduced into the ImQMD model: nucleon ready to escape from the compound nuclei can coalesce with the other nucleon(s) to form light complex particle and be emitted. With updated ImQMD model, the description on the experimental data of light complex particles produced in nucleon-induced reactions are great improved.

  14. Adjuvant effects of chitosan and calcium phosphate particles in an inactivated Newcastle disease vaccine.

    PubMed

    Volkova, Marina A; Irza, Anna V; Chvala, Irina A; Frolov, Sergy F; Drygin, Vladimir V; Kapczynski, Darrell R

    2014-03-01

    The adjuvant activity of chitosan (CS) and calcium phosphate (CAP) particles was studied following intranasal (mucosal) administration to commercial chickens with inactivated Newcastle disease virus (NDV) vaccine. After three vaccinations with inactivated NDV in combination with CS or CAP an increase in antibody titers in blood and mucosal samples in chickens was observed when compared with the administration of NDV antigen only. A lower level of humoral immunity was observed in broiler chickens compared to layer-type birds. The CS-based vaccine demonstrated higher antigenic and protective activity following lethal challenge than the vaccine containing CAP. Because CS particles efficiently changed mucosal and humoral immunity and protective activity, CS may in the future be considered for use as a potential adjuvant for production of vaccines for poultry. PMID:24758112

  15. Asian dust storm particles induce a broad toxicological transcriptional program in human epidermal keratinocytes.

    PubMed

    Choi, Hyun; Shin, Dong Wook; Kim, Wonnyon; Doh, Seong-Jae; Lee, Soo Hwan; Noh, Minsoo

    2011-01-15

    Exposure to airborne dust particles originated from seasonal Asian dust storms in Chinese and Mongolian deserts results in increased incidence of a range of diseases including asthma, contact dermatitis and conjunctivitis. The areas affected by Asian dust particles extend from East China to the west coast of North America. In order to study toxicological mechanisms in human skin, we evaluated the effects of dust particles collected during Asian dust storms (Asian dust particles) on gene expression in human epidermal keratinocytes (HEK). In HEK, exposure to Asian dust particles significantly increased gene expressions of cytochrome P450 1A1 (CYP1A1), CYP1A2, and CYP1B1, which is an indication of aryl hydrocarbon receptor (AHR) activation. In addition, Asian dust particles increased gene transcription of the cytokines IL-6, IL-8, and GM-CSF, which have broad pro-inflammatory and immunomodulatory properties. Asian dust particles significantly up-regulated expression of caspase 14 in HEK, suggesting that Asian dust particles directly affect keratinocyte differentiation. We also demonstrated that protein extract of pollen, a material frequently adsorbed onto Asian dust particles, potentially contributes to the increased transcription of IL-6, CYP1A1, CYP1A2, and CYP1B1. Taken together, these studies suggest that Asian dust particles can exert toxicological effects on human skin through the activation of the cellular detoxification system, the production of pro-inflammatory and immunomodulatory cytokines, and changes in the expression of proteins essential in normal epidermal differentiation. PMID:21056094

  16. Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats.

    PubMed Central

    Batalha, Joao R F; Saldiva, Paulo H N; Clarke, Robert W; Coull, Brent A; Stearns, Rebecca C; Lawrence, Joy; Murthy, G G Krishna; Koutrakis, Petros; Godleski, John J

    2002-01-01

    The objective of this study was to determine whether short-term exposures to concentrated ambient particles (CAPs) alter the morphology of small pulmonary arteries in normal rats and rats with chronic bronchitis (CB). Sprague-Dawley male rats were exposed to CAPs, using the Harvard Ambient Particle Concentrator, or to particle-free air (sham) under identical conditions during 3 consecutive days (5 hr/day) in six experimental sets. CB was induced by exposure to 276 +/- 9 ppm of sulfur dioxide (5 hr/day, 5 days/week, 6 weeks). Physicochemical characterization of CAPs included measurements of particle mass, size distribution, and composition. Rats were sacrificed 24 hr after the last CAPs exposure. Histologic slides were prepared from random sections of lung lobes and coded for blinded analysis. The lumen/wall area (L/W) ratio was determined morphometrically on transverse sections of small pulmonary arteries. When all animal data (normal and CB) were analyzed together, the L/W ratios decreased as concentrations of fine particle mass, silicon, lead, sulfate, elemental carbon, and organic carbon increased. In separate univariate analyses of animal data, the association for sulfate was significant only in normal rats, whereas silicon was significantly associated in both CB and normal rats. In multivariate analyses including all particle factors, the association with silicon remained significant. Our results indicate that short-term CAPs exposures (median, 182.75 micro g/m3; range, 73.50-733.00 micro g/m3) can induce vasoconstriction of small pulmonary arteries in normal and CB rats. This effect was correlated with specific particle components and suggests that the pulmonary vasculature might be an important target for ambient air particle toxicity. PMID:12460797

  17. Magneto-induced stress enhancing effect in a colloidal suspension of paramagnetic and superparamagnetic particles dispersed in a ferrofluid medium.

    PubMed

    Liu, Taixiang; Gong, Xinglong; Xu, Yangguang; Xuan, Shouhu

    2014-02-14

    The magneto-induced stress and relative microstructure in a colloidal suspension of paramagnetic and superparamagnetic particles dispersed in a ferrofluid medium is studied using particle-level dynamics simulation. It shows that the stress perpendicular to the direction of an external uniaxial magnetic field can be strongly enhanced by increasing the ratio of paramagnetic particles to approaching that of superparamagnetic particles. The magnetic field-induced net-like or embedded chain-like microstructures formed by paramagnetic and superparamagnetic particles contribute to this stress enhancing effect. PMID:24837318

  18. Respiratory disease and particulate air pollution in Santiago Chile: contribution of erosion particles from fine sediments.

    PubMed

    Garcia-Chevesich, Pablo A; Alvarado, Sergio; Neary, Daniel G; Valdes, Rodrigo; Valdes, Juan; Aguirre, Juan José; Mena, Marcelo; Pizarro, Roberto; Jofré, Paola; Vera, Mauricio; Olivares, Claudio

    2014-04-01

    Air pollution in Santiago is a serious problem every winter, causing thousands of cases of breathing problems within the population. With more than 6 million people and almost two million vehicles, this large city receives rainfall only during winters. Depending on the frequency of storms, statistics show that every time it rains, air quality improves for a couple of days, followed by extreme levels of air pollution. Current regulations focus mostly on PM10 and PM2.5, due to its strong influence on respiratory diseases. Though more than 50% of the ambient PM10s in Santiago is represented by soil particles, most of the efforts have been focused on the remaining 50%, i.e. particulate material originating from fossil and wood fuel combustion, among others. This document emphasizes the need for the creation of erosion/sediment control regulations in Chile, to decrease respiratory diseases on Chilean polluted cities. PMID:24485904

  19. Detecting disease outbreaks using a combined Bayesian network and particle filter approach.

    PubMed

    Dawson, Peter; Gailis, Ralph; Meehan, Alaster

    2015-04-01

    Evaluating whether a disease outbreak has occurred based on limited information in medical records is inherently a probabilistic problem. This paper presents a methodology for consistently analysing the probability that a disease targeted by a surveillance system has appeared in the population, based on the medical records of the individuals within the target population, using a Bayesian network. To enable the system to produce a probability density function of the fraction of the population that is infected, a mathematically consistent conjoining of Bayesian networks and particle filters is used. This approach is tested against the default algorithm of ESSENCE Desktop Edition (which adaptively uses Poisson, exponentially weighted moving average and linear regression techniques as needed), and is shown, for the simulated test data used, to give significantly shorter detection times at false alarm rates of practical interest. This methodology shows promise to greatly improve detection times for outbreaks in populations where timely electronic health records are available for data-mining. PMID:25637764

  20. Lateral aggregation induced by magnetic perturbations in a magnetorheological fluid based on non-Brownian particles.

    PubMed

    Moctezuma, R E; Donado, F; Arauz-Lara, J L

    2013-09-01

    A study of lateral aggregation, induced by an oscillatory field, in a magnetorheological fluid based on non-Brownian magnetic particles is presented. We investigate the behavior of chains formed by the particles, due to the simultaneous application of a static magnetic field and a sinusoidal magnetic field transverse to each other. We show that the effective oscillating field enhances the aggregation process. We discuss this result in terms of an effective particle concentration induced by the oscillating field when chains oscillate angularly and sweep the area around them. The oscillating field produces a lateral aggregation similar to that observed in systems composed of Brownian particles which is induced by thermal fluctuations. We study the effect of the oscillating field on the angular amplitude described by single chains. It is observed that the angular amplitude decreases as the frequency of the oscillating field increases; we discuss this behavior numerically in terms of a simple model for this system. Lateral aggregation is studied in detail in isolated pairs of chains of equal length at several conditions of separation and displacement. From the results, a phase diagram is obtained showing the conditions under which aggregation is possible. PMID:24125266

  1. Experimental determination of the respiratory tract deposition of diesel combustion particles in patients with chronic obstructive pulmonary disease

    PubMed Central

    2012-01-01

    Background Air pollution, mainly from combustion, is one of the leading global health risk factors. A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD). There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles. Objectives To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing. Methods Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber. The respiratory tract deposition of the particles was measured in the size range 10–500?nm during spontaneous breathing. Results The deposited dose rate increased with increasing severity of the disease. However, the deposition probability of the ultrafine combustion particles (< 100?nm) was decreased in COPD patients. The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function. Conclusions The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability. The strong correlations between lung function and particle deposition, especially in the size range of 20–30?nm, suggest that altered particle deposition could be used as an indicator respiratory disease. PMID:22839109

  2. A sandwiched flexible polymer mold for control of particle-induced defects in nanoimprint lithography

    NASA Astrophysics Data System (ADS)

    Li, Bin; Zhang, Jizong; Ge, Haixiong

    2013-01-01

    Particle related defects are one of the key concerns for nanoimprint lithography, since the particle can amplify the defect to become much larger than the particle itself. We developed a flexible tri-layer mold for control of particle-induced defects. The mold was composed of a PDMS cushion layer sandwiched between a rigid imprint pattern layer and a plastic polyethylene terephthalate (PET) backplane. The PET foil was used as the backplane of the mold to protect the sticky PDMS surface. The PDMS as a cushion layer could locally deform to conform the shape of substrate due to its high elasticity. The multifunctional epoxysiloxane was used for the formation of an imprint layer because of its insensitivity toward oxygen during curing, high transparency, excellent mechanical strength and high resistance to oxygen plasma after cross-linking. Nanostructures with different geometries and sizes were faithfully duplicated by this mold through a UV-curing imprint process. The particle-induced defectivity was dramatically improved by the deformation of the PDMS cushion layer with a slight external pressure. 500 nm pitch grating structures were successfully imprinted on a microposts array surface, both the top and the intervening bottom portions between the microposts.

  3. Prediction of Lung Cells Oncogenic Transformation for Induced Radon Progeny Alpha Particles Using Sugarscape Cellular Automata

    PubMed Central

    Baradaran, Samaneh; Maleknasr, Niaz; Setayeshi, Saeed; Akbari, Mohammad Esmaeil

    2014-01-01

    Background Alpha particle irradiation from radon progeny is one of the major natural sources of effective dose in the public population. Oncogenic transformation is a biological effectiveness of radon progeny alpha particle hits. The biological effects which has caused by exposure to radon, were the main result of a complex series of physical, chemical, biological and physiological interactions. The cellular and molecular mechanisms for radon-induced carcinogenesis have not been clear yet. Methods Various biological models, including cultured cells and animals, have been found useful for studying the carcinogenesis effects of radon progeny alpha particles. In this paper, sugars cape cellular automata have been presented for computational study of complex biological effect of radon progeny alpha particles in lung bronchial airways. The model has included mechanism of DNA damage, which has been induced alpha particles hits, and then formation of transformation in the lung cells. Biomarkers were an objective measure or evaluation of normal or abnormal biological processes. In the model, the metabolism rate of infected cell has been induced alpha particles traversals, as a biomarker, has been followed to reach oncogenic transformation. Results The model results have successfully validated in comparison with “in vitro oncogenic transformation data” for C3H 10T1/2 cells. This model has provided an opportunity to study the cellular and molecular changes, at the various stages in radiation carcinogenesis, involving human cells. Conclusion It has become well known that simulation could be used to investigate complex biomedical systems, in situations where traditional methodologies were difficult or too costly to employ. PMID:25250147

  4. Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

    E-print Network

    Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Zhi responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy COPD patients, as indicated by electron microscopic analysis, as well as by increased activation

  5. Neurobiology of Disease Oxytocin Reverses Amphetamine-Induced Deficits in Social

    E-print Network

    McQuade, D. Tyler

    Neurobiology of Disease Oxytocin Reverses Amphetamine-Induced Deficits in Social Bonding: Evidence of social bonding. Accumulating evidence indicates that alterations in oxytocin (OT) and dopamine (DA: addiction; amphetamine; dopamine; oxytocin; social bonding Introduction Drug addiction has devastating

  6. Emerging mechanistic targets in lung injury induced by combustion-generated particles.

    PubMed

    Fariss, Marc W; Gilmour, M Ian; Reilly, Christopher A; Liedtke, Wolfgang; Ghio, Andrew J

    2013-04-01

    The mechanism for biological effect following exposure to combustion-generated particles is incompletely defined. The identification of pathways regulating the acute toxicological effects of these particles provides specific targets for therapeutic manipulation in an attempt to impact disease following exposures. Transient receptor potential (TRP) cation channels were identified as "particle sensors" in that their activation was coupled with the initiation of protective responses limiting airway deposition and inflammatory responses, which promote degradation and clearance of the particles. TRPA1, V1, V4, and M8 have a capacity to mediate adverse effects after exposure to combustion-generated particulate matter (PM); relative contributions of each depend upon particle composition, dose, and deposition. Exposure of human bronchial epithelial cells to an organic extract of diesel exhaust particle was followed by TRPV4 mediating Ca(++) influx, increased RAS expression, mitogen-activated protein kinase signaling, and matrix metalloproteinase-1 activation. These novel pathways of biological effect can be targeted by compounds that specifically inhibit critical signaling reactions. In addition to TRPs and calcium biochemistry, humic-like substances (HLS) and cell/tissue iron equilibrium were identified as potential mechanistic targets in lung injury after particle exposure. In respiratory epithelial cells, iron sequestration by HLS in wood smoke particle (WSP) was associated with oxidant generation, cell signaling, transcription factor activation, and release of inflammatory mediators. Similar to WSP, cytotoxic insoluble nanosized spherical particles composed of HLS were isolated from cigarette smoke condensate. Therapies that promote bioelimination of HLS and prevent the disruption of iron homeostasis could function to reduce the harmful effects of combustion-generated PM exposure. PMID:23322347

  7. Quantitative elemental detection of size-segregated particles using laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Wang, Zhen Zhen; Deguchi, Yoshihiro; Kuwahara, Masakazu; Taira, Takuya; Zhang, Xiao Bo; Yan, Jun Jie; Liu, Ji Ping; Watanabe, Hiroaki; Kurose, Ryoichi

    2013-09-01

    In order to simulate coal combustion and develop optimal and stable boiler control systems in real power plants, it is imperative to obtain the detailed information in coal combustion processes as well as to measure species contents in fly ash, which should be controlled and analyzed for enhancing boiler efficiency and reducing environmental pollution. The fly ash consists of oxides (SiO2, Al2O3, Fe2O3, CaO, and so on), unburned carbon, and other minor elements. Recently laser-induced breakdown spectroscopy (LIBS) technique has been applied to coal combustion and other industrial fields because of the fast response, high sensitivity, real-time and non-contact features. In these applications it is important to measure controlling factors without any sample preparation to maintain the real-time measurement feature. The relation between particle content and particle diameter is also one of the vital researches, because compositions of particles are dependent on their diameter. In this study, we have detected the contents of size-segregated particles using LIBS. Particles were classified by an Anderson cascade impactor and their contents were measured using the output of 1064 nm YAG laser, a spectrograph and an ICCD camera. The plasma conditions such as plasma temperature are dependent on the size of particles and these effects must be corrected to obtain quantitative information. The plasma temperature was corrected by the emission intensity ratio from the same atom. Using this correction method, the contents of particles can be measured quantitatively in fixed experimental parameters. This method was applied to coal and fly ash from a coal-fired burner to measure unburned carbon and other contents according to the particle diameter. The acquired results demonstrate that the LIBS technique is applicable to measure size-segregated particle contents in real time and this method is useful for the analysis of coal combustion and its control because of its sensitive and fast analysis features.

  8. Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials

    PubMed Central

    2012-01-01

    Background Reactive oxygen species (ROS) are vital regulators of many cellular functions in the body. The intracellular ROS concentration is highly regulated by a balance between pro-oxidants and anti-oxidants. A chronic excess of pro-oxidants leads to elevated ROS concentrations and inflammation, possibly initiating or enhancing disease onset. Mineral-induced generation of ROS, the role of minerals in upregulating cellular ROS, and their role in the development of several occupational diseases are now widely recognized. However, there is no standard protocol to determine changes in ROS production in cells after exposure to mineral dust or earth materials in general. In this study, a new method for determining the degree of cellular toxicity (i.e., cytotoxicity) of particles is described that will help bridge the gap in knowledge. Results By measuring the production of ROS and the viability of cells, an inflammatory stress response (ISR) indicator is defined. This approach normalizes the ROS upregulation with respect to the number of viable cells at the time of measurement. We conducted experiments on a series of minerals and soils that represent materials that are inert (i.e., glass beads, anatase, and a soil with low trace element content), moderately reactive (i.e., soil with high trace element content), and highly reactive (i.e., pyrite). Inert materials generated the lowest ISR, averaging 350% compared to the control. Acid washed pyrite produced the highest ISR (1,100 fold higher than the control). The measurements conducted as a function of time showed a complex response. Most materials showed an increase in ISR with particle loading. Conclusions The amount of cellularly generated ROS and cell viability combined provide a better understanding of particle-induced oxidative stress. The results indicate that some earth materials may solicit an initial burst of ROS, followed by a second phase in which cell viability decreases and ROS production increases, leading to a high ISR value. Hence, measurements conducted over a range of particle loading combined with multiple data measurements up to 24 hours can provide new insights in the possible effect of exposure to earth materials on human health. PMID:22513118

  9. ORIGINAL ARTICLE Evidence that disease-induced population decline

    E-print Network

    Storfer, Andrew

    , Australia; 2 Institute for Antarctic and Southern Ocean Studies, University of Tasmania, Hobart, Tasmania of Zoology, University of Tasmania, Hobart, Tasmania, Australia Infectious disease has been shown the east coast of Tasmania. We observed a significant increase in inbreed- ing (FIS pre/post-disease Ã?0

  10. Extract of motorcycle exhaust particles induced macrophages apoptosis by calcium-dependent manner.

    PubMed

    Lee, Chen-Chen; Kang, Jaw-Jou

    2002-12-01

    Large survey and experiments have reported that environment pollutants from fossil fuel combustion would cause immune system deleterious by enhancement of allergic reaction and damage to respiratory tract. In this study, we reported that the extract of motorcycle exhaust particles (MEP) might affect the immune system by inducing cell apoptosis on macrophages. The motorcycle exhaust particles were collected from a two-stoke engine and their cytotoxic effect on macrophages was investigated. We found MEP is cytotoxic and induced apoptosis in RAW 264.7 cells, murine peritoneal macrophage, and rat alveolar macrophage. Pretreatment with mitochondria permeability transition inhibitor (cyclosporin A), intracellular (BAPTA-AM) and extracellular (EGTA) Ca(2+) chelator, and antioxidants (NAC, GSH, catalase, SOD) attenuated the MEP-induced cell apoptosis, and BAPTA-AM was the most effective one. Utilized Fura-2/AM loaded RAW 264.7 cells to directly detect the change of intracellular Ca(2+) concentration ([Ca(2+)](i)), we found that MEP could induce a sustained increase of [Ca(2+)](i). The raise of [Ca(2+)](i) induced by MEP could be completely blocked by the intracellular Ca(2+) chelator, BAPTA-AM, however, only partially inhibited by the extracellular Ca(2+) chelator, EGTA. These results suggested that both influx of extracellular Ca(2+) and release of Ca(2+) from the internal storage were involved. We also found that MEP caused a decrease of mitochondria membrane potential and an increase of oxidative stress in RAW 264.7 cells. In conclusion, we found that the particles, collected from the motorcycle exhaust, contain chemicals that will induce apoptosis of macrophage in calcium-dependent manner. PMID:12482235

  11. Kinetic Arrest in Polyion-Induced Inhomogeneously-Charged Colloidal Particle Aggregation

    E-print Network

    D. Truzzolillo; F. Bordi; F. Sciortino; C. Cametti

    2008-05-26

    Polymer chains adsorbed onto oppositely charged spherical colloidal particles can significantly modify the particle-particle interactions. For sufficient amounts of added polymers, the original electrostatic repulsion can even turn into an effective attraction and relatively large kinetically stable aggregates can form which display several unexpected and interesting peculiarities and some intriguing biotechnological implications. The attractive interaction contribution between two oppositely particles arises from the correlated adsorption of polyions at the oppositely charged particle surfaces, resulting in a non-homogeneous surface charge distribution. Here, we investigate the aggregation kinetics of polyion-induced colloidal complexes through Monte Carlo simulation, in which the effect of charge anisotropy is taken into account by a DLVO-like intra-particle potential, as recentely proposed by Velegol and Thwar [D. Velegol and P.K. Thwar, Langmuir, 17, 2001]. The results reveal that in the presence of a charge heterogeneity the aggregation process slows down due to the progressive increase of the potential barrier height upon clustering. Within this framework, the experimentally observed cluster phases in polyelectrolyte-liposomes solutions should be considered as a kinetic arrested state.

  12. Fiber Bragg grating filter using evaporated induced self assembly of silica nano particles

    NASA Astrophysics Data System (ADS)

    Hammarling, Krister; Zhang, Renyung; Manuilskiy, Anatoliy; Nilsson, Hans-Erik

    2014-03-01

    In the present work we conduct a study of fiber filters produced by evaporation of silica particles upon a MM-fiber core. A band filter was designed and theoretically verified using a 2D Comsol simulation model of a 3D problem, and calculated in the frequency domain in respect to refractive index. The fiber filters were fabricated by stripping and chemically etching the middle part of an MM-fiber until the core was exposed. A mono layer of silica nano particles were evaporated on the core using an Evaporation Induced Self-Assembly (EISA) method. The experimental results indicated a broader bandwidth than indicated by the simulations which can be explained by the mismatch in the particle size distributions, uneven particle packing and finally by effects from multiple mode angles. Thus, there are several closely connected Bragg wavelengths that build up the broader bandwidth. The experimental part shows that it is possible by narrowing the particle size distributing and better control of the particle packing, the filter effectiveness can be greatly improved.

  13. Mutilocus genetic determinants of LDL particle size in coronary artery disease families

    SciTech Connect

    Rotter, J.I.; Bu, X.; Cantor, R.M. [and others

    1996-03-01

    Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (1) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (2) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair-analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P = .008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P = .06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P = .01) and the manganese superoxide dismutase locus (chromosome 6) (P = .001), thus indicating multilocus determination of this atherogenic trait. 73 refs., 3 figs., 4 tabs.

  14. Exposure to Concentrated Ambient Particles Does Not Affect Vascular Function in Patients with Coronary Heart Disease

    PubMed Central

    Mills, Nicholas L.; Robinson, Simon D.; Fokkens, Paul H. B.; Leseman, Daan L. A. C.; Miller, Mark R.; Anderson, David; Freney, Evelyn J.; Heal, Mathew R.; Donovan, Robert J.; Blomberg, Anders; Sandström, Thomas; MacNee, William; Boon, Nicholas A.; Donaldson, Ken; Newby, David E.; Cassee, Flemming R.

    2008-01-01

    Background Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans. Objectives We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. Methods Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables—including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine—6–8 hr after both exposures. Results Particulate concentrations (mean ± SE) in the exposure chamber (190 ± 37 ?g/m3) were higher than ambient levels (31 ± 8 ?g/m3) and levels in filtered air (0.5 ± 0.4 ?g/m3; p < 0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. Conclusions Despite achieving marked increases in particulate matter, exposure to CAPs—low in combustion-derived particles—did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans. PMID:18560524

  15. Parkinson's disease induced pluripotent stem cells with triplication of the ?-synuclein locus

    PubMed Central

    Devine, Michael J.; Ryten, Mina; Vodicka, Petr; Thomson, Alison J.; Burdon, Tom; Houlden, Henry; Cavaleri, Fatima; Nagano, Masumi; Drummond, Nicola J.; Taanman, Jan-Willem; Schapira, Anthony H.; Gwinn, Katrina; Hardy, John; Lewis, Patrick A.; Kunath, Tilo

    2011-01-01

    A major barrier to research on Parkinson's disease is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells from patients and differentiate them into neurons affected by disease. Triplication of SNCA, encoding ?-synuclein, causes a fully penetrant, aggressive form of Parkinson's disease with dementia. ?-Synuclein dysfunction is the critical pathogenic event in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. Here we produce multiple induced pluripotent stem cell lines from an SNCA triplication patient and an unaffected first-degree relative. When these cells are differentiated into midbrain dopaminergic neurons, those from the patient produce double the amount of ?-synuclein protein as neurons from the unaffected relative, precisely recapitulating the cause of Parkinson's disease in these individuals. This model represents a new experimental system to identify compounds that reduce levels of ?-synuclein, and to investigate the mechanistic basis of neurodegeneration caused by ?-synuclein dysfunction. PMID:21863007

  16. Detoxification and antioxidative therapy for levodopa-induced neurodegeneration in Parkinson's disease.

    PubMed

    Müller, Thomas

    2013-06-01

    Levodopa is the most efficacious drug treatment option for Parkinson's disease. However, in particular, high levodopa dosing may contribute to disease progression. Chronic levodopa metabolism reduces the methylation capacity and the antioxidant defense. Thus, this levodopa-induced free radical production complements the disease process, which considerably depends on free radical-induced, apoptotic neuronal cell death. Accordingly, clinical long-term studies with in the laboratory neuroprotective compounds failed in clinical investigations, as these studies were performed in levodopa-naive patients with Parkinson's disease over a relative short interval. Therefore, the likelihood for a positive outcome was rather low, since trials only focused on the disease process in levodopa-naive patients. However, studies on antioxidant therapeutic strategies were positive in levodopa-treated Parkinson's disease patients. To counteract these metabolic long-term levodopa-associated effects, chronic levodopa therapy should be combined with supplemental application of free radical scavengers and methyl group donating vitamins. PMID:23739007

  17. Ultrasonic and elasticity imaging to model disease-induced changes in soft-tissue structure

    Microsoft Academic Search

    Pawan Chaturvedi; Michael F. Insana; Timothy J. Hall

    1998-01-01

    Ultrasonic techniques are presented for the study of soft biological tissue structure and function. Changes in echo waveforms caused by microscopic variations in the mechanical properties of tissue can reveal disease mechanism, in vivo. On a larger scale, elasticity imaging describes the macroscopic mechanical properties of soft tissues. We summarize the approach and present preliminary results for studying disease-induced changes

  18. Fluorescent Light-Induced Chromatid Breaks Distinguish Alzheimer Disease Cells from Normal Cells in Tissue Culture

    Microsoft Academic Search

    Ram Parshad; Katherine K. Sanford; Floyd M. Price; Lynn K. Melnick; Linda E. Nee; Mark B. Schapiro; Robert E. Tarone; Jay H. Robbins

    1996-01-01

    The neurodegeneration and amyloid deposition of sporadic Alzheimer disease (AD) also occur in familial AD and in all trisomy-21 Down syndrome (DS) patients, suggesting a common pathogenetic mechanism. We investigated whether defective processing of damaged DNA might be that mechanism, as postulated for the neurodegeneration in xeroderma pigmentosum, a disease with defective repair not only of UV radiation-induced, but also

  19. Examination of Susceptibility to Libby Amphibole Asbestos-Induced Injury in Rat Models of Cardiovascular Disease

    EPA Science Inventory

    Although cardiovascular disease (CVD) is considered a risk factor for the exacerbation of air pollution health effects, no studies have been done assessing the influence of the disease on the development of lung injury induced by asbestos exposure. In this study we examined lung ...

  20. Anomalous effect of trench-oxide depth on alpha-particle-induced charge collection

    Microsoft Academic Search

    Hyungsoon Shin; Nak-Myeong Kim

    1999-01-01

    The effect of trench-oxide depth on the alpha-particle-induced charge collection is analyzed for the first time. From the simulation results, it was found that the depth of trench oxide has a considerable influence on the amount of collected charge. The confining of generated charge by the trench oxide was identified as a cause of this anomalous effect. Therefore, the tradeoff

  1. Alpha-particle-induced collected charge model in SOI-DRAM's

    Microsoft Academic Search

    Shigeo Satoh; Yoshiharu Tosaka; Kunihiro Suzuki; Toru Itakura

    1999-01-01

    We have developed a model for collected charges induced by an alpha-particle for SOI-DRAMs which assumes that the body capacitance equals the gate capacitance and that holes do not recombine with electrons. The validity of our model was supported by three-dimensional (3-D) device simulations that considered various gate lengths, gate oxide thicknesses, and flat-band voltages. The work function difference between

  2. On inducing finite dimensional physical field representations for massless particles in even dimensions

    NASA Technical Reports Server (NTRS)

    Bhansali, Vineer

    1993-01-01

    Assuming trivial action of Euclidean translations, the method of induced representations is used to derive a correspondence between massless field representations transforming under the full generalized even dimensional Lorentz group, and highest weight states of the relevant little group. This gives a connection between 'helicity' and 'chirality' in all dimensions. Restrictions on 'gauge independent' representations for physical particles that this induction imposes are also stated.

  3. Underwater pressure amplification of laser-induced plasma shock waves for particle removal applications

    Microsoft Academic Search

    Thomas J. Dunbar; Cetin Cetinkaya

    2007-01-01

    Underwater amplification of laser-induced plasma (LIP)-generated transient pressure waves using shock tubes is introduced and demonstrated. Previously, it has been shown that LIP for noncontact particle removal is possible on the sub-100-nm level. This is now enhanced through shock tube utilization in a medium such as water by substantially increasing shock wave pressure for the same pulse energy. A shock

  4. Ebola Virus VP40Induced Particle Formation and Association with the Lipid Bilayer

    Microsoft Academic Search

    LUKE D. JASENOSKY; GABRIELE NEUMANN; IGOR LUKASHEVICH; YOSHIHIRO KAWAOKA

    2001-01-01

    Viral protein 40 (VP40) of Ebola virus appears equivalent to matrix proteins of other viruses, yet little is known about its role in the viral life cycle. To elucidate the functions of VP40, we investigated its ability to induce the formation of membrane-bound particles when it was expressed apart from other viral proteins. We found that VP40 is indeed able

  5. Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

    Microsoft Academic Search

    Sarah X. L. Huang; Marie-Claude Jaurand; David W. Kamp; John Whysner; Tom K. Hei

    2011-01-01

    The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be

  6. Periodically Forced Discrete-Time SIS Epidemic Model With Disease Induced Mortality

    E-print Network

    Franke, J. E.

    Periodically Forced Discrete-Time SIS Epidemic Model With Disease Induced Mortality John E. Franke@howard.edu. July 29, 2010 Abstract We use a periodically forced SIS epidemic model with dieases induced mortality;SIS MODEL IN SEASONAL ENVIRONMENTS 2 tion sizes are often either enhanced via resonance or diminished

  7. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease

    Microsoft Academic Search

    Ellen M. Nilsen; Frode L. Jahnsen; Knut E. A. Lundin; Olav Fausa; Ludvig M. Sollid; Jørgen Jahnsen; Helge Scott; Per Brandtzaeg

    1998-01-01

    Background & Aims: Celiac disease appears to be a T cell–mediated enteropathy induced by gluten in genetically predisposed individuals. Duodenal biopsy specimens from patients with celiac disease and histologically normal controls were investigated to see if cytokine expression is related to disease activity. Methods: Cytokine messenger RNA (mRNA) expression was determined by quantitative reverse-transcription polymerase chain reaction and in situ

  8. Enveloped Virus-Like Particle Expression of Human Cytomegalovirus Glycoprotein B Antigen Induces Antibodies with Potent and Broad Neutralizing Activity

    PubMed Central

    Kirchmeier, Marc; Fluckiger, Anne-Catherine; Soare, Catalina; Bozic, Jasminka; Ontsouka, Barthelemy; Ahmed, Tanvir; Diress, Abebaw; Pereira, Lenore; Schödel, Florian; Plotkin, Stanley; Dalba, Charlotte; Klatzmann, David

    2014-01-01

    A prophylactic vaccine to prevent the congenital transmission of human cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in immunosuppressed recipients of HCMV-infected solid organ transplants is highly desirable. Neutralizing antibodies against HCMV confer significant protection against infection, and glycoprotein B (gB) is a major target of such neutralizing antibodies. However, one shortcoming of past HCMV vaccines may have been their failure to induce high-titer persistent neutralizing antibody responses that prevent the infection of epithelial cells. We used enveloped virus-like particles (eVLPs), in which particles were produced in cells after the expression of murine leukemia virus (MLV) viral matrix protein Gag, to express either full-length CMV gB (gB eVLPs) or the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV)-G protein (gB-G eVLPs). gB-G-expressing eVLPs induced potent neutralizing antibodies in mice with a much greater propensity toward epithelial cell-neutralizing activity than that induced with soluble recombinant gB protein. An analysis of gB antibody binding titers and T-helper cell responses demonstrated that high neutralizing antibody titers were not simply due to enhanced immunogenicity of the gB-G eVLPs. The cells transiently transfected with gB-G but not gB plasmid formed syncytia, consistent with a prefusion gB conformation like those of infected cells and viral particles. Two of the five gB-G eVLP-induced monoclonal antibodies we examined in detail had neutralizing activities, one of which possessed particularly potent epithelial cell-neutralizing activity. These data differentiate gB-G eVLPs from gB antigens used in the past and support their use in a CMV vaccine candidate with improved neutralizing activity against epithelial cell infection. PMID:24334684

  9. Generating SNP barcode to evaluate SNP-SNP interaction of disease by particle swarm optimization.

    PubMed

    Chang, Hsueh-Wei; Yang, Cheng-Hong; Ho, Chang-Hsuan; Wen, Cheng-Hao; Chuang, Li-Yeh

    2009-02-01

    Genome-wide association analysis involved many single-nucleotide polymorphisms (SNPs) data is challenging mathematically and computationally. Hence, we propose the odds ratio-based discrete binary particle swarm optimization (OR-DBPSO) method that uses the OR as a new quantitative measure of disease risk among many SNP combinations with genotypes called "SNP barcode". DBPSO are applied to generate SNP barcode, which computes the maximal difference of occurrence between the case and control groups, to predict disease susceptibility such as osteoporosis. Different SNP barcode patterns may occur several times in either low or high bone mineral density (BMD) groups. Our results showed that a DBPSO can effectively identify a specific SNP barcode with an optimized fitness value. SNP barcodes with a low fitness value will naturally be discarded from the population. A representative SNP barcode with a variable number of SNPs is processed to OR analysis to determine the maximum difference between the low and high BMD groups in statistics manner. Therefore, this paper introduces a powerful procedure to analyze disease-associated SNP-SNP interaction in genome-wide genes. PMID:18789770

  10. Potential applications of magnetic particles to detect and treat Alzheimer's disease

    PubMed Central

    2014-01-01

    Nanotechnology is an exciting and promising scientific discipline. At the nanoscale, a material displays novel physical properties that offer many new and beneficial products and applications. In particular, magnetic nanoparticles - a core/shell nanoparticle - present considerable diagnostic and therapeutic potentials, and superparamagnetic iron oxide nanoparticles (SPIONs) are considered promising theranostic tools. Alzheimer's disease (AD) is a neurodegenerative disorder that predominantly affects people over 65 years of age. The disease is characterized by the presence of extracellular plaques in the brain which are formed by interwoven fibrils composed of variants of the ?-amyloid peptide. Medication can temporarily retard worsening of symptoms, but only in the first stages of the disease; early detection is thus of crucial importance. This minireview covers the progress made in research on the use of magnetic nanoparticles for ex vivo and/or in vivo detection and diagnosis of AD by means of magnetic resonance imaging (MRI), or to label peptides and fibrils. Of particular importance is the use of these nanoparticles to detect AD biomarkers in biological fluids. A description is given of the bio-barcode amplification assay using functionalized magnetic particles, as well as the use of such nanoparticles as a system for inhibiting or delaying the assembly of peptide monomers into oligomers and fibrils. Lastly, a brief overview is given of possible future lines of research in this. PMID:25288921

  11. On the equivalence of ?(t) and gravitationally induced particle production cosmologies

    NASA Astrophysics Data System (ADS)

    Graef, L. L.; Costa, F. E. M.; Lima, J. A. S.

    2014-01-01

    The correspondence between cosmological models powered by a decaying vacuum energy density and gravitationally induced particle production is investigated. Although being physically different in the physics behind them we show that both classes of cosmologies under certain conditions can exhibit the same dynamic and thermodynamic behavior. Our method is applied to obtain three specific models that may be described either as ?(t)CDM or gravitationally induced particle creation. In the point of view of particle production models, such cosmologies can be interpreted as a kind of one-component unification of the dark sector. By using current type Ia supernovae data, recent estimates of the cosmic microwave background shift parameter and baryon acoustic oscillations measurements we also perform a statistical analysis to test the observational viability within the two equivalent classes of models and we obtain the best-fit of the free parameters. By adopting the Akaike information criterion we also determine the rank of the models considered here. Finally, the particle production cosmologies (and the associated decaying ?(t)-models) are modeled in the framework of field theory by a phenomenological scalar field model.

  12. Human alkaloid biosynthesis : chemical inducers of Parkinson's disease?

    E-print Network

    Hatzios, Stavroula K. (Stavroula-Artemis K.)

    2005-01-01

    The occurrence of certain alkaloids in the human brain appears to be associated with the onset of Parkinson's disease (PD). Recently, a human protein bearing homology to an alkaloid synthase in plants was identified. This ...

  13. Exploiting the wall-induced non-inertial lift in electrokinetic flow for a continuous particle separation by size.

    PubMed

    Lu, Xinyu; Hsu, Jyh-Ping; Xuan, Xiangchun

    2015-01-13

    Separating particles from a heterogeneous mixture is important and necessary in many engineering and biomedical applications. Electrokinetic flow-based continuous particle separation has thus far been realized primarily by the use of particle dielectrophoresis induced in constricted and/or curved microchannels. We develop in this work a new electrokinetic method that exploits the wall-induced non-inertial lift in a straight uniform microchannel to continuously separate particles by intrinsic properties (e.g., size and surface charge). Such an electrically originated lift force arises from the asymmetric electric field distribution around a particle nearby a planar dielectric wall. We demonstrate this method through separating both a binary and ternary mixture of dispersed polystyrene microspheres by size in a T-shaped microchannel. A semi-analytical model is also developed to simulate and understand the particle separation process. The predicted particle trajectories in the entire microchannel agree reasonably well with the experimental measurements. PMID:25521509

  14. Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer

    NASA Technical Reports Server (NTRS)

    Zhu, L. X.; Waldren, C. A.; Vannias, D.; Hei, T. K.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Mutation induction by charged particles of defined linear energy transfer (LET) and gamma rays was scored using human-hamster hybrid AL cells. The LET values for charged particles accelerated at the Radiological Research Accelerator Facility ranged from 10 keV/microm protons to 150 keV/microm 4He ions. The induced mutant fractions at both the S1 and HGPRT loci were dependent on the dose and LET. In addition, for each dose examined, the mutant yield at the S1 locus was 30-60 fold higher than at the corresponding HGPRT locus. To determine whether the mutation spectrum was comparably dependent on dose and LET, independent S1- and HGPRT- mutants induced by 150 keV/microm 4He ions and gamma rays were isolated, and their DNA was analyzed by both Southern blotting and multiplex PCR methods. While the majority of radiation-induced mutants showed deletions of varying sizes, the relative percentage of large deletions was found to be related to both the dose and LET of the radiation examined. Using a mutation system that can detect multilocus changes, results of the present study show that radiation-induced chromosomal loss can be in the millions of base pairs.

  15. Brain signaling and behavioral responses induced by exposure to (56)Fe-particle radiation

    NASA Technical Reports Server (NTRS)

    Denisova, N. A.; Shukitt-Hale, B.; Rabin, B. M.; Joseph, J. A.

    2002-01-01

    Previous experiments have demonstrated that exposure to 56Fe-particle irradiation (1.5 Gy, 1 GeV) produced aging-like accelerations in neuronal and behavioral deficits. Astronauts on long-term space flights will be exposed to similar heavy-particle radiations that might have similar deleterious effects on neuronal signaling and cognitive behavior. Therefore, the present study evaluated whether radiation-induced spatial learning and memory behavioral deficits are associated with region-specific brain signaling deficits by measuring signaling molecules previously found to be essential for behavior [pre-synaptic vesicle proteins, synaptobrevin and synaptophysin, and protein kinases, calcium-dependent PRKCs (also known as PKCs) and PRKA (PRKA RIIbeta)]. The results demonstrated a significant radiation-induced increase in reference memory errors. The increases in reference memory errors were significantly negatively correlated with striatal synaptobrevin and frontal cortical synaptophysin expression. Both synaptophysin and synaptobrevin are synaptic vesicle proteins that are important in cognition. Striatal PRKA, a memory signaling molecule, was also significantly negatively correlated with reference memory errors. Overall, our findings suggest that radiation-induced pre-synaptic facilitation may contribute to some previously reported radiation-induced decrease in striatal dopamine release and for the disruption of the central dopaminergic system integrity and dopamine-mediated behavior.

  16. Nimesulide Improves the Symptomatic and Disease Modifying Effects of Leflunomide in Collagen Induced Arthritis

    PubMed Central

    Al-Abd, Ahmed M.; Al-Abbasi, Fahad A.; Nofal, Salwa M.; Khalifa, Amani E.; Williams, Richard O.; El-Eraky, Wafaa I.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-01-01

    Nimesulide is a COX-2 inhibitor used for symptomatic relief of rheumatoid arthritis. Leflunomide is an anti-pyrimidine used to manage the progression of rheumatoid arthritis. Herein we studied the influence of nimesulide and leflunomide combination in terms of disease symptoms and progression using collagen-induced arthritis model in mice, as a model for rheumatoid arthritis. Collagen induced arthritis was induced by immunization with type II collagen. Assessment of joint stiffness and articular hyperalgesia were evaluated using a locomotor activity cage and the Hargreaves method, respectively. Disease progression was assessed via arthritic index scoring, X-ray imaging, myeloperoxidase enzyme activity and histopathologic examination. Nimesulide induced only transient symptomatic alleviation on the top of decreased leucocytic infiltration compared to arthritis group. However, nimesulide alone failed to induce any significant improvement in the radiological or pathological disease progression. Leflunomide alone moderately alleviates the symptoms of arthritis and moderately retarded the radiological and pathological disease progression. Combination of nimesulide and leflunomide significantly improved symptomatic (analgesia and joint stiffness) and arthritic disease progression (radiological, pathological and Myeloperoxidase enzyme activity) in collagen induced arthritis animal model. PMID:25375820

  17. Fine Ambient Particles Induce Oxidative Stress and Metal Binding Genes in Human Alveolar Macrophages

    PubMed Central

    Huang, Yuh-Chin T.; Li, Zhuowei; Carter, Jacqueline D.; Soukup, Joleen M.; Schwartz, David A.; Yang, Ivana V.

    2009-01-01

    Exposure to pollutant particles increased respiratory morbidity and mortality. The alveolar macrophages (AMs) are one cell type in the lung directly exposed to particles. Upon contact with particles, AMs are activated and produce reactive oxygen species, but the scope of this oxidative stress response remains poorly defined. In this study, we determined the gene expression profile in human AMs exposed to particles, and sought to characterize the global response of pro- and antioxidant genes. We exposed AMs obtained by bronchoscopy from normal individuals to Chapel Hill particulate matter of 2.5-?m diameter or smaller (PM2.5; 1 ?g/ml) or vehicle for 4 hours (n = 6 independent samples). mRNAs were extracted, amplified, and hybridized to Agilent human 1A microarray. Significant genes were identified by significance analysis of microarrays (false discovery rate, 10%; P ? 0.05) and mapped with Gene Ontology in the Database for Annotation, Visualization, and Integrated Discovery. We found 34 and 41 up- and down-regulated genes, respectively; 22 genes (?30%) were involved in metal binding, and 11 were linked to oxidative stress, including up-regulation of five metallothionein (MT)-1 isoforms. Exogenous MT1 attenuated PM2.5-induced H2O2 release. PM2.5 premixed with MT1 stimulated less H2O2 release. Knockdown of MT1F gene increased PM2.5-induced H2O2 release. PM2.5 at 1 ?g/ml did not increase H2O2 release. Mount St. Helens PM2.5 and acid-extracted Chapel Hill PM2.5, both poor in metals, did not induce MT1F or H2O2 release. Our results show that PM2.5 induced a gene expression profile prevalent with genes related to metal binding and oxidative stress in human AMs, independent of oxidative stress. Metals associated with PM may play an important role in particle-induced gene changes. PMID:19251948

  18. Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

    PubMed Central

    Johnson, Christopher J; Pedersen, Joel A; Chappell, Rick J; McKenzie, Debbie; Aiken, Judd M

    2007-01-01

    Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent. PMID:17616973

  19. Oral transmissibility of prion disease is enhanced by binding to soil particles.

    PubMed

    Johnson, Christopher J; Pedersen, Joel A; Chappell, Rick J; McKenzie, Debbie; Aiken, Judd M

    2007-07-01

    Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent. PMID:17616973

  20. Preliminary investigation of the relationship between bovine congenital lathyrism induced by aminoacetonitrile and the lupine induced crooked calf disease.

    PubMed

    Keeler, R F; Binns, W; James, L F; Shupe, J L

    1969-04-01

    Maternal feeding of the lathyrogen aminoacetonitrile, the range plant Lupinus caudatus, and an extract of this plant - expected to contain lathyrogens if present in the plant - all produced clinically similar congenital defects in calves. The defects included excessive flexure, malpositioning, malalignment and rotation of the front limbs. The results suggest a possible relationship between lathyrism and lupine-induced crooked calf disease. PMID:4238569

  1. The Effect of Surface Induced Flows on Bubble and Particle Aggregation

    NASA Technical Reports Server (NTRS)

    Guelcher, Scott A.; Solomentsev, Yuri E.; Anderson, John L.; Boehmer, Marcel; Sides, Paul J.

    1999-01-01

    Almost 20 years have elapsed since a phenomenon called "radial specific coalescence" was identified. During studies of electrolytic oxygen evolution from the back side of a vertically oriented, transparent tin oxide electrode in alkaline electrolyte, one of the authors (Sides) observed that large "collector" bubbles appeared to attract smaller bubbles. The bubbles moved parallel to the surface of the electrode, while the electric field was normal to the electrode surface. The phenomenon was reported but not explained. More recently self ordering of latex particles was observed during electrophoretic deposition at low DC voltages likewise on a transparent tin oxide electrode. As in the bubble work, the field was normal to the electrode while the particles moved parallel to it. Fluid convection caused by surface induced flows (SIF) can explain these two apparently different experimental observations: the aggregation of particles on an electrode during electrophoretic deposition, and a radial bubble coalescence pattern on an electrode during electrolytic gas evolution. An externally imposed driving force (the gradient of electrical potential or temperature), interacting with the surface of particles or bubbles very near a planar conducting surface, drives the convection of fluid that causes particles and bubbles to approach each other on the electrode.

  2. Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect

    NASA Astrophysics Data System (ADS)

    Kim, Jong-Ki; Seo, Seung-Jun; Kim, Ki-Hong; Kim, Tae-Jeong; Chung, Myung-Hwan; Kim, Kye-Ryung; Yang, Tae-Keun

    2010-10-01

    Metallic nanoparticles (MNP) are able to release localized x-rays when activated with a high energy proton beam by the particle-induced x-ray emission (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based x-ray emission directed at CT26 tumor cells in vitro, when administered with either gold (average diameter 2 and 13 nm) or iron (average diameter 14 nm) nanoparticles (GNP or SNP), increased with MNP solution concentration over the range of 0.1-2 mg ml - 1. With irradiation by a 45 MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study in CT26 mouse tumor models with tumor regression assay demonstrated significant tumor dose enhancement, thought to be a result of the PIXE effect when compared to conventional PT without MNP (radiation-only group) using a 45 MeV proton beam (p < 0.02). Those receiving GNP or SNP injection doses of 300 mg kg - 1 body weight before proton beam therapy demonstrated 90% or 75% tumor volume reduction (TVR) in 20 days post-PT while the radiation-only group showed only 18% TVR and re-growth of tumor volume after 20 days. Higher complete tumor regression (CTR) was observed in 14-24 days after a single treatment of PT with an average rate of 33-65% for those receiving MNP compared with 25% for the radiation-only group. A lower bound of therapeutic effective MNP concentration range, in vivo, was estimated as 30-79 µg g - 1 tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread-out Bragg peak (SOBP) technique. The use of a combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone, may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases.

  3. Toll-like receptors-2 and 4 are overexpressed in an experimental model of particle-induced osteolysis.

    PubMed

    Valladares, Roberto D; Nich, Christophe; Zwingenberger, Stefan; Li, Chenguang; Swank, Katherine R; Gibon, Emmanuel; Rao, Allison J; Yao, Zhenyu; Goodman, Stuart B

    2014-09-01

    Aseptic loosening secondary to particle-associated periprosthetic osteolysis remains a major cause of failure of total joint replacements (TJR) in the mid- and long term. As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll-like receptors (TLRs) are involved in the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle-induced osteolysis remain largely unknown. We hypothesized that TLR-2, -4, and -9 mediated responses play a critical role in the development of PE wear particle-induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE-treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR-2 and TLR-4 were highly expressed in PE particle-induced osteolytic lesions, whereas TLR-9 was downregulated. TLR-2 and -4 may represent novel therapeutic targets for prevention of wear particle-induced osteolysis and accompanying TJR failure. PMID:24115330

  4. Labetalol-induced Peyronie's disease? A case report.

    PubMed

    Kristensen, B O

    1979-01-01

    Peyronie's disease (induratio penis plastica) has been observed in a 58-year-old man 8 months after initiation of treatment with the new combined alpha- and beta-blocking agent, labetalol. During the last 2 months before onset of symptoms he had received 2400 mg labetalol daily. He showed no other signs of abnormal fibrous tissue production and the ANF test was negative. Cessation of the drug revealed no improvement. Peyronie's disease has also been observed in relation to treatment with propranolol, practolol and metoprolol and might be due to an impaired balance between alpha- and beta-receptors in connective tissue, but there may also be an immunological basis for the fibrosis. A possible coincidence is stressed, as the ages of the reported cases are within the range where this disease most often develops. PMID:231377

  5. Epigenetic Transgenerational Inheritance of Vinclozolin Induced Mouse Adult Onset Disease and Associated Sperm Epigenome Biomarkers

    PubMed Central

    Guerrero-Bosagna, Carlos; Covert, Trevor R.; Haque, Md. M.; Settles, Matthew; Nilsson, Eric E.; Anway, Matthew D.; Skinner, Michael K.

    2012-01-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. PMID:23041264

  6. Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease.

    PubMed

    Dong, Yan-Mei; Zhang, Guo-Guang; Huang, Xiao-Jun; Chen, Liang; Chen, Hao-Tai

    2015-05-01

    Foot-and-mouth disease (FMD) has caused severe economic losses to millions of farmers worldwide. In this work, the coding genes of 141-160 epitope peptide (EP141-160) of VP1 were inserted into the coat protein (CP) genes of MS2 in prokaryotic expression vector, and the recombinant protein self-assembled into virus-like particles (VLP). Results showed that the CP-EP141-160 VLP had a strong immunoreaction with the FMD virus (FMDV) antigen in vitro, and also had an effective immune response in mice. Further virus challenge tests were carried out on guinea pigs and swine, high-titer neutralizing antibodies were produced and the CP-EP141-160 VLP vaccine could protect most of the animals against FMDV. PMID:25676866

  7. Patient-specific induced pluripotent stem cell models in mitochondrial diseases.

    PubMed

    Zhang, Xuan; Li, Shishi; Yang, Wei; Qin, Dajiang; Yu, Luyang; Yan, Qingfeng

    2014-03-01

    Mitochondrial diseases are clinical phenotypes associated with mitochondrial dysfunction, which can be caused by mutations of mitochondrial DNA (mtDNA) or of nuclear genes. Since there are no high-performance transfect systems yet to make particular mtDNA mutation, and tissue sources are limited by ethical issue and injury, the molecular pathogenesis of mitochondrial diseases remains poorly understood. The generation of induced pluripotent stem (iPS) cells from adult somatic cells has opened a remarkable avenue for theoretic study and therapeutic application. Patient-specific induced pluripotent stem cells and differentiated cells derived from them are attracting increasing attention to elucidate the mechanisms underlying mitochondrial diseases. In this review, we summarize the advances of iPS cells, advantages of patient- specific iPS cells as a novel disease model, especially in mitochondrial disease. Occurring challenges and perspectives of patient-specific iPS cells research are also discussed. PMID:24372327

  8. Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-?B activation and titanium particle-induced osteolysis in a mouse model.

    PubMed

    Huang, Jianbin; Zhou, Lin; Wu, Huafei; Pavlos, Nathan; Chim, Shek Man; Liu, Qian; Zhao, Jinmin; Xue, Wei; Tan, Ren Xiang; Ye, Jiming; Xu, Jun; Ang, Estabelle S; Feng, Haotian; Tickner, Jennifer; Xu, Jiake; Ding, Yue

    2015-01-01

    The RANKL-induced NF-?B signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-?B activation using a luciferase reporter gene assay in RAW264.7 cells, we identified triptolide (PG490), as a candidate compound targeting osteoclast differentiation and osteoclast-mediated osteolysis. Triptolide (PG490) is an active compound of the medicinal herb Tripterygium wilfordii Hook F (TWHF) or Lei Gong Teng with known anti-inflammatory properties. We found that triptolide inhibited osteoclastogenesis and bone resorption, as well as RANKL-induced NF-?B activities as monitored by luciferase reporter gene assays and the nuclear translocation of p65. In vivo studies showed that triptolide attenuates titanium-induced osteolysis and osteoclast formation in a mouse calvarial model. Considering that drugs which protect against localized bone loss are critically needed for the effective treatment of particle-induced osteolysis, our data suggest that triptolide might have therapeutic potential for the treatment of bone lytic diseases caused by prosthetic wear particles. PMID:25448849

  9. HIV-1 Gag-virus-like particles induce natural killer cell immune responses via activation and maturation of dendritic cells.

    PubMed

    Chang, Myint Oo; Suzuki, Tomoyuki; Suzuki, Hitoshi; Takaku, Hiroshi

    2012-01-01

    Despite the extensive efforts that have been made to combat acquired immune deficiency syndrome (AIDS), the number of people infected each year with human immunodeficiency virus type 1 (HIV-1) is still increasing worldwide, and a safe and effective vaccine to control HIV infection is urgently needed. Recently, the natural killer (NK) cell-mediated innate immune response, which represents the first line of defense against infections, has attracted attention for its role in combating HIV infection and disease progression. In the present study, we investigated the immunogenic ability of HIV-1 Gag-virus-like particles (Gag-VLPs) to induce NK cell immune responses in vitro and in vivo. Gag-VLPs efficiently activated human monocyte-derived dendritic cells (MDDCs), eliciting MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II, MDDC proliferation and proinflammatory cytokine production. Gag-VLP-treated MDDCs subsequently activated autologous NK cells, leading to their proliferation and production of interferon-? and to the upregulation of NK cell cytotoxicity against YAC-1 cells and HIV-1-infected CD4(+) T cells. In addition, we introduced a 2-phase immunization strategy in BALB/c mice to assess the role of DCs in the induction of NK cell immune responses by Gag-VLPs in vivo. Our findings reveal that Gag-VLPs efficiently activate DCs, which in turn induce innate and Gag-specific immune responses in NK cells. PMID:21778700

  10. Dopamine-Induced Nonmotor Symptoms of Parkinson's Disease

    PubMed Central

    Park, Ariane; Stacy, Mark

    2011-01-01

    Nonmotor symptoms of Parkinson's disease (PD) may emerge secondary to the underlying pathogenesis of the disease, while others are recognized side effects of treatment. Inevitably, there is an overlap as the disease advances and patients require higher dosages and more complex medical regimens. The non-motor symptoms that emerge secondary to dopaminergic therapy encompass several domains, including neuropsychiatric, autonomic, and sleep. These are detailed in the paper. Neuropsychiatric complications include hallucinations and psychosis. In addition, compulsive behaviors, such as pathological gambling, hypersexuality, shopping, binge eating, and punding, have been shown to have a clear association with dopaminergic medications. Dopamine dysregulation syndrome (DDS) is a compulsive behavior that is typically viewed through the lens of addiction, with patients needing escalating dosages of dopamine replacement therapy. Treatment side effects on the autonomic system include nausea, orthostatic hypotension, and constipation. Sleep disturbances include fragmented sleep, nighttime sleep problems, daytime sleepiness, and sleep attacks. Recognizing the non-motor symptoms that can arise specifically from dopamine therapy is useful to help optimize treatment regimens for this complex disease. PMID:21603184

  11. Preventing diet induced disease: bioavailable nutrient-rich, low-

    E-print Network

    Paris-Sud XI, Université de

    of pregnancy and continues throughout life of the new born and includes consuming more DhA and EPA omega-3 fats) foods (e.g. land-based cereal, chocolate, alcohol and refined sugar, fat and oil), so tissues synthesize as long as possible in good health (disease free). to achieve that future potential, it is necessary

  12. Lupine Induced "Crooked Calf Disease": The Last 20 Years

    Technology Transfer Automated Retrieval System (TEKTRAN)

    “Crooked calf disease” is used to describe a number of skeletal malformations in newborn calves, including a twisted spine, neck, and one or both forelimbs. These malformations develop when the pregnant cow eats toxic lupines containing the alkaloids anagyrine, ammodendrine, and N-methyl ammodendri...

  13. Rosuvastatin-Induced Arrest in Progression of Renal Disease

    Microsoft Academic Search

    Donald G. Vidt; Michael D. Cressman; Susan Harris; John S. Pears; Howard G. Hutchinson

    2004-01-01

    Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor®) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants

  14. Mechanisms of lead-induced hypertension and cardiovascular disease

    PubMed Central

    Vaziri, Nosratola D.

    2008-01-01

    Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension (HTN) and cardiovascular disease. In vivo and in vitro studies have shown that chronic lead exposure causes HTN and cardiovascular disease by promoting oxidative stress, limiting nitric oxide availability, impairing nitric oxide signaling, augmenting adrenergic activity, increasing endothelin production, altering the renin-angiotensin system, raising vasoconstrictor prostaglandins, lowering vasodilator prostaglandins, promoting inflammation, disturbing vascular smooth muscle Ca2+ signaling, diminishing endothelium-dependent vasorelaxation, and modifying the vascular response to vasoactive agonists. Moreover, lead has been shown to cause endothelial injury, impede endothelial repair, inhibit angiogenesis, reduce endothelial cell growth, suppress proteoglycan production, stimulate vascular smooth muscle cell proliferation and phenotypic transformation, reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production. Via these and other actions, lead exposure causes HTN and promotes arteriosclerosis, atherosclerosis, thrombosis, and cardiovascular disease. In conclusion, studies performed in experimental animals, isolated tissues, and cultured cells have provided compelling evidence that chronic exposure to low levels of lead can cause HTN, endothelial injury/dysfunction, arteriosclerosis, and cardiovascular disease. More importantly, these studies have elucidated the cellular and molecular mechanisms of lead's action on cardiovascular/renal systems, a task that is impossible to accomplish using clinical and epidemiological investigations alone. PMID:18567711

  15. Altered particle size distribution of apolipoprotein A=l=containing lipoproteins in subjects with coronary artery disease

    Microsoft Academic Search

    Marian C. Cheung; B. Greg Brown; Anitra C. Wolf; John J. Albers

    Plasma high density lipoproteins (HDL) can be separated into two subpopulations of apolipoprotein A-I- containing particles: those that also contain apoA-I1 ( Lp(A1 w AH)) and those that do not (Lp(AI w\\/o AH)). These particles were isolated by immunoaffinity Chromatography from 17 men (9 normolipidemic (NL), 8 hyperlipidemic (HL)) with sympto- matic coronary artery disease (CAD), from 17 NL men

  16. Repair of HZE-particle-induced DNA double-strand breaks in normal human fibroblasts.

    PubMed

    Asaithamby, Aroumougame; Uematsu, Naoya; Chatterjee, Aloke; Story, Michael D; Burma, Sandeep; Chen, David J

    2008-04-01

    DNA damage generated by high-energy and high-Z (HZE) particles is more skewed toward multiply damaged sites or clustered DNA damage than damage induced by low-linear energy transfer (LET) X and gamma rays. Clustered DNA damage includes abasic sites, base damages and single- (SSBs) and double-strand breaks (DSBs). This complex DNA damage is difficult to repair and may require coordinated recruitment of multiple DNA repair factors. As a consequence of the production of irreparable clustered lesions, a greater biological effectiveness is observed for HZE-particle radiation than for low-LET radiation. To understand how the inability of cells to rejoin DSBs contributes to the greater biological effectiveness of HZE particles, the kinetics of DSB rejoining and cell survival after exposure of normal human skin fibroblasts to a spectrum of HZE particles was examined. Using gamma-H2AX as a surrogate marker for DSB formation and rejoining, the ability of cells to rejoin DSBs was found to decrease with increasing Z; specifically, iron-ion-induced DSBs were repaired at a rate similar to those induced by silicon ions, oxygen ions and gamma radiation, but a larger fraction of iron-ion-induced damage was irreparable. Furthermore, both DNA-PKcs (DSB repair factor) and 53BP1 (DSB sensing protein) co-localized with gamma-H2AX along the track of dense ionization produced by iron and silicon ions and their focus dissolution kinetics was similar to that of gamma-H2AX. Spatial co-localization analysis showed that unlike gamma-H2AX and 53BP1, phosphorylated DNA-PKcs was localized only at very specific regions, presumably representing the sites of DSBs within the tracks. Examination of cell survival by clonogenic assay indicated that cell killing was greater for iron ions than for silicon and oxygen ions and gamma rays. Collectively, these data demonstrate that the inability of cells to rejoin DSBs within clustered DNA lesions likely contributes to the greater biological effectiveness of HZE particles. PMID:18363429

  17. Non-random distribution of DNA double-strand breaks induced by particle irradiation

    NASA Technical Reports Server (NTRS)

    Lobrich, M.; Cooper, P. K.; Rydberg, B.; Chatterjee, A. (Principal Investigator)

    1996-01-01

    Induction of DNA double-strand breaks (dsbs) in mammalian cells is dependent on the spatial distribution of energy deposition from the ionizing radiation. For high LET particle radiations the primary ionization sites occur in a correlated manner along the track of the particles, while for X-rays these sites are much more randomly distributed throughout the volume of the cell. It can therefore be expected that the distribution of dsbs linearly along the DNA molecule also varies with the type of radiation and the ionization density. Using pulsed-field gel and conventional gel techniques, we measured the size distribution of DNA molecules from irradiated human fibroblasts in the total range of 0.1 kbp-10 Mbp for X-rays and high LET particles (N ions, 97 keV/microns and Fe ions, 150 keV/microns). On a mega base pair scale we applied conventional pulsed-field gel electrophoresis techniques such as measurement of the fraction of DNA released from the well (FAR) and measurement of breakage within a specific NotI restriction fragment (hybridization assay). The induction rate for widely spaced breaks was found to decrease with LET. However, when the entire distribution of radiation-induced fragments was analysed, we detected an excess of fragments with sizes below about 200 kbp for the particles compared with X-irradiation. X-rays are thus more effective than high LET radiations in producing large DNA fragments but less effective in the production of smaller fragments. We determined the total induction rate of dsbs for the three radiations based on a quantitative analysis of all the measured radiation-induced fragments and found that the high LET particles were more efficient than X-rays at inducing dsbs, indicating an increasing total efficiency with LET. Conventional assays that are based only on the measurement of large fragments are therefore misleading when determining total dsb induction rates of high LET particles. The possible biological significance of this non-randomness for dsb induction is discussed.

  18. Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

    PubMed Central

    2015-01-01

    Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

  19. A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury

    SciTech Connect

    Yannam, Govardhana Rao [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Han, Bing [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi (China); Setoyama, Kentaro [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamamoto, Toshiyuki [Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska (United States); Ito, Ryotaro; Brooks, Jenna M. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Guzman-Lepe, Jorge [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Galambos, Csaba [Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Fong, Jason V. [Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Deutsch, Melvin; Quader, Mubina A. [Department of Radiation Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Yamanouchi, Kosho [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kabarriti, Rafi; Mehta, Keyur [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Soto-Gutierrez, Alejandro [Department of Pathology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); and others

    2014-02-01

    Background: Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease. Methods and Materials: We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals. Results: At doses ?40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis. Conclusions: The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of venocclusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.

  20. Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases.

    PubMed

    Huang, Sarah X L; Jaurand, Marie-Claude; Kamp, David W; Whysner, John; Hei, Tom K

    2011-01-01

    The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

  1. Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

    PubMed Central

    Huang, Sarah X. L.; Jaurand, Marie-Claude; Kamp, David W.; Whysner, John; Hei, Tom K.

    2011-01-01

    The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

  2. Particle Generation by Pulsed Excimer Laser Ablation in Liquid: Hollow Structures and Laser-Induced Reactions

    NASA Astrophysics Data System (ADS)

    Yan, Zijie

    2011-12-01

    Pulsed laser ablation of solid targets in liquid media is a powerful method to fabricate micro-/nanoparticles, which has attracted much interest in the past decade. It represents a combinatorial library of constituents and interactions, and one can explore disparate regions of parameter space with outcomes that are impossible to envision a priori. In this work, a pulsed excimer laser (wavelength 248 nm, pulse width 30 ns) has been used to ablate targets in liquid media with varying laser fluences, frequencies, ablation times and surfactants. It is observed that hollow particles could be fabricated by excimer laser ablation of Al, Pt, Zn, Mg, Ag, Si, TiO2, and Nb2O5 in water or aqueous solutions. The hollow particles, with sizes from tens of nanometers to micrometers, may have smooth and continuous shells or have morphologies demonstrating that they were assembled from nanoparticles. A new mechanism has been proposed to explain the formation of these novel particle geometries. They were formed on laser-produced bubbles through bubble interface pinning by laser-produced solid species. Considering the bubble dynamics, thermodynamic and kinetic requirements have been discussed in the mechanism that can explain some phenomena associated with the formation of hollow particles, especially (1) larger particles are more likely to be hollow particles; (2) Mg and Al targets have stronger tendency to generate hollow particles; and (3) the 248 nm excimer laser is more beneficial to fabricate hollow particles in water than other lasers with longer wavelengths. The work has also demonstrated the possiblities to fabricate novel nanostructures through laser-induced reactions. Zn(OH)2/dodecyl sulfate flower-like nanostructures, AgCl cubes, and Ag2O cubes, pyramids, triangular plates, pentagonal rods and bars have been obtained via reactions between laser-produced species with water, electrolyes, or surfactant molecules. The underlying mechanisms of forming these structures have been discussed. The experimental results and the associated mechanisms developed in my research, and described in this thesis, have enriched the current understanding of particle generation by pulsed laser ablation in liquid. In so doing, my research has expanded the mechanistic routes for novel, or designer, nanoparticle geometries. Within the combinatorial and non-equilibrium environment provided by the unique experimental arrangement, the basic laws of material science still apply. Understanding and utilizing the laws will help researchers to fabricate new nanostructures by this and other methods providing similar environment.

  3. Selective removal of 10–40-nm particles from silicon wafers using laser-induced plasma shockwaves

    Microsoft Academic Search

    M. D. Murthy Peri; Vamsi K. Devarapalli; Cetin Cetinkaya

    2007-01-01

    Current and projected nanoparticle cleaning requirements, especially in semiconductor and nano-manufacturing, necessitate a technique that is not only capable of removing sub-100 nm particles, but also is damage-free and able to perform localized (selective) area cleaning of a relatively small number of particles. A particle cleaning technique based on laser-induced plasma (LIP) shockwaves has been considered and investigated in recent

  4. Correlation of light transmittance with asthma attack: fine water particles as a possible inducing factor of asthma

    Microsoft Academic Search

    Kazuo Kanaya; Koji Okamoto; Shinichiro Shimbo; Masayuki Ikeda

    2011-01-01

    Background and objectives  It has been postulated that air-borne fine water particles (or mist) can induce asthma attacks in asthmatic children. To date,\\u000a no attempt has been made to quantify the density of air-borne fine water particles with the aim of relating particle density\\u000a to the etiology of asthma among children. The aim of this study was to investigate the relation

  5. [Itai-itai disease: cadmium-induced renal tubular osteomalacia].

    PubMed

    Aoshima, Keiko

    2012-01-01

    Cadmium (Cd) is one of the most toxic elements to which humans could be exposed at work or in the environment. The outbreak of itai-itai disease, which is the most severe stage of chronic Cd poisoning, occurred in the Cd-polluted Jinzu River basin in Toyama. In this area, the river was contaminated by slag from a mine upstream; as a consequence, the soil in rice paddies was polluted with heavy metals including Cd through irrigation water from around 1910 to the 1960s. The government of Toyama prefecture carried out an extensive survey on Cd concentration in rice and soil of the paddy fields and declared that the upper layer of a total of 1500 ha of paddy fields should be replaced by nonpolluted soil. Then, an intervention program of soil replacement in the polluted paddy fields was continually carried out from 1980 to 2011. As a result, Cd concentration in rice markedly decreased. The kidney is the organ critically affected after long-term exposure to Cd. Proximal tubular dysfunction (RTD) has been found among the inhabitants of the Jinzu River basin. The very recent report by the Environmental Agency in Japan in 2009 has disclosed that b2-microglobulinuria with RTD is still found at a high prevalence among the inhabitants of the Jinzu River basin of both sexes. Twenty patients with itai-itai disease (1 male and 19 females), who attended our hospital and received medical examination during 2000 to 2008, had applied for recognition as itai-itai disease patients to the government of Toyama prefecture. In this paper, the recent epidemiological and clinical features of itai-itai disease are discussed on the basis of a review of the cases of these 19 female patients. PMID:23095355

  6. CCR2 regulates development of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed

    Bennett, Jami L; Elhofy, Adam; Charo, Israel; Miller, Stephen D; Dal Canto, Mauro C; Karpus, William J

    2007-01-01

    Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a murine model for multiple sclerosis, involves recruitment of T cells and macrophages to the CNS after infection. We hypothesized that CCR2, the only known receptor for CCL2, would be required for TMEV-induced demyelinating disease development because of its role in macrophage recruitment. TMEV-infected SJL CCR2 knockout (KO) mice showed decreased long-term clinical disease severity and less demyelination compared with controls. Flow cytometric data indicated that macrophages (CD45(high) CD11b(+) ) in the CNS of TMEV-infected CCR2 KO mice were decreased compared with control mice throughout disease. CD4(+) and CD8(+) T cell percentages in the CNS of TMEV-infected control and CCR2 KO mice were similar over the course of disease. There were no apparent differences between CCR2 KO and control peripheral immune responses. The frequency of interferon-gamma-producing T cells in response to proteolipid protein 139-151 in the CNS was also similar during the autoimmunity stage of TMEV-induced demyelinating disease. These data suggest that CCR2 is important for development of clinical disease by regulating macrophage accumulation after TMEV infection. PMID:17425418

  7. Transport of particles by a thermally induced gradient of the order parameter in nematic liquid crystals

    NASA Astrophysics Data System (ADS)

    Škarabot, M.; Lokar, Ž.; Muševi?, I.

    2013-06-01

    We demonstrate manipulation and transport of microparticles and even fluorescent molecules by the thermally induced gradient of the order parameter in the nematic liquid crystal. We use IR light absorption of the tightly focused beam of laser tweezers to heat locally a thin layer of the nematic liquid crystal by several degrees. This creates a spatial gradient of temperature of the nematic liquid crystal over separations of several tens of micrometers. We show that a dipolar colloidal particle is attracted into the hot spot of the laser tweezers. The depth of the trapping potential scales linearly with particle radius, indicating that the trapping mechanism is due to elastic self-energy of the distorted nematic liquid crystal around the particle and softening of the elasticity with increased temperature of the liquid crystal. We also demonstrate that this thermal trapping mechanism is efficient down to the nanoscale, as fluorescent molecules are also transported into hotter regions of the liquid crystal. This effect is absent in the isotropic phase, which calls into question particle transport due to the Soret effect.

  8. Quantification of nanoparticles in aqueous food matrices using Particle-Induced X-ray Emission.

    PubMed

    Lozano, Omar; Mejia, Jorge; Tabarrant, Tijani; Masereel, Bernard; Dogné, Jean-Michel; Toussaint, Olivier; Lucas, Stéphane

    2012-07-01

    Nanoparticles (NPs) of SiO(2) (15 nm) or Ag (20 - 40 nm) were dispersed in water, coffee and milk at several aqueous dilutions. The NPs dispersions concentrations were quantified with an ion beam technique: Particle-Induced X-ray Emission. Additional measurements in relation to the state of the NPs dispersions were done: particle size distribution by centrifuge liquid sedimentation and the extreme surface composition by X-ray photoelectron spectroscopy. The particle size distribution of SiO(2) and Ag NPs dispersions in water and Ag NPs in coffee remained mostly as primary particles with hydrodynamic diameters close to the reported pristine NPs diameter. SiO(2) NPs agglomerated in coffee. In milk, both NPs presented an adsorption with milk lipids. Extreme surface composition corroborated adsorption in milk and showed that SiO(2) agglomerates adsorb some coffee components. A linear tendency in the measurement of the concentration dilutions of all dispersions was measured, and a lack of media influence in the slope of each curve was found. Limits of detection with the current setup were estimated at 0.5 and 0.3 mg/ml for SiO(2) and Ag NPs, respectively. PMID:22411536

  9. Diagnosis and prevention of diseases induced by isocyanate

    Microsoft Academic Search

    Kazuko Nakashima; Tatsuya Takeshita; Kanehisa Morimoto

    2002-01-01

    Isocyanates are among the most frequent causes of occupational asthma in industrialized countries. Early diagnosis of diisocyanate\\u000a asthma followed by prompt termination of chemical exposure can prevent chronic morbidity due to persistent asthma. Chronic\\u000a exposure to isocyanates also induces hypersensitivity pneumonitis (HP). The accurate diagnosis of diisocynate asthma requires\\u000a a systematic approach that combines information obtained from the occupational history,

  10. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology

    Microsoft Academic Search

    Gregg L. Semenza

    2001-01-01

    Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to reduced oxygen availability. The HIF-1? subunit is constitutively expressed, whereas the HIF-1? subunit is subject to ubiquitination and proteasomal degradation, a process that is inhibited under hypoxic conditions. Recent data indicate that HIF-1 plays major roles in the prevention of myocardial and cerebral ischemia and

  11. Light-particle emission in reactions induced with carbon and oxygen ions

    SciTech Connect

    Plasil, F.; Beene, J.R.; Ferguson, R.L.

    1980-01-01

    Preliminary results are presented from three different experiments in which light particles emitted during the course of heavy-ion-induced reactions have been studied. The three experiments involved measurements of energies, angular correlations, and multiplicities of neutrons or alpha particles emitted in coincidence with deeply inelastic products or with evaporation residue produced as follows: (1) neutrons from reactions of /sup 16/O with /sup 93/Nb at 12.9 MeV/u; (2) alphas produced in the same system; and (3) neutrons produced in /sup 12/C reactions with /sup 158/Gd and in /sup 13/C reactions with /sup 157/Gd at about 12.4 MeV/u. (GHT)

  12. Soybean (Glycine max L. Merr.) Sprouts Germinated under Red Light Irradiation Induce Disease Resistance against Bacterial Rotting Disease

    PubMed Central

    Dhakal, Radhika; Park, Euiho; Lee, Se-Weon; Baek, Kwang-Hyun

    2015-01-01

    Specific wavelengths of light can exert various physiological changes in plants, including effects on responses to disease incidence. To determine whether specific light wavelength had effects on rotting disease caused by Pseudomonas putida 229, soybean sprouts were germinated under a narrow range of wavelengths from light emitting diodes (LEDs), including red (650–660), far red (720–730) and blue (440–450 nm) or broad range of wavelength from daylight fluorescence bulbs. The controls were composed of soybean sprouts germinated in darkness. After germination under different conditions for 5 days, the soybean sprouts were inoculated with P. putida 229 and the disease incidence was observed for 5 days. The sprouts exposed to red light showed increased resistance against P. putida 229 relative to those grown under other conditions. Soybean sprouts germinated under red light accumulated high levels of salicylic acid (SA) accompanied with up-regulation of the biosynthetic gene ICS and the pathogenesis- related (PR) gene PR-1, indicating that the resistance was induced by the action of SA via de novo synthesis of SA in the soybean sprouts by red light irradiation. Taken together, these data suggest that only the narrow range of red light can induce disease resistance in soybean sprouts, regulated by the SA-dependent pathway via the de novo synthesis of SA and up-regulation of PR genes. PMID:25679808

  13. CD28 Costimulatory Blockade Exacerbates Disease Severity and Accelerates Epitope Spreading in a Virus-Induced Autoimmune Disease

    PubMed Central

    Neville, Katherine L.; Dal Canto, Mauro C.; Bluestone, Jeffrey A.; Miller, Stephen D.

    2000-01-01

    Theiler's murine encephalomyelitis virus (TMEV) is a natural mouse pathogen which causes a lifelong persistent infection of the central nervous system (CNS) accompanied by T-cell-mediated myelin destruction leading to chronic, progressive hind limb paralysis. TMEV-induced demyelinating disease (TMEV-IDD) is considered to be a highly relevant animal model for the human autoimmune disease multiple sclerosis (MS), which is thought to be initiated as a secondary consequence of a virus infection. Although TMEV-IDD is initiated by virus-specific CD4+ T cells targeting CNS-persistent virus, CD4+ T-cell responses against self myelin protein epitopes activated via epitope spreading contribute to chronic disease pathogenesis. We thus examined the ability of antibodies directed against B7 costimulatory molecules to regulate this chronic virus-induced immunopathologic process. Contrary to previous studies showing that blockade of B7-CD28 costimulatory interactions inhibit the initiation of experimental autoimmune encephalomyelitis, treatment of SJL mice at the time of TMEV infection with murine CTLA-4 immunoglobulin or a combination of anti-B7-1 and anti-B7-2 antibodies significantly enhanced clinical disease severity. Costimulatory blockade inhibited early TMEV-specific T-cell and antibody responses critical in clearing peripheral virus infection. The inhibition of virus-specific immune responses led to significantly increased CNS viral titers resulting in increased damage to myelin-producing oligodendrocytes. Following clearance of the costimulatory antagonists, epitope spreading to myelin epitopes was accelerated as a result of the increased availability of myelin epitopes leading to a more severe chronic disease course. Our results raise concern about the potential use of B7-CD28 costimulatory blockade to treat human autoimmune diseases potentially associated with acute or persistent virus infections. PMID:10954534

  14. Analytical Applications Of Particle-Induced X-Ray Emission (PIXE)

    NASA Astrophysics Data System (ADS)

    Popescu, I. V.; Ene, A.; Stihi, C.; Bancuta, A.; Dima, G.; Badica, T.; Ghisa, V.

    2007-04-01

    In this paper a complex study of the capabilities of Particle-Induced X-ray Emission (PIXE) technique for the determination of major, minor and trace constituents of metallurgical, biological and environmental samples has been done. The elements identified in the metallurgical samples (steels) using PIXE were: K, Ca, V, Cr, Mn, Fe, Co, Cu, Ni, Zn, W, Ga, As, Pb, Mo, Rb, In, Rh, Zr, Pd, Nb, Sn and Sb. In the investigated biological and environmental samples (vegetals leaves, soil and mosses) PIXE analysis allowed determination of: S, Cl, K, Ca, Ti, Mn, Fe, Ni, Cu, Zn, As, Hg and Pb.

  15. Analysis of radiation-induced small Cu particle cluster formation in aqueous CuCl2

    USGS Publications Warehouse

    Jayanetti, S.; Mayanovic, Robert A.; Anderson, Alan J.; Bassett, William A.; Chou, I.-Ming

    2001-01-01

    Radition-induced small Cu particle cluster formation in aqueous CuCl2 was analyzed. It was noticed that nearest neighbor distance increased with the increase in the time of irradiation. This showed that the clusters approached the lattice dimension of bulk copper. As the average cluster size approached its bulk dimensions, an increase in the nearest neighbor coordination number was found with the decrease in the surface to volume ratio. Radiolysis of water by incident x-ray beam led to the reduction of copper ions in the solution to themetallic state.

  16. Particle induced X-ray emission: a valuable tool for the analysis of metalpoint drawings

    NASA Astrophysics Data System (ADS)

    Duval, A.; Guicharnaud, H.; Dran, J. C.

    2004-11-01

    For several years, we carry out a research on metalpoint drawings, a graphic technique mainly employed by European artists during the 15th and 16th centuries. As a non-destructive and very sensitive analytical technique is required, particle induced X-ray emission (PIXE) analysis with an external beam has been used for this purpose. More than 70 artworks drawn by Italian, Flemish and German artists have been analysed, including leadpoint and silverpoint drawings. Following a short description of the metalpoint technique, the results are compared with the recipes written by Cennino Cennini at the beginning of the 15th century and specific examples are presented.

  17. Ropinirole-induced Pisa syndrome in Parkinson disease.

    PubMed

    Galati, Salvatore; Möller, Jens Carsten; Städler, Claudio

    2014-01-01

    Pisa syndrome (PS), also known as pleurothotonus, is an abnormal posture characterized by lateral flexion of the trunk that typically disappears in supine position. In Parkinson disease (PD), an abnormal forward flexion of the trunk (defined as camptocormia) is a common observation and has been interpreted as a sign of dystonia. Few reports have described PS mainly related to dopaminergic therapy in this kind of patients.Levodopa/carbidopa, levodopa/benserazide, levodopa/carbidopa/entacapone, pergolide, and pramipexole may cause PS, whereas no reports for ropinirole have been described.Here, we describe a case of a patient with PD who developed severe and reversible PS due to ropinirole intake. PMID:24614668

  18. Clinical Features, Pathophysiology, and Treatment of Levodopa-Induced Dyskinesias in Parkinson's Disease

    PubMed Central

    Guridi, J.; González-Redondo, R.; Obeso, J. A.

    2012-01-01

    Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood. PMID:23125942

  19. Recombinant prion protein induces a new transmissible prion disease in wild-type animals

    Microsoft Academic Search

    Natallia Makarava; Gabor G. Kovacs; Olga Bocharova; Regina Savtchenko; Irina Alexeeva; Herbert Budka; Robert G. Rohwer; Ilia V. Baskakov

    2010-01-01

    Prion disease is a neurodegenerative malady, which is believed to be transmitted via a prion protein in its abnormal conformation\\u000a (PrPSc). Previous studies have failed to demonstrate that prion disease could be induced in wild-type animals using recombinant\\u000a prion protein (rPrP) produced in Escherichia coli. Here, we report that prion infectivity was generated in Syrian hamsters after inoculating full-length rPrP

  20. Effect of atenolol and celiprolol on acetylcholine-induced coronary vasomotion in coronary artery disease

    Microsoft Academic Search

    Wolfram Burger; Christian Hampel; Martin Kaltenbach; Andreas Hartmann; Manfred Herrmann; Josef A Hoffmann; Harald Klepzig

    2000-01-01

    Earlier studies have reported on the potentiated muscarinic vasoconstriction of intracoronary acetylcholine after metoprolol application in patients with coronary artery disease. The present study investigated the effect of celiprolol, atenolol, and placebo on acetylcholine-induced vasomotion in patients with coronary artery disease. Furthermore, direct effects on coronary vasomotion and on hemodynamics were evaluated. Acetylcholine (intracoronary concentrations of 6.3 × 10?7, 2.0

  1. Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced Aging

    PubMed Central

    Miller, Justine D.; Ganat, Yosif M.; Kishinevsky, Sarah; Bowman, Robert L.; Liu, Becky; Tu, Edmund Y.; Mandal, Pankaj; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J.; Krainc, Dimitri; Milner, Teresa A.; Rossi, Derrick J.; Studer, Lorenz

    2014-01-01

    Summary Reprogramming somatic cells to induced pluripotent stem cells (iPSCs), resets their identity back to an embryonic age, and thus presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson’s disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD-iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine-hydroxylase (TH) expression and enlarged mitochondria or Lewy body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  2. Human iPSC-based modeling of late-onset disease via progerin-induced aging.

    PubMed

    Miller, Justine D; Ganat, Yosif M; Kishinevsky, Sarah; Bowman, Robert L; Liu, Becky; Tu, Edmund Y; Mandal, Pankaj K; Vera, Elsa; Shim, Jae-won; Kriks, Sonja; Taldone, Tony; Fusaki, Noemi; Tomishima, Mark J; Krainc, Dimitri; Milner, Teresa A; Rossi, Derrick J; Studer, Lorenz

    2013-12-01

    Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets their identity back to an embryonic age and, thus, presents a significant hurdle for modeling late-onset disorders. In this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson's disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models. PMID:24315443

  3. Radioiodine-induced hypothyroidism in Graves' disease: factors associated

    SciTech Connect

    Cunnien, A.J.; Hay, I.D.; Gorman, C.A.; Offord, K.P.; Scanlon, P.W.

    1982-11-01

    A retrospective analysis was done of the records of 454 patients who received their first /sup 131/I treatment for Graves' disease during six periods covering 1951 to 1978. In the earliest group, 3% of patients were hypothyroid 3 mo after /sup 131/I use, and 40% were hypothyroid at 1 yr. In the most recent group, 36% of patients were hypothyroid at 3 mo and 91% were myxedematous at 1 yr. Although no obvious trends were noted, whether in the number of patients pretreated with thionamide drugs, in the mean 24-hr /sup 131/I uptake, or in the calculated dose of /sup 131/I (muCi/estimated gram of thyroid tissue) during the years of the study, the initial mean dose of /sup 131/I administered increased from 8.1 mCi in the earliest group to 13.8 mCi in the latest group. Concurrently, estimates of gland size increased from a mean of 26 g in the first group to 43 g in the last. If, in patients with Graves' disease, the thyroid gland size did not truly increase during the years of the study, the increasing occurrence of early hypothyroidism seen after /sup 131/I use may reflect the conscious or unconscious decision to use larger doses of /sup 131/I calculated on the basis of inflated estimates of thyroid gland weight.

  4. Chemical characterization of single micro- and nano-particles by optical catapulting-optical trapping-laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Fortes, Francisco J.; Fernández-Bravo, Angel; Javier Laserna, J.

    2014-10-01

    Spectral identification of individual micro- and nano-sized particles by the sequential intervention of optical catapulting, optical trapping and laser-induced breakdown spectroscopy is presented. The three techniques are used for different purposes. Optical catapulting (OC) serves to put the particulate material under inspection in aerosol form. Optical trapping (OT) permits the isolation and manipulation of individual particles from the aerosol, which are subsequently analyzed by laser-induced breakdown spectroscopy (LIBS). Once catapulted, the dynamics of particle trapping depends both on the laser beam characteristics (power and intensity gradient) and on the particle properties (size, mass and shape). Particles are stably trapped in air at atmospheric pressure and can be conveniently manipulated for a precise positioning for LIBS analysis. The spectra acquired from the individually trapped particles permit a straightforward identification of the material inspected. Variability of LIBS signal for the inspection of Ni microspheres was 30% relative standard deviation. OC-OT-LIBS permits the separation of particles in a heterogeneous mixture and the subsequent analysis of the isolated particle of interest. In order to evaluate the sensitivity of the approach, the number of absolute photons emitted by a single trapped particle was calculated. The limit of detection (LOD) for Al2O3 particles was calculated to be 200 attograms aluminium.

  5. The Pathogenic Role of Macrophage Migration Inhibitory Factor in Immunologically Induced Kidney Disease in the Rat

    Microsoft Academic Search

    Hui Y. Lan; Michael Bacher; Niansheng Yang; Wei Mu; David J. Nikolic-Paterson; Christine Metz; Andreas Meinhardt; Richard Bucala; Robert C. Atkins

    2010-01-01

    Summary Macrophage migration inhibitory factor (MIF) plays a pivotal role in the inflammatory response in endotoxemia and in the delayed-type hypersensitivity response, but its potential as a regula- tor of immunologically induced disease is unknown. We have addressed this issue by adminis- tering a neutralizing anti-MIF antibody in a rat model of immunologically induced crescentic anti-glomerular basement membrane (GBM) glomerulonephritis.

  6. Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model

    Microsoft Academic Search

    Anna-Liisa Brownell; Kelly Canales; Y. Iris Chen; Bruce G Jenkins; Christopher Owen; Elijahu Livni; Meixiang Yu; Francesca Cicchetti; Rosario Sanchez-Pernaute; Ole Isacson

    2003-01-01

    Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor

  7. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles

    SciTech Connect

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of)] [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Shahverdi, Ahmad Reza [Department of Pharmaceutical Biotechnology and Biotechnology Research Centre, Faculty of Pharmacy, TUMS, Tehran (Iran, Islamic Republic of)] [Department of Pharmaceutical Biotechnology and Biotechnology Research Centre, Faculty of Pharmacy, TUMS, Tehran (Iran, Islamic Republic of); Ahmadi, Abbas [Department of Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia (Iran, Islamic Republic of)] [Department of Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia (Iran, Islamic Republic of); Baeeri, Maryam; Mohammadirad, Azadeh [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of)] [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Abdollahi, Mohammad, E-mail: mohammad.abdollahi@utoronto.ca [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of)] [Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of)

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. Highlights: ? Cisplatin (CIS) affects spermatozoa as a male reproductive toxicant. ? Effect of Nano-Se on CIS-induced spermatotoxicity was investigated. ? CIS-exposure induces oxidative sperm DNA damage and impairs steroidogenesis. ? Nano-Se retained sperm quality against CIS-induced free radicals toxic stress.

  8. The KDEL receptor induces autophagy to promote the clearance of neurodegenerative disease-related proteins.

    PubMed

    Wang, P; Li, B; Zhou, L; Fei, E; Wang, G

    2011-09-01

    Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases, and the KDEL (Lys-Asp-Glu-Leu motif) receptor (KDELR) plays a key role in ER quality control and in the ER stress response. The subcellular distribution of KDELR is dynamic and related to its ligand binding status and its expression level. Here, we show that KDELR mRNA is upregulated upon thapsigargin treatment, which induces ER stress. Moreover, overexpressed KDELR partially redistributes to the lysosome and activates autophagy. The R169N mutant, a ligand binding-defective form of KDELR, and D193N, a transport-defective form of KDELR, both fail to trigger autophagy. Overexpression of KDELR activates extracellular signal-regulated kinases (ERKs). Both the activation of ERKs and autophagy induced by KDELR could be blocked by PD98059, an inhibitor of mitogen extracellular kinase 1 (MEK1). The overexpression of some neurodegenerative disease-related proteins, such as amyotrophic lateral sclerosis (ALS)-linked G93A superoxide dismutase 1 (SOD1), Parkinson's disease-associated A53T alpha-synuclein and Huntington's disease-related expanded huntingtin, increase the mRNA levels of KDELR. Moreover, the overexpressed KDELR promotes the clearance of these disease proteins through autophagy. Taken together, our data provide evidence that KDELR, as a novel inducer of autophagy, participates in the degradation of misfolded neurodegenerative disease-related proteins. PMID:21684323

  9. Fluid fragmentation shapes rain-induced foliar disease transmission.

    PubMed

    Gilet, T; Bourouiba, L

    2015-03-01

    Plant diseases represent a growing threat to the global food supply. The factors contributing to pathogen transmission from plant to plant remain poorly understood. Statistical correlations between rainfalls and plant disease outbreaks were reported; however, the detailed mechanisms linking the two were relegated to a black box. In this combined experimental and theoretical study, we focus on the impact dynamics of raindrops on infected leaves, one drop at a time. We find that the deposition range of most of the pathogen-bearing droplets is constrained by a hydrodynamical condition and we quantify the effect of leaf size and compliance on such constraint. Moreover, we identify and characterize two dominant fluid fragmentation scenarios as responsible for the dispersal of most pathogen-bearing droplets emitted from infected leaves: (i) the crescent-moon ejection is driven by the direct interaction between the impacting raindrop and the contaminated sessile drop and (ii) the inertial detachment is driven by the motion imparted to the leaf by the raindrop, leading to catapult-like droplet ejections. We find that at first, decreasing leaf size or increasing compliance reduces the range of pathogen-bearing droplets and the subsequent epidemic onset efficiency. However, this conclusion only applies for the crescent moon ejection. Above a certain compliance threshold a more effective mechanism of contaminated fluid ejection, the inertial detachment, emerges. This compliance threshold is determined by the ratio between the leaf velocity and the characteristic velocity of fluid fragmentation. The inertial detachment mechanism enhances the range of deposition of the larger contaminated droplets and suggests a change in epidemic onset pattern and a more efficient potential of infection of neighbouring plants. Dimensionless parameters and scaling laws are provided to rationalize our observations. Our results link for the first time the mechanical properties of foliage with the onset dynamics of foliar epidemics through the lens of fluid fragmentation. We discuss how the reported findings can inform the design of mitigation strategies acting at the early stage of a foliar disease outbreak. PMID:25652459

  10. Induce systemic resistance in lupine against root rot diseases.

    PubMed

    Ali, Abeer A; Ghoneem, K M; El-Metwally, M A; Abd El-Hai, K M

    2009-02-01

    Root rot caused by soil borne pathogenic fungi is the most sever disease attacks lupine plants. Isolation trials from diseased plants in some areas of Dakahlia Province (Egypt) was carried out. Rhizoctonia solani and Fusarium solani proved to be the most dominant isolates. Meanwhile, Fusarium oxysporum and Sclerotium rolfsii were less frequent. Efficacies of some plant resistance elicitors viz.: chitosan (CHI), Salicylic Acid (SA) and hydroquinone (HQ) in comparing to the fungicide Rhizolex T-50 as seed treatments showed significant reduction in the fungal growth in vitro. Chitosan at 8 g L(-1) and fungicide completely inhibited the growth of all isolated fungi, while SA at 1.4 g L(-1) and HQ at 1.2 g L(-1) inhibited the growth of Fusarium solani and F. oxysporum, respectively. The greenhouse experiments showed that S. rolfesii (No. 6) and R. solani (No. 2) followed by F. solani (No. 5) and F. oxysporum (No. 9) were the most aggressive root rot fungi. Soaking susceptible lupine seeds (Giza 1) in each one of the three selected elicitors showed a significant reduction in seedlings mortality. CHI at 8 g L(-1) was superior in increasing the percentage of healthy plants to record 72.5, 80.9, 62.7and 64.3%, when seeds were grown in soil infested with of F. solani, F. oxysporum, R. solani and S. rolfesii, respectively. These results were confirmed under field conditions in two different locations i.e., Tag El-Ezz and El-Serow Research Stations. CHI 8 g L(-1) proved to be the best elicitor after fungicide, in reducing lupine root rot disease. It showed 41 and 60% reduction in the plants mortality comparing to 56.37 and 69.13% in case of Rhizolex-T in Tag El-Ezz and El-Serow locations, respectively. The treatments were accompanied with a significant increase in lupine growth parameters, yield components and physiological aspects. Application of CHI at 8 g L(-1) or HQ at 1.2 g L(-1) was the most potent in this respect as compared to check treatment. PMID:19579949

  11. Preliminary Investigation of the Relationship Between Bovine Congenital Lathyrism Induced by Aminoacetonitrile and the Lupine Induced Crooked Calf Disease

    PubMed Central

    Keeler, R. F.; Binns, W.; James, L. F.; Shupe, J. L.

    1969-01-01

    Maternal feeding of the lathyrogen aminoacetonitrile, the range plant Lupinus caudatus, and an extract of this plant — expected to contain lathyrogens if present in the plant — all produced clinically similar congenital defects in calves. The defects included excessive flexure, malpositioning, malalignment and rotation of the front limbs. The results suggest a possible relationship between lathyrism and lupine-induced crooked calf disease. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6. PMID:4238569

  12. Interaction of the human cytomegalovirus particle with the host cell induces hypoxia-inducible factor 1 alpha

    SciTech Connect

    McFarlane, Steven; Nicholl, Mary Jane; Sutherland, Jane S.; Preston, Chris M., E-mail: Christopher.preston@glasgow.ac.u

    2011-05-25

    The cellular protein hypoxia-inducible factor 1 alpha (HIF-1{alpha}) was induced after infection of human fibroblasts with human cytomegalovirus (HCMV). HCMV irradiated with ultraviolet light (uv-HCMV) also elicited the effect, demonstrating that the response was provoked by interaction of the infecting virion with the cell and that viral gene expression was not required. Although induction of HIF-1{alpha} was initiated by an early event, accumulation of the protein was not detected until 9 hours post infection, with levels increasing thereafter. Infection with uv-HCMV resulted in increased abundance of HIF-1{alpha}-specific RNA, indicating stimulation of transcription. In addition, greater phosphorylation of the protein kinase Akt was observed, and the activity of this enzyme was required for induction of HIF-1{alpha} to occur. HIF-1{alpha} controls the expression of many cellular gene products; therefore the findings reveal new ways in which interaction of the HCMV particle with the host cell may cause significant alterations to cellular physiology.

  13. Resistance to mineralocorticoid-induced hypertensive vascular disease.

    PubMed

    Sciotti, V; Gallant, S

    1987-08-01

    To support our contention that the Wistar-Furth rat is resistant to mineralocorticoid hypertension, we assessed the effects of deoxycorticosterone (DOC) administration or renal artery stenosis on the development of hypertension in the Sprague-Dawley and Wistar-Furth rat strains. Weekly administration of mineralocorticoid in the form of DOC pivalate resulted in rapid, severe hypertensive cardiovascular disease in Sprague-Dawley rats. Within 5 weeks the mean conscious systolic blood pressures in steroid-treated and control rats were 186 +/- 4 and 118 +/- 5 mm Hg, respectively. In contrast, blood pressures of Wistar-Furth rats were only moderately elevated, even after 10 weeks of DOC pivalate administration (136 +/- 2 vs 116 +/- 2 mm Hg for controls). Furthermore, none of the steroid-treated Wistar-Furth animals exhibited cardiovascular lesions. In parallel studies, littermates of these rat strains were subjected to renal artery stenosis and blood pressures were determined weekly in conscious rats. Silver clip constriction of the left renal artery, in the presence of the contralateral kidney, resulted in a rapid, sustained elevation of blood pressure in both Sprague-Dawley and Wistar-Furth rat strains (177 +/- 4 and 176 +/- 5 mm Hg, respectively). Corticosteroid levels were also determined in DOC-treated Sprague-Dawley and Wistar-Furth rats. The regimen employed resulted in a 10-fold increase in DOC levels as compared with controls, and the levels achieved were comparable in both strains. Thus, the Wistar-Furth rat appears to be selectively resistant to mineralocorticoid hypertensive vascular disease and thus affords a model for studying mechanisms of steroid hypertension. PMID:3610293

  14. Excess copper chelating therapy for Wilson disease induces anemia and liver dysfunction.

    PubMed

    Harada, Masaru; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Shibata, Michihiko; Matsuhashi, Toru; Abe, Shintaro; Harada, Riko; Tabaru, Akinari

    2011-01-01

    A 37-year-old man was diagnosed with Wilson disease at the age of 14. His first manifestations were neurological. He was treated with trientine for more than 10 years and suffered from anemia and liver dysfunction. Wilson disease is a genetic disorder characterized by accumulation of copper in the body. Excess copper is toxic, but copper is an essential trace element. Copper-binding ceruloplasmin is important for iron metabolism. Excess copper chelating treatment-induced anemia and iron deposition in the liver was suspected. Proper monitoring of copper status is important for the management of Wilson disease. PMID:21757830

  15. HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Kanazawa, N.; Lutze-Mann, L.; Winegar, R.

    2001-01-01

    Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.

  16. Plant Virus Particles Carrying Tumour Antigen Activate TLR7 and Induce High Levels of Protective Antibody

    PubMed Central

    Jobsri, Jantipa; Allen, Alex; Rajagopal, Deepa; Shipton, Michael; Kanyuka, Kostya; Lomonossoff, George P.; Ottensmeier, Christian; Diebold, Sandra S.; Stevenson, Freda K.; Savelyeva, Natalia

    2015-01-01

    Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the “gold standard” Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe “in-built” ssRNA adjuvant. PMID:25692288

  17. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

    PubMed Central

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan ET; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-01-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet?/? Rag2?/? mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  18. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission.

    PubMed

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan E T; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-07-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet(-/-) Rag2(-/-) mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  19. Angular distribution in two-particle emission induced by neutrinos and electrons

    E-print Network

    I. Ruiz Simo; C. Albertus; J. E. Amaro; M. B. Barbaro; J. A. Caballero; T. W. Donnelly

    2014-10-15

    The angular distribution of the phase space arising in two-particle emission reactions induced by electrons and neutrinos is computed in the laboratory (Lab) system by boosting the isotropic distribution in the center of mass (CM) system used in Monte Carlo generators. The Lab distribution has a singularity for some angular values, coming from the Jacobian of the angular transformation between CM and Lab systems. We recover the formula we obtained in a previous calculation for the Lab angular distribution. This is in accordance with the Monte Carlo method used to generate two-particle events for neutrino scattering\\cite{Sob12}. Inversely, by performing the transformation to the CM system, it can be shown that the phase-space function, which is proportional to the two particle-two hole (2p-2h) hadronic tensor for a constant current operator, can be computed analytically in the frozen nucleon approximation, if Pauli blocking is absent. The results in the CM frame confirm our previous work done using an alternative approach in the Lab frame. The possibilities of using this method to compute the hadronic tensor by a boost to the CM system are analyzed.

  20. The effect of flow geometry on shear-induced particle segregation and resuspension

    NASA Astrophysics Data System (ADS)

    Ramachandran, Arun

    2007-05-01

    In this thesis, we investigate through theory and experiment the influence of the flow geometry on various shear-induced migration phenomena such as particle demixing, viscous resuspension and meniscus accumulation for a suspension of rigid, non-colloidal particles. The major focus of this thesis is the elucidation of a particle flux mechanism that has been ignored in the literature in the theoretical calculation of the concentration distribution in shear-induced migration phenomena. This mechanism is the convective flux due to the secondary currents arising from the non-Newtonian rheology of suspensions. Historically, suspensions have been modeled as Newtonian fluids with concentration dependent viscosities when calculating velocity distributions due to the tremendous simplification of the governing equations. The results presented in this thesis, however, demonstrate that it is critical to consider the complete rheology of a concentrated suspension when modeling flows in complex geometries. While the magnitude of the secondary currents is small, in many cases they are the dominant mechanism governing the resulting particle concentration distribution. In chapters 2 through 4, we investigate the impact of these secondary currents on the concentration profiles developed in suspension flow through conduits of arbitrary geometry, and in resuspension flow through a tube. In chapter 5, we examine the radial segregation of particles in the squeeze flow of concentrated suspensions. This flow is identical to that produced in loading suspensions on to a parallel plate viscometer and thus the concentration inhomogeneities generated during the loading phenomenon may play a role in the well known scatter of torque measurements in this system. We develop a criterion in terms of the experimental parameters in a parallel plate experiment for the onset of radial inhomogeneities. In the final investigation reported in this thesis, we develop a theoretical model for describing the droplet distribution in the Poiseuille flow of an emulsion through a tube. We show that the mathematical problem that results from this model is amenable to self-similar analysis via the trial function approach. The self-similar solution so obtained is used to evaluate oscillatory flows as a possible technique for separation of the dispersed phase from suspending fluid.

  1. NELL1 promotes bone regeneration in polyethylene particle-induced osteolysis.

    PubMed

    Guo, Xu; Peng, Jiang; Wang, Yu; Wang, Aiyuan; Zhang, Xinli; Yuan, Mei; Zhang, Li; Zhao, Bin; Liu, Bin; Fan, Meng; Xue, Jing; Guo, Quanyi; Xu, Wenjing; Lu, Qiang; Ting, Kang; Lu, Shibi

    2012-07-01

    We investigated the therapeutic effects of a craniosynostosis-associated molecule, NEL-like molecule-1 (NELL1; NEL [a protein strongly expressed in neural tissue encoding the epidermal growth factor-like domain]), on osteolysis induced by polyethylene (PE)-particle debris. We used a murine calvarial osteolysis model with in vivo adenovirus (Ad)-mediated gene transfer. In total, 76 female Balb/c mice were randomly assigned to four groups for treatment 1 day postoperation: SHAM (injected with 0.1?mL saline without implantation of particles); PE control (injected with 0.1?mL saline after implantation of particles); PE+(Ad-GFP-NELL1) (injected with 0.1?mL Ad-GFP-NELL1 in saline after implantation of particles); and PE+(Ad-GFP) group (injected with 0.1?mL Ad-GFP in saline after implantation of particles). Green fluorescent protein (GFP) and NELL1 delivery in vivo after the injection were validated by optical imaging at 10 day postop, and then, all mice were sacrificed for analysis by three-dimensional (3D) microcomputed tomography (micro-CT), real-time polymerase chain reaction (PCR), histology, and biomechanical testing. Exogenous NELL1 and GFP were expressed in the osteolysis area for at least 9 days after the Ad-GFP-NELL1 injection. Serial 3D micro-CT images and testing of bone volume, bone mineral density, trabecular thickness, bone surface density, and connectivity density revealed that the new bone promoted with the Ad-GFP-NELL1 injection could almost compensate the PE-induced osteolysis and regenerate significantly better than with the Ad-GFP treatment. The expression of osteopontin (OPN) was significantly higher with Ad-GFP-NELL1 transduction among all the samples. Real-time PCR examination confirmed the augmented expression of OPN, Runx-2, and receptor activator of nuclear factor-kappa B ligand (RANKL). The elastic modulus was significantly greater with Ad-GFP-NELL1 than with the PE and/or Ad-GFP group (p<0.01). We found no transgene-associated toxic effects. Ad-GFP-NELL1 gene transfer effectively reversed the calvarial osteolysis and could be considered a new treatment for osteolysis through promoting bone regeneration. PMID:22404332

  2. Understanding the mechanisms of sickle cell disease by simulations with a discrete particle model

    NASA Astrophysics Data System (ADS)

    Hui, Katrina; Lin, Guang; Pan, Wenxiao

    2013-01-01

    Sickle cell disease (SCD) is an inherited blood disorder characterized by rigid, sickle-shaped red blood cells (RBCs). Because of their rigidity and shape, sickle cells can get stuck in smaller blood vessels, causing blockages and depriving oxygen to tissues. This study develops and applies mathematical models to better understand the mechanism of SCD. Two-dimensional models of RBCs and blood vessels have been constructed by representing them as discrete particles interacting with different forces. The nonlinear, elastic property of healthy RBCs could be adequately reproduced using a cosine angle bending force and a worm-like chain spring force. With the ability to deform, RBCs can squeeze through narrow blood vessels. In modeling sickle cells as rigid bodies and applying repelling and friction forces from the blood vessel, this study shows that geometrical factors (dimensions of the sickle cell and blood vessels) as well as rigidity and adhesiveness of the sickle cell all play an important role in determining how, and if, sickle cells become trapped within narrow blood capillaries. With lack of data to validate the model, this study primarily provides a sensitivity analysis of factors influencing sickle cell occlusion and identified critical data to support future modeling.

  3. Establishment of Induced Pluripotent Stem Cells from Centenarians for Neurodegenerative Disease Research

    PubMed Central

    Yagi, Takuya; Kosakai, Arifumi; Ito, Daisuke; Okada, Yohei; Akamatsu, Wado; Nihei, Yoshihiro; Nabetani, Akira; Ishikawa, Fuyuki; Arai, Yasumichi; Hirose, Nobuyoshi; Okano, Hideyuki; Suzuki, Norihiro

    2012-01-01

    Induced pluripotent stem cell (iPSC) technology can be used to model human disorders, create cell-based models of human diseases, including neurodegenerative diseases, and in establishing therapeutic strategies. To detect subtle cellular abnormalities associated with common late-onset disease in iPSCs, valid control iPSCs derived from healthy donors free of serious late-onset diseases are necessary. Here, we report the generation of iPSCs from fibroblasts obtained immediately postmortem from centenarian donors (106- and 109-years-old) who were extremely healthy until an advanced age. The iPSCs were generated using a conventional method involving OCT4, SOX2, KLF4, and c-MYC, and then differentiated into neuronal cells using a neurosphere method. The expression of molecules that play critical roles in late-onset neurodegenerative diseases by neurons differentiated from the centenarian-iPSCs was compared to that of neurons differentiated from iPSCs derived from familial Alzheimer's disease and familial Parkinson's disease (PARK4: triplication of the ? synuclein gene) patients. The results indicated that our series of iPSCs would be useful in neurodegeneration research. The iPSCs we describe, which were derived from donors with exceptional longevity who were presumed to have no serious disease risk factors, would be useful in longevity research and as valid super-controls for use in studies of various late-onset diseases. PMID:22848530

  4. Luteolin reduces Alzheimer's disease pathologies induced by traumatic brain injury.

    PubMed

    Sawmiller, Darrell; Li, Song; Shahaduzzaman, Md; Smith, Adam J; Obregon, Demian; Giunta, Brian; Borlongan, Cesar V; Sanberg, Paul R; Tan, Jun

    2014-01-01

    Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer's disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (A?) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in A? depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI. PMID:24413756

  5. Fructose induced endotoxemia in pediatric nonalcoholic Fatty liver disease.

    PubMed

    Jin, Ran; Willment, Andrew; Patel, Shivani S; Sun, Xiaoyan; Song, Ming; Mannery, Yanci O; Kosters, Astrid; McClain, Craig J; Vos, Miriam B

    2014-01-01

    In preclinical studies of fructose-induced NAFLD, endotoxin appears to play an important role. We retrospectively examined samples from three pediatric cohorts (1) to investigate whether endotoxemia is associated with the presence of hepatic steatosis; (2) to evaluate postprandial endotoxin levels in response to fructose beverage in an acute 24-hour feeding challenge, and (3) to determine the change of fasting endotoxin amounts in a 4-week randomized controlled trial comparing fructose to glucose beverages in NAFLD. We found that adolescents with hepatic steatosis had elevated endotoxin levels compared to obese controls and that the endotoxin level correlated with insulin resistance and several inflammatory cytokines. In a 24-hour feeding study, endotoxin levels in NAFLD adolescents increased after fructose beverages (consumed with meals) as compared to healthy children. Similarly, endotoxin was significantly increased after adolescents consumed fructose beverages for 2 weeks and remained high although not significantly at 4 weeks. In conclusion, these data provide support for the concept of low level endotoxemia contributing to pediatric NAFLD and the possible role of fructose in this process. Further studies are needed to determine if manipulation of the microbiome or other methods of endotoxin reduction would be useful as a therapy for pediatric NAFLD. PMID:25328713

  6. Appraisal of experimental and commercial Marek's disease vaccines to induce bursal and thymic atrophy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently, several experimental Marek’s disease (MD) vaccines were developed that appear to protect equally or better than the best commercial vaccines. However, some of the experimental vaccines were reported to induce transient bursal and thymic atrophies. We will report on two promising experiment...

  7. Gene disruption of caspace-3 prevents MPTP-induced Parkinson's disease in mice

    PubMed Central

    Yamada, Marina; Kida, Kotaro; Amutuhaire, Willington; Ichinose, Fumito; Kaneki, Masao

    2010-01-01

    The development of Parkinson's disease is accompanied by concurrent activation of caspase-3 and apoptosis of dopaminergic neurons of human patients and rodent models. The role of caspase-3, a final executioner of apoptosis, in the pathogenesis of Parkinson's disease, however, remains to be determined. Here, we show that gene disruption of caspase-3 protects mice from 1-methyle-4-phenyl-1,2,3,6-tetrahmydropyridine (MPTP)-induced Parkinsonian syndrome, as reflected by reversal of MPTP-induced bradykinesia and decreased tyrosine hydroxylase expression in the nigra-striatum. MPTP treatment resulted in increased caspase-3 activation and apoptosis in the substantia nigra of wild-type mice at 24 h after the inception of MPTP treatment, as compared with vehicle-treated control animals. Gene disruption of caspase-3 prevented MPTP-induced apoptosis in the substantia nigra. At 7 days after MPTP treatment, tyrosine hydroxylase expression was suppressed and infiltration of activated microglia and astrocytes was markedly increased in the nigra-striatum of wild-type mice. All of these alterations following MPTP treatment were blocked by disruption of caspase-3 in mice. These results clearly indicate that caspase-3 activation is required for the development of MPTP-induced Parkinson's disease in mice. These findings suggest that activation of caspase-3-mediated apoptosis of dopaminergic neurons in the early stage may play an important role in the pathogenesis of Parkinson's disease. PMID:20937256

  8. Gynura root induces hepatic veno-occlusive disease: A case report and review of the literature

    Microsoft Academic Search

    Ning Dai; Ying-Cong Yu; Tian-Hua Ren; Jia-Guo Wu; Yuan Jiang; Lai-Gen Shen; Jing Zhang

    Gynura root has been used extensively in Chinese folk medicine and plays a role in promoting microcirculation and relieving pain. However, its hepatic toxicity should not be neglected. Recently, we admitted a 62-year old female who developed hepatic veno-occlusive disease (HVOD) after ingestion of Gynura root. Only a few articles on HVOD induced by Gynura root have been reported in

  9. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we ...

  10. Neurobiology of Disease Cisplatin-Induced Hair Cell Death Requires STAT1 and Is

    E-print Network

    Rubel, Edwin

    primarily affects the hearing of high frequencies and corresponds to loss of mechanosensory hair cellsNeurobiology of Disease Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated that frequently causes auditory impairment due to the death of mechanosensory hair cells. Cisplatin ototoxicity

  11. New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

    PubMed Central

    2014-01-01

    Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also? in vivo??in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer. PMID:24868470

  12. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO AIRWAY DISEASE INDUCED BY SULFUR DIOXIDE

    EPA Science Inventory

    Rodent models of chronic pulmonary diseases induced by sulfur dioxide (SO2), elastase or tobacco smoke have limited utility because of their lack of chronicity of inflammation, and they demonstrate limited sensitivity to a given experimental manipulation. We hypothesized that dis...

  13. EFFECTS OF SYSTEMIC NEUTROPHIL DEPLETION ON LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    Effects of Systemic Neutrophil Depletion on LPS-induced Airway Disease Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, David A. Schwartz Pulmonary and Critical Care Division, Dept of Medicine ? Duke University Medical Center * National Health and E...

  14. NEUTROPHILS PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF LPS-INDUCED AIRWAY DISEASE

    EPA Science Inventory

    ETD-02-045 (GAVETT) GPRA # 10108 Neutrophils Play a Critical Role in the Development of LPS-Induced Airway Disease. Jordan D. Savov, Stephen H. Gavett*, David M. Brass, Daniel L. Costa*, and David A. Schwartz ABSTRACT We investigated the role of neutrophils...

  15. AN EPIZOOTIC OF ADENOVIRUS-INDUCED HEMORRHAGIC DISEASE IN CAPTIVE BLACK-TAILED DEER (ODOCOILEUS HEMIONUS)

    Microsoft Academic Search

    Walter M. Boyce; Leslie W. Woods; M. Kevin Keel; N. James MacLachlan; Charles O. Porter; Howard D. Lehmkuhl

    Ten fawns and four adult black-tailed deer (Odocoileus hemionus) in a captive herd died as a result of adenovirus-induced hemorrhagic disease. Acute, systemic infections were characterized by hemorrhagic enteropathy, pulmonary edema, and occasional ulceration of the upper alimentary tract. Localized infections were limited to the upper alimentary tract and included stomatitis, pharyngitis, mandibular osteomyelitis, and rumenitis. In deer with acute,

  16. Virus-induced modulation of lower airway diseases: pathogenesis and pharmacologic approaches to treatment.

    PubMed

    Leigh, Richard; Proud, David

    2015-04-01

    Uncomplicated upper respiratory viral infections are the most common cause of days lost from work and school and exert a major economic burden. In susceptible individuals, however, common respiratory viruses, particularly human rhinoviruses, also can have a major impact on diseases that involve the lower airways, including asthma, chronic obstructive pulmonary diseases (COPD) and cystic fibrosis (CF). Respiratory virus-induced wheezing illnesses in early life are a significant risk factor for the subsequent development of asthma, and virus infections may also play a role in the development and progression of airway remodeling in asthma. It is clear that upper respiratory tract virus infections can spread to the lower airway and trigger acute attacks of asthma, COPD or CF. These exacerbations can be life-threatening, and exert an enormous burden on health care systems. In recent years we have gained new insights into the mechanisms by which respiratory viruses may induce acute exacerbations of lower airway diseases, as well as into host defense pathways that may regulate the outcomes to viral infections. In the current article we review the role of viruses in lower airway diseases, including our current understanding on pathways by which they may cause remodeling and trigger acute exacerbations. We also review the efficacy of current and emerging therapies used to treat these lower airway diseases on the outcomes due to viral infection, and discuss alternative therapeutic approaches for the management of virus-induced airway inflammation. PMID:25550230

  17. Macromolecular prodrug of dexamethasone prevents particle-induced peri-implant osteolysis with reduced systemic side effects

    PubMed Central

    Ren, Ke; Dusad, Anand; Yuan, Fang; Yuan, Hongjiang; Purdue, P. Edward; Fehringer, Edward V.; Garvin, Kevin L.; Goldring, Steven R.; Wang, Dong

    2014-01-01

    Aseptic implant loosening related to implant wear particle-induced inflammation is the most common cause of failure after joint replacement. Modulation of the inflammatory reaction to the wear products represents a rational approach for preventing aseptic implant failure. Long-term treatment using anti-inflammatory agents, however, can be associated with significant systemic side effects due to the drugs' lack of tissue specificity. To address this issue, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) was developed and evaluated for prevention of wear particle-induced osteolysis and the loss of fixation in a murine prosthesis failure model. Daily administration of free dexamethasone (Dex) was able to prevent wear particle-induced osteolysis, as assessed by micro-CT and histological analysis. Remarkably, monthly P-Dex administration (dose equivalent to free Dex treatment) was equally effective as free dexamethasone, but was not associated with systemic bone loss (a major adverse side effect of glucocorticoids). The reduced systemic toxicity of P-Dex is related to preferential targeting of the sites of wear particle-induced inflammation and its subcellular sequestration and retention by local inflammatory cell populations, resulting in sustained therapeutic action. These results demonstrate the feasibility of utilizing a macromolecular prodrug with reduced systemic toxicity to prevent wear particle-induced osteolysis. PMID:24326124

  18. The severity of alpha-particle-induced DNA damage is revealed by exposure to cell-free extracts

    SciTech Connect

    Hodgkins, P.S.; O`Neill, P.; Stevens, D.; Fairman, M.P. [Medical Research Council, Oxfordshire (United Kingdom)

    1996-12-01

    The rejoining of single-strand breaks induced by {alpha}-particle and {gamma} irradiation in plasmid DNA under two scavenging conditions has been compared. At the two scavenger conditions has been compared. At the two scavenger capacities used of 1.5 {times} 10{sup 7} and 3 {times} 10{sup 8}s{sup {minus}1} using Tris-HCl as the scavenger, the ratio of single- to double-strand breaks for {alpha} particles is fivefold less than the corresponding ratios for {gamma} irradiation. The repair of such radiation-induced single-strand breaks has been examined using a cell-free system derived from human whole-cell extracts. We show that the rejoining of single-strand breaks for both {alpha}-particle- and {gamma}-irradiated plasmid is dependent upon the scavenging capacity and that the efficiency of rejoining of {alpha}-particle-induced single-strand breaks is significantly less than that observed for {gamma}-ray-induced breaks. In addition, for DNA that had been irradiated under conditions that mimic the cellular environment with respect to the radical scavenging capacity, 50 of {alpha}-particle-induced single-strand breaks are converted to double-strand breaks, in contrast with only {approximately}12% conversion of {gamma}-ray-induced single-strand breaks, indicating that the initial damage caused by {alpha} particles is more severe. These studies provide experimental evidence for increased clustering of damage which may have important implications for the induction of cancer by low-level {alpha}-particle sources such as domestic radon. 37 refs., 5 figs., 1 tab.

  19. A new mechanism for DNA alterations induced by alpha particles such as those emitted by radon and radon progeny.

    PubMed Central

    Lehnert, B E; Goodwin, E H

    1997-01-01

    The mechanism(s) by which alpha (alpha) particles like those emitted from inhaled radon and radon progeny cause their carcinogenic effects in the lung remains unclear. Although direct nuclear traversals by alpha-particles may be involved in mediating these outcomes, increasing evidence indicates that a particles can cause alterations in DNA in the absence of direct hits to cell nuclei. Using the occurrence of excessive sister chromatid exchanges (SCE) as an index of DNA damage in human lung fibroblasts, we investigated the hypothesis that alpha-particles may induce DNA damage through the generation of extracellular factors. We have found that a relatively low dose of alpha-particles can result in the generation of extracellular factors, which, upon transfer to unexposed normal human cells, can cause excessive SCE to an extent equivalent to that observed when the cells are directly irradiated with the same irradiation dose. A short-lived, SCE-inducing factor(s) is generated in alpha-irradiated culture medium containing serum in the absence of cells. A more persistent SCE-inducing factor(s), which can survive freeze-thaw and is heat labile is produced by fibroblasts after exposure to the alpha-particles. These results indicate that the initiating target for alpha-particle-induced genetic changes can be larger than a cell's nucleus or even a whole cell. How transmissible factors like those observed here in vitro may extend to the in vivo condition in the context of a-particle-induced carcinogenesis in the respiratory tract remains to be determined. PMID:9400706

  20. Management of a pregnant patient with Graves' disease complicated by propylthiouracil induced agranulocytosis.

    PubMed

    Cho, Yoon-Young; Shon, Ho Sang; Yoon, Hyun Dae

    2005-12-01

    Relapse and exacerbation of Graves' disease during pregnancy is rare, and thionamide induced agranulocytosis is an uncommon side effect. We report a case of a pregnant woman in her 24th week of gestation that experienced a relapse of Graves' disease that was complicated by propylthiouracil induced agranulocytosis. Following the discontinuation of propylthiouracil and administration of a broad-spectrum of antibiotics, agranulocytosis subsided within 10 days. A total thyroidectomy to avoid any future relapse was planned and a short course of a beta-adrenergic blocker and Lugol solution were prescribed before the operation. At the 28th week of gestation, a total thyroidectomy was performed without complications and thyroxine replacement therapy was commenced. At the 40th week of gestation, labor was induced and a 3,370 g healthy male infant was born without clinical features of thyrotoxicosis. We report herein on the patient and the treatment options for this rare and complicated case. PMID:16491833

  1. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    PubMed

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-01

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. PMID:25437537

  2. Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

    PubMed Central

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Torres, Larissa Helena Lobo; Durão, Ana Carolina Cardoso Santos; Shimada, Ana Lucia Borges; Almeida, Francine Maria; Hebeda, Cristina Bichels; Lopes, Fernanda Degobbi Tenorio Quirino Santos; Dolhnikoff, Marisa; Martins, Milton Arruda; Silva, Luiz Fernando Ferraz; Farsky, Sandra Helena Poliselli; Saldiva, Paulo Hilário Nascimento; Ulrich, Cornelia M.; Owen, Robert W.; Marcourakis, Tania; Trevisan, Maria Teresa Salles; Mauad, Thais

    2013-01-01

    Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50??g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250?mg/kg of anacardic acids or vehicle (100??L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50?mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs. PMID:23533495

  3. FE2O3 PARTICLE-INDUCED PROSTAGLANDIN E2 (PGE2) SYNTHESIS IN ALVEOLAR MACROPHAGES (AM) DETERMINES PARTICULATE INFLAMMATORY POTENTIAL

    EPA Science Inventory

    As shown by epidemiologic studies, acute exposure to ambient particles is associated with exacerbation of pulmonary and cardiovascular diseases. Metals associated with particles are able to mediate lung injury via oxidant-catalyzed reactions. However, the underlying mechanism i...

  4. Linking genetic susceptibility and T cell activation in beryllium-induced disease.

    PubMed

    Falta, Michael T; Bowerman, Natalie A; Dai, Shaodong; Kappler, John W; Fontenot, Andrew P

    2010-05-01

    Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium (Be) exposure in the workplace. It is characterized by the accumulation of Be-specific CD4(+) T cells in the lung as well as persistent lung inflammation, culminating in the development of lung fibrosis. CBD occurs in 2 to 16% of Be-exposed workers depending on the individuals' genetic susceptibility and the characteristics of the exposure. Genetic susceptibility to Be-induced disease has been linked to major histocompatibility complex class II molecules. In particular, HLA-DP alleles possessing a glutamic acid at the 69th position of the beta-chain (betaGlu69) are most strongly linked to disease susceptibility. The HLA-DP alleles that present Be to T cells match those implicated in the genetic susceptibility, suggesting that the HLA contribution to disease is based on the ability of those molecules to bind and present Be to T cells. However, the structural features of betaGlu69-containing HLA-DP molecules that explain the disease association remain unknown. We have recently crystallized HLA-DP2, which is the most prevalent of the betaGlu69-containing HLA-DP molecules. Its unique structure, which includes surface exposure of betaGlu69, provides an explanation of the genetic linkage between betaGlu69-containing HLA-DP alleles and Be-induced disease. PMID:20427584

  5. Linking Genetic Susceptibility and T Cell Activation in Beryllium-induced Disease

    PubMed Central

    Falta, Michael T.; Bowerman, Natalie A.; Dai, Shaodong; Kappler, John W.; Fontenot, Andrew P.

    2010-01-01

    Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium (Be) exposure in the workplace. It is characterized by the accumulation of Be-specific CD4+ T cells in the lung as well as persistent lung inflammation, culminating in the development of lung fibrosis. CBD occurs in 2 to 16% of Be-exposed workers depending on the individuals' genetic susceptibility and the characteristics of the exposure. Genetic susceptibility to Be-induced disease has been linked to major histocompatibility complex class II molecules. In particular, HLA-DP alleles possessing a glutamic acid at the 69th position of the ?-chain (?Glu69) are most strongly linked to disease susceptibility. The HLA-DP alleles that present Be to T cells match those implicated in the genetic susceptibility, suggesting that the HLA contribution to disease is based on the ability of those molecules to bind and present Be to T cells. However, the structural features of ?Glu69-containing HLA-DP molecules that explain the disease association remain unknown. We have recently crystallized HLA-DP2, which is the most prevalent of the ?Glu69-containing HLA-DP molecules. Its unique structure, which includes surface exposure of ?Glu69, provides an explanation of the genetic linkage between ?Glu69-containing HLA-DP alleles and Be-induced disease. PMID:20427584

  6. Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

    PubMed Central

    Nemmar, Abderrahim; Subramaniyan, Deepa; Ali, Badreldin H.

    2012-01-01

    Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15µg/animal) every 2nd day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor ? (TNF ?) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF ? concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF ? in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF ?, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNF? release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNF? and protects against the pulmonary and cardiovascular effects of DEP. PMID:22745783

  7. A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents

    PubMed Central

    Randhawa, Puneet Kaur; Singh, Kavinder; Singh, Nirmal

    2014-01-01

    Ulcerative colitis and Crohn's disease are a set of chronic, idiopathic, immunological and relapsing inflammatory disorders of the gastrointestinal tract referred to as inflammatory bowel disorder (IBD). Although the etiological factors involved in the perpetuation of IBD remain uncertain, development of various animal models provides new insights to unveil the onset and the progression of IBD. Various chemical-induced colitis models are widely used on laboratory scale. Furthermore, these models closely mimic morphological, histopathological and symptomatical features of human IBD. Among the chemical-induced colitis models, trinitrobenzene sulfonic acid (TNBS)-induced colitis, oxazolone induced-colitis and dextran sulphate sodium (DSS)-induced colitis models are most widely used. TNBS elicits Th-1 driven immune response, whereas oxazolone predominantly exhibits immune response of Th-2 phenotype. DSS-induced colitis model also induces changes in Th-1/Th-2 cytokine profile. The present review discusses the methodology and rationale of using various chemical-induced colitis models for evaluating the pathogenesis of IBD. PMID:25177159

  8. Alpha-particle-induced charge collection in p-n junction diodes in semi-insulating GaAs substrates

    Microsoft Academic Search

    Yasunari Umemoto; Osamu Kagaya; Yukihiro Kawata

    1991-01-01

    The bias and angle dependences of the alpha-particle-induced charge collected by GaAs p-n junction diodes are investigated. These diodes, in which the n-layer overlays the p-layer, are fabricated in a semi-insulating GaAs substrate by Si and Mg ion implantation. 241 Am placed in a vacuum is used as an alpha-particle source with an initial energy of 4.03 MeV and a

  9. Bubbling behavior of a fluidized bed of fine particles caused by vibration-induced air inflow

    PubMed Central

    Matsusaka, Shuji; Kobayakawa, Murino; Mizutani, Megumi; Imran, Mohd; Yasuda, Masatoshi

    2013-01-01

    We demonstrate that a vibration-induced air inflow can cause vigorous bubbling in a bed of fine particles and report the mechanism by which this phenomenon occurs. When convective flow occurs in a powder bed as a result of vibrations, the upper powder layer with a high void ratio moves downward and is compressed. This process forces the air in the powder layer out, which leads to the formation of bubbles that rise and eventually burst at the top surface of the powder bed. A negative pressure is created below the rising bubbles. A narrow opening at the bottom allows the outside air to flow into the powder bed, which produces a vigorously bubbling fluidized bed that does not require the use of an external air supply system. PMID:23378921

  10. Water-soluble core/shell nanoparticles for proton therapy through particle-induced radiation

    NASA Astrophysics Data System (ADS)

    Park, Jeong Chan; Jung, Myung-Hwan; Kim, Maeng Jun; Kim, Kye-Ryung

    2015-02-01

    Metallic nanoparticles have been used in biomedical applications such as magnetic resonance imaging (MRI), therapy, and drug delivery systems. Metallic nanoparticles as therapeutic tools have been demonstrated using radio-frequency magnetic fields or near-infrared light. Recently, therapeutic applications of metallic nanomaterials combined with proton beams have been reported. Particle-induced radiation from metallic nanoparticles, which can enhance the therapeutic effects of proton therapy, was released when the nanoparticles were bombarded by a high-energy proton beam. Core/shell nanoparticles, especially Au-coated magnetic nanoparticles, have drawn attention in biological applications due to their attractive characteristics. However, studies on the phase transfer of organic-ligand-based core/shell nanoparticles into water are limited. Herein, we demonstrated that hydrophobic core/shell structured nanomaterials could be successfully dispersed in water through chloroform/surfactant mixtures. The effects of the core/shell nanomaterials and the proton irradiation on Escherichia coli (E. coli) were also explored.

  11. Excitation function of (3)He-particle induced nuclear reactions on natural palladium.

    PubMed

    Al-Abyad, M; Tárkányi, F; Ditrói, F; Takács, S

    2014-12-01

    Excitation functions of (3)He-particle induced nuclear reactions on natural palladium were measured using the standard stacked foil technique and high resolution ?-ray spectroscopy. From their threshold energies up to 27MeV, cross-sections for (nat)Pd((3)He,x)(103,104,105,106m,110m,111,112)Ag and (nat)Pd((3)He,x)(104,105,107,111m)Cd reactions were measured. The nuclear model codes TALYS-1.4, and EMPIRE-3.1 were used to describe the formation of these products. The present data were compared to theoretical results and to the available experimental data. Integral yields for some important radioisotopes were determined. PMID:25218461

  12. Lidar remote sensing of laser-induced incandescence on light absorbing particles in the atmosphere.

    PubMed

    Miffre, Alain; Anselmo, Christophe; Geffroy, Sylvain; Fréjafon, Emeric; Rairoux, Patrick

    2015-02-01

    Carbon aerosol is now recognized as a major uncertainty on climate change and public health, and specific instruments are required to address the time and space evolution of this aerosol, which efficiently absorbs light. In this paper, we report an experiment, based on coupling lidar remote sensing with Laser-Induced-Incandescence (LII), which allows, in agreement with Planck's law, to retrieve the vertical profile of very low thermal radiation emitted by light-absorbing particles in an urban atmosphere over several hundred meters altitude. Accordingly, we set the LII-lidar formalism and equation and addressed the main features of LII-lidar in the atmosphere by numerically simulating the LII-lidar signal. We believe atmospheric LII-lidar to be a promising tool for radiative transfer, especially when combined with elastic backscattering lidar, as it may then allow a remote partitioning between strong/less light absorbing carbon aerosols. PMID:25836102

  13. The merits of particle induced X-ray emission in revealing painting techniques

    NASA Astrophysics Data System (ADS)

    Neelmeijer, C.; Mäder, M.

    2002-04-01

    Particle induced X-ray emission (PIXE) at the external proton beam has proved ideal to study individual techniques of creating art objects. In particular, PIXE is suitable for examining paintings because of the low level of background produced by organic components like binders and paper backings. Thus, traces of pigments as deposited from pens on cardboard can be identified by this method. The combination of PIXE with external Rutherford backscattering spectrometry (RBS) allows non-destructive characterisation of near surface and thin film arrangements of paint materials. Thicker but less complex layers of oil paintings can be identified by special procedures of depth-resolved PIXE investigation. In this case, RBS provides additional information on organic coverings like madder lake or varnishes.

  14. Chronic kidney disease worsens sepsis and sepsis-induced acute kidney injury by releasing High Mobility Group Box Protein1

    Microsoft Academic Search

    Asada Leelahavanichkul; Yuning Huang; Xuzhen Hu; Hua Zhou; Takayuki Tsuji; Richard Chen; Jeffrey B Kopp; Jürgen Schnermann; Peter S T Yuen; Robert A Star

    2011-01-01

    We have shown that folate-induced kidney dysfunction and interstitial fibrosis predisposes mice to sepsis mortality. Agents that increase survival in normal septic mice were ineffective in a two-stage kidney disease model. Here we used the 5\\/6 nephrectomy mouse model of progressive chronic kidney disease (CKD) to study how CKD affects acute kidney injury (AKI) induced by sepsis. We induced sepsis

  15. Periodontal Disease and Bisphosphonates Induce Osteonecrosis of the Jaws in the Rat

    PubMed Central

    Aghaloo, Tara L; Kang, Ben; Sung, Eric C; Shoff, Michael; Ronconi, Matthew; Gotcher, Jack E; Bezouglaia, Olga; Dry, Sarah M; Tetradis, Sotirios

    2012-01-01

    Bisphosphonates (BPs) are medications used commonly to treat primary and metastatic bone cancer, as well as osteoporosis. Although BPs improve bone mineral density, reduce fracture risk, and reduce hypercalcemia of malignancy, some patients develop BP-related osteonecrosis of the jaws (BRONJ). This devastating complication is defined as clinically exposed bone in the maxillofacial region for more than 8 weeks. Despite an increasing number of BRONJ cases since first reported, the disease pathophysiology remains largely unknown. Since published studies suggest a significant role for dental disease in the pathophysiology of BRONJ, we developed a BRONJ animal model where aggressive periodontal disease is induced by ligature placement around the crown of the right maxillary first molar in the presence of vehicle (veh) or zoledronic acid (ZA), a potent BP. Ligature placement induced significant alveolar bone loss, which was attenuated by ZA treatment. Osteonecrosis was observed associated with ligature-induced periodontitis in the ZA-treated group. This was seen as sequestration and extensive periosteal alveolar bone formation on micro–computed tomography (?CT) in the ligated site of BP-treated animals. Histologic examination confirmed these findings, seen as necrotic bone with diffuse loss of osteocytes and empty lacunae, rimming of the necrotic bone by squamous epithelium and inflammation, and exposure to the oral cavity. Importantly, the rat lesions were strikingly similar to those of BRONJ patients. Our data suggest that dental disease and potent BP therapy are sufficient for BRONJ development in the rat. PMID:21351151

  16. Reply to Comment on ‘Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect’

    NASA Astrophysics Data System (ADS)

    Kim, Jong-Ki

    2012-02-01

    Upon receiving a comment (Le Sech et al 2012 Nanotechnology 23 078001) on the mechanism in therapeutic effects of proton-irradiation on a tumor model given metallic nanoparticles (MNP), potential dose enhancements due to particle induced radiation (PIR) from MNP including x-ray and Auger electrons were explained, and newly termed as particle induced radiation therapy (PIRT). All other biological or chemical modulation including enhanced ROS due to PIR are also subject to further investigation. In addition, new works in this field since our original paper (Kim et al 2010 Nanotechnology 21 425102) was published were briefly introduced.

  17. SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease

    PubMed Central

    2014-01-01

    Background Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, and increasing evidence demonstrates significant neuronal damage also occurs and is associated with permanent functional impairment. Current MS therapies have limited ability to prevent neuronal damage, suggesting additional neuroprotective therapies are needed. Compounds that activate the NAD+-dependent SIRT1 deacetylase prevent neuronal loss in an autoimmune-mediated MS model, but the mechanism of this effect is unknown, and it is unclear whether SIRT1 activating compounds exert similar effects in demyelinating disease induced by other etiologies. We measured neuronal loss in C57BL/6 mice inoculated with a neurotropic strain of mouse hepatitis virus, MHV-A59, that induces an MS-like disease. Results Oral treatment with the SIRT1 activating compound SRTAW04 significantly increased SIRT1 activity within optic nerves and prevented neuronal loss during optic neuritis, an inflammatory demyelinating optic nerve lesion that occurs in MS and its animal models. MHV-A59 induced neuronal loss was associated with reactive oxygen species (ROS) accumulation, and SRTAW04 treatment significantly reduced ROS levels while promoting increased expression of enzymes involved in mitochondrial function and reduction of ROS. SRTAW04 exerted similar protective effects in EAE spinal cords, with decreased demyelination. Conclusions Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease. One mechanism of this neuroprotective effect involves increasing mitochondrial biogenesis with reduction of oxidative stress. SIRT1 activators represent a potential neuroprotective therapy for MS. Understanding common mechanisms of these effects in distinct disease models will help identify targets for more specific therapies. PMID:24383546

  18. Staphylococcus ?-toxin promotes mouse allergic skin disease by inducing mast cell degranulation

    PubMed Central

    Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15 to 30% of children and ~5% of adults in industrialized countries1. Although the pathogenesis of AD is not fully understood, the disease is mediated by an abnormal immunoglobulin E (IgE) immune response in the setting of skin barrier dysfunction2. Mast cells (MCs) contribute to IgE-mediated allergic disorders including AD3. Upon activation, MCs release their membrane-bound cytosolic granules leading to the release of multiple molecules that are important in the pathogenesis of AD and host defense4. More than 90% of AD patients are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbor the pathogen5. Several Staphylococcal exotoxins (SEs) can act as superantigens and/or antigens in models of AD6. However, the role of these SEs in disease pathogenesis remains unclear. Here, we report that culture supernatants of S. aureus contain potent MC degranulation activity. Biochemical analysis identified ?-toxin as the MC degranulation-inducing factor produced by S. aureus. MC degranulation induced by ?-toxin depended on phosphoinositide 3-kinase (PI3K) and calcium (Ca2+) influx, but unlike that mediated by IgE crosslinking, it did not require the spleen tyrosine kinase (Syk). In addition, IgE enhanced ?-toxin-induced MC degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from AD patients produced high levels of ?-toxin. Importantly, skin colonization with S. aureus, but not a mutant deficient in ?-toxin, promoted IgE and IL-4 production, as well as inflammatory skin disease. Furthermore, enhancement of IgE production and dermatitis by ?-toxin was abrogated in KitW-sh/W-sh MC-deficient mice and restored by MC reconstitution. These studies identify ?-toxin as a potent inducer of MC degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease. PMID:24172897

  19. Spatial learning and memory deficits induced by exposure to iron-56-particle radiation

    NASA Technical Reports Server (NTRS)

    Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.

    2000-01-01

    It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  20. Review of heavy-ion induced desorption studies for particle accelerators

    NASA Astrophysics Data System (ADS)

    Mahner, Edgar

    2008-10-01

    During high-intensity heavy-ion operation of several particle accelerators worldwide, large dynamic pressure rises of orders of magnitude were caused by lost beam ions that impacted under grazing angle onto the vacuum chamber walls. This ion-induced desorption, observed, for example, at CERN, GSI, and BNL, can seriously limit the ion intensity, luminosity, and beam lifetime of the accelerator. For the heavy-ion program at CERN’s Large Hadron Collider collisions between beams of fully stripped lead (Pb82+208) ions with a beam energy of 2.76TeV/u and a nominal luminosity of 1027cm-2s-1 are foreseen. The GSI future project FAIR (Facility for Antiproton and Ion Research) aims at a beam intensity of 1012 uranium (U28+238) ions per second to be extracted from the synchrotron SIS18. Over the past years an experimental effort has been made to study the observed dynamic vacuum degradations, which are important to understand and overcome for present and future particle accelerators. The paper reviews the results obtained in several laboratories using dedicated test setups, the mitigation techniques found, and their implementation in accelerators.

  1. Spatial learning and memory deficits induced by exposure to iron-56-particle radiation.

    PubMed

    Shukitt-Hale, B; Casadesus, G; McEwen, J J; Rabin, B M; Joseph, J A

    2000-07-01

    It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. PMID:10856962

  2. Mechanism of vibration-induced repulsion force on a particle in a viscous fluid cell.

    PubMed

    Saadatmand, Mehrrad; Kawaji, Masahiro

    2013-08-01

    Space platforms such as the Space Shuttle and International Space Station have been considered an ideal environment for production of protein and semiconductor crystals of superior quality due to the negligible gravity-induced convection. Although it was believed that under microgravity environment diffusive mass transport would dominate the growth of the crystals, some related experiments have not shown satisfactory results possibly due to the movement of the growing crystals in fluid cells caused by small vibrations present in the space platforms called g-jitter. In ground-based experiments, there have been clear observations of attraction and repulsion of a solid particle with respect to a nearby wall of the fluid cell due to small vibrations. The present work is a numerical investigation on the physical mechanisms responsible for the repulsion force, which has been predicted to increase with the cell vibration frequency and amplitude, as well as the fluid viscosity. Moreover, the simulations have revealed that the repulsion force occurs mostly due to the increased pressure in the narrow gap between the particle and the nearest wall. PMID:24032936

  3. Modeling particle-induced electron emission in a simplified plasma Test Cell

    SciTech Connect

    Giuliano, Paul N.; Boyd, Iain D. [Department of Aerospace Engineering, University of Michigan, Ann Arbor, Michigan 48109 (United States)

    2013-03-21

    Particle-induced electron emission (PIE) is modeled in a simplified, well-characterized plasma Test Cell operated at UCLA. In order for PIE to be a useful model in this environment, its governing equations are first reduced to lower-order models which can be implemented in a direct simulation Monte Carlo and Particle-in-Cell framework. These reduced-order models are described in full and presented as semi-empirical models. The models are implemented to analyze the interaction of low- and high-energy ({approx}1-2 keV) xenon ions and atoms with the stainless steel electrodes of the Test Cell in order to gain insight into the emission and transport of secondary electrons. Furthermore, there is a lack of data for xenon-stainless steel atom- and ion-surface interactions for similar environments. Using experimental data as a reference, both total yields and emitted electron energy distribution functions can be deduced by observing sensitivities of current collection results to these numerical models and their parameters.

  4. Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pincha)

    NASA Astrophysics Data System (ADS)

    Lin, L.; Anderson, J. K.; Brower, D. L.; Capecchi, W.; Ding, W. X.; Eilerman, S.; Forest, C. B.; Koliner, J. J.; Liu, D.; Nornberg, M. D.; Reusch, J.; Sarff, J. S.

    2014-05-01

    Multiple bursty energetic-particle (EP) driven modes with fishbone-like structure are observed during 1 MW tangential neutral-beam injection in a reversed field pinch (RFP) device. The distinguishing features of the RFP, including large magnetic shear (tending to add stability) and weak toroidal magnetic field (leading to stronger drive), provide a complementary environment to tokamak and stellarator configurations for exploring basic understanding of EP instabilities. Detailed measurements of the EP mode characteristics and temporal-spatial dynamics reveal their influence on fast ion transport. Density fluctuations exhibit a dynamically evolving, inboard-outboard asymmetric spatial structure that peaks in the core where fast ions reside. The measured mode frequencies are close to the computed shear Alfvén frequency, a feature consistent with continuum modes destabilized by strong drive. The frequency pattern of the dominant mode depends on the fast-ion species. Multiple frequencies occur with deuterium fast ions compared to single frequency for hydrogen fast ions. Furthermore, as the safety factor (q) decreases, the toroidal mode number of the dominant EP mode transits from n =5 to n =6 while retaining the same poloidal mode number m =1. The transition occurs when the m =1, n =5 wave-particle resonance condition cannot be satisfied as the fast-ion safety factor (qfi) decreases. The fast-ion temporal dynamics, measured by a neutral particle analyzer, resemble a classical predator-prey relaxation oscillation. It contains a slow-growth phase arising from the beam fueling followed by a rapid drop when the EP modes peak, indicating that the fluctuation-induced transport maintains a stiff fast-ion density profile. The inferred transport rate is strongly enhanced with the onset of multiple EP modes.

  5. Salt-induced reentrant stability of polyion-decorated particles with tunable surface charge density

    E-print Network

    Simona Sennato; Laura Carlini; Domenico Truzzolillo; Federico Bordi

    2015-03-10

    The electrostatic complexation between DOTAP-DOPC unilamellar liposomes and an oppositely charged polyelectrolyte (NaPA) has been investigated in a wide range of the liposome surface charge density. We systematically characterized the "reentrant condensation" and the charge inversion of polyelectrolyte-decorated liposomes by means of dynamic light scattering and electrophoresis. We explored the stability of this model polyelectrolyte/colloid system by fixing each time the charge of the bare liposomes and by changing two independent control parameters of the suspensions: the polyelectrolyte/colloid charge ratio and the ionic strength of the aqueous suspending medium. The progressive addition of neutral DOPC lipid within the liposome membrane gave rise to a new intriguing phenomenon: the stability diagram of the suspensions showed a novel reentrance due to the crossing of the desorption threshold of the polyelectrolyte. Indeed, at fixed charge density of the bare DOTAP/DOPC liposomes and for a wide range of polyion concentrations, we showed that the simple electrolyte addition first (low salt regime) destabilizes the suspensions because of the enhanced screening of the residual repulsion between the complexes, and then (high salt regime) determines the onset of a new stable phase, originated by the absence of polyelectrolyte adsorption on the particle surfaces. We show that the observed phenomenology can be rationalized within the Velegol-Thwar model for heterogeneously charged particles and that the polyelectrolyte desorption fits well the predictions of the adsorption theory of Winkler and Cherstvy. Our findings unambiguously support the picture of the reentrant condensation as driven by the correlated adsorption of the polyelectrolyte chains on the particle surface, providing interesting insights into possible mechanisms for tailoring complex colloids via salt-induced effects.

  6. Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pinch

    SciTech Connect

    Lin, L.; Brower, D. L.; Ding, W. X. [Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, California 90095 (United States)] [Department of Physics and Astronomy, University of California Los Angeles, Los Angeles, California 90095 (United States); Anderson, J. K.; Capecchi, W.; Eilerman, S.; Forest, C. B.; Koliner, J. J.; Nornberg, M. D.; Reusch, J.; Sarff, J. S. [Department of Physics, University of Wisconsin–Madison, Madison, Wisconsin 53706 (United States)] [Department of Physics, University of Wisconsin–Madison, Madison, Wisconsin 53706 (United States); Liu, D. [Department of Physics and Astronomy, University of California Irvine, Irvine, California 92697 (United States)] [Department of Physics and Astronomy, University of California Irvine, Irvine, California 92697 (United States)

    2014-05-15

    Multiple bursty energetic-particle (EP) driven modes with fishbone-like structure are observed during 1?MW tangential neutral-beam injection in a reversed field pinch (RFP) device. The distinguishing features of the RFP, including large magnetic shear (tending to add stability) and weak toroidal magnetic field (leading to stronger drive), provide a complementary environment to tokamak and stellarator configurations for exploring basic understanding of EP instabilities. Detailed measurements of the EP mode characteristics and temporal-spatial dynamics reveal their influence on fast ion transport. Density fluctuations exhibit a dynamically evolving, inboard-outboard asymmetric spatial structure that peaks in the core where fast ions reside. The measured mode frequencies are close to the computed shear Alfvén frequency, a feature consistent with continuum modes destabilized by strong drive. The frequency pattern of the dominant mode depends on the fast-ion species. Multiple frequencies occur with deuterium fast ions compared to single frequency for hydrogen fast ions. Furthermore, as the safety factor (q) decreases, the toroidal mode number of the dominant EP mode transits from n=5 to n=6 while retaining the same poloidal mode number m=1. The transition occurs when the m=1, n=5 wave-particle resonance condition cannot be satisfied as the fast-ion safety factor (q{sub fi}) decreases. The fast-ion temporal dynamics, measured by a neutral particle analyzer, resemble a classical predator-prey relaxation oscillation. It contains a slow-growth phase arising from the beam fueling followed by a rapid drop when the EP modes peak, indicating that the fluctuation-induced transport maintains a stiff fast-ion density profile. The inferred transport rate is strongly enhanced with the onset of multiple EP modes.

  7. Continuum- and particle-based modeling of shapes and dynamics of red blood cells in health and disease.

    PubMed

    Li, Xuejin; Vlahovska, Petia M; Karniadakis, George Em

    2013-01-01

    We review recent advances in multiscale modeling of the mechanics of healthy and diseased red blood cells (RBCs), and blood flow in the microcirculation. We cover the traditional continuum-based methods but also particle-based methods used to model both the RBCs and the blood plasma. We highlight examples of successful simulations of blood flow including malaria and sickle cell anemia. PMID:23230450

  8. Role of Serotoninergic Pathways in Drug-induced Valvular Heart Disease and Diagnostic Features by Echocardiography

    PubMed Central

    Smith, Sakima A.; Waggoner, Alan D.; de las Fuentes, Lisa; Davila-Roman, Victor G.

    2013-01-01

    Serotonin plays a significant role in the development of carcinoid heart disease, which primarily leads to fibrosis and contraction of right-sided heart valves. Recently, strong evidence has emerged that the use of specific drug classes such as ergot alkaloids (for migraine headaches), 5-hydroxytryptamine (5-HT or serotonin) uptake regulators/inhibitors (for weight reduction), and ergot-derived dopamine agonists (for Parkinson’s disease) can result in left-sided heart valve damage that resembles carcinoid heart disease. Recent studies suggest that both right- and left-sided drug-induced heart valve disease involves increased serotoninergic activity and in particular activation of the 5-HT receptors, including the 5-HT2B receptor subtype, which mediate many of the central and peripheral functions of serotonin. G-proteins that inhibit adenylate cyclase activity mediate the activity of the 5-HT2B receptor subunit which is widely expressed in a variety of tissues including liver, lung, heart, and coronary and pulmonary arteries; and it has also been reported in embryonic mouse heart, particularly on mouse heart valve leaflets. In this review we discuss the salient features of serotoninergic manifestations of both carcinoid heart disease and drug-induced cardiac valvulopathy with an emphasis on echocardiographic diagnosis. PMID:19553085

  9. FINE AMBIENT AIR PARTICULAR MATTER EXPOSURE INDUCES MOLECULAR ALTERATIONS INDICATIVE OF CARDIOVASCULAR DISEASE PROGRESSION IN ATHEROSCLEROTIC SUSCEPTIBLE MICE

    EPA Science Inventory

    Epidemiological, clinical, and toxicological studies have demonstrated that exposure to ambient air particulate matter (PM) can alter cardiovascular function and may influence cardiovascular disease (CVD). It has been shown that exposure to concentrated ambient air particles (CA...

  10. Methotrexate-induced Hodgkin disease in a patient with systemic lupus erythematosus.

    PubMed

    Sliesoraitis, Sarunas; Khan, Rizwan; Rothman, Jan

    2009-06-01

    Methotrexate sodium use in the management of various immunologic disorders has increased--as have the number of reported adverse effects associated with this therapy. While methotrexate has helped combat various autoimmune and cancerous disorders, the paradoxical risk of causing an often fatal malignancy may still occur as a result of the drug's effect on suppressing immune function. We present a case of methotrexate-induced Hodgkin disease in a 48-year-old man with a history of systemic lupus erythematosus (SLE). Discontinuation of methotrexate facilitated Hodgkin disease reversal. In addition, we review other lymphoproliferative hematologic malignancies caused by methotrexate. PMID:19556391

  11. Cholesteryl ester transfer protein, low density lipoprotein particle size and intima media thickness in patients with coronary heart disease

    PubMed Central

    Tosheska, Katerina; Labudovic, Danica; Jovanova, Silvana; Jaglikovski, Branko; Alabakovska, Sonja

    2011-01-01

    Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport and high density lipoprotein (HDL) metabolism. Predominance of small, dense LDL particles is associated with an increased risk of atherosclerosis and coronary heart disease (CHD). The aim of the study was to determine the potential relationship between the CETP concentration and low density lipoprotein (LDL) particle size and their association with intima media thickness (IMT) in patients with CHD. Lipid parameters, CETP concentration and LDL particle size were determined in 100 healthy subjects (control group) and in 100 patients with CHD, aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses were separated by nondenaturing polyacrilamide 3-31% gradient gel electrophoresis. CETP concentration was higher in patients compared to controls (2.02 ± 0.75 mg/ml vs. 1.74 ± 0.63 mg/ml, p<0.01). Mean LDL particle size (nm) was significantly smaller in patients than in controls (24.5 ± 1.1 vs. 26.1 ± 0.9; p<0.001). There was no relation between LDL particle size and CETP concentration (r=-0.1807, p=0.072). Age, diastolic blood pressure, CETP concentration and LDL particle size were independent factors for determing IMT by multiple linear regression analysis. They accounted for 35.2 % of the observed variability in IMT. CETP is not an independent contributor of LDL particle size. CETP might play a role in determining lipoprotein distributions, but did not seem to be the sole factor in the formation of small LDL particles. PMID:21875419

  12. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles.

    PubMed

    Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali; Shahverdi, Ahmad Reza; Ahmadi, Abbas; Baeeri, Maryam; Mohammadirad, Azadeh; Abdollahi, Mohammad

    2013-02-01

    Cisplatin (CIS), an anticancer alkylating agent, induces DNA adducts and effectively cross links the DNA strands and so affects spermatozoa as a male reproductive toxicant. The present study investigated the cellular/biochemical mechanisms underlying possible protective effect of selenium nano-particles (Nano-Se) as an established strong antioxidant with more bioavailability and less toxicity, on reproductive toxicity of CIS by assessment of sperm characteristics, sperm DNA integrity, chromatin quality and spermatogenic disorders. To determine the role of oxidative stress (OS) in the pathogenesis of CIS gonadotoxicity, the level of lipid peroxidation (LPO), antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and peroxynitrite (ONOO) as a marker of nitrosative stress (NS) and testosterone (T) concentration as a biomarker of testicular function were measured in the blood and testes. Thirty-two male Wistar rats were equally divided into four groups. A single IP dose of CIS (7 mg/kg) and protective dose of Nano-Se (2 mg/kg/day) were administered alone or in combination. The CIS-exposed rats showed a significant increase in testicular and serum LPO and ONOO level, along with a significant decrease in enzymatic antioxidants levels, diminished serum T concentration and abnormal histologic findings with impaired sperm quality associated with increased DNA damage and decreased chromatin quality. Coadministration of Nano-Se significantly improved the serum T, sperm quality, and spermatogenesis and reduced CIS-induced free radical toxic stress and spermatic DNA damage. In conclusion, the current study demonstrated that Nano-Se may be useful to prevent CIS-induced gonadotoxicity through its antioxidant potential. PMID:23260366

  13. Concentrated ambient ultrafine particle exposure induces cardiac change in young healthy volunteers

    EPA Science Inventory

    Exposure to ambient ultrafine particles has been associated with cardiopulmonary toxicity and mortality. Adverse effects specifically linked to ultrafine particles include loss of sympathovagal balance and altered hemostasis. To characterize the effects of ultrafine particles in ...

  14. Intracellular influx of calcium induced by quartz particles in alveolar macrophages

    SciTech Connect

    Feng Tian [State Key Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871 (China); Tong Zhu, E-mail: tzhu@pku.edu.c [State Key Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871 (China); Yu Shang [State Key Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871 (China)

    2010-01-15

    Historical studies report that cellular injury and silicosis are related to cytosolic free calcium (Ca{sup 2+}). Moreover, reactive oxygen species (ROS) have been linked to cellular injury. However, the detail mechanism of the increase in [Ca{sup 2+}]{sub i} and the relationship between [Ca{sup 2+}]{sub i} and ROS production remains unknown. Quartz particle has been found to increase [Ca{sup 2+}]{sub i} and activate the generation of ROS. Our hypothesis is that [Ca{sup 2+}]{sub i} increase induced by quartz particle is from extracellular Ca{sup 2+} through the Ca{sup 2+} channel, and [Ca{sup 2+}]{sub i} increase is believed to activate ROS production. In order to examine this hypothesis, we treated rat alveolar macrophages with quartz (SiO{sub 2}) particles and used laser scanning confocal microscopy to measure [Ca{sup 2+}]{sub i} and the fluorescence intensity of ROS. Time- and dose-dependent increases in [Ca{sup 2+}]{sub I} and ROS in macrophages as well as cell viability were observed. Through chelating extracellular Ca{sup 2+} with ethylene glycol tetraacetic acid and releasing intracellular Ca{sup 2+} with thapsigargin, we found that 72.7% of the [Ca{sup 2+}]{sub i} increase was due to the influx of Ca{sup 2+} from the extracellular environment, via Ca{sup 2+} channels in the plasma membrane. By adding mannitol to scavenge hydroxyl radicals (OH.), and removing surface iron from the quartz particles to reduce OH. generation, we observed a reduced level of ROS generation, whereas the increase in [Ca{sup 2+}]{sub i} was unaffected. When using EGTA to reduce [Ca{sup 2+}]{sub i}, we observed a decrease in ROS production. This study suggests that the [Ca{sup 2+}]{sub i} influx was independent of OH. production, and the [Ca{sup 2+}]{sub i} increase resulted in ROS production. These results further indicate that there is a strong relationship between cytosolic free Ca{sup 2+} content and cellular injury as well as silica exposure.

  15. Large animal induced pluripotent stem cells as pre-clinical models for studying human disease.

    PubMed

    Plews, Jordan R; Gu, Mingxia; Longaker, Michael T; Wu, Joseph C

    2012-06-01

    The path to induced pluripotency Discovery of a pan-species pluripotency network Animal iPSCs and disease modelling Issues with large animal iPSCs Conclusions The derivation of human embryonic stem cells and subsequently human induced pluripotent stem cells (iPSCs) has energized regenerative medicine research and enabled seemingly limitless applications. Although small animal models, such as mouse models, have played an important role in the progression of the field, typically, they are poor representations of the human disease phenotype. As an alternative, large animal models should be explored as a potentially better approach for clinical translation of cellular therapies. However, only fragmented information regarding the derivation, characterization and clinical usefulness of pluripotent large animal cells is currently available. Here, we briefly review the latest advances regarding the derivation and use of large animal iPSCs. PMID:22212700

  16. Susceptibility of inflamed ariway and alveolar epithelial cells to injury induced by diesel exhaust particles of varying organic carbon content

    EPA Science Inventory

    Exposure to traffic-related ambient air pollution, such as diesel exhaust particles (DEP), is associated with adverse health outcomes, especially in individuals with preexisting inflammatory respiratory diseases. Using an analogous in vitro system to model both the healthy and a...

  17. Disease modeling using human induced pluripotent stem cells: Lessons from the liver?

    PubMed Central

    Gieseck, Richard L.; Colquhoun, Jennifer; Hannan, Nicholas R.F.

    2014-01-01

    Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. PMID:24943800

  18. Disease modeling using human induced pluripotent stem cells: lessons from the liver.

    PubMed

    Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

    2015-01-01

    Human pluripotent stem cells (hPSCs) have the capacity to differentiate into any of the hundreds of distinct cell types that comprise the human body. This unique characteristic has resulted in considerable interest in the field of regenerative medicine, given the potential for these cells to be used to protect, repair, or replace diseased, injured, and aged cells within the human body. In addition to their potential in therapeutics, hPSCs can be used to study the earliest stages of human development and to provide a platform for both drug screening and disease modeling using human cells. Recently, the description of human induced pluripotent stem cells (hIPSCs) has allowed the field of disease modeling to become far more accessible and physiologically relevant, as pluripotent cells can be generated from patients of any genetic background. Disease models derived from hIPSCs that manifest cellular disease phenotypes have been established to study several monogenic diseases; furthermore, hIPSCs can be used for phenotype-based drug screens to investigate complex diseases for which the underlying genetic mechanism is unknown. As a result, the use of stem cells as research tools has seen an unprecedented growth within the last decade as researchers look for in vitro disease models which closely mimic in vivo responses in humans. Here, we discuss the beginnings of hPSCs, starting with isolation of human embryonic stem cells, moving into the development and optimization of hIPSC technology, and ending with the application of hIPSCs towards disease modeling and drug screening applications, with specific examples highlighting the modeling of inherited metabolic disorders of the liver. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. PMID:24943800

  19. Newcastle disease virus-like particles as a platform for the development of vaccines for human and agricultural pathogens

    PubMed Central

    Morrison, Trudy G

    2011-01-01

    Vaccination is the single most effective way to control viral diseases. However, many currently used vaccines have safety concerns, efficacy issues or production problems. For other viral pathogens, classic approaches to vaccine development have, thus far, been unsuccessful. Virus-like particles (VLPs) are increasingly being considered as vaccine candidates because they offer significant advantages over many currently used vaccines or developing vaccine technologies. VLPs formed with structural proteins of Newcastle disease virus, an avian paramyxovirus, are a potential vaccine candidate for Newcastle disease in poultry. More importantly, these VLPs are a novel, uniquely versatile VLP platform for the rapid construction of effective vaccine candidates for many human pathogens, including genetically complex viruses and viruses for which no vaccines currently exist. PMID:21339837

  20. Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

    Microsoft Academic Search

    Brooke T Mossman; Paul J Borm; Vincent Castranova; Daniel L Costa; Kenneth Donaldson; Steven R Kleeberger

    2007-01-01

    BACKGROUND: A symposium on the mechanisms of action of inhaled airborne particulate matter (PM), pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental Protection Agency (EPA) Conference Center in Research Triangle Park, North Carolina. The

  1. MECHANISMS OF ACTION OF INHALED FIBERS, PARTICLES AND NANOPARTICLES IN LUNG AND CARDIOVASCULAR DISEASES

    EPA Science Inventory

    ABSTRACT: A symposium on the mechanisms of action of inhaled airborne particulate matter (PM),pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, ...

  2. Elevation of Serum Thioredoxin in Patients with Gefitinib-induced Interstitial Lung Disease

    Microsoft Academic Search

    Keiichiro Sakuma; Hajime Nakamura; Takayuki Nakamura; Yuma Hoshino; Shugo Ueda; Masataka Ichikawa; Chiharu Tabata; Shiro Fujita; Katsuhiro Masago; Junji Yodoi; Michiaki Mishima; Tadashi Mio

    2007-01-01

    Objective Interstitial lung disease (ILD) is a severe adverse event of gefitinib therapy. However, the mecha- nism still remains unclear. The objective of this study was to examine whether or not oxidative stress, one of the common factors in drug-associated ILD, is involved in the pathogenesis of gefitinib-induced ILD. Patients and Methods Using an enzyme-linked immunosorbent assay (ELISA), we measured

  3. Identification of antigenic proteins associated with trichloroethylene-induced autoimmune disease by serological proteome analysis

    SciTech Connect

    Liu Jianjun; Xing Xiumei; Huang Haiyan; Jiang Yingzhi; He Haowei; Xu Xinyun; Yuan Jianhui; Zhou Li; Yang Linqing [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 21, Rd 1st Tianbei, 518020 Shenzhen (China); Zhuang Zhixiong, E-mail: bio-research@hotmail.co [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, No. 21, Rd 1st Tianbei, 518020 Shenzhen (China)

    2009-11-01

    Although many studies indicated that trichloroethylene (TCE) could induce autoimmune diseases and some protein adducts were detected, the proteins were not identified and mechanisms remain unknown. To screen and identify autoantigens which might be involved in TCE-induced autoimmune diseases, three groups of sera were collected from healthy donors (I), patients suffering from TCE-induced exfoliative dermatitis (ED) (II), and the healed ones (III). Serological proteome analysis (SERPA) was performed with total proteins of TCE-treated L-02 liver cells as antigen sources and immunoglobins of the above sera as probes. Highly immunogenic spots (2-fold or above increase compared with group I) in group II and III were submitted to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing. Western blot analysis was followed using commercial antibodies and individual serum. Six proteins were identified. Among them, Enoyl Coenzyme A hydratase peroxisoma 1 and lactate dehydrogenase B only showed stronger immunogenicity for group II sera, while Purine nucleoside phosphorylase, ribosomal protein P0 and proteasome activator subunit1 isoform1 also showed stronger immunogenicity for group III sera. Noteworthy, NM23 reacted only with group II sera. Western blot analysis of NM23 expression indicated that all of the individual serum of group II showed immune activity, which confirmed the validity of SERPA result. These findings revealed that there exist autoantibodies in group II and III sera. Besides, autoantibodies of the two stages of disease course were different. These autoantigens might serve as biomarkers to elucidate mechanisms underlying TCE toxicity and are helpful for diagnosis, therapy and prognosis of TCE-induced autoimmune diseases.

  4. Argatroban Therapy in Patients with Coronary Artery Disease and Heparin-Induced Thrombocytopenia

    Microsoft Academic Search

    Ik-Kyung Jang; Marcie J. Hursting; David McCollum

    2008-01-01

    The efficacy of the direct thrombin inhibitor argatroban was investigated in patients who developed heparin-induced thrombocytopenia following heparin therapy for coronary artery disease. The outcome of 121 patients treated with argatroban was compared with that of 26 patients in a historical control (i.e. patients who did not receive direct thrombin inhibition therapy). Argatroban, compared with controls, significantly reduced the 37-day

  5. Cyclosporine-induced optic neuropathy, ophthalmoplegia, and nystagmus in a patient with Crohn disease

    Microsoft Academic Search

    Yair Porges; Sergiu Blumen; Zvi Fireman; Amos Sternberg; Doron Zamir

    1998-01-01

    PURPOSE: To report the cyclosporine-induced complications of optic neuropathy, partial external ophthalmoplegia, and other neurologic abnormalities.METHODS: Case report. A 22-year-old man with severe active Crohn disease developed bilateral optic neuropathy, nystagmus, external ophthalmoplegia, and ataxia on the fifth day of cyclosporine A (CyA) parenteral therapy.RESULTS: Cyclosporine therapy was discontinued as soon as toxic clinical manifestations appeared. Cyclosporine blood level detected

  6. Mannan induces ROS-regulated, IL-17A–dependent psoriasis arthritis-like disease in mice

    PubMed Central

    Khmaladze, Ia; Kelkka, Tiina; Guerard, Simon; Wing, Kajsa; Pizzolla, Angela; Saxena, Amit; Lundqvist, Katarina; Holmdahl, Meirav; Nandakumar, Kutty Selva; Holmdahl, Rikard

    2014-01-01

    Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common diseases, induced by unknown environmental factors, affecting skin and articular joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an acute inflammation in inbred mouse strains resembling human Ps and PsA-like disease, whereas multiple injections induced a relapsing disease. Exacerbation of disease severity was observed in mice deficient for generation of reactive oxygen species (ROS). Interestingly, restoration of ROS production, specifically in macrophages, ameliorated both skin and joint disease. Neutralization of IL-17A, mainly produced by ?? T cells, completely blocked disease symptoms. Furthermore, mice depleted of granulocytes were resistant to disease development. In contrast, certain acute inflammatory mediators (C5, Fc? receptor III, mast cells, and histamine) and adaptive immune players (?? T and B cells) were redundant in disease induction. Hence, we propose that mannan-induced activation of macrophages leads to TNF-? secretion and stimulation of local ?? T cells secreting IL-17A. The combined action of activated macrophages and IL-17A produced in situ drives neutrophil infiltration in the epidermis and dermis of the skin, leading to disease manifestations. Thus, our finding suggests a new mechanism triggered by exposure to exogenous microbial components, such as mannan, that can induce and exacerbate Ps and PsA. PMID:25136095

  7. Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

    PubMed Central

    Brown, Kirsty; DeCoffe, Daniella; Molcan, Erin; Gibson, Deanna L.

    2012-01-01

    The gastrointestinal (GI) microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed. PMID:23016134

  8. Amphetamine-Induced Taste Aversion Learning in Young and Old F-344 Rats Following Exposure to 56Fe Particles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposure to 56Fe particles produces changes in dopaminergic function and in dopamine dependent behaviors, including amphetamine-induced conditioned taste aversion (CTA) learning. Because many of these changes are characteristic of the changes that accompany the aging process, the present study was ...

  9. Pressure induced increase of particle size and resulting weakening of elastic stiffness of CeO2 nanocrystals

    E-print Network

    Downs, Robert T.

    Pressure induced increase of particle size and resulting weakening of elastic stiffness of CeO2 10 nm increases at pressures above 20 GPa. At ambient pressure, CeO2 nanocrystals exhibit larger cell, above 20 GPa, the bulk modulus is reduced to 230 10 GPa. Thus, a critical pressure of 20 GPa

  10. LONG-TERM CHANGES IN AMPHETAMINE-INDUCED REINFORCEMENT AND AVERSION IN RATS FOLLOWING EXPOSURE TO 56FE PARTICLES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measured using the conditioned place ...

  11. Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease.

    PubMed

    Michaut, Anaïs; Moreau, Caroline; Robin, Marie-Anne; Fromenty, Bernard

    2014-08-01

    Although acetaminophen (APAP) is usually considered as a safe drug, this painkiller can lead to acute liver failure after overdoses. Moreover, there is evidence that the maximum recommended dosage can induce hepatic cytolysis in some individuals. Several predisposing factors appear to enhance the risk and severity of APAP-induced liver injury including chronic alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions linked to obesity. In contrast, obesity by itself does not seem to be associated with a higher risk of APAP-induced liver injury. Since 1987, seven studies dealt with APAP-induced hepatotoxicity in rodent models of NAFLD and five of them found that this liver disease was associated with higher APAP toxicity. Unfortunately, these studies did not unequivocally established the mechanism(s) whereby NAFLD could favour APAP hepatotoxicity, although some investigations suggested that pre-existent induction of hepatic cytochrome P450 2E1 (CYP2E1) could play a significant role by increasing the generation of N-acetyl-p-benzoquinone imine (NAPQI), the toxic metabolite of APAP. Moreover, pre-existent mitochondrial dysfunction associated with NAFLD could also be involved. In contrast, some investigations suggested that factors that could reduce the risk and severity of APAP hepatotoxicity in obesity and NAFLD include higher hepatic APAP glucuronidation, reduced CYP3A4 activity and increased volume of body distribution. Thus, the occurrence and the outcome of APAP-induced liver injury in an obese individual with NAFLD might depend on a delicate balance between metabolic factors that can be protective and others that favour large hepatic levels of NAPQI. PMID:24575957

  12. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2013-07-01

    No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism. PMID:23416846

  13. Analysis of Clonostachys rosea-Induced Resistance to Tomato Gray Mold Disease in Tomato Leaves

    PubMed Central

    Guan, Xin; Chen, Xiuling; Chen, Hongyu; Zhang, Jian; Zhang, Junfeng; Li, Jingfu; Yang, Yijun; Wang, Aoxue

    2014-01-01

    Tomato gray mold disease, caused by Botrytis cinerea, is a serious disease in tomato. Clonostachys rosea is an antagonistic microorganism to B. cinerea. To investigate the induced resistance mechanism of C. rosea, we examined the effects of these microorganisms on tomato leaves, along with changes in the activities of three defense enzymes (PAL, PPO, GST), second messengers (NO, H2O2, O2?) and phytohormones (IAA, ABA, GA3, ZT, MeJA, SA and C2H4). Compared to the control, all treatments induced higher levels of PAL, PPO and GST activity in tomato leaves and increased NO, SA and GA3 levels. The expression of WRKY and MAPK, two important transcription factors in plant disease resistance, was upregulated in C. rosea- and C. rosea plus B. cinerea-treated samples. Two-dimensional gel electrophoresis analysis showed that two abundant proteins were present in the C. rosea plus B. cinerea-treated samples but not in the other samples. These proteins were determined (by mass spectrum analysis) to be LEXYL2 (?-xylosidase) and ATP synthase CF1 alpha subunit. Therefore, C. rosea plus B. cinerea treatment induces gray mold resistance in tomato. This study provides a basis for elucidating the mechanism of C. rosea as a biocontrol agent. PMID:25061981

  14. Analysis of Clonostachys rosea-induced resistance to tomato gray mold disease in tomato leaves.

    PubMed

    Mouekouba, Liana Dalcantara Ongouya; Zhang, Lili; Guan, Xin; Chen, Xiuling; Chen, Hongyu; Zhang, Jian; Zhang, Junfeng; Li, Jingfu; Yang, Yijun; Wang, Aoxue

    2014-01-01

    Tomato gray mold disease, caused by Botrytis cinerea, is a serious disease in tomato. Clonostachys rosea is an antagonistic microorganism to B. cinerea. To investigate the induced resistance mechanism of C. rosea, we examined the effects of these microorganisms on tomato leaves, along with changes in the activities of three defense enzymes (PAL, PPO, GST), second messengers (NO, H2O2, O2(-)) and phytohormones (IAA, ABA, GA3, ZT, MeJA, SA and C2H4). Compared to the control, all treatments induced higher levels of PAL, PPO and GST activity in tomato leaves and increased NO, SA and GA3 levels. The expression of WRKY and MAPK, two important transcription factors in plant disease resistance, was upregulated in C. rosea- and C. rosea plus B. cinerea-treated samples. Two-dimensional gel electrophoresis analysis showed that two abundant proteins were present in the C. rosea plus B. cinerea-treated samples but not in the other samples. These proteins were determined (by mass spectrum analysis) to be LEXYL2 (?-xylosidase) and ATP synthase CF1 alpha subunit. Therefore, C. rosea plus B. cinerea treatment induces gray mold resistance in tomato. This study provides a basis for elucidating the mechanism of C. rosea as a biocontrol agent. PMID:25061981

  15. Neuroprotective activity of Stereospermum suaveolens DC against 6-OHDA induced Parkinson's disease model

    PubMed Central

    Shalavadi, M. H.; Chandrashekhar, V. M.; Avinash, S. P.; Sowmya, C.; Ramkishan, A.

    2012-01-01

    Objectives: To evaluate the neuroprotective effect of Stereospermum suaveolens DC on 6-hydroxy dopamine induced Parkinson's disease model. Materials and Methods: The study was conducted on Sprague-Dawley rats where parkinson's disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received methanolic extract of Stereospermum suaveolens at dose of 125, 250 and 500 mg/kg for 42 days. Behavioral assessment, spontaneous locomotor activity and muscular coordination were studied. Antioxidant levels, striatal infraction area were assessed and histopathological studies were carried out. Results: The Stereospermum suaveolens DC methanolic extract showed significant dose dependent increase in behavioral activity, improved muscular coordination. Significant reduction of lipid peroxidation (LPO), increased antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and non-enzymatic activity of glutathione (GSH) and total thiol levels in extract treated groups was observed in test groups as compared to control group. Striatal infarction area was significantly reduced in extract treated groups as compared to control group. Conclusion: The methanolic extract of Stereospermum suaveolens DC showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson's disease in rats. PMID:23248404

  16. Near-infrared light responsive multi-compartmental hydrogel particles synthesized through droplets assembly induced by superhydrophobic surface.

    PubMed

    Luo, Rongcong; Cao, Ye; Shi, Peng; Chen, Chia-Hung

    2014-12-10

    Light-responsive hydrogel particles with multi-compartmental structure are useful for applications in microreactors, drug delivery and tissue engineering because of their remotely-triggerable releasing ability and combinational functionalities. The current methods of synthesizing multi-compartmental hydrogel particles typically involve multi-step interrupted gelation of polysaccharides or complicated microfluidic procedures with limited throughput. In this study, a two-step sequential gelation process is developed to produce agarose/alginate double network multi-compartmental hydrogel particles using droplets assemblies induced by superhydrophobic surface as templates. The agarose/alginate double network multi-compartmental hydrogel particles can be formed with diverse hierarchical structures showing combinational functionalities. The synthesized hydrogel particles, when loaded with polypyrrole (PPy) nanoparticles that act as photothermal nanotransducers, are demonstrated to function as near-infrared (NIR) light triggerable and deformation-free hydrogel materials. Periodic NIR laser switching is applied to stimulate these hydrogel particles, and pulsatile release profiles are collected. Compared with massive reagents released from single-compartmental hydrogel particles, more regulated release profiles of the multi-compartmental hydrogel particles are observed. PMID:25059988

  17. Formation of silver particles and periodic precipitate layers in silicate glass induced by thermally assisted hydrogen permeation

    NASA Astrophysics Data System (ADS)

    Mohr, C.; Dubiel, M.; Hofmeister, H.

    2001-01-01

    Nanoscale silver particles embedded in sodium silicate glass were produced by Na/Ag ion exchange and subsequent thermal treatment in a hydrogen atmosphere. Their structure and spatial distribution were studied by conventional and high-resolution electron microscopy (HREM). Two different mechanisms of particle formation could be identified: (i) reduction of ionic silver by hydrogen and formation of mostly defective particles (twinned) within a near-surface region; and (ii) formation of single-crystalline particles in the interior of the glass resulting from reduction by means of polyvalent iron ions. Electron microscopy investigation revealed the completion of periodic layers of silver particles in near-surface regions with high silver concentration induced by thermally assisted hydrogen permeation. The self-organized periodic layer formation may be explained in terms of Ostwald's supersaturation theory, assuming interdiffusion of two mobile species. Analysis of lattice plane spacings from HREM images of silver particles revealed the typical size-dependent lattice contraction. The extent of this, however, was found to be different for particles formed by hydrogen permeation and those formed by interaction with polyvalent iron ions. These differences reflect different influences of the surrounding glass matrix, probably originating from the conditions of particle formation (thermal history).

  18. Determination of small soot particles in the presence of large ones from time-resolved laser-induced incandescence

    NASA Astrophysics Data System (ADS)

    Cenker, E.; Bruneaux, G.; Dreier, T.; Schulz, C.

    2015-02-01

    A novel strategy for the analysis of time-resolved laser-induced incandescence (TiRe-LII), called two-exponential reverse fitting (TERF), is introduced. The method is based on combined monoexponential fits to the LII signal decay at various delay times and approximates the particle-size distribution as a weighted combination of one large and one small monodisperse equivalent mean particle size without requiring assumption on the particle-size distribution. The effects of particle size, heat-up temperature, aggregate size, and pressure on the uncertainty of this method are evaluated using numerical experiments for lognormal and bimodal size distributions. TERF is applied to TiRe-LII measured in an atmospheric pressure laminar non-premixed ethylene/air flame at various heights above burner. The results are compared to transmission electron microscopy (TEM) measurements of thermophoretically sampled soot. The particle size of the large particle-size class agreed well for both methods. The size of the small particle-size class and the relative contribution did not agree which is attributed to missing information in the TEM results for very small particles. These limitations of TEM measurements are discussed and the effect of the exposure time of the sampling grid is evaluated.

  19. Contributions of the host microenvironment to cancer-induced bone disease

    PubMed Central

    Olechnowicz, Sam W. Z.; Edwards, Claire M.

    2014-01-01

    The bone marrow provides a specialised and highly supportive microenvironment for tumour growth and development of the associated bone disease. It is a preferred site for breast and prostate cancer bone metastasis and the haematological malignancy, multiple myeloma. For many years, researchers have focused upon the interactions between tumour cells and the cells directly responsible for bone remodelling, namely osteoclasts and osteoblasts. However, there is ever-increasing evidence for a multitude of ways in which the bone marrow microenvironment can promote disease pathogenesis, including via cancer-associated fibroblasts, the hematopoietic stem cell niche, myeloid-derived suppressor cells and the sympathetic nervous system. This review discusses the recent advances in our understanding of the contribution of the host microenvironment to the development of cancer-induced bone disease. PMID:24599133

  20. Contributions of the host microenvironment to cancer-induced bone disease.

    PubMed

    Olechnowicz, Sam W Z; Edwards, Claire M

    2014-03-15

    The bone marrow provides a specialized and highly supportive microenvironment for tumor growth and development of the associated bone disease. It is a preferred site for breast and prostate cancer bone metastasis and the hematologic malignancy, multiple myeloma. For many years, researchers have focused upon the interactions between tumor cells and the cells directly responsible for bone remodeling, namely osteoclasts and osteoblasts. However, there is ever-increasing evidence for a multitude of ways in which the bone marrow microenvironment can promote disease pathogenesis, including via cancer-associated fibroblasts, the hematopoietic stem cell niche, myeloid-derived suppressor cells, and the sympathetic nervous system. This review discusses the recent advances in our understanding of the contribution of the host microenvironment to the development of cancer-induced bone disease. PMID:24599133

  1. Impaired Neural Differentiation of Induced Pluripotent Stem Cells Generated from a Mouse Model of Sandhoff Disease

    PubMed Central

    Ogawa, Yasuhiro; Tanaka, Makoto; Tanabe, Miho; Suzuki, Toshihiro; Togawa, Tadayasu; Fukushige, Tomoko; Kanekura, Takuro; Sakuraba, Hitoshi; Oishi, Kazuhiko

    2013-01-01

    Sandhoff disease (SD) is a glycosphingolipid storage disease that arises from mutations in the Hexb gene and the resultant deficiency in ?-hexosaminidase activity. This deficiency results in aberrant lysosomal accumulation of the ganglioside GM2 and related glycolipids, and progressive deterioration of the central nervous system. Dysfunctional glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. Induced pluripotent stem cell (iPSC) technology offers new opportunities for both elucidation of the pathogenesis of diseases and the development of stem cell-based therapies. Here, we report the generation of disease-specific iPSCs from a mouse model of SD. These mouse model-derived iPSCs (SD-iPSCs) exhibited pluripotent stem cell properties and significant accumulation of GM2 ganglioside. In lineage-directed differentiation studies using the stromal cell-derived inducing activity method, SD-iPSCs showed an impaired ability to differentiate into early stage neural precursors. Moreover, fewer neurons differentiated from neural precursors in SD-iPSCs than in the case of the wild type. Recovery of the Hexb gene in SD-iPSCs improved this impairment of neuronal differentiation. These results provide new insights as to understanding the complex pathogenic mechanisms of SD. PMID:23383290

  2. Pathobiology and subgroup specificity of disease induced by Rous associated virus 7 (RAV-7)

    SciTech Connect

    Carter, J.Y.

    1983-01-01

    When Rous associated virus 7 (RAV-7) was injected intravenously into 10-day old chicken embryos, a disease syndrome developed which was characterized by stunting, hyperlipidemia, hypothyroidism, and hyperinsulinemia. Stocks of RAV-7, a subgroup C avian leukosis virus, were obtained by end-point purification on chick embryo fibroblast cells. The size of the viral RNA was 8.2 kb and the protein banding pattern on polyacrylamide gels was typical of avian leukosis viruses. These results indicated that RAV-7 was a non-defective avian leukosis virus and no sarcoma or defective leukemia viruses were present in the RAV-7 stock. RAV-7 induced a unique disease syndrome although infection by three other subgroup C avian leukosis viruses (tdB77, tdPrC, and RAV-49) resulted in an identical lymphoblastoid infiltration of the thyroid and pancreas. An examination of disease induced by avian leukosis viruses from subgroups A, B, D, and F showed that infection by any of these subgroups did not result in the typical RAV-7 disease syndrome.

  3. Lesion bacterial communities in American lobsters with diet-induced shell disease.

    PubMed

    Quinn, Robert A; Metzler, Anita; Tlusty, Michael; Smolowitz, Roxanna M; Leberg, Paul; Chistoserdov, Andrei Y

    2012-04-26

    In southern New England, USA, shell disease affects the profitability of the American lobster Homarus americanus fishery. In laboratory trials using juvenile lobsters, exclusive feeding of herring Clupea harengus induces shell disease typified initially by small melanized spots that progress into distinct lesions. Amongst a cohabitated, but segregated, cohort of 11 juvenile lobsters fed exclusively herring, bacterial communities colonizing spots and lesions were investigated by denaturing gradient gel electrophoresis of 16S rDNA amplified using 1 group-specific and 2 universal primer sets. The Bacteroidetes and Proteobacteria predominated in both spots and lesions and included members of the orders Flavobacteriales (Bacteriodetes), Rhodobacterales, Rhodospirillales and Rhizobiales (Alphaproteobacteria), Xanthomonadales (Gammaproteobacteria) and unclassified Gammaproteobacteria. Bacterial communities in spot lesions displayed more diversity than communities with larger (older) lesions, indicating that the lesion communities stabilize over time. At least 8 bacterial types persisted as lesions developed from spots. Aquimarina 'homaria', a species commonly cultured from lesions present on wild lobsters with epizootic shell disease, was found ubiquitously in spots and lesions, as was the 'Candidatus Kopriimonas aquarianus', implicating putative roles of these species in diet-induced shell disease of captive lobsters. PMID:22535872

  4. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    NASA Technical Reports Server (NTRS)

    Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

    2002-01-01

    Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

  5. Tumor necrosis factor-like weak inducer of apoptosis regulates particle-induced inflammatory osteolysis via the p38 mitogen-activated protein kinase signaling pathway.

    PubMed

    Zhang, Zhiqiang; Fang, Yongchao; Wang, Qiang; Sun, Yu; Xiong, Chuanzhi; Cao, Li; Wang, Beiyue; Bao, Nirong; Zhao, Jianning

    2015-07-01

    Periprosthetic osteolysis is the predominant cause of artificial joint loosening. Previous studies have demonstrated that p38 mitogen?activated protein kinase (p38 MAPK) may be involved in periprosthetic osteolysis. Tumor necrosis factor (TNF)?like weak inducer of apoptosis (TWEAK) is a member of the TNF family and is a multifunctional cytokine, which regulates cellular proliferation, angiogenesis, inflammation and apoptosis via the p38 MAPK signaling pathway. The present study investigated the expression levels of TWEAK and p38 MAPK in periprosthetic interface membranes and in RAW264.7 monocyte/macrophage cells, which were treated with titanium (Ti) particle stimulation, with or without a p38 inhibitor (SB203580). This was performed to determine whether TWEAK was involved in the particle?induced inflammatory osteolysis via the p38 MAPK signaling pathway. The expression levels of TWEAK, p38 MAPK and phosphorylated (p?)p38 MAPK were evaluated in the periprosthetic interface membrane tissues and the RAW cells by reverse transcription?quantitative polymerase chain reaction and western blotting. The contents of interleukin?6 and monocyte chemoattractant protein?1 in the supernatant were measured by ELISA. The results demonstrated that the expression levels of TWEAK and p?p38 MAPK increased in the periprosthetic interface membrane tissues and the RAW cells stimulated with Ti particles, suggesting that TWEAK was involved in particle?induced inflammatory osteolysis via the p38 MAPK signaling pathway. PMID:25815691

  6. Induced Fractional Zero-Point Canonical Angular Momentum on Charged Particles of Aharonov - Bohm Vector Potential and "Spectator" Magnetic Field

    E-print Network

    Jian-Zu Zhang

    2007-11-02

    The induced fractional zero-point canonical angular momentum on charged particles by the Aharonov - Bohm (AB) vector potential is realized via modified combined traps. It explores new features for this type of quantum effects: In a limit of vanishing mechanical kinetic energy the AB vector potential alone cannot induce a fractional zero-point canonical angular momentum on charged particles at the quantum mechanical level in the AB magnetic field-free region; But for the case of the AB vector potential with another one of a "spectator" magnetic field the AB vector potential induces a fractional zero-point canonical angular momentum in the same limit. The "spectator" one does not contribute to such a fractional zero-point quantity, but plays essential role in guaranteeing non-trivial dynamics survived in this limit at the quantum mechanical level. These results are significance in investigations of the AB effects and related fields for both theories and experiments.

  7. Amyloid ?-Peptide (1–42)-Induced Oxidative Stress in Alzheimer Disease: Importance in Disease Pathogenesis and Progression

    PubMed Central

    Swomley, Aaron M.; Sultana, Rukhsana

    2013-01-01

    Abstract Significance: Alzheimer disease (AD) is an age-related neurodegenerative disease. AD is characterized by progressive cognitive impairment. One of the main histopathological hallmarks of AD brain is the presence of senile plaques (SPs) and another is elevated oxidative stress. The main component of SPs is amyloid beta-peptide (A?) that is derived from the proteolytic cleavage of amyloid precursor protein. Recent Advances: Recent studies are consistent with the notion that methionine present at 35 position of A? is critical to A?-induced oxidative stress and neurotoxicity. Further, we also discuss the signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during the progression of AD. Critical Issues: The exact relationships of the specifically oxidatively modified proteins in AD pathogenesis require additional investigation. Future Directions: Further studies are needed to address whether the therapies directed toward brain oxidative stress and oxidatively modified key brain proteins might help delay or prevent the progression of AD. Antioxid. Redox Signal. 19, 823–835. PMID:23249141

  8. Gravitational perturbation of the BTZ black hole induced by test particles and weak cosmic censorship in AdS spacetime

    SciTech Connect

    Rocha, Jorge V. [CENTRA, Departamento de Fisica, Instituto Superior Tecnico, Universidade Tecnica de Lisboa, Av. Rovisco Pais 1, 1049 Lisboa (Portugal); Cardoso, Vitor [CENTRA, Departamento de Fisica, Instituto Superior Tecnico, Universidade Tecnica de Lisboa, Av. Rovisco Pais 1, 1049 Lisboa (Portugal); Department of Physics and Astronomy, University of Mississippi, University, Mississippi 38677 (United States)

    2011-05-15

    We analyze the gravitational perturbations induced by particles falling into a three dimensional, asymptotically AdS black hole geometry. More specifically, we solve the linearized perturbation equations obtained from the geodesic motion of a ringlike distribution of test particles in the BTZ background. This setup ensures that the U(1) symmetry of the background is preserved. The nonasymptotic flatness of the background raises difficulties in attributing the significance of energy and angular momentum to the conserved quantities of the test particles. This issue is well known but, to the best of our knowledge, has never been addressed in the literature. We confirm that the naive expressions for energy and angular momentum are the correct definitions. Finally, we put an asymptotically AdS version of the weak cosmic censorship to a test: by attempting to overspin the BTZ black hole with test particles it is found that the black hole cannot be spun-up past its extremal limit.

  9. Results and perspectives of the investigation of traditional and thermal stress induced thermophoresis of particles in gas in microgravity

    NASA Astrophysics Data System (ADS)

    Vedernikov, Andrei; Balapanov, Daniyar; Beresnev, Sergey; Queeckers, Patrick

    Thermophoretic motion of particles suspended in a gas has been a subject of extensive theoretical and experimental investigations for many years because of its wide spread in nature, significance for fundamental and applied aerosol physic. Negative thermophoresis, i.e. solid particle motion towards hotter region in a gas and not as usually from hotter region, was predicted more than 40 years ago and remains an unsolved problem for a choice between different models treating main driving mechanisms -- thermal slip and thermal stress induced gas motion. For a problem of negative thermophoresis, we present experimental evidences in favor of the latter mechanism based on direct observation of particle motion at microgravity; Knudsen particle number 2\\cdot 10(-3) (Kn being the ratio of the molecular mean free path to the particle size); particle-to-gas heat conductivity ratios 2\\cdot 10(4) for copper solid particles and 1.8 for glass bubbles. For both types of particles the experimental results fit well the gas kinetic model of Beresnev and Chernyak [1]. We present characteristics of a set-up and procedures that are able to provide sufficient accuracy and volume of experimental data for testing any model of particle thermophoresis. High quality microgravity is a necessity for such investigations. The short duration microgravity of drop towers suits well this requirement. The sign and value of the thermophoretic force strongly depends on the Knudsen number, particle-to-gas heat conductivity ratio and accommodation coefficients, all of which vary within several decimal orders of magnitude. In order to make crucial conclusions on the choice of the adequate model, there should be hundreds of short duration microgravity experiments. The European Space Agency scientific project Interaction in Cosmic and Atmospheric Particle Systems (ICAPS) [2] planned for the International Space Station, provides complementary opportunities for the investigation of thermophoresis at large and very large Knudsen numbers for single particles and large clusters of particles under wide range of experimental parameters, i.e. different particle sizes, shapes, materials; different properties of gases; several types of additional forces and their time-space variation. ESA PRODEX Program, Belgian Federal Science Policy Office and Bremen Drop Tower Operation and Service Company ZARM FABmbH (Germany) are greatly acknowledged for their support. [1] Beresnev S., Chernyak V. Thermophoresis of a spherical particle in a rarefied gas: Numerical analysis based on the model kinetic equations // Phys. Fluids. 1995. V.7. P.1743. [2] Blum, J. et al. "Dust in Space", Europhysicsnews, Vol. 39, pp. 27-29, 2008.

  10. Neuroprotective effects of swimming training in a mouse model of Parkinson's disease induced by 6-hydroxydopamine.

    PubMed

    Goes, A T R; Souza, L C; Filho, C B; Del Fabbro, L; De Gomes, M G; Boeira, S P; Jesse, C R

    2014-01-01

    Parkinson's disease (PD) is characterized by progressive dopamine (DA) depletion in the striatum. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegeneration diseases. This study was designed to investigate the potential neuroprotective effect of swimming training (ST) in a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) in mice. The present study demonstrated that a 4-week ST was effective in attenuating the following impairments resulting from 6-OHDA exposure: (i) depressive-like behavior in the tail suspension test; (ii) increase in the number of falls in the rotarod test; (iii) impairment on long-term memory in the object recognition test; (iv) increase of the reactive species and interleukin 1-beta (IL-1?) levels; (v) inhibition of the glutathione peroxidase (GPx) activity; (vi) rise of the glutathione reductase (GR) and glutathione S-transferase (GST) activities and vii) decrease of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. The mechanisms involved in this study are the modulation of GPx, GR and GST activities as well as IL-1? level in a PD model induced by 6-OHDA, protecting against the decrease of DA, DOPAC and HVA levels in the striatum of mice. These findings reinforce that one of the effects induced by exercise on neurodegenerative disease, such as PD, is due to antioxidant and anti-inflammatory properties. We suggest that exercise attenuates cognitive and motor declines, depression, oxidative stress, and neuroinflammation induced by 6-OHDA supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of PD. PMID:24090962

  11. Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity*

    PubMed Central

    Björkblom, Benny; Adilbayeva, Altynai; Maple-Grødem, Jodi; Piston, Dominik; Ökvist, Mats; Xu, Xiang Ming; Brede, Cato; Larsen, Jan Petter; Møller, Simon Geir

    2013-01-01

    The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional non-motor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD. PMID:23792957

  12. The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease

    PubMed Central

    Huang, Jin; DeGraves, Fred J.; Lenz, Stephen D.; Gao, Dongya; Feng, Pu; Li, Dan; Schlapp, Tobias; Kaltenboeck, Bernhard

    2002-01-01

    Intracellular bacteria of the genus Chlamydia cause numerous typically chronic diseases, frequently with debilitating sequelae. Genetic determinants of disease susceptibility after infection with Chlamydia bacteria are unknown. C57BL/6 mice develop severe pneumonia and poor immunity against Chlamydia after moderate respiratory infection whereas BALB/c mice are protected from disease and develop vigorous Th1 immunity. Here we show that infected C57BL/6 macrophages release more NO synthesized by NO synthase 2 (NOS2) than BALB/c macrophages and have lower mRNA concentrations of arginase II, a competitor of NOS2 for the common substrate, l-arginine. Reduction, but not elimination, of NO production by incomplete inhibition of NOS2 abolishes susceptibility of C57BL/6 mice to Chlamydia-induced disease. Thus, the quantity of NO released by infected macrophages is the effector mechanism that regulates between pathogenic and protective responses to chlamydial infection, and genes controlling NO production determine susceptibility to chlamydial disease. PMID:11904441

  13. Interferon-alpha-induced hyperthyroidism: a three-stage evolution from silent thyroiditis towards Graves' disease.

    PubMed

    Bohbot, Nathalie Lévy; Young, Jacques; Orgiazzi, Jacques; Buffet, Catherine; François, Maud; Bernard-Chabert, Brigitte; Lukas-Croisier, Céline; Delemer, Brigitte

    2006-03-01

    Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy. PMID:16498048

  14. Interspecific transmission and recovery of TCBS-induced disease between Acanthaster planci and Linckia guildingi.

    PubMed

    Caballes, C F; Schupp, P J; Pratchett, M S; Rivera-Posada, J A

    2012-09-12

    The susceptibility of the coral-feeding crown-of-thorns starfish Acanthaster planci to disease may provide an avenue with which to effectively control population outbreaks that have caused severe and widespread coral loss in the Indo-Pacific. Injecting thiosulfate-citrate-bile-sucrose (TCBS) agar into A. planci tissues induced a disease characterized by dermal lesions, loss of skin turgor, collapsed spines, and accumulation of mucus on spine tips. Moreover, the symptoms (and presumably the agent) of this disease would spread rapidly intraspecifically, but interspecific transmission (to other species of echinoderms) is yet to be examined. Vibrio rotiferianus, which was previously reported as a pathogen isolated from lesions of experimentally infected A. planci, was also recovered from Linckia guildingi lesions after several days of direct contact with diseased A. planci, demonstrating disease transmission. However, all L. guildingi fully recovered after 31 ± 16 d. Further studies are in progress to understand the ecology of Vibrio infection in A. planci and the potential transmission risk to corals, fishes, and other echinoderms to evaluate whether injections of TCBS could be a viable tool for controlling A. planci outbreaks. PMID:22968793

  15. Concise review: modeling central nervous system diseases using induced pluripotent stem cells.

    PubMed

    Zeng, Xianmin; Hunsberger, Joshua G; Simeonov, Anton; Malik, Nasir; Pei, Ying; Rao, Mahendra

    2014-12-01

    Induced pluripotent stem cells (iPSCs) offer an opportunity to delve into the mechanisms underlying development while also affording the potential to take advantage of a number of naturally occurring mutations that contribute to either disease susceptibility or resistance. Just as with any new field, several models of screening are being explored, and innovators are working on the most efficient methods to overcome the inherent limitations of primary cell screens using iPSCs. In the present review, we provide a background regarding why iPSCs represent a paradigm shift for central nervous system (CNS) disease modeling. We describe the efforts in the field to develop more biologically relevant CNS disease models, which should provide screening assays useful for the pharmaceutical industry. We also provide some examples of successful uses for iPSC-based screens and suggest that additional development could revolutionize the field of drug discovery. The development and implementation of these advanced iPSC-based screens will create a more efficient disease-specific process underpinned by the biological mechanism in a patient- and disease-specific manner rather than by trial-and-error. Moreover, with careful and strategic planning, shared resources can be developed that will enable exponential advances in the field. This will undoubtedly lead to more sensitive and accurate screens for early diagnosis and allow the identification of patient-specific therapies, thus, paving the way to personalized medicine. PMID:25368377

  16. Anti-Tumor Necrosis Factor Ameliorates Joint Disease in Murine Collagen- Induced Arthritis

    NASA Astrophysics Data System (ADS)

    Williams, Richard O.; Feldmann, Marc; Maini, Ravinder N.

    1992-10-01

    There is considerable evidence implicating tumor necrosis factor ? (TNF-?) in the pathogenesis of rheumatoid arthritis. This evidence is based not only on the universal presence of TNF-? in arthritic joints accompanied by the upregulation of TNF-? receptors but also on the effects of neutralizing TNF-? in joint cell cultures. Thus, neutralization of TNF-? in vitro results in inhibition of the production of interleukin 1, which like TNF-?, is believed to contribute to joint inflammation and erosion. To determine the validity of this concept in vivo, the effect of administering TNF-neutralizing antibodies to mice with collagen-induced arthritis has been studied. This disease model was chosen because of its many immunological and pathological similarities to human rheumatoid arthritis. TN3-19.12, a hamster IgG1 monoclonal antibody to murine TNF-?/?, was injected i.p. into mice either before the onset of arthritis or after the establishment of clinical disease. Anti-TNF administered prior to disease onset significantly reduced paw swelling and histological severity of arthritis without reducing the incidence of arthritis or the level of circulating anti-type II collagen IgG. More relevant to human disease was the capacity of the antibody to reduce the clinical score, paw swelling, and the histological severity of disease even when injected after the onset of clinical arthritis. These results have implications for possible modes of therapy of human arthritis.

  17. Photo induced multiple fragmentation of atoms and molecules: Dynamics of Coulombic many-particle systems studied with the COLTRIMS reaction microscope

    Microsoft Academic Search

    A. Czasch; L. Ph. H. Schmidt; T. Jahnke; Th. Weber; O. Jagutzki; S. Schössler; M. S. Schöffler; R. Dörner; H. Schmidt-Böcking

    2005-01-01

    Many-particle dynamics in atomic and molecular physics has been investigated by using the COLTRIMS reaction microscope. The COLTRIMS technique visualizes photon and ion induced many-particle fragmentation processes in the eV and milli-eV regime. It reveals the complete momentum pattern in atomic and molecular many-particle reactions comparable to the bubble chamber in nuclear physics.

  18. Composition of Renaissance paint layers: simultaneous particle induced X-ray emission and backscattering spectrometry.

    PubMed

    de Viguerie, L; Beck, L; Salomon, J; Pichon, L; Walter, Ph

    2009-10-01

    Particle induced X-ray emission spectroscopy (PIXE) is now routinely used in the field of cultural heritage. Various setups have been developed to investigate the elemental composition of wood/canvas paintings or of cross-section samples. However, it is not possible to obtain information concerning the quantity of organic binder. Backscattering spectrometry (BS) can be a useful complementary method to overcome this limitation. In the case of paint layers, PIXE brings the elemental composition (major elements to traces) and the BS spectrum can give access to the proportion of pigment and binder. With the use of 3 MeV protons for PIXE and BS simultaneously, it was possible to perform quantitative analysis including C and O for which the non-Rutherford cross sections are intense. Furthermore, with the use of the same conditions for PIXE and BS, the experiment time and the potential damage by the ion beam were reduced. The results obtained with the external beam of the Accélérateur Grand Louvre pour l'Analyse Elementaire (AGLAE) facility on various test painting samples and on cross sections from Italian Renaissance masterpieces are shown. Simultaneous combination of PIXE and BS leads to a complete characterization of the paint layers: elemental composition and proportion of the organic binder have been determined and thus provide useful information about ancient oil painting recipes. PMID:19731942

  19. Transition-Edge Sensors for Particle Induced X-ray Emission Measurements

    NASA Astrophysics Data System (ADS)

    Palosaari, M. R. J.; Kinnunen, K. M.; Julin, J.; Laitinen, M.; Napari, M.; Sajavaara, T.; Doriese, W. B.; Fowler, J.; Reintsema, C.; Swetz, D.; Schmidt, D.; Ullom, J.; Maasilta, I. J.

    2014-08-01

    In this paper we present a new measurement setup, where a transition-edge sensor detector array is used to detect X-rays in particle induced X-ray emission (PIXE) measurements with a 2 MeV proton beam. Transition-edge sensors offer orders of magnitude improvement in energy resolution compared to conventional silicon or germanium detectors, making it possible to recognize spectral lines in materials analysis that have previously been impossible to resolve, and to get chemical information from the elements. Our sensors are cooled to the operation temperature (65 mK) with a cryogen-free adiabatic demagnetization refrigerator, which houses a specially designed X-ray snout that has a vacuum tight window to couple in the radiation. For the best pixel, the measured instrumental energy resolution was 3.06 eV full width at half maximum at 5.9 keV. We discuss the current status of the project, benefits of transition-edge sensors when used in PIXE spectroscopy, and the results from the first measurements.

  20. Particle-Induced X-Ray Emission (PIXE) Of Silicate Coatings On High Impact Resistance Polycarbonates

    NASA Astrophysics Data System (ADS)

    Xing, Qian; Hart, M. A.; Culbertson, R. J.; Bradley, J. D.; Herbots, N.; Wilkens, Barry J.; Sell, David A.; Watson, Clarizza Fiel

    2011-06-01

    Particle-Induced X-ray Emission (PIXE) analysis was employed to characterize hydroxypropyl methylcellulose (HPMC) C32H60O19 polymer film via areal density measurement on silicon-based substrates utilizing the differential PIXE concept, and compared with Rutherford backscattering spectrometry (RBS) results. It is demonstrated in this paper that PIXE and RBS measurements both yield comparable results for areal densities ranging from 1018 atom/cm2 to several 1019 atom/cm2. A collection of techniques including PIXE, RBS, tapping mode atomic force microscopy (TMAFM), and contact angle analysis were used to compute surface free energy, analyze surface topography and roughness parameters, determine surface composition and areal density, and to predict the water affinity and condensation behaviors of silicates and other compounds used for high impact resistance vision ware coatings. The visor surface under study is slightly hydrophilic, with root mean square of surface roughness on the order of one nm, and surface wavelength between 200 nm and 300 nm. Water condensation can be controlled on such surfaces via polymers adsorption. HPMC polymer areal density measurement supports the analysis of the surface water affinity and topography and the subsequent control of condensation behavior. HPMC film between 1018 atom/cm2 and 1019 atom/cm2 was found to effectively alter the water condensation pattern and prevents fogging by forming a wetting layer during condensation.

  1. Underwater pressure amplification of laser-induced plasma shock waves for particle removal applications

    SciTech Connect

    Dunbar, Thomas J.; Cetinkaya, Cetin [Department of Mechanical and Aeronautical Engineering, Clarkson University, Potsdam, New York 13699-5725 (United States) and Center for Advanced Materials Processing, Clarkson University, Potsdam, New York 13699-5725 (United States)

    2007-07-30

    Underwater amplification of laser-induced plasma (LIP)-generated transient pressure waves using shock tubes is introduced and demonstrated. Previously, it has been shown that LIP for noncontact particle removal is possible on the sub-100-nm level. This is now enhanced through shock tube utilization in a medium such as water by substantially increasing shock wave pressure for the same pulse energy. A shock tube constrains the volume and changes the propagation direction of the expanding plasma core by focusing a pulsed-laser beam inside a tube with a blind end, thus increasing the wave front pressure generated. Current amplification approach can reduce radiation exposure of the substrate from the shock wave because of the increased distance from the LIP core to the substrate provided by the increased pressure per unit pulse energy. For the same pulsed laser, with the aid of a shock tube, substantial levels of pressure amplitude amplification (8.95) and maximum pressure (6.48 MPa) are observed and reported.

  2. Underwater pressure amplification of laser-induced plasma shock waves for particle removal applications

    NASA Astrophysics Data System (ADS)

    Dunbar, Thomas J.; Cetinkaya, Cetin

    2007-07-01

    Underwater amplification of laser-induced plasma (LIP)-generated transient pressure waves using shock tubes is introduced and demonstrated. Previously, it has been shown that LIP for noncontact particle removal is possible on the sub-100-nm level. This is now enhanced through shock tube utilization in a medium such as water by substantially increasing shock wave pressure for the same pulse energy. A shock tube constrains the volume and changes the propagation direction of the expanding plasma core by focusing a pulsed-laser beam inside a tube with a blind end, thus increasing the wave front pressure generated. Current amplification approach can reduce radiation exposure of the substrate from the shock wave because of the increased distance from the LIP core to the substrate provided by the increased pressure per unit pulse energy. For the same pulsed laser, with the aid of a shock tube, substantial levels of pressure amplitude amplification (8.95) and maximum pressure (6.48MPa) are observed and reported.

  3. Search for wave-induced particle precipitation from lightning and transmitter sources. Master's thesis

    SciTech Connect

    Lundberg, J.E.

    1988-01-01

    Wave-induced particle precipitation is introduced and examined for whistlers whose sources are within the plasmapause. The possible correlation between lightning strokes that carry positive charge to the ground and the observed Trimpi events is discussed, sudden phase and/or amplitude shifts of a received VLF signal with gradual return to predisturbed values. The thunderstorm charging mechanisms that lead to the observed charge distribution and the advection of the positively charged cirrus anvil away from the body of the thunderstorm are briefly examined. The comparative current strengths and the relative frequency of positive and negative strokes is studied for different types of thunderstorms. The magnetospheric ducting of the lightning-generated whistler wave and the interaction with trapped electrons is examined. The detectable effects the precipitating electrons have on the ionosphere is introduced. Included are testing and design of the x-ray detector and balloon-launch considerations. The problems encountered during the x-ray-detector's balloon flights are examined. The riometer and x-ray-detector data-analysis methods are mentioned. The results were negative for the data analyzed, but the limiting factors severely restricted the usable data. Possible experimental methods are mentioned.

  4. Light induced heterogeneous ozone processing on the pesticides adsorbed on silica particles

    NASA Astrophysics Data System (ADS)

    Socorro, J.; Désert, M.; Quivet, E.; Gligorovski, S.; Wortham, H.

    2013-12-01

    In France, in 2010, the sales of pesticides reached 1.8 billion euros for 61 900 tons of active ingredients, positioning France as a first European consumer of pesticides, as reported by the European Crop Protection Association. About 19 million hectares of crops are sprayed annually with pesticides, i.e., 35% of the total surface area of France. This corresponds to an average pesticide dose of 3.2 kg ha-1. The consumption of herbicide and fungicide is favoured in comparison to the use of insecticides in France and the other European countries, as well. The partitioning of pesticides between the gas and particulate phases influences the atmospheric fate of these compounds such as their photo-chemical degradation. There is much uncertainty concerning the behavior of the pesticides in the atmosphere. Especially, there is a gap of knowledge concerning the degradation of the pesticides induced by heterogeneous reactions in absence and especially in presence of solar light. Considering that most of the pesticides currently used are semi-volatile, it is of crucial importance to investigate the heterogeneous reactivity of particulate pesticides with light and with atmospheric oxidants such as ozone and OH radical. The aim of the present work is to evaluate the light induced heterogeneous ozonation of suspended pesticide particles. 8 pesticides (cyprodinil, deltamethrin, difenoconazole, fipronil, oxadiazon, pendimethalin, permethrin and tetraconazole) were chosen for their physico-chemical properties and their concentration levels in the PACA (Région Provence-Alpes-Côte d'Azur) region, France. Silica particles with well-known properties were chosen as model particles of atmospheric relevance. Kinetic rate constants were determined to allow estimate the atmospheric lifetimes relating to ozone. The rate constants were determined as follows: k = (6.6 × 0.2) 10-19, (7.2 × 0.3) 10-19, (5.1 × 0.5) 10-19, (3.9 × 0.3) 10-19 [cm3 molecules-1 s-1] for Cyprodinil, delthamethrine, permethrine and pendimethaline, respectively. Concerning the other four pesticides under study i.e. difenoconazole, fipronil, oxadiazon and tetraconazole the obtained rate constants were extremely slow, < 3.9 10-19 [cm3 molecules-1 s-1]. In addition, we identified the condensed phase products in such heterogeneous reactions of ozone with the particulate pesticides by GC-MS coupled with the derivatization technique. The gas-phase products were followed on-line by PTR-MS-TOF. The obtained results will allow to recognize the impact of the pesticides and their degradation products on the human health, and to make recommendations in order to reduce population exposure to the pesticide plume. The results of this work will contribute to better describe and understand the pollution by phyto-sanitary products on the regional scale, which constitutes a necessary step in the development of environmental strategies. As a result the obtained results will help in the development of future environmental strategies to better understand and control phyto-sanitary product application and human exposure.

  5. Anti-oxidative and inflammatory responses induced by fly ash particles and carbon black in lung epithelial cells.

    PubMed

    Diabaté, Silvia; Bergfeldt, Britta; Plaumann, Diana; Ubel, Caroline; Weiss, Carsten

    2011-12-01

    Combustion-derived nanoparticles as constituents of ambient particulate matter have been shown to induce adverse health effects due to inhalation. However, the components inducing these effects as well as the biological mechanisms are still not fully understood. The fine fraction of fly ash particles collected from the electrostatic precipitator of a municipal solid waste incinerator was taken as an example for real particles with complex composition released into the atmosphere to study the mechanism of early biological responses of BEAS-2B human lung epithelial cells. The studies include the effects of the water-soluble and -insoluble fractions of the fly ash and the well-studied carbon black nanoparticles were used as a reference. Fly ash induced reactive oxygen species (ROS) and increased the total cellular glutathione (tGSH) content. Carbon black also induced ROS generation; however, in contrast to the fly ash, it decreased the intracellular tGSH. The fly ash-induced oxidative stress was correlated with induction of the anti-oxidant enzyme heme oxygenase-1 and increase of the redox-sensitive transcription factor Nrf2. Carbon black was not able to induce HO-1. ROS generation, tGSH increase and HO-1 induction were only induced by the insoluble fraction of the fly ash, not by the water-soluble fraction. ROS generation and HO-1 induction were markedly inhibited by pre-incubation of the cells with the anti-oxidant N-acetyl cysteine which confirmed the involvement of oxidative stress. Both effects were also reduced by the metal chelator deferoxamine indicating a contribution of bioavailable transition metals. In summary, both fly ash and carbon black induce ROS but only fly ash induced an increase of intracellular tGSH and HO-1 production. Bioavailable transition metals in the solid water-insoluble matrix of the fly ash mostly contribute to the effects. PMID:21626191

  6. Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

    PubMed Central

    Gardner, Sarah Y; McGee, John K; Kodavanti, Urmila P; Ledbetter, Allen; Everitt, Jeffrey I; Winsett, Darrell W; Doerfler, Donald L; Costa, Daniel L

    2004-01-01

    Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation (IT) and inhalation (INH) of residual oil fly ash (ROFA) in a rat model of pulmonary hypertension induced by monocrotaline (MCT). The present study was conducted to examine the effects of ROFA in this model on ventilatory function in unanesthetized, unrestrained animals. Sixty-day-old male CD rats were injected with MCT (60 mg/kg) or vehicle (VEH) intraperitoneally 10 days before IT of ROFA (8.3 mg/kg) or saline (SAL) (control) or nose-only INH of ROFA [15 mg/m3 for 6 hr on 3 consecutive days or air (control)]. At 24 and 72 hr after exposure, rats were studied individually in a simultaneous gas uptake/whole-body plethysmograph. Lungs were removed at 72 hr for histology. Pulmonary test results showed that tidal volume (VT) decreased 24 hr after IT of ROFA in MCT-treated rats. Breathing frequency, minute volume (VE), and the ventilatory equivalent for oxygen increased in MCT- and VEH-treated rats 24 hr after IT or INH of ROFA and remained elevated 72 hr post-IT. O2 uptake (VO2) decreased after IT of ROFA in MCT-treated rats. Carbon monoxide uptake decreased 24 hr after IT of ROFA, returning to control values in VEH-treated rats but remaining low in MCT-treated rats 72 hr post-IT. ROFA exposure induced histologic changes and abnormalities in several ventilatory parameters, many of which were enhanced by MCT treatment. PMID:15175175

  7. Schisandra chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats

    PubMed Central

    Park, Hyoung Joon; Lee, Soo-Jung; Song, Yuno; Jang, Sun-Hee; Ko, Yeoung-Gyu; Kang, Suk Nam; Chung, Byung Yeoup; Kim, Hong-Duck; Kim, Gon-Sup

    2014-01-01

    Abstract Schisandra chinensis (SC), a traditional herbal medicine, has been prescribed for patients suffering from various liver diseases, including hepatic cancer, hypercholesterolemia, and CCl4-induced liver injury. We investigated whether SC extract has a protective effect on alcohol-induced fatty liver and studied its underlying mechanisms. Rats were fed with ethanol by intragastric administration every day for 5 weeks to induce alcoholic fatty liver. Ethanol treatment resulted in a significant increase in alanine aminotransferase, aspartate aminotransferase, and hepatic triglyceride (TG) levels and caused fatty degeneration of liver. Ethanol administration also elevated serum TG and total cholesterol (TC) and decreased high-density lipoprotein (HDL) cholesterol levels. However, after administration of ethanol plus SC extracts, the ethanol-induced elevation in liver TC and TG levels was reversed. Elevation in serum TG was not observed after treatment with SC. Moreover, compared with the ethanol-fed group, the rats administered ethanol along with SC extracts for 5 weeks showed attenuated fatty degeneration and an altered lipid profile with decreased serum TC and TG, and increased HDL cholesterol levels. Chronic ethanol consumption did not affect peroxisome proliferator-activated receptor ? (PPAR?) levels, but it decreased PPAR? and phospho-AMP-activated protein kinase (AMPK) levels in the liver. However, SC prevented the ethanol-induced decrease in PPAR? expression and induced a significant decrease in sterol regulatory element-binding protein-1 expression and increase in phospho-AMPK expression in rats with alcoholic fatty liver. SC administration resulted in a significant decrease in intracellular lipid accumulation in hepatocytes along with a decrease in serum TG levels, and it reversed fatty liver to normal conditions, as measured by biochemical and histological analyses. Our results indicate that the protective effect of SC is accompanied by a significant increase in phospho-AMPK and PPAR? expression in hepatic tissue of alcoholic rats, thereby suggesting that SC has the ability to prevent ethanol-induced fatty liver, possibly through activation of AMPK and PPAR? signaling. PMID:24456360

  8. Does Methylmercury-Induced Hypercholesterolemia Play a Causal Role in Its Neurotoxicity and Cardiovascular Disease?

    PubMed Central

    Farina, Marcelo

    2012-01-01

    Methylmercury (MeHg) is an environmental pollutant that biomagnifies throughout the aquatic food chain, thus representing a toxicological concern for humans subsiding on fish for their dietary intake. Although the developing brain is considered the critical target organ of MeHg toxicity, recent evidence indicates that the cardiovascular system may be the most sensitive in adults. However, data on the mechanisms mediating MeHg-induced cardiovascular toxicity are scarce. Based on the close relationship between cardiovascular disease and dyslipidemia, this study was designed to investigate the effects of long-term MeHg exposure on plasma lipid levels in mice, as well as their underlying mechanisms and potential relationships to MeHg-induced neurotoxicity. Our major finding was that long-term MeHg exposure induced dyslipidemia in rodents. Specifically, Swiss and C57BL/6 mice treated for 21 days with a drinking solution of MeHg (40mg/l, ad libitum) diluted in tap water showed increased total and non-HDL plasma cholesterol levels. MeHg-induced hypercholesterolemia was also observed in low-density lipoprotein receptor knockout (LDLr–/–) mice, indicating that this effect was not related to decreased LDLr-mediated cholesterol transport from blood to other tissues. Although the hepatic synthesis of cholesterol was unchanged, significant signs of nephrotoxicity (glomerular shrinkage, tubular vacuolization, and changed urea levels) were observed in MeHg-exposed mice, indicating that the involvement of nephropathy in MeHg-induced lipid dyshomeostasis may not be ruled out. Notably, Probucol (a lipid-lowering drug) prevented the development of hypercholesterolemia when coadministered with MeHg. Finally, hypercholesterolemic LDLr–/– mice were more susceptible to MeHg-induced cerebellar glial activation, suggesting that hypercholesterolemia in itself may pose a risk factor in MeHg-induced neurotoxicity. Overall, based on the strong and graded positive association between total as well as LDL cholesterol and risk of cardiovascular diseases, our data support the concept of MeHg-induced cardiovascular toxicity. PMID:22903822

  9. Does methylmercury-induced hypercholesterolemia play a causal role in its neurotoxicity and cardiovascular disease?

    PubMed

    Moreira, Eduardo Luiz; de Oliveira, Jade; Dutra, Márcio Ferreira; Santos, Danúbia Bonfanti; Gonçalves, Carlos Alberto; Goldfeder, Eliane Maria; de Bem, Andreza Fabro; Prediger, Rui Daniel; Aschner, Michael; Farina, Marcelo

    2012-12-01

    Methylmercury (MeHg) is an environmental pollutant that biomagnifies throughout the aquatic food chain, thus representing a toxicological concern for humans subsiding on fish for their dietary intake. Although the developing brain is considered the critical target organ of MeHg toxicity, recent evidence indicates that the cardiovascular system may be the most sensitive in adults. However, data on the mechanisms mediating MeHg-induced cardiovascular toxicity are scarce. Based on the close relationship between cardiovascular disease and dyslipidemia, this study was designed to investigate the effects of long-term MeHg exposure on plasma lipid levels in mice, as well as their underlying mechanisms and potential relationships to MeHg-induced neurotoxicity. Our major finding was that long-term MeHg exposure induced dyslipidemia in rodents. Specifically, Swiss and C57BL/6 mice treated for 21 days with a drinking solution of MeHg (40 mg/l, ad libitum) diluted in tap water showed increased total and non-HDL plasma cholesterol levels. MeHg-induced hypercholesterolemia was also observed in low-density lipoprotein receptor knockout (LDLr?/?) mice, indicating that this effect was not related to decreased LDLr-mediated cholesterol transport from blood to other tissues. Although the hepatic synthesis of cholesterol was unchanged, significant signs of nephrotoxicity (glomerular shrinkage, tubular vacuolization, and changed urea levels) were observed in MeHg-exposed mice, indicating that the involvement of nephropathy in MeHg-induced lipid dyshomeostasis may not be ruled out. Notably, Probucol (a lipid-lowering drug) prevented the development of hypercholesterolemia when coadministered with MeHg. Finally, hypercholesterolemic LDLr?/? mice were more susceptible to MeHg-induced cerebellar glial activation, suggesting that hypercholesterolemia in itself may pose a risk factor in MeHg-induced neurotoxicity. Overall, based on the strong and graded positive association between total as well as LDL cholesterol and risk of cardiovascular diseases, our data support the concept of MeHg-induced cardiovascular toxicity. PMID:22903822

  10. Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data?

    SciTech Connect

    Schultz-Hector, Susanne [Helmholtz-Gemeinschaft, Berlin (Germany)]. E-mail: susanne.schultz-hector@helmholtz.de; Trott, Klaus-Ruediger Prof. [Gray Cancer Institute, Northwood (United Kingdom)

    2007-01-01

    The Life Span Study of Japanese atomic bomb survivors demonstrates that radiation exposure significantly increased the risk of developing ischemic heart disease, in particular myocardial infarction. Similarly, epidemiologic investigations in very large populations of patients who had received postoperative radiotherapy for breast cancer or for peptic ulcer demonstrate that radiation exposure of the heart with an average equivalent single dose of approximately 2 Gy significantly increased the risk of developing ischemic heart disease more than 10 years after irradiation. These epidemiologic findings are compatible with radiobiologic data on the pathogenesis of radiation-induced heart disease in experimental animals. The critical target structure appears to be the endothelial lining of blood vessels, in particular arteries, leading to early functional alterations such as pro-inflammatory responses and other changes, which are slowly progressive. Research should concentrate on the interaction of these radiation-induced endothelial changes with the early stages of age-related atherosclerosis to develop criteria for optimizing treatment plans in radiotherapy and also potential interventional strategies.

  11. Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson's disease

    PubMed Central

    Esteves, Marta; Cristóvão, Ana C.; Saraiva, Tatiana; Rocha, Sandra M.; Baltazar, Graça; Ferreira, Lino; Bernardino, Liliana

    2015-01-01

    Retinoic acid (RA) plays an important role in the commitment, maturation and survival of neural cells. Recently, RA was pointed as a therapeutic option for some neurodegenerative diseases, including Parkinson's disease (PD). The administration of RA has been defying, and in this sense we have previously developed novel RA-loaded polymeric nanoparticles (RA-NPs) that ensure the efficient intracellular transport and controlled release of RA. Herein, we show that nanoformulation as an efficient neuroprotective effect on dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mouse model for PD. The results showed that the RA-NPs administration induced a significant reduction of DA neuron loss in the substantia nigra (SN) as well as their neuronal fiber/axonal innervations in the striatum. Furthermore, we observed an increase in the expression levels of the transcription factors Pitx3 and Nurr1 induced by RA-NPs, showing its supportive effect on the development and functional maintenance of DA neurons in PD. This is the first study showing that RA-NPs can be an innovative strategy to halt the progression of PD pathogenesis, suggesting that this nanoformulation could be of particular interest for the development of new approaches for PD therapeutics. PMID:25798108

  12. Increasing both CoCrMo-alloy Particle Size and Surface Irregularity Induces Increased Macrophage Inflammasome Activation In vitro Potentially through Lysosomal Destabilization Mechanisms

    PubMed Central

    Caicedo, Marco S; Samelko, Lauryn; McAllister, Kyron; Jacobs, Joshua J; Hallab, Nadim J

    2014-01-01

    Recent investigations indicate that innate immune “danger-signaling” pathways mediate metal implant debris induced-inflammatory responses, e.g. NALP3 inflammasome. How the physical characteristics of particles, (size, shape and chemical composition) affect this inflammatory reactivity remains controversial. We examined the role of Cobalt-Chromium-Molybdenum (CoCrMo) alloy particle shape and size on human macrophage phagocytosis, lysosomal destabilization, and inflammasome activation. Round/smooth vs. irregularly shaped/rough CoCrMo-alloy particles of ~1µm and 6 to 7µm diameter were investigated for differential lysosomal damage and inflammasome activation in human monocytes/macrophages. While spherical/smooth 1µm CoCrMo-alloy particles did not measurably affect macrophage IL-1? production, irregular 1µm CoCrMo-alloy particles induced significant IL-1? increases over controls. Both round/smooth particles and irregular CoCrMo-alloy particles that were 6 to 7µ min size induced >10-fold increases in IL-1? production compared to similarly shaped smaller particles (p<0.05). Larger irregular particles induced a greater degree of intracellular lysosomal damage and a >3-fold increase in IL-1? vs. similarly sized round/smooth particles (at an equal dose, particles/cell). CoCrMo-alloy particle-size-induced IL-1? production was dependent on the lysosomal protease Cathepsin B, further supporting lysosomal destabilization as causative in inflammation. Phagocytosable larger/irregular shaped particles (6µm) demonstrated the greatest lysosomal destabilization (observed immunofluorescently) and inflammatory reactivity when compared on an equal dose basis (particles/cell) to smaller/spherical 1µm particles in vitro. PMID:23794526

  13. Emerging mechanistic targets in lung injury induced by combustion-generated particles.

    EPA Science Inventory

    ABSTRACT The mechanism for biological effect following pulmonary exposure to combustion-generated particles is incompletely defined. Transient receptor potential (TRP) cation channels were identified as ?particle sensors? in that their activation was coupled with the initiation ...

  14. Nrf2 Is a Protective Factor against Oxidative Stresses Induced by Diesel Exhaust Particle in Allergic Asthma

    PubMed Central

    Kawada, Tomoyuki; Azuma, Arata

    2013-01-01

    Epidemiological studies have shown that air pollutants, such as diesel exhaust particle (DEP), are implicated in the increased incidence of allergic airway disorders. In vitro studies of molecular mechanisms have focused on the role of reactive oxygen species generated directly and indirectly by the exposure to DEP. Antioxidants effectively reduce the allergic inflammatory effects induced by DEP both in vitro and in vivo. On the other hand, Nrf2 is a transcription factor essential for the inducible and/or constitutive expression of phase II and antioxidant enzymes. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses and exacerbation of allergic inflammation induced by DEP in mice. Host responses to DEP are regulated by a balance between antioxidants and proinflammatory responses. Nrf2 may be an important protective factor against oxidative stresses induced by DEP in airway inflammation and allergic asthma and is expected to contribute to chemoprevention against DEP health effects in susceptible individuals. PMID:23738037

  15. GENOMIC IDENTIFICATION OF POTENTIAL RISK FACTORS DURING ACETAMINOPHEN-INDUCED LIVER DISEASE IN SUSCEPTIBLE AND RESISTANT STRAINS OF MICE

    EPA Science Inventory

    Drug-induced liver disease (DILD) continues to cause significant morbidity and mortality and impair new drug development. Mounting evidence suggests that DILD is a complex, multifactorial disease in which no one factor is likely to be an absolute indicator of susceptibility. As a...

  16. G Protein-Mediated Neuronal DNA Fragmentation Induced by Familial Alzheimer's Disease-Associated Mutants of APP

    Microsoft Academic Search

    Tomoki Yamatsuji; Takashi Matsui; Takashi Okamoto; Katsumi Komatsuzaki; Shizu Takeda; Hiroaki Fukumoto; Takeshi Iwatsubo; Nobuhiro Suzuki; Asano Asami-Odaka; Scott Ireland; T. Bernard Kinane; Ugo Giambarella; Ikuo Nishimoto

    1996-01-01

    Missense mutations in the 695-amino acid form of the amyloid precursor protein (APP695) cosegregate with disease phenotype in families with dominantly inherited Alzheimer's disease. These mutations convert valine at position 642 to isoleucine, phenylalanine, or glycine. Expression of these mutant proteins, but not of normal APP695, was shown to induce nucleosomal DNA fragmentation in neuronal cells. Induction of DNA fragmentation

  17. The 2.6Angstrom Structure of Infectious Bursal Disease Virus-Derived T=1 Particles Reveals New Stabilizing Elements of the Virus Capsid

    Microsoft Academic Search

    D. Garriga; J. Querol-Audi; F. Abaitua; I. Saugar; J. Pous; N. Verdaguer; J. R. Caston; J. F. Rodriguez

    2006-01-01

    Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is a double-stranded RNA virus that causes a highly contagious disease in young chickens leading to significant economic losses in the poultry industry. The VP2 protein, the only structural component of the IBDV icosahedral capsid, spontaneously assembles into T1 subviral particles (SVP) when individually expressed as a chimeric gene.

  18. Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: Implication of chemical components and NF-?B signaling

    PubMed Central

    2010-01-01

    Background Epidemiological evidence supports the association between exposure to ambient particulate matter (PM) and cardiovascular diseases. Chronic exposure to ultrafine particles (UFP; Dp <100 nm) is reported to promote atherosclerosis in ApoE knockout mice. Atherogenesis-prone factors induce endothelial dysfunction that contributes to the initiation and progression of atherosclerosis. We previously demonstrated that UFP induced oxidative stress via c-Jun N-terminal Kinases (JNK) activation in endothelial cells. In this study, we investigated pro-inflammatory responses of human aortic endothelial cells (HAEC) exposed to UFP emitted from a diesel truck under an idling mode (UFP1) and an urban dynamometer driving schedule (UFP2), respectively. We hypothesize that UFP1 and UFP2 with distinct chemical compositions induce differential pro-inflammatory responses in endothelial cells. Results UFP2 contained a higher level of redox active organic compounds and metals on a per PM mass basis than UFP1. While both UFP1 and UFP2 induced superoxide production and up-regulated stress response genes such as heme oxygenease-1 (HO-1), OKL38, and tissue factor (TF), only UFP2 induced the expression of pro-inflammatory genes such as IL-8 (2.8 ± 0.3-fold), MCP-1 (3.9 ± 0.4-fold), and VCAM (6.5 ± 1.1-fold) (n = 3, P < 0.05). UFP2-exposed HAEC also bound to a higher number of monocytes than UFP1-exposed HAEC (Control = 70 ± 7.5, UFP1 = 106.7 ± 12.5, UFP2 = 137.0 ± 8.0, n = 3, P < 0.05). Adenovirus NF-?B Luciferase reporter assays revealed that UFP2, but not UFP1, significantly induced NF-?B activities. NF-?B inhibitor, CAY10512, significantly abrogated UFP2-induced pro-inflammatory gene expression and monocyte binding. Conclusion While UFP1 induced higher level of oxidative stress and stress response gene expression, only UFP2, with higher levels of redox active organic compounds and metals, induced pro-inflammatory responses via NF-?B signaling. Thus, UFP with distinct chemical compositions caused differential response patterns in endothelial cells. PMID:20307321

  19. Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson's disease: a dose-finding study.

    PubMed

    Svenningsson, Per; Rosenblad, Carl; Af Edholm Arvidsson, Karolina; Wictorin, Klas; Keywood, Charlotte; Shankar, Bavani; Lowe, David A; Björklund, Anders; Widner, Håkan

    2015-04-01

    In advanced stages of Parkinson's disease, serotonergic terminals take up l-DOPA and convert it to dopamine. Abnormally released dopamine may participate in the development of l-DOPA-induced dyskinesias. Simultaneous activation of 5-HT1A and 5-HT1B receptors effectively blocks l-DOPA-induced dyskinesias in animal models of dopamine depletion, justifying a clinical study with eltoprazine, a 5-HT1A/B receptor agonist, against l-DOPA-induced dyskinesias in patients with Parkinson's disease. A double-blind, randomized, placebo-controlled and dose-finding phase I/IIa study was conducted. Single oral treatment with placebo or eltoprazine, at 2.5, 5 and 7.5 mg, was tested in combination with a suprathreshold dose of l-DOPA (Sinemet®) in 22 patients with Parkinson's disease (16 male/six female; 66.6 ± 8.8 years old) with l-DOPA-induced dyskinesias. A Wilcoxon Signed Ranked Test was used to compare each eltoprazine dose level to paired randomized placebo on the prespecified primary efficacy variables; area under the curve scores on Clinical Dyskinesia Rating Scale for 3 h post-dose and maximum change of Unified Parkinson's Disease Rating Scale part III for 3 h post-dose. Secondary objectives included effects on maximum Clinical Dyskinesia Rating Scale score, area under the curve of Rush Dyskinesia Rating Scale score for 3 h post-dose, mood parameters measured by Hospital Anxiety Depression Scale and Montgomery Asberg Depression Rating Scale along with the pharmacokinetics, safety and tolerability profile of eltoprazine. A mixed model repeated measures was used for post hoc analyses of the area under the curve and peak Clinical Dyskinesia Rating Scale scores. It was found that serum concentrations of eltoprazine increased in a dose-proportional manner. Following levodopa challenge, 5 mg eltoprazine caused a significant reduction of l-DOPA-induced dyskinesias on area under the curves of Clinical Dyskinesia Rating Scale [-1.02(1.49); P = 0.004] and Rush Dyskinesia Rating Scale [-0.15(0.23); P = 0.003]; and maximum Clinical Dyskinesia Rating Scale score [-1.14(1.59); P = 0.005]. The post hoc analysis confirmed these results and also showed an antidyskinetic effect of 7.5 mg eltoprazine. Unified Parkinson's Disease Rating Scale part III scores did not differ between the placebo and eltoprazine treatments. The most frequent adverse effects after eltoprazine were nausea and dizziness. It can be concluded that a single dose, oral treatment with eltoprazine has beneficial antidyskinetic effects without altering normal motor responses to l-DOPA. All doses of eltoprazine were well tolerated, with no major adverse effects. Eltoprazine has a favourable risk-benefit and pharmacokinetic profile in patients with Parkinson's disease. The data support further clinical studies with chronic oral eltoprazine to treat l-DOPA-induced-dyskinesias. PMID:25669730

  20. Role of Cardiovascular Disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation

    EPA Science Inventory

    Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-ove...

  1. Brain antioxidant capacity in rat models of betacytotoxic-induced experimental sporadic Alzheimer’s disease and diabetes mellitus

    Microsoft Academic Search

    I. Tahirovic; E. Sofic; A. Sapcanin; I. Gavrankapetanovic; L. Bach-Rojecky; M. Salkovic-Petrisic; Z. Lackovic; S. Hoyer; P. Riederer

    It is believed that oxidative stress plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus\\u000a (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer’s\\u000a disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly\\u000a (STZ-icv) treated rats, in which antioxidant capacity against peroxyl (ORAC_roo

  2. Reduced Brain Antioxidant Capacity in Rat Models of Betacytotoxic-Induced Experimental Sporadic Alzheimer’s Disease and Diabetes Mellitus

    Microsoft Academic Search

    Ismet Tahirovic; Emin Sofic; Aida Sapcanin; Ismet Gavrankapetanovic; Lidija Bach-Rojecky; Melita Salkovic-Petrisic; Zdravko Lackovic; Siegfried Hoyer; Peter Riederer

    2007-01-01

    It is believed that oxidative stress (OS) plays a central role in the pathogenesis of metabolic diseases like diabetes mellitus\\u000a (DM) and its complications (like peripheral neuropathy) as well as in neurodegenerative disorders like sporadic Alzheimer’s\\u000a disease (sAD). Representative experimental models of these diseases are streptozotocin (STZ)-induced diabetic rats and STZ-intracerebroventricularly\\u000a (STZ-icv) treated rats, in which antioxidant capacity (AC) against

  3. Modeling climate impact on an emerging disease, the Phytophthora alni-induced alder decline.

    PubMed

    Aguayo, Jaime; Elegbede, Fabrice; Husson, Claude; Saintonge, François-Xavier; Marçais, Benoît

    2014-10-01

    Alder decline caused by Phytophthora alni is one of the most important emerging diseases in natural ecosystems in Europe, where it has threatened riparian ecosystems for the past 20 years. Environmental factors, such as mean site temperature and soil characteristics, play an important role in the occurrence of the disease. The objective of the present work was to model and forecast the effect of environment on the severity of alder Phytophthora outbreaks, and to determine whether recent climate change might explain the disease emergence. Two alder sites networks in NE and SW France were surveyed to assess the crown health of trees; the oomycete soil inoculum was also monitored in the NE network. The main factors explaining the temporal annual variation in alder crown decline or crown recovery were the mean previous winter and previous summer temperatures. Both low winter temperatures and high summer temperatures were unfavorable to the disease. Cold winters promoted tree recovery because of poor survival of the pathogen, while hot summer temperature limited the incidence of tree decline. An SIS model explaining the dynamics of the P. alni-induced alder decline was developed using the data of the NE site network and validated using the SW site network. This model was then used to simulate the frequency of declining alder over time with historical climate data. The last 40 years' weather conditions have been generally favorable to the establishment of the disease, indicating that others factors may be implicated in its emergence. The model, however, showed that the climate of SW France was much more favorable for the disease than that of the Northeast, because it seldom limited the overwintering of the pathogen. Depending on the European area, climate change could either enhance or decrease the severity of the alder decline. PMID:24729529

  4. Prevention of House Dust Mite Induced Allergic Airways Disease in Mice through Immune Tolerance

    PubMed Central

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens. PMID:21818308

  5. Effect of media-induced social distancing on disease transmission in a two patch setting.

    PubMed

    Sun, Chengjun; Yang, Wei; Arino, Julien; Khan, Kamran

    2011-04-01

    We formulate an SIS epidemic model on two patches. In each patch, media coverage about the cases present in the local population leads individuals to limit the number of contacts they have with others, inducing a reduction in the rate of transmission of the infection. A global qualitative analysis is carried out, showing that the typical threshold behavior holds, with solutions either tending to an equilibrium without disease, or the system being persistent and solutions converging to an endemic equilibrium. Numerical analysis is employed to gain insight in both the analytically tractable and intractable cases; these simulations indicate that media coverage can reduce the burden of the epidemic and shorten the duration of the disease outbreak. PMID:21296092

  6. Homocysteine May Involve in the Pathogenesis of Behcet's Disease by Inducing Inflammation

    PubMed Central

    Kartal Durmazlar, Selda Pelin; Akgul, Ahmet; Eskioglu, Fatma

    2008-01-01

    Objective. Our aim was to evaluate the significance of homocysteine (Hcy) in Behcet's disease (BD) and the association of elevated Hcy levels associated with the indices of inflammation in BD. Methods. Untreated 70 patients with BD and 33 healthy individuals were included into the study. Hcy, tumor necrosis alpha (TNF-?), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated with respect to activity and specific individual clinical manifestations of the disease. Results. Hcy levels were found significantly elevated in active BD when compared to inactive BD and healthy controls. Hcy levels were found to have high correlation with the number of active clinical manifestations increased. A significant positive correlation was found between serum Hcy and TNF-? levels, CRP, and ESR. Hcy was found to be the best predictor of TNF-? among other parameters. Conclusion. Hcy may involve in the pathogenesis of BD by inducing inflammation. PMID:19197380

  7. Avian oncogenesis induced by lymphoproliferative disease virus: a neglected or emerging retroviral pathogen?

    PubMed Central

    Allison, Andrew B.; Keel, M. Kevin; Philips, Jamie E.; Cartoceti, Andrew N.; Munk, Brandon A.; Nemeth, Nicole M.; Welsh, Trista I.; Thomas, Jesse M.; Crum, James M.; Lichtenwalner, Anne B.; Fadly, Aly M.; Zavala, Guillermo; Holmes, Edward C.; Brown, Justin D.

    2014-01-01

    Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown. PMID:24503062

  8. High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A.

    PubMed

    Gabandé-Rodríguez, E; Boya, P; Labrador, V; Dotti, C G; Ledesma, M D

    2014-06-01

    Niemann Pick disease type A (NPA), which is caused by loss of function mutations in the acid sphingomyelinase (ASM) gene, is a lysosomal storage disorder leading to neurodegeneration. Yet, lysosomal dysfunction and its consequences in the disease are poorly characterized. Here we show that undegraded molecules build up in neurons of acid sphingomyelinase knockout mice and in fibroblasts from NPA patients in which autophagolysosomes accumulate. The latter is not due to alterations in autophagy initiation or autophagosome-lysosome fusion but because of inefficient autophago-lysosomal clearance. This, in turn, can be explained by lysosomal membrane permeabilization leading to cytosolic release of Cathepsin B. High sphingomyelin (SM) levels account for these effects as they can be induced in control cells on addition of the lipid and reverted on SM-lowering strategies in ASM-deficient cells. These results unveil a relevant role for SM in autophagy modulation and characterize autophagy anomalies in NPA, opening new perspectives for therapeutic interventions. PMID:24488099

  9. Assay of mutation induced in human lymphoblastoid cells by combustion-generated soot particles.

    PubMed Central

    Bolsaitis, P P; Feitelberg, A S; Dekermendjian, V; Elliott, J F; Sarofim, A F; Thilly, W G

    1991-01-01

    A human lymphoblastoid cell line has been used to test for mutations caused by combustion-generated soot particles and their constituent components, which are substrate carbon-black and adsorbed condensate, principally in the form of polycyclic aromatic hydrocarbons (PAH). It was found that the mutagenicity of the PAH fraction is higher when it is contacted with cells as a liquid extract than when it is supplied as a coating on soot particles. The substrate particles were found to be nonmutagenic. The rate of transfer of mutagens from the surface of particles, combined with the retention time of respirable aerosol particles, are deemed to define their mutagenic potential. PMID:1820270

  10. Levodopa-induced dyskinesias in Parkinson’s disease: emerging treatments

    PubMed Central

    Bargiotas, Panagiotis; Konitsiotis, Spyridon

    2013-01-01

    Parkinson’s disease therapy is still focused on the use of L-3,4-dihydroxyphenylalanine (levodopa or L-dopa) for the symptomatic treatment of the main clinical features of the disease, despite intensive pharmacological research in the last few decades. However, regardless of its effectiveness, the long-term use of levodopa causes, in combination with disease progression, the development of motor complications termed levodopa-induced dyskinesias (LIDs). LIDs are the result of profound modifications in the functional organization of the basal ganglia circuitry, possibly related to the chronic and pulsatile stimulation of striatal dopaminergic receptors by levodopa. Hence, for decades the key feature of a potentially effective agent against LIDs has been its ability to ensure more continuous dopaminergic stimulation in the brain. The growing knowledge regarding the pathophysiology of LIDs and the increasing evidence on involvement of nondopaminergic systems raises the possibility of more promising therapeutic approaches in the future. In the current review, we focus on novel therapies for LIDs in Parkinson’s disease, based mainly on agents that interfere with glutamatergic, serotonergic, adenosine, adrenergic, and cholinergic neurotransmission that are currently in testing or clinical development. PMID:24174877

  11. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats

    PubMed Central

    Guimarães, Morgana R.; de Aquino, Sabrina Garcia; Coimbra, Leila S.; Spolidorio, Luis C.; Kirkwood, Keith L.; Rossa, Carlos

    2011-01-01

    Curcumin is a plant-derived dietary spice ascribed various biological activities. Curcumin therapeutic applications have been studied in a variety of conditions, but not on periodontal disease. Periodontal disease is a chronic inflammatory condition initiated by an immune response to microorganisms of the dental biofilm. Experimental periodontal disease was induced in rats by injecting LPS in the gingival tissues on the palatal aspect of upper first molars (30 ug LPS, 3 times/week for 2 weeks). Curcumin was administered to rats daily via oral gavage at 30 and 100 mg/Kg. RT-qPCR and ELISA were used to determine the expression of IL-6, TNF-? and PGE2 synthase on the gingival tissues. The inflammatory status was evaluated by stereometric and descriptive analysis on H&E-stained sections, whereas modulation of p38 MAPK and NK-?B signaling was assessed by Western blot. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels, but NF-kB was inhibited only with the lower dose of curcumin, whereas p38 MAPK activation was not affected. Curcumin produced a significant reduction on the inflammatory infiltrate and increased collagen content and fibroblastic cell numbers. Curcumin potently inhibits innate immune responses associated with periodontal disease, suggesting a therapeutic potential in this chronic inflammatory condition. PMID:21242275

  12. Baculovirus infection triggers a positive phototactic response in caterpillars to induce 'tree-top' disease.

    PubMed

    van Houte, Stineke; van Oers, Monique M; Han, Yue; Vlak, Just M; Ros, Vera I D

    2014-12-01

    Many parasites manipulate host behaviour to enhance parasite transmission and survival. A fascinating example is baculoviruses, which often induce death in caterpillar hosts at elevated positions ('tree-top' disease). To date, little is known about the underlying processes leading to this adaptive host manipulation. Here, we show that the baculovirus Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) triggers a positive phototactic response in S. exigua larvae prior to death and causes the caterpillars to die at elevated positions. This light-dependent climbing behaviour is specific for infected larvae, as movement of uninfected caterpillars during larval development was light-independent. We hypothesize that upon infection, SeMNPV captures a host pathway involved in phototaxis and/or light perception to induce this remarkable behavioural change. PMID:25540154

  13. Gynura root induces hepatic veno-occlusive disease: a case report and review of the literature.

    PubMed

    Dai, Ning; Yu, Ying-Cong; Ren, Tian-Hua; Wu, Jia-Guo; Jiang, Yuan; Shen, Lai-Gen; Zhang, Jing

    2007-03-14

    Gynura root has been used extensively in Chinese folk medicine and plays a role in promoting microcirculation and relieving pain. However, its hepatic toxicity should not be neglected. Recently, we admitted a 62-year old female who developed hepatic veno-occlusive disease (HVOD) after ingestion of Gynura root. Only a few articles on HVOD induced by Gynura root have been reported in the literature. It is suspected that pyrrolizidine alkaloids in Gynura root might be responsible for HVOD. In this paper, we report a case of HVOD and review the literature. PMID:17461462

  14. Structural Defects in the Regulatory Particle-Core Particle Interface of the Proteasome Induce a Novel Proteasome Stress Response*

    PubMed Central

    Park, Soyeon; Kim, Woong; Tian, Geng; Gygi, Steven P.; Finley, Daniel

    2011-01-01

    Proteasomes consist of a 19-subunit regulatory particle (RP) and 28-subunit core particle (CP), an ?7?7?7?7 structure. The RP recognizes substrates and translocates them into the CP for degradation. At the RP-CP interface, a heterohexameric Rpt ring joins to a heteroheptameric CP ? ring. Rpt C termini insert individually into the ? ring pockets to form a salt bridge with a pocket lysine residue. We report that substitutions of ? pocket lysine residues produce an unexpected block to CP assembly, arising from a late stage defect in ? ring assembly. Substitutions ?5K66A and ?6K62A resulted in abundant incorporation of immature CP ? subunits, associated with a complete ? ring, into proteasome holoenzymes. Incorporation of immature CP into the proteasome depended on a proteasome-associated protein, Ecm29. Using ump1 mutants, we identified Ecm29 as a potent negative regulator of RP assembly and confirmed our previous findings that proper RP assembly requires the CP. Ecm29 was enriched on proteasomes of pocket lysine mutants, as well as those of rpt4-?1 and rpt6-?1 mutants, in which the C-terminal residue, thought to contact the pocket lysine, is deleted. In both rpt6-?1 and ?6K62A proteasomes, Ecm29 suppressed opening of the CP substrate translocation channel, which is gated through interactions between Rpt C termini and the ? pockets. The ubiquitin ligase Hul5 was recruited to these proteasomes together with Ecm29. Proteasome remodeling through the addition of Ecm29 and Hul5 suggests a new layer of the proteasome stress response and may be a common response to structurally aberrant proteasomes or deficient proteasome function. PMID:21878652

  15. Size-partitioning of an urban aerosol to identify particle determinants involved in the proinflammatory response induced in airway epithelial cells

    PubMed Central

    Ramgolam, Kiran; Favez, Olivier; Cachier, Hélène; Gaudichet, Annie; Marano, Francelyne; Martinon, Laurent; Baeza-Squiban, Armelle

    2009-01-01

    Background The contribution of air particles in human cardio-respiratory diseases has been enlightened by several epidemiological studies. However the respective involvement of coarse, fine and ultrafine particles in health effects is still unclear. The aim of the present study is to determine which size fraction from a chemically characterized background aerosol has the most important short term biological effect and to decipher the determinants of such a behaviour. Results Ambient aerosols were collected at an urban background site in Paris using four 13-stage low pressure cascade impactors running in parallel (winter and summer 2005) in order to separate four size-classes (PM0.03–0.17 (defined here as ultrafine particles), PM0.17–1 (fine), PM1–2.5(intermediate) and PM2.5–10 (coarse)). Accordingly, their chemical composition and their pro-inflammatory potential on human airway epithelial cells were investigated. Considering isomass exposures (same particle concentrations for each size fractions) the pro-inflammatory response characterized by Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) release was found to decrease with aerosol size with no seasonal dependency. When cells were exposed to isovolume of particle suspensions in order to respect the particle proportions observed in ambient air, the GM-CSF release was maximal with the fine fraction. In presence of a recombinant endotoxin neutralizing protein, the GM-CSF release induced by particles is reduced for all size-fractions, with exception of the ultra-fine fraction which response is not modified. The different aerosol size-fractions were found to display important chemical differences related to the various contributing primary and secondary sources and aerosol age. The GM-CSF release was correlated to the organic component of the aerosols and especially its water soluble fraction. Finally, Cytochrome P450 1A1 activity that reflects PAH bioavailability varied as a function of the season: it was maximal for the fine fraction in winter and for the ultrafine fraction in summer. Conclusion In the frame of future regulations, a particular attention should thus be paid to the ultrafine/fine (here referred to as PM1) fraction due to their overwhelming anthropogenic origin and predominance in the urban aerosol and their pro-inflammatory potential. PMID:19302717

  16. Differential proinflammatory responses induced by diesel exhaust particles with contrasting PAH and metal content.

    PubMed

    Totlandsdal, Annike I; Låg, Marit; Lilleaas, Edel; Cassee, Flemming; Schwarze, Per

    2015-02-01

    Exposure to diesel engine exhaust particles (DEPs), representing a complex and variable mixture of components, has been linked with cellular production and release of several types of mediators related to pulmonary inflammation. A key challenge is to identify the specific components, which may be responsible for these effects. The aim of this study was to compare the proinflammatory potential of two DEP-samples with contrasting contents of polycyclic aromatic hydrocarbons (PAHs) and metals. The DEP-samples were compared with respect to their ability to induce cytotoxicity, expression and release of proinflammatory mediators (IL-6, IL-8), activation of mitogen-activated protein kinases (MAPKs) and expression of CYP1A1 and heme oxygenase-1 (HO-1) in human bronchial epithelial (BEAS-2B) cells. In addition, dithiothreitol and ascorbic acid assays were performed in order to examine the oxidative potential of the PM samples. The DEP-sample with the highest PAH and lowest metal content was more potent with respect to cytotoxicity and expression and release of proinflammatory mediators, CYP1A1 and HO-1 expression and MAPK activation, than the DEP-sample with lower PAH and higher metal content. The DEP-sample with the highest PAH and lowest metal content also possessed a greater oxidative potential. The present results indicate that the content of organic components may be determinant for the proinflammatory effects of DEP. The findings underscore the importance of considering the chemical composition of particulate matter-emissions, when evaluating the potential health impact and implementation of air pollution regulations. PMID:23900936

  17. Immunoreactivity and trypsin sensitivity of recombinant virus-like particles of foot-and-mouth disease virus.

    PubMed

    Basagoudanavar, S H; Hosamani, M; Tamil, R P; Sreenivasa, B P; Chandrasekhar, B K; Venkataramanan, R

    2015-01-01

    Foot-and-mouth disease (FMD) is an important infection affecting the health and productivity of cloven-hoofed livestock. Development of improved vaccines and diagnostic reagents is being explored to facilitate the disease control. There is an emerging interest in virus-like particles (VLPs), as their constituent structural proteins are the major immunogens. The VLPs are similar to natural virus particles but lack viral nucleic acid. The objective of the present study was to express the VLPs of FMD virus (FMDV) serotype Asia-1 (IND 63/72), using baculovirus system and characterize them for antigenic structure. The VLPs expressed in insect cells showed immunoreactivity similar to inactivated cell culture FMDV. Further they possess similar sensitivity to trypsin as the inactivated cell culture FMDV, suggesting that trypsin-sensitive antigenic sites could be similarly arranged. Our findings suggest that the FMD VLPs have similar antigenic conformational feature like the wild type virus, thus supporting their utility in development of non-infectious FMD vaccines and/or diagnostic assays. PMID:25790055

  18. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    SciTech Connect

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  19. Effects of Diesel Exhaust Particles on Left Ventricular Function in Isoproterenol-Induced Myocardial Injury and Healthy Rats

    Microsoft Academic Search

    Yuan-Horng Yan; Chien-Hua Huang; Wen-Jone Chen; Ming-Fang Wu; Tsun-Jen Cheng

    2008-01-01

    The associations between ambient particulate matter with an aerodiameter less than 2.5 µm (PM2.5) and congestive heart failure (CHF) have been reported. However, the underlying mech- anisms remain unclear. We investigated the effect of diesel exhaust particles (DEPs) on left ventricular function in isoproterenol (ISO)-induced myocardial injury and healthy rats. Male Sprague-Dawley (SD) rats were injected with ISO or normal

  20. A 3D numerical simulation of laser-induced incandescence of soot particles in coal combustion products

    Microsoft Academic Search

    Ling-hong Chen; Ke-fa Cen; Annie Garo; Gérard Grehan

    2009-01-01

    Laser-induced incandescence (LII) has received increasing attention as a potentially powerful technique for in-situ measuring\\u000a of the volume fraction and primary size of soot particles in combustion systems. In this study, a 3D Monte Carlo simulation\\u000a combined with a Mie equation was developed to analyze the influence of spectral absorption and scattering on the measured\\u000a LII flux emitted by soot

  1. Designing experimental setup and procedures for studying alpha-particle-induced adaptive response in zebrafish embryos in vivo

    E-print Network

    Yu, K.N.

    in zebrafish embryos in vivo V.W.Y. Choi a , R.K.K. Lam a , E.Y.W. Chong a , S.H. Cheng b , K.N. Yu a track detector PADC Biological effects Adaptive response Zebrafish embryos a b s t r a c t The present-particle-induced adaptive response in zebrafish embryos in vivo. Thin PADC films with a thickness of 16 lm were fabricated

  2. Respiratory disease and particulate air pollution in Santiago Chile: Contribution of erosion particles from fine sediments

    E-print Network

    Commentary Respiratory disease and particulate air pollution in Santiago Chile: Contribution pollution Santiago Erosion Sedimentation a b s t r a c t Air pollution in Santiago is a serious problem for a couple of days, followed by extreme levels of air pollution. Current regulations focus mostly on PM10

  3. Key Node Selection for Containing Infectious Disease Spread Using Particle Swarm Optimization

    E-print Network

    Wong, Limsoon

    weeks, as an effort to block a rising wave of seasonal influenza. The economic cost is high when of infectious diseases. Considering the cost in manpower and limited screening machines available, we face, feasible direct interventions include non-pharmaceutical interventions [6] and health-care interventions

  4. Subthalamic 6-OHDA-induced lesion attenuates levodopa-induced dyskinesias in the rat model of Parkinson's disease.

    PubMed

    Marin, C; Bonastre, M; Mengod, G; Cortés, R; Rodríguez-Oroz, M C; Obeso, J A

    2013-12-01

    The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta that degenerates in Parkinson's disease. The present study aimed to investigate the role of dopaminergic denervation of STN in the origin of levodopa-induced dyskinesias. Rats were distributed in four groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the STN and in the medial forebrain bundle (MFB) as follows: a) MFB-sham plus STN-sham, b) MFB-sham plus STN-lesion, c) MFB-lesion plus STN-sham, and d) MFB-lesion plus STN-lesion. Four weeks after lesions, animals were treated with levodopa (6mg/kg with 15mg/kg benserazide i.p.) twice daily for 22 consecutive days. Abnormal involuntary movements were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin, STN cytochrome oxidase (CO) and nigral GAD67 mRNAs. STN 6-OHDA denervation did not induce dyskinesias in levodopa-treated MFB-sham animals but attenuated axial (p<0.05), limb (p<0.05) and orolingual (p<0.01) dyskinesias in rats with a concomitant lesion of the nigrostriatal pathway. The attenuation of dyskinesias was associated with a decrease in the ipsilateral STN CO mRNA levels (p<0.05). No significant differences between MFB-lesion plus STN-sham and MFB-lesion plus STN-lesion groups in the extent of STN dopaminergic denervation were observed. Moreover, intrasubthalamic microinfusion of dopamine in the MFB-lesion plus STN-lesion group triggered orolingual (p<0.01), but not axial or limb, dyskinesias. These results suggest that dopaminergic STN innervation influences the expression of levodopa-induced dyskinesias but also the existence of non dopaminergic-mediated mechanisms. STN noradrenergic depletion induced by 6-OHDA in the STN needs to be taken in account as a possible mechanism explaining the attenuation of dyskinesias in the combined lesion group. PMID:24140562

  5. High glucose-induced proteome alterations in hepatocytes and its possible relevance to diabetic liver disease.

    PubMed

    Chen, Jing-Yi; Chou, Hsiu-Chuan; Chen, You-Hsuan; Chan, Hong-Lin

    2013-11-01

    Hyperglycemia can cause several abnormalities in liver cells, including diabetic liver disease. Previous research has shown that high blood glucose levels can damage liver cells through glycoxidation. However, the detailed molecular mechanisms underlying the effects of high blood glucose on the development of diabetic liver disease have yet to be elucidated. In this study, we cultured a liver cell line (Chang liver cell) in mannitol-balanced 5.5 mM, 25 mM and 100 mM d-glucose media and evaluated protein expression and redox regulation. We identified 141 proteins that showed significant changes in protein expression and 29 proteins that showed significant changes in thiol reactivity, in response to high glucose concentration. Several proteins involved in transcription-control, signal transduction, redox regulation and cytoskeleton regulation showed significant changes in expression, whereas proteins involved in protein folding and gene regulation displayed changes in thiol reactivity. Further analyses of clinical plasma specimens confirmed that the proteins AKAP8L, galectin-3, PGK 1, syntenin-1, Abin 2, aldose reductase, CD63, GRP-78, GST-pi, RXR-gamma, TPI and vimentin showed type 2 diabetic liver disease-dependent alterations. In summary, in this study we used a comprehensive hepatocyte-based proteomic approach to identify changes in protein expression and to identify redox-associated diabetic liver disease markers induced by high glucose concentration. Some of the identified proteins were validated with clinical samples and are presented as potential targets for the prognosis and diagnosis of diabetic liver disease. PMID:24011924

  6. Role of serotonin in fatty acid-induced non-alcoholic fatty liver disease in mice

    PubMed Central

    2013-01-01

    Background Saturated fatty acids are thought to be of relevance for the development of non-alcoholic fatty liver disease and obesity. However, the underlying mechanisms are poorly understood. In previous studies we found that food-derived carbohydrates such as fructose alter the intestinal serotonergic system while inducing fatty liver disease in mice. Here, we examined the effect of fatty acid quantity (11% versus 15%) and quality (saturated, monounsaturated, or polyunsaturated fatty acids) on hepatic fat accumulation, intestinal barrier and the intestinal serotonergic system. Methods C57BL/6 mice had free access to diets enriched with one of the three fatty acids or standard diet, for 8 weeks. In an additional experiment mice were fed diets enriched with saturated, monounsaturated fatty acids or standard diet supplemented with tryptophan (0.4 g/(kg.d), 8 weeks) or not. Hepatic fat accumulation, small intestinal barrier impairment and components of the serotonergic system were measured with RT-PCR, western blot or immunoassays. For statistical analysis t-test and one-way ANOVA with Tukey’s post hoc test and Bartlett’s test for equal variances was used. Results Hepatic triglycerides, liver weight and liver to body weight ratio were significantly changed depending on the fat quality but not fat quantity. In contrast, fat quantity but not quality decreased the expression of the tight junction proteins occludin and claudin-1 in the small intestine. These changes seemed to result in enhanced portal vein endotoxin concentrations and fatty liver disease after feeding diet enriched with saturated and monounsaturated fatty acids but not polyunsaturated fatty acids. Neither fatty acid quantity nor quality significantly influenced the intestinal serotonergic system. Similarly, tryptophan supplementation had no impact on small intestinal barrier or fatty liver disease. Conclusion In conclusion, diets rich in saturated or monounsaturated fatty acids promote the development of fatty liver disease in mice, likely by a dysfunction of the small intestinal mucosal barrier. PMID:24321090

  7. Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

    PubMed Central

    Casaravilla, Cecilia; Pittini, Álvaro; Rückerl, Dominik; Seoane, Paula I.; Jenkins, Stephen J.; MacDonald, Andrew S.; Ferreira, Ana M.; Allen, Judith E.

    2014-01-01

    The larval stage of the cestode parasite Echinococcus granulosus causes hydatid disease in humans and livestock. This infection is characterized by the growth in internal organ parenchymae of fluid-filled structures (hydatids) that elicit surprisingly little inflammation in spite of their massive size and persistence. Hydatids are protected by a millimeter-thick layer of mucin-based extracellular matrix, termed the laminated layer (LL), which is thought to be a major factor determining the host response to the infection. Host cells can interact both with the LL surface and with materials that are shed from it to allow parasite growth. In this work, we analyzed the response of dendritic cells (DCs) to microscopic pieces of the native mucin-based gel of the LL (pLL). In vitro, this material induced an unusual activation state characterized by upregulation of CD86 without concomitant upregulation of CD40 or secretion of cytokines (interleukin 12 [IL-12], IL-10, tumor necrosis factor alpha [TNF-?], and IL-6). When added to Toll-like receptor (TLR) agonists, pLL-potentiated CD86 upregulation and IL-10 secretion while inhibiting CD40 upregulation and IL-12 secretion. In vivo, pLL also caused upregulation of CD86 and inhibited CD40 upregulation in DCs. Contrary to expectations, oxidation of the mucin glycans in pLL with periodate did not abrogate the effects on cells. Reduction of disulfide bonds, which are known to be important for LL structure, strongly diminished the impact of pLL on DCs without altering the particulate nature of the material. In summary, DCs respond to the LL mucin meshwork with a “semimature” activation phenotype, both in vitro and in vivo. PMID:24842926

  8. COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1

    EPA Science Inventory

    Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary dis...

  9. Photoelectric charging of dust particles: Effect of spontaneous and light induced field emission of electrons

    SciTech Connect

    Sodha, M. S.; Dixit, A. [Disha Institute of Management and Technology, Satya Vihar, Vidhan Sabha-Chandrakhuri Marg, Mandir Hasaud, Raipur, 492101 Chattisgarh (India)

    2009-09-07

    The authors have analyzed the charging of dust particles in a plasma, taking into account the electron/ion currents to the particles, electron/ion generation and recombination, electric field emission, photoelectric emission and photoelectric field emission of electrons under the influence of light irradiation; the irradiance has been assumed to be at a level, which lets the particles retain the negative sign of the charge. Numerical results and discussion conclude the papers.

  10. Visible light induced water cleavage in colloidal solutions of chromium-doped titanium dioxide particles

    Microsoft Academic Search

    Enrico Borgarello; John Kiwi; M. Gratzel; Ezio Pelizzetti; Mario Visca

    1982-01-01

    Surface doping of colloidal TiOâ particles with chromic ions precipitated from aqueous HâSOâ solution produces very small (<0.1 ..mu..m) mixed-oxide particles which absorb light in the 400-550-nm region in addition to the band-gap absorption of anatase. Sustained water cleavage by visible light is observed in aqueous solutions of these particles. Ultrafine deposits of Pt or RuOâ are necessary to promote

  11. Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson's disease patients.

    PubMed

    Politis, Marios; Wu, Kit; Loane, Clare; Brooks, David J; Kiferle, Lorenzo; Turkheimer, Federico E; Bain, Peter; Molloy, Sophie; Piccini, Paola

    2014-03-01

    Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson's disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD. PMID:24531549

  12. Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease.

    PubMed

    French, Curtis R; Seshadri, Sudha; Destefano, Anita L; Fornage, Myriam; Arnold, Corey R; Gage, Philip J; Skarie, Jonathan M; Dobyns, William B; Millen, Kathleen J; Liu, Ting; Dietz, William; Kume, Tsutomu; Hofker, Marten; Emery, Derek J; Childs, Sarah J; Waskiewicz, Andrew J; Lehmann, Ordan J

    2014-11-01

    Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2-/- mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease. PMID:25250569

  13. Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease

    PubMed Central

    French, Curtis R.; Seshadri, Sudha; Destefano, Anita L.; Fornage, Myriam; Arnold, Corey R.; Gage, Philip J.; Skarie, Jonathan M.; Dobyns, William B.; Millen, Kathleen J.; Liu, Ting; Dietz, William; Kume, Tsutomu; Hofker, Marten; Emery, Derek J.; Childs, Sarah J.; Waskiewicz, Andrew J.; Lehmann, Ordan J.

    2014-01-01

    Patients with cerebral small-vessel disease (CSVD) exhibit perturbed end-artery function and have an increased risk for stroke and age-related cognitive decline. Here, we used targeted genome-wide association (GWA) analysis and defined a CSVD locus adjacent to the forkhead transcription factor FOXC1. Moreover, we determined that the linked SNPs influence FOXC1 transcript levels and demonstrated that patients as young as 1 year of age with altered FOXC1 function exhibit CSVD. MRI analysis of patients with missense and nonsense mutations as well as FOXC1-encompassing segmental duplication and deletion revealed white matter hyperintensities, dilated perivascular spaces, and lacunar infarction. In a zebrafish model, overexpression or morpholino-induced suppression of foxc1 induced cerebral hemorrhage. Inhibition of foxc1 perturbed platelet-derived growth factor (Pdgf) signaling, impairing neural crest migration and the recruitment of mural cells, which are essential for vascular stability. GWA analysis also linked the FOXC1-interacting transcription factor PITX2 to CSVD, and both patients with PITX2 mutations and murine Pitx2–/– mutants displayed brain vascular phenotypes. Together, these results extend the genetic etiology of stroke and demonstrate an increasing developmental basis for human cerebrovascular disease. PMID:25250569

  14. Prostaglandins in the perilymph of guinea pig with type II collagen induced ear diseases

    SciTech Connect

    Takeda, T.; Chiang, T.; Kitano, H.; Sudo, N.; Kim, S.Y.; Ha, S.; Woo, V.; Wolf, B.; Floyd, R.; Yoo, T.J.

    1986-03-01

    The authors have studied the prostaglandins (PGs) in the perilymph from guinea pig with type II collagen induced autoimmune ear disease. Hartly guinea pigs were immunized with type II collagen in CFA and auditory brain stem responses (ABR) were measured at 2, 3, 4, and 6 months after initial immunization perilymph was obtained and the levels of PGE2 and 6 keto-PGFl..cap alpha.. were measured by radioimmunoassays. Temporal bones were examined for the histopathologic changes. Immunized guinea pigs showed the evidence of hearing loss by ABR. The temporal bones showed the following changes: spiral ganglia degeneration, mild to moderate degree of degeneration in organ of Corti, infrequent very mild endolymphatic hydrops and labrynthitis. The perilymph from immunized animals contained about 5 times more PGE2 and about 3 times more 6 keto-PGFl..cap alpha.. than control animals. However, between these two groups, there was no difference in the CSF and sera levels of PGE2 and 6 keto-PGFl..cap alpha... Thus, this study suggests that these inflammatory mediators might be involved in the pathogenesis of collagen induced autoimmune inner ear disease.

  15. Reactivity against microsatellite instability-induced frameshift mutations in patients with inflammatory bowel disease

    PubMed Central

    Kuehn, Florian; Klar, Ernst; Bliemeister, Anja; Linnebacher, Michael

    2015-01-01

    AIM: To analyze the cellular immune response towards microsatellite-instability (MSI)-induced frameshift-peptides (FSPs) in patients suffering from inflammatory bowel disease (IBD) with and without thiopurine-based immunosuppressive treatment. METHODS: Frequencies of peripheral blood T cell responses of IBD patients (n = 75) against FSPs derived from 14 microsatellite-containing candidate genes were quantified by interferon-? enzyme-linked immunospot. T cells derived from 20 healthy individuals served as controls. RESULTS: Significant T cell reactivities against MSI-induced FSPs were observed in 59 of 75 IBD patients (78.7%). This was significantly more as we could observe in 20 healthy controls (P = 0.001). Overall, the reactivity was significantly influenced by thiopurine treatment (P = 0.032) and duration of disease (P = 0.002) but not by duration or cumulative amount of thiopurine therapy (P = 0.476). Unexpected, 15 of 24 (62.5%) IBD patients without prior thiopurine treatment also showed increased FSP-specific immune responses (P = 0.001). CONCLUSION: These findings propose FSPs as potential novel class of inflammation-associated antigens and this in turn may have implications for screening, diagnosis as well as clinical management of patients suffering from IBD and other inflammatory conditions. PMID:25574094

  16. Protective effects of curcumin against rotenone and salsolinol-induced toxicity: implications for Parkinson's disease.

    PubMed

    Qualls, Zakiya; Brown, Dwayne; Ramlochansingh, Carlana; Hurley, Laura L; Tizabi, Yousef

    2014-01-01

    Parkinson's disease (PD) is a debilitating neurodegenerative disorder that results from the loss of or damage to dopaminergic cells in the substantia nigra. Exposure to either the pesticide rotenone or the endogenous neurotoxin salsolinol has been shown to mimic this dopaminergic cell loss. In this study, we first sought to determine whether combination of rotenone and salsolinol would result in an additive or synergistic toxicity. For this purpose we utilized SH-SY5Y cells, a human neuroblastoma cell line that is commonly used to model dopaminergic neurodegeneration. We then tested whether curcumin, a natural plant compound with known health benefits including potential neuroprotective properties, could also protect against rotenone and/or salsolinol-induced toxicity. Moreover, since apoptotic mechanism has been implicated in toxicity of these compounds the anti-apoptotic effect of curcumin was also evaluated. Our results indicate a synergistic toxicity of low concentrations of rotenone (1 and 5 µM) and salsolinol (25 and 50 µM) that was associated with apoptosis as determined by cell flow cytometry. There was also an increase in caspase-3 levels. Pretreatment with curcumin (1-µM) dose-dependently attenuated rotenone and/or salsolinol-induced toxicity and the associated apoptosis. These results suggest that exposure to a combination of rotenone and salsolinol may contribute to the pathology of PD, and that curcumin has a therapeutic potential in this disease. PMID:24122264

  17. An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease

    PubMed Central

    Onuki, Reiko; Bando, Yoshio; Suyama, Eigo; Katayama, Taiichi; Kawasaki, Hiroaki; Baba, Tadashi; Tohyama, Masaya; Taira, Kazunari

    2004-01-01

    Various types of stress, such as disruption of calcium homeostasis, inhibition of protein glycosylation and reduction of disulfide bonds, result in accumulation of misfolded proteins in the endoplasmic reticulum (ER). The initial cellular response involves removal of such proteins by the ER, but excessive and/or long-term stress results in apoptosis. In this study, we used a randomized ribozyme library and ER stress-mediated apoptosis (tunicamycin-induced apoptosis) in SK-N-SH human neuroblastoma cells as a selective phenotype to identify factors involved in this process. We identified a double-stranded RNA-dependent protein kinase (PKR) as one of the participants in this process. The level of nuclear PKR was elevated, but the level of cytoplasmic PKR barely changed in tunicamycin-treated SK-N-SH cells. Furthermore, tunicamycin also raised levels of phosphorylated PKR in the nucleus. We also detected the accumulation of phosphorylated PKR in the nuclei of autopsied brain tissues in Alzheimer's disease. Thus, PKR might play a role in ER stress-induced apoptosis and in Alzheimer's disease. PMID:14765129

  18. Anti-cytochrome P450 autoantibodies in drug-induced disease.

    PubMed

    Beaune, P H; Lecoeur, S; Bourdi, M; Gauffre, A; Belloc, C; Dansette, P; Mansuy, D

    1996-01-01

    Drugs may induce hepatitis through immune mechanisms. In this review we have used the examples of 2 drugs to elucidate the first steps leading to the triggering of such disease, namely tienilic acid (TA) and dihydralazine (DH). These drugs are transformed into reactive metabolite(s) by cytochrome P450 (2C9 for TA and 1A2 for DH) (step 1). The reactive metabolites produced are very short-lived and bind directly to the enzymes which generated them (step 2). A neoantigen is thus formed which triggers an immune response (step 3), characterized by the presence of autoantibodies in the patient's serum (step 4). The autoantibodies are directed against the cytochrome P450 which generated the metabolite(s). Although the process by which TA and DH induce-hepatitis has been elucidated, further studies are necessary to generalize this mechanism. In addition, an animal model will also be useful to fully understand the immune mechanism of this type of disease. PMID:8987248

  19. Solving the puzzle of Parkinson's disease using induced pluripotent stem cells.

    PubMed

    Zhao, Ping; Luo, Zhiwei; Tian, Weihua; Yang, Jiayin; Ibáñez, David P; Huang, Zhijian; Tortorella, Micky D; Esteban, Miguel A; Fan, Wenxia

    2014-11-01

    The prevalence and incidence of Parkinson's disease (PD) is increasing due to a prolonged life expectancy. This highlights the need for a better mechanistic understanding and new therapeutic approaches. However, traditional in vitro and in vivo experimental models to study PD are suboptimal, thus hampering the progress in the field. The epigenetic reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) offers a unique way to overcome this problem, as these cells share many properties of embryonic stem cells (ESCs) including the potential to be transformed into different lineages. PD modeling with iPSCs is nowadays facilitated by the growing availability of high-efficiency neural-specific differentiation protocols and the possibility to correct or induce mutations as well as creating marker cell lines using designer nucleases. These technologies, together with steady advances in human genetics, will likely introduce profound changes in the way we interpret PD and develop new treatments. Here, we summarize the different PD iPSCs reported so far and discuss the challenges for disease modeling using these cell lines. PMID:24939824

  20. Hydrogen absorption induced metal deposition on palladium and palladium-alloy particles

    DOEpatents

    Wang, Jia X. (East Setauket, NY); Adzic, Radoslav R. (East Setauket, NY)

    2009-03-24

    The present invention relates to methods for producing metal-coated palladium or palladium-alloy particles. The method includes contacting hydrogen-absorbed palladium or palladium-alloy particles with one or more metal salts to produce a sub-monoatomic or monoatomic metal- or metal-alloy coating on the surface of the hydrogen-absorbed palladium or palladium-alloy particles. The invention also relates to methods for producing catalysts and methods for producing electrical energy using the metal-coated palladium or palladium-alloy particles of the present invention.

  1. Use of a Soluble Epoxide Hydrolase Inhibitor in Smoke-Induced Chronic Obstructive Pulmonary Disease

    PubMed Central

    Wang, Lei; Yang, Jun; Guo, Lei; Uyeminami, Dale; Dong, Hua; Hammock, Bruce D.

    2012-01-01

    Tobacco smoke-induced chronic obstructive pulmonary disease (COPD) is a prolonged inflammatory condition of the lungs characterized by progressive and largely irreversible airflow limitation attributable to a number of pathologic mechanisms, including bronchitis, bronchiolitis, emphysema, mucus plugging, pulmonary hypertension, and small-airway obstruction. Soluble epoxide hydrolase inhibitors (sEHIs) demonstrated anti-inflammatory properties in a rat model after acute exposure to tobacco smoke. We compared the efficacy of sEHI t-TUCB (trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) and the phosphodiesterase-4 (PDE4) inhibitor Rolipram (Biomol International, Enzo Life Sciences, Farmingdale, NY) to reduce lung injury and inflammation after subacute exposure to tobacco smoke over a period of 4 weeks. Pulmonary physiology, bronchoalveolar lavage, cytokine production, and histopathology were analyzed to determine the efficacy of sEHI and Rolipram to ameliorate tobacco smoke–induced inflammation and injury in the spontaneously hypertensive rat. Both t-TUCB and Rolipram inhibited neutrophil elevation in bronchoalveolar lavage. sEHI t-TUCB suppressed IFN-?, while improving lung function by reducing tobacco smoke–induced total respiratory resistance and tissue damping (small-airway and peripheral tissue resistance). Increases in tobacco smoke–induced alveolar airspace size were attenuated by t-TUCB. Rolipram inhibited the production of airway mucus. Both t-TUCB and Rolipram inhibited vascular remodeling–related growth factor. These findings suggest that sEHI t-TUCB has therapeutic potential for treating COPD by improving lung function and attenuating the lung inflammation and emphysematous changes caused by tobacco smoke. To the best of our knowledge, this is the first report to demonstrate that sEHI exerts significant protective effects after repeated, subacute tobacco smoke–induced lung injury in a rat model of COPD. PMID:22180869

  2. A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8–induced IL-1

    PubMed Central

    Hedl, Matija; Abraham, Clara

    2014-01-01

    Inflammatory diseases are characterized by dysregulated cytokine production. Altered functions for most risk loci, including the inflammatory bowel disease and leprosy-associated tumor necrosis factor ligand superfamily member 15 (TNFSF15) region, are unclear. Regulation of pattern-recognition-receptor (PRR)-induced signaling and cytokines is crucial for immune homeostasis; TNFSF15:death receptor 3 (DR3) contributions to PRR responses have not been described. We found that human macrophages expressed DR3 and that TNFSF15:DR3 interactions were critical for amplifying PRR-initiated MAPK/NF-?B/PI3K signaling and cytokine secretion in macrophages. Mechanisms mediating TNFSF15:DR3 contributions to PRR outcomes included TACE-induced TNFSF15 cleavage to soluble TNFSF15; soluble TNFSF15 then led to TRADD/FADD/MALT-1– and caspase-8–mediated autocrine IL-1 secretion. Notably, TNFSF15 treatment also induced cytokine secretion through a caspase-8–dependent pathway in intestinal myeloid cells. Importantly, rs6478108 A disease risk-carrier macrophages demonstrated increased TNFSF15 expression and PRR-induced signaling and cytokines. Taken together, TNFSF15:DR3 interactions amplify PRR-induced signaling and cytokines, and the rs6478108 TNFSF15 disease-risk polymorphism results in a gain of function. PMID:25197060

  3. Oral immunization of rabbits with VP60 particles confers protection against rabbit hemorrhagic disease

    Microsoft Academic Search

    J. Plana-Duran; M. Bastons; M. J. Rodriguez; I. Climent; E. Cortés; C. Vela; I. Casal

    1996-01-01

    Summary Rabbit hemorrhagic disease virus (RHDV) causes more than 90% mortality in adult rabbits. In this study, the cDNA of the VP60 coding sequence of RHDV was cloned under the control of the polyhedrin and p10 promoters of baculovirus to be expressed in insect cells. The expression of RHDV VP60 under the control of the p10 promoter was 5–10 times

  4. Ultrafine particles and platelet activation in patients with coronary heart disease – results from a prospective panel study

    PubMed Central

    Rückerl, Regina; Phipps, Richard P; Schneider, Alexandra; Frampton, Mark; Cyrys, Josef; Oberdörster, Günther; Wichmann, H Erich; Peters, Annette

    2007-01-01

    Background Epidemiological studies on health effects of air pollution have consistently shown adverse cardiovascular effects. Toxicological studies have provided evidence for thrombogenic effects of particles. A prospective panel study in a susceptible population was conducted in Erfurt, Germany, to study the effects of daily changes in ambient particles on various blood cells and soluble CD40ligand (sCD40L, also known as CD154), a marker for platelet activation that can cause increased coagulation and inflammation. Blood cells and plasma sCD40L levels were repeatedly measured in 57 male patients with coronary heart disease (CHD) during winter 2000/2001. Fixed effects linear regression models were applied, adjusting for trend, weekday and meteorological parameters. Hourly data on ultrafine particles (UFP, number concentration of particles from 0.01 to 0.1 ?m), mass concentration of particles less than 10 and 2.5 ?m in diameter (PM10, PM2.5), accumulation mode particle counts (AP, 0.1–1.0 ?m), elemental and organic carbon, gaseous pollutants and meteorological data were collected at central monitoring sites. Results An immediate increase in plasma sCD40L was found in association with UFP and AP (% change from geometric mean: 7.1; CI: [0.1, 14.5] and 6.9; CI: [0.5, 13.8], respectively). Platelet counts decreased in association with UFP showing an immediate, a three days delayed (lag 3) and a 5-day average response (% change from the mean: -1.8; CI: [-3.4,-0.2]; -2.4; CI: [-4.5,-0.3] and -2.2; CI: [-4.0,-0.3] respectively). Conclusion The increased plasma sCD40L levels support the hypothesis that higher levels of ambient air pollution lead to an inflammatory response in patients with CHD thus providing a possible explanation for the observed association between air pollution and cardiovascular morbidity and mortality in susceptible parts of the population. PMID:17241467

  5. Alteration of Striatal Tetrahydrobiopterin in Iron-Induced Unilateral Model of Parkinson's Disease

    PubMed Central

    Aryal, Bijay; Lee, Jin-Koo; Kim, Hak Rim

    2014-01-01

    It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin (BH4) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of BH4 into neuron would induce the neuronal toxicity in vitro. To elucidate a role of BH4 in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and BH4 at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and BH4 levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of BH4 was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of BH4 in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both BH4 and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of BH4 can deteriorate the disease progression in early phase of PD, and the inhibition of BH4 increase could be a strategy for PD treatment. PMID:24757374

  6. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery

    PubMed Central

    Singh, Vimal K.; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner. PMID:25699255

  7. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery.

    PubMed

    Singh, Vimal K; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    Recent progresses in the field of Induced Pluripotent Stem Cells (iPSCs) have opened up many gateways for the research in therapeutics. iPSCs are the cells which are reprogrammed from somatic cells using different transcription factors. iPSCs possess unique properties of self renewal and differentiation to many types of cell lineage. Hence could replace the use of embryonic stem cells (ESC), and may overcome the various ethical issues regarding the use of embryos in research and clinics. Overwhelming responses prompted worldwide by a large number of researchers about the use of iPSCs evoked a large number of peple to establish more authentic methods for iPSC generation. This would require understanding the underlying mechanism in a detailed manner. There have been a large number of reports showing potential role of different molecules as putative regulators of iPSC generating methods. The molecular mechanisms that play role in reprogramming to generate iPSCs from different types of somatic cell sources involves a plethora of molecules including miRNAs, DNA modifying agents (viz. DNA methyl transferases), NANOG, etc. While promising a number of important roles in various clinical/research studies, iPSCs could also be of great use in studying molecular mechanism of many diseases. There are various diseases that have been modeled by uing iPSCs for better understanding of their etiology which maybe further utilized for developing putative treatments for these diseases. In addition, iPSCs are used for the production of patient-specific cells which can be transplanted to the site of injury or the site of tissue degeneration due to various disease conditions. The use of iPSCs may eliminate the chances of immune rejection as patient specific cells may be used for transplantation in various engraftment processes. Moreover, iPSC technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner. PMID:25699255

  8. Levels of circulating TNF-related apoptosis-inducing ligand in celiac disease.

    PubMed

    Celeghini, Claudio; Not, Tarcisio; Norcio, Alessia; Monasta, Lorenzo; Secchiero, Paola

    2014-12-01

    It has previously been demonstrated that the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL) are significantly lower in patients with type 1 diabetes (T1D) than in normal age- and gender-matched controls. Since celiac disease (CD) is often associated with T1D, a retrospective study was performed to analyze the sera of a cohort of pediatric subjects: i) patients with CD at onset (n=100); ii) patients with potential CD (n=45); iii) patients with CD associated with other auto-immune diseases (n=17); and iv) patients with eosinophilic esophagitis (n=15). Among the patients with CD, 49 were also analyzed after six months on a gluten-free diet, while data were also available for 13 patients after one year on a gluten-free diet. No significant differences were found in the circulating levels of TRAIL between the patients with CD and the patients with either eosinophilic esophagitis or potential CD. Patients with CD associated with other auto-immune diseases showed significantly lower levels of TRAIL when compared with patients with CD alone. The gluten-free diet did not significantly modify the levels of circulating TRAIL at 6 or 12 months. Thus, although T1D and CD share common immunological features, the circulating levels of TRAIL show a significant difference between the two pathologies, and do not appear to be modulated in CD. PMID:25371753

  9. Mechanisms of aluminum-induced neurodegeneration in animals: Implications for Alzheimer's disease.

    PubMed

    Savory, John; Herman, Mary M; Ghribi, Othman

    2006-11-01

    For four decades the controversial question concerning a possible role for aluminum neurotoxicity in contributing to the pathogenesis of Alzheimer's disease has been debated, and studies by different investigators have yielded contradictory results. The lack of sensitivity to aluminum neurotoxicity in transgenic mouse models of Alzheimer's disease has not allowed the system to be used to explore important aspects of this toxicity. Rabbits are particularly sensitive to aluminum neurotoxicity and they develop severe neurological changes that are dependent on dose, age and route of administration. The most prominent feature induced by aluminum in rabbit brain is a neurofibrillary degeneration that shares some similarity with the neurofibrillary tangles found in Alzheimer's disease patients. In the present review we discuss data from our laboratory and others, on the effects of aluminum on behaviour, neurologic function and morphology, using aluminum administered to rabbits via different routes. Finally, we will examine data on the possible cellular mechanisms underlying aluminum neurotoxicity, and potential neuroprotective strategies against aluminum toxicity. PMID:17119283

  10. Levels of circulating TNF-related apoptosis-inducing ligand in celiac disease

    PubMed Central

    CELEGHINI, CLAUDIO; NOT, TARCISIO; NORCIO, ALESSIA; MONASTA, LORENZO; SECCHIERO, PAOLA

    2014-01-01

    It has previously been demonstrated that the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL) are significantly lower in patients with type 1 diabetes (T1D) than in normal age- and gender-matched controls. Since celiac disease (CD) is often associated with T1D, a retrospective study was performed to analyze the sera of a cohort of pediatric subjects: i) patients with CD at onset (n=100); ii) patients with potential CD (n=45); iii) patients with CD associated with other auto-immune diseases (n=17); and iv) patients with eosinophilic esophagitis (n=15). Among the patients with CD, 49 were also analyzed after six months on a gluten-free diet, while data were also available for 13 patients after one year on a gluten-free diet. No significant differences were found in the circulating levels of TRAIL between the patients with CD and the patients with either eosinophilic esophagitis or potential CD. Patients with CD associated with other auto-immune diseases showed significantly lower levels of TRAIL when compared with patients with CD alone. The gluten-free diet did not significantly modify the levels of circulating TRAIL at 6 or 12 months. Thus, although T1D and CD share common immunological features, the circulating levels of TRAIL show a significant difference between the two pathologies, and do not appear to be modulated in CD. PMID:25371753

  11. Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimer's disease.

    PubMed

    Hassanzadeh, Gholamreza; Hosseini, Amir; Pasbakhsh, Parichehr; Akbari, Mohammad; Ghaffarpour, Massoud; Takzare, Nasrin; Zahmatkesh, Maryam

    2015-01-01

    Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease (AD) of sporadic origin. The expression of DHCR24 (Seladin-1), marker for neuronal oxidative stress and degeneration, has been reported to be altered in the brains of AD patients. In the present study, we investigated the effect of trimetazidine (TMZ) on the hippocampal oxidative parameters and the expression of DHCR24 (Seladin-1) in an animal model of sporadic AD. Male rats were pre-treated with TMZ (25 mg/kg) after which injected with intracerebroventricular-streptozotocin (ICV-STZ)/Saline. Following 2, 7 and 14 days, animals of different groups were sacrificed with their brain excised to detect the hippocampal lipid peroxidation, superoxide dismutase (SOD), catalase activity, DHCR24 (Seladin-1) expression and possible histopathological changes. ICV-STZ administration induced significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment showed to ameliorate the oxidative stress, which was demonstrated by a significant rise in the hippocampal SOD and catalase activity, as well as a significant decrease in the malondialdehyde (MDA) level. TMZ administration also increased the expression of DHCR24 (Seladin-1) gene in the hippocampus. In conclusion, our findings indicated a neuroprotective effect of TMZ possibly related to its antioxidant activity resulting in the up-regulation of DHCR24 (Seladin-1). Such TMZ effects may be beneficial in minimizing oxidative stress in sporadic Alzheimer's disease and possible prevention of disease progression. PMID:25597600

  12. Ganjam virus/Nairobi sheep disease virus induces a pro-inflammatory response in infected sheep

    PubMed Central

    2012-01-01

    Partly due to climate change, and partly due to changes of human habitat occupation, the impact of tick-borne viruses is increasing. Nairobi sheep disease virus (NSDV) and Ganjam virus (GV) are two names for the same virus, which causes disease in sheep and goats and is currently known to be circulating in India and East Africa. The virus is transmitted by ixodid ticks and causes a severe hemorrhagic disease. We have developed a real-time PCR assay for the virus genome and validated it in a pilot study of the pathogenicity induced by two different isolates of NSDV/GV. One isolate was highly adapted to tissue culture, grew in most cell lines tested, and was essentially apathogenic in sheep. The second isolate appeared to be poorly adapted to cell culture and retained pathogenicity in sheep. The real-time PCR assay for virus easily detected 4 copies or less of the viral genome, and allowed a quantitative measure of the virus in whole blood. Measurement of the changes in cytokine mRNAs showed similar changes to those observed in humans infected by the closely related virus Crimean Congo hemorrhagic fever virus. PMID:23083136

  13. Lentiviral overexpression of GRK6 alleviates L-dopa-induced dyskinesia in experimental Parkinson's disease.

    PubMed

    Ahmed, Mohamed R; Berthet, Amandine; Bychkov, Evgeny; Porras, Gregory; Li, Qin; Bioulac, Bernard H; Carl, Yonatan T; Bloch, Bertrand; Kook, Seunghyi; Aubert, Incarnation; Dovero, Sandra; Doudnikoff, Evelyne; Gurevich, Vsevolod V; Gurevich, Eugenia V; Bezard, Erwan

    2010-04-21

    Parkinson's disease is caused primarily by degeneration of brain dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine in the striatum. Dopamine replacement therapy with the dopamine precursor l-dopa is the mainstay of current treatment. After several years, however, the patients develop l-dopa-induced dyskinesia, or abnormal involuntary movements, thought to be due to excessive signaling via dopamine receptors. G protein-coupled receptor kinases (GRKs) control desensitization of dopamine receptors. We found that dyskinesia is attenuated by lentivirus-mediated overexpression of GRK6 in the striatum in rodent and primate models of Parkinson's disease. Conversely, reduction of GRK6 concentration by microRNA delivered with lentiviral vector exacerbated dyskinesia in parkinsonian rats. GRK6 suppressed dyskinesia in monkeys without compromising the antiparkinsonian effects of l-dopa and even prolonged the antiparkinsonian effect of a lower dose of l-dopa. Our finding that increased availability of GRK6 ameliorates dyskinesia and increases duration of the antiparkinsonian action of l-dopa suggests a promising approach for controlling both dyskinesia and motor fluctuations in Parkinson's disease. PMID:20410529

  14. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells

    PubMed Central

    Raya, Ángel; Rodríguez-Pizà, Ignasi; Guenechea, Guillermo; Vassena, Rita; Navarro, Susana; Barrero, María José; Consiglio, Antonella; Castellà, Maria; Río, Paula; Sleep, Eduard; González, Federico; Tiscornia, Gustavo; Garreta, Elena; Aasen, Trond; Veiga, Anna; Verma, Inder M.; Surrallés, Jordi; Bueren, Juan; Belmonte, Juan Carlos Izpisúa

    2009-01-01

    The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells and provided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold great therapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect, somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications. PMID:19483674

  15. Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodegenerative diseases.

    PubMed

    Gu, Zezong; Nakamura, Tomohiro; Lipton, Stuart A

    2010-06-01

    Overstimulation of N-methyl-D-aspartate (NMDA)-type glutamate receptors accounts, at least in part, for excitotoxic neuronal damage, potentially contributing to a wide range of acute and chronic neurologic diseases. Neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's disease (PD), manifest deposits of misfolded or aggregated proteins, and result from synaptic injury and neuronal death. Recent studies have suggested that nitrosative stress due to generation of excessive nitric oxide (NO) can mediate excitotoxicity in part by triggering protein misfolding and aggregation, and mitochondrial fragmentation in the absence of genetic predisposition. S-Nitrosylation, or covalent reaction of NO with specific protein thiol groups, represents a convergent signal pathway contributing to NO-induced protein misfolding and aggregation, compromised dynamics of mitochondrial fission-fusion process, thus leading to neurotoxicity. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence suggesting that NO contributes to protein misfolding and aggregation via S-nitrosylating protein-disulfide isomerase or the E3 ubiquitin ligase parkin, and mitochondrial fragmentation through beta-amyloid-related S-nitrosylation of dynamin-related protein-1. Moreover, we also discuss that inhibition of excessive NMDA receptor activity by memantine, an uncompetitive/fast off-rate (UFO) drug can ameliorate excessive production of NO, protein misfolding and aggregation, mitochondrial fragmentation, and neurodegeneration. PMID:20333559

  16. Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson's disease model rats?

    PubMed Central

    Li, Chun; Chen, Xin; Zhang, Nan; Song, Yangwen; Mu, Yang

    2012-01-01

    The present study showed that the latency of rats moving on a vertical grid was significantly prolonged, and the number of rats sliding down from the declined plane was increased remarkably, in rotenone-induced Parkinson's disease model rats compared with control rats. The moving latency recovered to normal levels, but the number of slides was significantly increased at 28 days after model establishment. The slope test is a meaningful approach to evaluate the symptoms of Parkinson's disease model rats treated with rotenone. In addition, loss of substantia nigral dopaminergic neurons in model rats was observed at 1 day after the model was established, and continued gradually at 14 and 28 days. The expression of tyrosine hydroxylase-positive cells was significantly increased in gastrodin-treated rats at 14 days. Significant numbers of activated microglia cells were observed in model rats at 14 and 28 days; treatment of rats with Madopar at 28 days suppressed microglial activation. Treatment of rats with gastrodin or Madopar at 28 days significantly reduced interleukin-1? expression. The loss of substantia nigral dopaminergic neurons paralleled the microglial activation in Parkinson's disease model rats treated with rotenone. The inflammatory factors tumor necrosis factor-? and interleukin-1? are involved in the substantia nigral damage. Gastrodin could protect dopaminergic neurons via inhibition of interleukin-1? expression and neuroinflammation in the substantia nigra.

  17. Identifying adverse drug reactions and drug-induced diseases using network-based drug mapping.

    PubMed

    Shoshi, Alban; Ogultarhan, Venus; Hoppe, Tobias; Kormeier, Benjamin; Müller, Ulrich; Hofestädt, Ralf

    2015-02-01

    Drugs are essential for the prevention and treatment of diseases. However, co-administration of multiple drugs may cause serious adverse drug reactions, which are usually known but sometimes unknown. Package inserts of prescription drugs are supposed to contain risks and side effects, but such information is not necessarily complete. At the core of efforts to improve prescription quality, there is reliance on the extent and quality of information used for decision of a medical doctor. To address this on-going need, GraphSAW provides users a comprehensive view on drug-related pharmacological and molecular information. The features of GraphSAW allow users to analyze drug cocktails for adverse drug reactions and drug-induced diseases. Network visualization by drug mapping enables exploring associative networks of drugs, pathways, and diseases to fully understand effects of drugs in an intuitive way. GraphSAW is meant to be a platform and starting point for health professionals and researchers for educational and scientific research in order to achieve substantial improvements in patient safety. PMID:25666653

  18. Enterovirus-71 Virus-Like Particles Induce the Activation and Maturation of Human Monocyte-Derived Dendritic Cells through TLR4 Signaling

    PubMed Central

    Lin, Yu-Li; Hu, Yu-Chen; Liang, Cheng-Chao; Lin, Shih-Yeh; Liang, Yu-Chih; Yuan, Hui-Ping; Chiang, Bor-Luen

    2014-01-01

    Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. We recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with EV71 virus-like particles (VLPs), with a morphology resembling that of infectious EV71 virions but not containing a viral genome, which could potentially be safe as a vaccine for EV71. To elucidate the mechanisms through which EV71 VLPs induce cell-mediated immunity, we studied the immunomodulatory effects of EV71 VLPs on human monocyte-derived dendritic cells (DCs), which bind to and incorporate EV71 VLPs. DC treatment with EV71 VLPs enhanced the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR on the cell surface; increased the production of interleukin (IL)-12 p40, IL-12 p70, and IL-10 by DCs; and suppressed the capacity of DCs for endocytosis. Treatment with EV71 VLPs also enhanced the ability of DCs to stimulate naïve T cells and induced secretion of interferon (IFN)-? by T cells and Th1 cell responses. Neutralization with antibodies against Toll-like receptor (TLR) 4 suppressed the capacity of EV71 VLPs to induce the production of IL-12 p40, IL-12 p70, and IL-10 by DCs and inhibited EV71 VLPs binding to DCs. Our study findings clarified the important role for TLR4 signaling in DCs in response to EV71 VLPs and showed that EV71 VLPs induced inhibitor of kappaB alpha (I?B?) degradation and nuclear factor of kappaB (NF-?B) activation. PMID:25360749

  19. Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T-cells.

    PubMed

    Preston, J A; Thorburn, A N; Starkey, M R; Beckett, E L; Horvat, J C; Wade, M A; O'Sullivan, B J; Thomas, R; Beagley, K W; Gibson, P G; Foster, P S; Hansbro, P M

    2011-01-01

    An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae. PMID:20525707

  20. Effects of Flow Induced Orientation of Ferromagnetic Particles on Relative Magnetic Permeability of

    E-print Network

    particles are mixed with polymeric binders, solvents, plasticizers, lubricants and other additives to form a paint. The paint is applied to a polymer substrate (coated) and the particles are oriented by applying application of the ferromagnetic compos- ites is in plastic magnets. Since their introduction (7) they have