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1

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

PubMed

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. PMID:24920450

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

2

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

PubMed Central

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

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

3

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

NASA Technical Reports Server (NTRS)

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.

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

4

Particle therapy for noncancer diseases  

SciTech Connect

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.

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

5

Drug-induced pulmonary disease  

MedlinePLUS

Drug-induced pulmonary disease is lung disease brought on by a bad reaction to a medicine. ... Maldonado F, Limper AH. Drug-induced pulmonary disease. In: Mason RJ, ... of Respiratory Medicine . 5th ed. Philadelphia, PA: Elsevier ...

6

Foot-and-mouth disease vaccination induces cross-reactive IFN-? responses in cattle that are dependent on the integrity of the 140S particles.  

PubMed

Interferon-? (IFN-?) recall responses against foot-and-mouth disease virus (FMDV) in FMD vaccinated cattle are utilized to study T-lymphocyte immunity against this virus. Here, a recall IFN-? assay based on a commercial ELISA was set up using 308 samples from naïve and vaccinated cattle. The assay was used to study cross-reactive responses between different FMDV vaccine strains. Blood samples from cattle immunized with monovalent vaccines containing A24/Cruzeiro/Brazil/55, A/Argentina/2001 or O1/Campos/Brazil/58 strains were tested using purified-inactivated FMDV from homologous and heterologous strains. A24/Cruzeiro was the most efficient IFN-? inducer in all vaccinated animals, both when included in the vaccine or as stimulating antigen. We demonstrate that this was mainly due to the structural stability of the whole viral particle. These results show that IFN-? production relies on the presence of 140S particles that can maintain their integrity along the incubation process in vitro, and throughout the vaccine´s shelf-life, when used in vivo. PMID:25496826

Bucafusco, Danilo; Di Giacomo, Sebastián; Pega, Juan; Schammas, Juan Manuel; Cardoso, Nancy; Capozzo, Alejandra Victoria; Perez-Filgueira, Mariano

2015-02-01

7

Drug Induced Interstitial Lung Disease  

PubMed Central

With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease. PMID:22896776

Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Märkl, Bruno; Foerg, Wolfgang; Berghaus, Thomas

2012-01-01

8

Chromium-induced kidney disease  

SciTech Connect

Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of {beta}{sub 2}-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome palters and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chromic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced chromic renal disease cannot be interpreted as evidence of the absence of such injury.

Wedeen, R.P. (VA Medical Center, East Orange, NJ (United States)); Qian, Lifen (New Jersey Medical School, Newark (United States))

1991-05-01

9

Nanolipidic particles improve the bioavailability and alpha-secretase inducing ability of epigallocatechin-3-gallate (EGCG) for the treatment of Alzheimer's disease.  

PubMed

Prevention of amyloidogenic processing of amyloid precursor protein with the use of natural phytochemicals capable of enhancing alpha-secretase activity may be a therapeutic approach for treatment of neurodegenerative diseases including Alzheimer's disease (AD) and HIV-associated dementia (HAD). We have recently shown promising preclinical results with the use of green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG) in mouse models of both diseases, however the translation into clinical use has been problematic primarily as a result of poor bioavailability and inefficient delivery to the central nervous system (CNS). While the antioxidant properties of EGCG are well known, we have shown that it is able to promote non-amyloidogenic processing of amyloid precursor protein (APP) by upregulating alpha-secretase, thus preventing brain beta amyloid plaque formation, a hallmark of AD pathology and common finding in HIV infection. In this preliminary study, we investigated the ability of one preformulation method to improve the oral bioavailability of EGCG. We found that forming nanolipidic EGCG particles improves the neuronal (SweAPP N2a cells) alpha-secretase enhancing ability in vitro by up to 91% (P<001) and it's oral bioavailability in vivo by more than two-fold over free EGCG. PMID:20083179

Smith, Adam; Giunta, Brian; Bickford, Paula C; Fountain, Michael; Tan, Jun; Shytle, R Douglas

2010-04-15

10

Asbestos-induced lung disease.  

PubMed Central

This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation. Images FIGURE 1. 1a FIGURE 1. 1b FIGURE 2. FIGURE 3. FIGURE 4. 4a FIGURE 4. 4b FIGURE 5. 5a FIGURE 5. 5b FIGURE 6. PMID:8354168

Brody, A R

1993-01-01

11

Prion ‘virus’ particles caused by lysosomal storage disease?  

Microsoft Academic Search

Virus-like particles are commonly found in highly infectious scrapie brain fractions and cell lines, suggesting a viral source of prion diseases. However, new evidence indicates that these particles are likely the result of mucopolysaccharidosis; a lysosomal storage disease where similar particles are observed, along with neuronal degeneration. Heparan sulfate proteoglycans (HSPGs) have long been implicated in prion diseases including demonstrated

J. F. McEwan; S. D. Cullis-Hill

2009-01-01

12

Energetic Particle-induced Geodesic Acoustic Mode  

SciTech Connect

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.

Fu, G.Y.

2008-09-12

13

Oestrogen deficiency modulates particle-induced osteolysis  

PubMed Central

Introduction Postmenopausal osteoporosis may modulate bone response to wear debris. In this article, we evaluate the influence of oestrogen deficiency on experimental particle-induced osteolysis. Methods Polyethylene (PE) particles were implanted onto the calvaria of normal controls, sham-ovariectomized (OVX), OVX mice and OVX mice supplemented with oestrogen (OVX+E). After 14 days, seven skulls per group were analyzed using a high-resolution micro-computed tomography (micro-CT) and histomorphometry, and for tartrate-specific alkaline phosphatase. Five calvariae per group were cultured for the assay of IL-1?, IL-6, TNF-? and receptor activator of the nuclear factor ?B (RANKL) secretion using quantitative ELISA. Serum IL-6 concentrations were obtained. The expression of RANKL and osteoprotegerin (OPG) mRNA were evaluated using real-time PCR. Results As assessed by ?CT and by histomorphometry, PE particles induced extensive bone resorption and an intense inflammatory reaction in normal controls, sham-OVX and OVX+E mice, but not in the OVX mice group. In normal controls, sham-OVX and OVX+E mice, PE particles induced an increase in serum IL-6, in TNF-? and RANKL local concentrations, and resulted in a significant increase in RANKL/OPG messenger RNA (mRNA) ratio. Conversely, these parameters remained unchanged in OVX mice after PE implantation. Conclusions Oestrogen privation in the osteolysis murine model ultimately attenuated osteolytic response to PE particles, suggesting a protective effect. This paradoxical phenomenon was associated with a down-regulation of pro-resorptive cytokines. It is hypothesized that excessive inflammatory response was controlled, illustrated by the absence of increase of serum IL-6 in OVX mice after PE implantation. PMID:21696618

2011-01-01

14

Quadrupole Induced Resonant Particle Transport in a Pure Electron Plasma  

E-print Network

Quadrupole Induced Resonant Particle Transport in a Pure Electron Plasma by Erik Peter Gilson B;Quadrupole Induced Resonant Particle Transport in a Pure Electron Plasma Copyright Fall 2001 by Erik Peter Gilson #12;1 Abstract Quadrupole Induced Resonant Particle Transport in a Pure Electron Plasma by Erik

Gilson, Erik

15

[Drug-induced interstitial lung diseases].  

PubMed

Drug-induced infiltrative lung disease may manifest as variable clinical radiological patterns, including subacute or chronic interstitial pneumonia, pulmonary fibrosis, eosinophilic pneumonia, organising pneumonia, pulmonary edema, or sarcoidosis. A large amount of drugs have been incriminated, including those used in cardiovascular diseases (amiodarone, statins and angiotensin converting enzyme inhibitors), antibiotics (minocycline, nitrofurantoin), most of anticancer drugs (and especially chemotherapy and chest radiation), treatment of rheumatoid arthritis, as well as more recent drugs. A high index of suspicion is therefore required in any patient with infiltrative lung disease and the web-based tool www.pneumotox.com will help to list possible causative drugs. The following steps are necessary: history and timing of drug exposure, clinical and imaging pattern, exclusion of other causes of infiltrative lung disease, improvement following drug discontinuation. Rechallenge, dangerous, is not recommended. PMID:25362778

Bonniaud, Philippe; Georges, Marjolaine; Favrolt, Nicolas; Camus, Philippe

2014-09-01

16

Cutaneous photosensitivity diseases induced by exogenous agents.  

PubMed

Cutaneous photosensitivity diseases may be idiopathic, produced by endogenous photosensitizers, or associated with exogenous photosensitizers. Those caused by exogenous agents include phototoxicity, photoallergy, and the exacerbation or induction of systemic disorders in which photosensitivity is a prominent clinical manifestation. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent. The action spectra for most phototoxins and photoallergens lie in the UVA range. Phototoxic and photoallergic reactions can be distinguished on the basis of pathogenesis, clinical characteristics, diagnosis, and management. Drugs capable of causing phototoxic reactions include psoralens, porphyrins, coal tar, antibiotics, and nonsteroidal antiinflammatory agents. Drugs capable of causing photoallergic reactions include topical antimicrobial agents, fragrances, sunscreens, nonsteroidal antiinflammatory agents, plants, and psychiatric medications. Drug-induced systemic diseases in which photosensitivity is a prominent component include drug-induced lupus erythematosus, porphyria, and pellagra. PMID:7673488

Gould, J W; Mercurio, M G; Elmets, C A

1995-10-01

17

[Drug induced interstitial lung disease in systemic diseases].  

PubMed

Immunosuppressants and immunomodulators are designed to regulate excessive immune response responsible for inflammatory lesions and are prescribed more and more in internal medicine. These drugs are known for their efficiency but with a significant toxicity including interstitial lung disease (ILD). Some factors liable to pulmonary toxicity include advanced age, genetic polymorphism and the existence of prior pulmonary disease. Cytotoxicity and hypersensitivity are the main mechanisms of pulmonary toxicity. There is no universal classification of drug induced-lung disease. Theoretically, drugs may be responsible for all histological aspects of ILD. Methotrexate is the most well-known drug as a provider of ILD with a prevalence of 0.3 to 11.6%. Some cases of ILD have also been reported with the new biologics used in systemic diseases. The diagnostic approach to the suspicion of drug ILD is to eliminate non-medicinal causes of pneumonia including infections and tumors before exploring the clinical symptomatology and the results of imaging and bronchoalveolar lavage cell profile. The analysis of the clinical symptomatology check the compatibility of the chronology of clinical and/or radiological pneumonia with the medication suspected. Subsequently, data from the clinical case are compared with those of the literature. Treatment involves stopping the suspected drug. The use of corticosteroids may be required in case of signs of severity or a lingering evolution. PMID:24183295

Essaadouni, L; Benjilali, L

2013-12-01

18

Modelling induced resistance to plant diseases.  

PubMed

Plant disease control has traditionally relied heavily on the use of agrochemicals despite their potentially negative impact on the environment. An alternative strategy is that of induced resistance (IR). However, while IR has proven effective in controlled environments, it has shown variable field efficacy, thus raising questions about its potential for disease management in a given crop. Mathematical modelling of IR assists researchers with understanding the dynamics of the phenomenon in a given plant cohort against a selected disease-causing pathogen. Here, a prototype mathematical model of IR promoted by a chemical elicitor is proposed and analysed. Standard epidemiological models describe that, under appropriate environmental conditions, Susceptible plants (S) may become Diseased (D) upon exposure to a compatible pathogen or are able to Resist the infection (R) via basal host defence mechanisms. The application of an elicitor enhances the basal defence response thereby affecting the relative proportion of plants in each of the S, R and D compartments. IR is a transient response and is modelled using reversible processes to describe the temporal evolution of the compartments. Over time, plants can move between these compartments. For example, a plant in the R-compartment can move into the S-compartment and can then become diseased. Once in the D-compartment, however, it is assumed that there is no recovery. The terms in the equations are identified using established principles governing disease transmission and this introduces parameters which are determined by matching data to the model using computer-based algorithms. These then give the best match of the model with experimental data. The model predicts the relative proportion of plants in each compartment and quantitatively estimates elicitor effectiveness. An illustrative case study will be given; however, the model is generic and will be applicable for a range of plant-pathogen-elicitor scenarios. PMID:24398025

Abdul Latif, Nurul S; Wake, Graeme C; Reglinski, Tony; Elmer, Philip A G

2014-04-21

19

Ionizing radiation-induced diseases in Korea.  

PubMed

Radiation risk has become well known through epidemiological studies of clinically or occupationally exposed populations, animal experiments, and in vitro studies; however, the study of radiation related or induced disease has been limited in Korea. This study is to find the level of occupational radiation exposure for various kinds of accidents, compensated occupational diseases, related studies, and estimations on future occupational disease risks. Research data of related institutions were additionally investigated. About 67% of 62,553 radiation workers had no exposure or less than 1.2 mSv per year. The 5 reported cases on radiation accident patients in Korea occurred during nondestructive testing. According to the recent rapid increase in the number of workers exposed to radiation, a higher social recognition of cancer, and an increasing cancer mortality rate, it is expected that occupational disease compensation will rapidly increase as well. Therefore, it is important to develop scientific and objective decision methods, such as probability of causation and screening dose in the establishment of an exposure and health surveillance system. PMID:21258594

Jin, Young-Woo; Jeong, Meeseon; Moon, Kieun; Jo, Min-Heui; Kang, Seong-Kyu

2010-12-01

20

Ionizing Radiation-induced Diseases in Korea  

PubMed Central

Radiation risk has become well known through epidemiological studies of clinically or occupationally exposed populations, animal experiments, and in vitro studies; however, the study of radiation related or induced disease has been limited in Korea. This study is to find the level of occupational radiation exposure for various kinds of accidents, compensated occupational diseases, related studies, and estimations on future occupational disease risks. Research data of related institutions were additionally investigated. About 67% of 62,553 radiation workers had no exposure or less than 1.2 mSv per year. The 5 reported cases on radiation accident patients in Korea occurred during nondestructive testing. According to the recent rapid increase in the number of workers exposed to radiation, a higher social recognition of cancer, and an increasing cancer mortality rate, it is expected that occupational disease compensation will rapidly increase as well. Therefore, it is important to develop scientific and objective decision methods, such as probability of causation and screening dose in the establishment of an exposure and health surveillance system. PMID:21258594

Jeong, Meeseon; Moon, Kieun; Jo, Min-Heui; Kang, Seong-Kyu

2010-01-01

21

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis  

PubMed Central

Background Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice. Methods We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells. Results Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution. Conclusions As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis. PMID:21843355

2011-01-01

22

Intrinsic particle-induced lateral transport in microchannels  

PubMed Central

In microfluidic systems at low Reynolds number, the flow field around a particle is assumed to maintain fore-aft symmetry, with fluid diverted by the presence of a particle, returning to its original streamline downstream. This current model considers particles as passive components of the system. However, we demonstrate that at finite Reynolds number, when inertia is taken into consideration, particles are not passive elements in the flow but significantly disturb and modify it. In response to the flow field, particles translate downstream while rotating. The combined effect of the flow of fluid around particles, particle rotation, channel confinement (i.e., particle dimensions approaching those of the channel), and finite fluid inertia creates a net recirculating flow perpendicular to the primary flow direction within straight channels that resembles the well-known Dean flow in curved channels. Significantly, the particle generating this flow remains laterally fixed as it translates downstream and only the fluid is laterally transferred. Therefore, as the particles remain inertially focused, operations can be performed around the particles in a way that is compatible with downstream assays such as flow cytometry. We apply this particle-induced transfer to perform fluid switching and mixing around rigid microparticles as well as deformable cells. This transport phenomenon, requiring only a simple channel geometry with no external forces to operate, offers a practical approach for fluid transfer at high flow rates with a wide range of applications, including sample preparation, flow reaction, and heat transfer. PMID:22761309

Amini, Hamed; Sollier, Elodie; Weaver, Westbrook M.; Di Carlo, Dino

2012-01-01

23

Intrinsic particle-induced lateral transport in microchannels.  

PubMed

In microfluidic systems at low Reynolds number, the flow field around a particle is assumed to maintain fore-aft symmetry, with fluid diverted by the presence of a particle, returning to its original streamline downstream. This current model considers particles as passive components of the system. However, we demonstrate that at finite Reynolds number, when inertia is taken into consideration, particles are not passive elements in the flow but significantly disturb and modify it. In response to the flow field, particles translate downstream while rotating. The combined effect of the flow of fluid around particles, particle rotation, channel confinement (i.e., particle dimensions approaching those of the channel), and finite fluid inertia creates a net recirculating flow perpendicular to the primary flow direction within straight channels that resembles the well-known Dean flow in curved channels. Significantly, the particle generating this flow remains laterally fixed as it translates downstream and only the fluid is laterally transferred. Therefore, as the particles remain inertially focused, operations can be performed around the particles in a way that is compatible with downstream assays such as flow cytometry. We apply this particle-induced transfer to perform fluid switching and mixing around rigid microparticles as well as deformable cells. This transport phenomenon, requiring only a simple channel geometry with no external forces to operate, offers a practical approach for fluid transfer at high flow rates with a wide range of applications, including sample preparation, flow reaction, and heat transfer. PMID:22761309

Amini, Hamed; Sollier, Elodie; Weaver, Westbrook M; Di Carlo, Dino

2012-07-17

24

Pan-caspase inhibition suppresses polyethylene particle-induced osteolysis.  

PubMed

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. Earlier studies demonstrated apoptotic macrophages, giant cells, fibroblasts and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening. The aim of the current study was to determine in a murine calvarial model of wear particle-induced osteolysis whether inhibition of apoptosis using the pan-caspase inhibitor BOC-D-FMK reduces aseptic loosening. Healthy 12-week-old male C57BL/6J mice were treated with UHMWPE particles and received a daily peritoneal injection of BOK-D-FMK, respectively only buffer at a dose of 3 mg/kg of body weight for 12 days until sacrifice. Bone resorption was measured by histomorphometry, micro CT (computed tomography) and TRAP-5b serum analysis. Apoptosis was measured using caspase-3 cleaved staining. The results demonstrated that UHMWPE particles induced stronger apoptotic reactions in macrophages and osteoblasts and increased bone resorption in non-specifically treated mice, whereas peritoneal application of BOC-D-FMK significantly counteracted these adverse particle-related effects. We think that in particle-induced osteolysis apoptosis is pathologically increased, and that failure to reduce the quantity of apoptotic bodies leads to an up-regulation of proinflammatory cytokines, which may be responsible for the induction of osteolysis. We showed for the first time in vivo that a reduction in apoptosis leads to a significant reduction in particle-induced osteolysis. Clinically, the apoptotic cascade could become an interesting novel therapeutic target to modulate particle-induced osteolysis. PMID:19130234

Landgraeber, Stefan; Jaeckel, Sandra; Löer, Franz; Wedemeyer, Christian; Hilken, Gero; Canbay, Ali; Totsch, Martin; von Knoch, Marius

2009-02-01

25

Method for ion implantation induced embedded particle formation via reduction  

DOEpatents

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.

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

2001-01-01

26

Ripple induced trapped particle loss in tokamaks  

SciTech Connect

The threshold for stochastic transport of high energy trapped particles in a tokamak due to toroidal field ripple is calculated by explicit construction of primary resonances, and a numerical examination of the route to chaos. Critical field ripple amplitude is determined for loss. The expression is given in magnetic coordinates and makes no assumptions regarding shape or up-down symmetry. An algorithm is developed including the effects of prompt axisymmetric orbit loss, ripple trapping, convective banana flow, and stochastic ripple loss, which gives accurate ripple loss predictions for representative Tokamak Fusion Test Reactor and International Thermonuclear Experimental Reactor equilibria. The algorithm is extended to include the effects of collisions and drag, allowing rapid estimation of alpha particle loss in tokamaks.

White, R.B.

1996-05-01

27

Aeolian Induced Erosion and Particle Entrainment  

NASA Technical Reports Server (NTRS)

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.

Saint, Brandon

2007-01-01

28

Transient Flow Induced by the Adsorption of Particles  

NASA Astrophysics Data System (ADS)

When small particles, e.g., glass, flour, pollen, etc., come in contact with a fluid-liquid interface they disperse so quickly to form a monolayer on the interface that it appears explosive, especially on the surface of mobile liquids like water. This is a consequence of the fact that the adsorption of a particle in an interface causes a lateral flow which on the interface away from the particle. In this study we use the particle image velocimetry (PIV) technique to measure the transient three-dimensional flow that arises due to the adsorption of spherical particles. The PIV measurements show that the flow develops a fraction of a second after the adsorption of the particle and persists for several seconds. The fluid below the particle rises upwards and on the surface moves away from the particle. These latter PIV results are consistent with the surface velocity measurements performed in earlier studies. The strength of the induced flow, and the time duration for which the flow persists, both decrease with decreasing particle size. For a spherical particle the flow is axisymmetric about the vertical line passing through the center of the particle.

Musunuri, Naga; Codjoe, Daniel; Dalal, Bhavin; Fischer, Ian; Singh, Pushpendra

2013-03-01

29

Test particle modeling of wave-induced energetic electron precipitation  

NASA Technical Reports Server (NTRS)

A test particle computer model of the precipitation of radiation belt electrons is extended to compute the dynamic energy spectrum of transient electron fluxes induced by short-duration VLF wave packets traveling along the geomagnetic field lines. The model is adapted to estimate the count rate and associated spectrum of precipitated electrons that would be observed by satellite-based particle detectors with given geometric factor and orientation with respect to the magnetic field. A constant-frequency wave pulse and a lightning-induced whistler wave packet are used as examples of the stimulating wave signals. The effects of asymmetry of particle mirror heights in the two hemispheres and the atmospheric backscatter of loss cone particles on the computed precipitated fluxes are discussed.

Chang, H. C.; Inan, U. S.

1985-01-01

30

Foot-and-mouth disease virus-like particles produced by a SUMO fusion protein system in Escherichia coli induce potent protective immune responses in guinea pigs, swine and cattle  

PubMed Central

Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. The format of FMD virus-like particles (VLP) as a non-replicating particulate vaccine candidate is a promising alternative to conventional inactivated FMDV vaccines. In this study, we explored a prokaryotic system to express and assemble the FMD VLP and validated the potential of VLP as an FMDV vaccine candidate. VLP composed entirely of FMDV (Asia1/Jiangsu/China/2005) capsid proteins (VP0, VP1 and VP3) were simultaneously produced as SUMO fusion proteins by an improved SUMO fusion protein system in E. coli. Proteolytic removal of the SUMO moiety from the fusion proteins resulted in the assembly of VLP with size and shape resembling the authentic FMDV. Immunization of guinea pigs, swine and cattle with FMD VLP by intramuscular inoculation stimulated the FMDV-specific antibody response, neutralizing antibody response, T-cell proliferation response and secretion of cytokine IFN-?. In addition, immunization with one dose of the VLP resulted in complete protection of these animals from homologous FMDV challenge. The 50% protection dose (PD50) of FMD VLP in cattle is up to 6.34. These results suggest that FMD VLP expressed in E. coli are an effective vaccine in guinea pigs, swine and cattle and support further development of these VLP as a vaccine candidate for protection against FMDV. PMID:23826638

2013-01-01

31

Gravitationally Induced Particle Production: Thermodynamics and Kinetic Theory  

E-print Network

A relativistic kinetic description for the irreversible thermodynamic process of gravitationally induced particle production is proposed in the context of an expanding Friedmann-Robertson-Walker (FRW) geometry. We show that the covariant thermodynamic treatment referred to as "adiabatic" particle production provoked by the cosmic time-varying gravitational field has a consistent kinetic counterpart. The variation of the distribution function is associated to a non-collisional kinetic term of quantum-gravitational origin which is proportional to the ratio $\\Gamma/H$, where $\\Gamma$ is the gravitational particle production rate and H is the Hubble parameter. For $\\Gamma reaction effects in the cosmic background.

J. A. S. Lima; I. P. Baranov

2014-11-24

32

Myricetin prevents titanium particle-induced osteolysis in vivo and inhibits RANKL-induced osteoclastogenesis in vitro.  

PubMed

Titanium (Ti) particle-induced periprosthetic osteolysis and subsequent aseptic loosening are a primary reason for total hip arthroplasty failure. The aim of this study was to assess the effect of myricetin on Ti particle-induced osteolysis and osteoclastogenesis. We demonstrated that myricetin, a natural plant extract, exerts potent inhibitory effects on Ti particle-induced osteolysis in a mouse calvarial model. Further histological analysis indicated that the inhibition of osteoclast formation and function, and the secretion of inflammatory factors, are key targets for therapeutic agents in the treatment of wear particle-induced osteolysis. In vitro, we found that myricetin suppressed receptor activator of nuclear factor-?B ligand (RANKL)-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Moreover, myricetin significantly reduced the expression of osteoclast-specific markers in mouse bone marrow-derived macrophages, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, the calcitonin receptor, V-ATPase d2, c-fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that myricetin inhibited osteoclastogenesis through the suppression of the nuclear factor-?B (NF-?B) signaling pathway and mitogen-activated protein kinase (MAPK) pathways involving extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2). While, the inhibition of TNF-? and IL-1? secretion was another reason for the suppressive effect of myricetin on Ti particle-induced osteolysis. Collectively, these findings suggest that myricetin is a potential natural agent for the treatment of periprosthetic osteolysis and other osteoclast-related osteolytic diseases. PMID:25449599

Wu, Chuanlong; Wang, Wengang; Tian, Bo; Liu, Xuqiang; Qu, Xinhua; Zhai, Zanjing; Li, Haowei; Liu, Fengxiang; Fan, Qiming; Tang, Tingting; Qin, An; Zhu, Zhenan

2015-01-01

33

Diabetes mellitus may induce cardiovascular disease by decreasing neuroplasticity  

PubMed Central

Summary Neuroplasticity has been defined “the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections”. The nervous system monitors and coordinates internal organ function. Thus neuroplasticity may be associated with the pathogenesis of other diseases besides neuropsychiatric diseases. Decreased neuroplasticity is associated with cardiovascular disease (CVD) and a disease related to decreased neuroplasticity may confer a greater CVD risk. Diabetes mellitus (DM) is related to CVD and DM induces decreased neuroplasticity, which is manifested as depression, Alzheimer’s disease and diabetic neuropathy. Therefore we conclude that DM may induce CVD by decreasing neuroplasticity. PMID:25014044

Zheng, Zhihua; Wu, Junyan; Wang, Ruolun; Zeng, Yingtong

2014-01-01

34

Quadrupole Induced Resonant Particle Transport in a Pure Electron Plasma  

E-print Network

Quadrupole Induced Resonant Particle Transport in a Pure Electron Plasma E. Gilson1 and J. Fajans2 that a certain class of resonant electrons follows trajectories that take them out of the plasma. Even though are o® resonance, the lifetime of the plasma is not greatly a®ected by the quadrupole ¯eld, but near

Gilson, Erik

35

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,...

36

A compilation of charged-particle induced thermonuclear reaction rates  

Microsoft Academic Search

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

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

37

Alpha particles induce apoptosis through the sphingomyelin pathway.  

PubMed

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 ? 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 ? particles emitted by the ²²?Ac-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 ? particles using a planar ²?¹Am 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 ? particles can activate the sphingomyelin pathway to induce apoptosis. PMID:21631289

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

2011-10-01

38

Obese mice are resistant to eosinophilic airway inflammation induced by diesel exhaust particles.  

PubMed

Particulate matter can exacerbate respiratory diseases such as asthma. Diesel exhaust particles are the substantial portion of ambient particulate matter with a <2.5 µm diameter in urban areas. Epidemiological data indicate increased respiratory health effects of particulate matter in obese individuals; however, the association between obesity and diesel exhaust particle-induced airway inflammation remains unclear. We aimed to investigate the differences in susceptibility to airway inflammation induced by exposure to diesel exhaust particles between obese mice (db/db) and lean mice (db/+m). Female db/db and db/+m mice were intratracheally administered diesel exhaust particles or vehicle every 2 weeks for a total of seven times. The cellular profile of bronchoalveolar lavage fluid and histological changes in the lungs were assessed and the lungs and serum were analyzed for the generation of cytokines, chemokines and soluble intercellular adhesion molecule 1. Diesel exhaust particle exposure-induced eosinophilic infiltration in db/+m mice accompanied by T-helper 2 cytokine, chemokine and soluble intercellular adhesion molecule 1 expression in the lungs. In contrast, it induced mild neutrophilic airway inflammation accompanied by elevated cytokines and chemokines in db/db mice. The lungs of db/db mice exhibited decreased expression of eosinophil activators/chemoattractants such as interleukin-5, interleukin-13 and eotaxin compared with those of db/+m mice. In addition, serum eotaxin and monocyte chemotactic protein-1 levels were significantly higher in db/db mice than in db/+m mice. In conclusion, obesity can affect susceptibility to diesel exhaust particle-induced airway inflammation, which is possibly due to differences in local and systemic inflammatory responses between lean and obese individuals. PMID:24105835

Yanagisawa, Rie; Koike, Eiko; Ichinose, Takamichi; Takano, Hirohisa

2014-06-01

39

Serious liver disease induced by infliximab  

Microsoft Academic Search

Infliximab, a chimeric monoclonal antibody that binds the tumor necrosis factor ? (TNF?), is used in the treatment of rheumatoid\\u000a arthritis (RA) and Crohn’s disease (CD). Previous cases of significant secondary liver disease associated with infliximab\\u000a treatment have been reported in patients with RA, CD, and psoriatic arthritis. Two additional patients with RA who developed\\u000a a serious liver disease associated

Gabriel J. Tobon; Carlos Cañas; Juan-Jose Jaller; Juan-Carlos Restrepo; Juan-Manuel Anaya

2007-01-01

40

Dual neutral particle induced transmutation in CINDER2008  

NASA Astrophysics Data System (ADS)

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.

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

2014-12-01

41

[Particle Induced X-ray Emission (PIXE) for analysis of trace elements in biological materials].  

PubMed

Outline of Particle Induced X-ray Emission (PIXE) and its application to biomedical samples are described. Charged particles from cyclotron or van de Graaff generator bombards analytical samples and semiconductor detector measures energy and intensity of induced characteristic x-ray. Simultaneous determination for 22Na to 92U is possible by PIXE. 100 nA of 3 MeV protons bombards biomedical samples and detection limits for almost all trace essential elements are sub microgram/g. Only 1 mg of biomedical sample is necessary for determination of trace elements and no chemical procedure is necessary for preparation of analytical sample. PIXE is powerful tool for determination of essential elements and applied for diagnosis for several diseases. PMID:8587194

Iwata, Y

1996-01-01

42

Nuclear reactions induced by high-energy alpha particles  

NASA Technical Reports Server (NTRS)

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.

Shen, B. S. P.

1974-01-01

43

Ion-beam-induced-charge characterisation of particle detectors  

Microsoft Academic Search

Ion-beam-induced-charge collection (IBIC) in a nuclear microprobe has been used to characterise detectors for the measurement of particles over a median energy range (100 keV–1 MeV). Three standard detector devices have been studied: a PIPS detector with a buried (ion-implanted) junction structure, a Schottky barrier junction device and a PN-junction photodiode. A 2.0 MeV focussed helium ion beam was used

C. Yang; D. N. Jamieson; S. M. Hearne; C. I. Pakes; B. Rout; E. Gauja; A. J. Dzurak; R. G. Clark

2002-01-01

44

SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES  

SciTech Connect

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.

Diaz-Sanchez, David

2000-08-20

45

Alpha Particles Induce Apoptosis through the Sphingomyelin Pathway  

PubMed Central

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

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

2011-01-01

46

Interferon Inducible Chemokines Correlate with Disease Severity in Systemic Sclerosis  

PubMed Central

Objective To measure interferon (IFN) inducible chemokines in plasma of patients with systemic sclerosis (SSc) and investigate their correlation with disease severity. Methods We examined the correlation of IFN-inducible chemokines, IFN?-inducible protein-10 (IP-10/CXCL10), IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11), and monocyte chemoattractant protein-1 (MCP-1/CCL2) with the IFN gene expression signature. We generated an IFN-inducible chemokine score with the correlated chemokines, IP-10 and I-TAC and compared it in 266 SSc patients enrolled in the GENISOS cohort to that of 97 matched controls. Subsequently, the correlation between the baseline IFN-inducible chemokine score and markers of disease severity was assessed. Finally, the course of IFN-inducible chemokine score over time was examined. Results The plasma IFN-inducible chemokine score correlated with the IFN gene expression signature and this score was higher in SSc patients. It also was associated with the absence of anti–RNA polymerase III antibodies, presence of anti–U1 ribonucleoprotein antibodies (RNP), but not with disease duration, type, or other autoantibodies. The chemokine scores correlated with concomitantly obtained muscle, skin and lung components of the Medsger Severity Index, as well as, FVC, DLco, creatine kinase. Its association with disease severity was independent of anti-RNP or other potential confounders (age, gender, ethnicity, disease duration, and treatment with immunosuppressive agents). Finally, there was not a significant change in the IFN-inducible chemokine score over time. Conclusions The IFN-inducible chemokine score is a stable serological marker of more severe subtype of SSc and may be useful for risk stratification regardless of disease type or duration. PMID:23055137

Liu, Xiaochun; Mayes, Maureen D.; Tan, Filemon K.; Wu, Minghua; Reveille, John D.; Harper, Brock E.; Draeger, Hilda T.; Gonzalez, Emilio B.; Assassi, Shervin

2013-01-01

47

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...

48

Theory of trapped-particle-induced resistive fluid turbulence  

SciTech Connect

A theory of anomalous electron heat transport, evolving from trapped-particle-induced resistive interchange modes, is proposed. The latter are a new branch of the resistive interchange-ballooning family of instabilities, destabilized when the pressure carried by the unfavorably drifting trapped particles is sufficiently large to overcome stabilizing contributions coming from favorable average curvature. Expressions for the turbulent heat diffusivity and anomalous electron thermal conductivity at saturation are derived for two regimes of trapped-particle energy: (I) a moderately energetic regime, which is ''fluidlike'' in the sense that the unstable mode grows faster than the time that it takes for particles in this energy range to precess once around the torus, and (II) a highly energetic regime, where the trapped species has sufficiently high energy as to be able to interact resonantly with the mode. Unlike previous theories of anomalous transport, the estimates of diffusion and transport obtained here are self-consistent since the trapped particles do not ''see'' the magnetic flutter due to their rapid bounce motion. The theory is valid for moderate electron-temperature, high ion-temperature (auxiliary heated) plasmas and as such, is relevant for present- and future-generation experimental fusion devices.

Biglari, H.; Diamond, P.H.

1987-12-01

49

Theory of trapped-particle-induced resistive fluid turbulence  

SciTech Connect

A theory of anomalous electron heat transport, evolving from trapped-particle-induced resistive interchange modes, is proposed. These latter are a new branch of the resistive interchange-ballooning family of instabilities, destabilized when the pressure carried by the unfavorably-drifting trapped particles is sufficiently large to overcome stabilizing contributions coming from favorable average curvature. Expressions for the turbulent heat diffusivity and anomalous electron thermal conductivity at saturation are derived for two regimes of trapped particle energy: (1) a moderately-energetic regime, which is ''fluid-like'' in the sense that the unstable mode grows faster than the time that it takes for particles in this energy range to precess once around the torus; and (2) a highly-energetic regime, where the trapped species has sufficiently high energy as to be able to resonantly interact with the mode. Unlike previous theories of anomalous transport, the estimates of diffusion and transport obtained here are self-consistent, since the trapped particles do not ''see'' the magnetic flutter due to their rapid bounce motion. The theory is valid for moderate electron-temperature, high ion-temperature (auxiliary-heated) plasmas, and as such, is relevant for present and future-generation experimental fusion devices.

Biglari, H.; Diamond, P.H.

1987-05-01

50

The EPIC-MOS Particle-Induced Background Spectrum  

NASA Technical Reports Server (NTRS)

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.

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

2006-01-01

51

Particle production in antiproton-induced nuclear reactions  

NASA Astrophysics Data System (ADS)

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 p¯ on C12, Ne20, Ca40, Sn112, Ta181, Au197, and U238 from a low to high incident momentum. The rapidity and momentum distributions of ?+ 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 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.

Feng, Zhao-Qing; Lenske, Horst

2014-04-01

52

Particles induce apical plasma membrane enlargement in epithelial lung cell line depending on particle surface area dose  

PubMed Central

Background Airborne particles entering the respiratory tract may interact with the apical plasma membrane (APM) of epithelial cells and enter them. Differences in the entering mechanisms of fine (between 0.1 ?m and 2.5 ?m) and ultrafine ( ? 0.1 ?m) particles may be associated with different effects on the APM. Therefore, we studied particle-induced changes in APM surface area in relation to applied and intracellular particle size, surface and number. Methods Human pulmonary epithelial cells (A549 cell line) were incubated with various concentrations of different sized fluorescent polystyrene spheres without surface charge (? fine – 1.062 ?m, ultrafine – 0.041 ?m) by submersed exposure for 24 h. APM surface area of A549 cells was estimated by design-based stereology and transmission electron microscopy. Intracellular particles were visualized and quantified by confocal laser scanning microscopy. Results Particle exposure induced an increase in APM surface area compared to negative control (p < 0.01) at the same surface area concentration of fine and ultrafine particles a finding not observed at low particle concentrations. Ultrafine particle entering was less pronounced than fine particle entering into epithelial cells, however, at the same particle surface area dose, the number of intracellular ultrafine particles was higher than that of fine particles. The number of intracellular particles showed a stronger increase for fine than for ultrafine particles at rising particle concentrations. Conclusion This study demonstrates a particle-induced enlargement of the APM surface area of a pulmonary epithelial cell line, depending on particle surface area dose. Particle uptake by epithelial cells does not seem to be responsible for this effect. We propose that direct interactions between particle surface area and cell membrane cause the enlargement of the APM. PMID:19284624

Brandenberger, Christina; Rothen-Rutishauser, Barbara; Blank, Fabian; Gehr, Peter; Mühlfeld, Christian

2009-01-01

53

Eugenol attenuates pulmonary damage induced by diesel exhaust particles.  

PubMed

Environmentally relevant doses of inhaled diesel particles elicit pulmonary inflammation and impair lung mechanics. Eugenol, a methoxyphenol component of clove oil, presents in vitro and in vivo anti-inflammatory and antioxidant properties. Our aim was to examine a possible protective role of eugenol against lung injuries induced by diesel particles. Male BALB/c mice were divided into four groups. Mice received saline (10 ?l in; CTRL group) or 15 ?g of diesel particles DEP (15 ?g in; DIE and DEUG groups). After 1 h, mice received saline (10 ?l; CTRL and DIE groups) or eugenol (164 mg/kg; EUG and DEUG group) by gavage. Twenty-four hours after gavage, pulmonary resistive (?P1), viscoelastic (?P2) and total (?Ptot) pressures, static elastance (Est), and viscoelastic component of elastance (?E) were measured. We also determined the fraction areas of normal and collapsed alveoli, amounts of polymorpho- (PMN) and mononuclear cells in lung parenchyma, apoptosis, and oxidative stress. Est, ?P2, ?Ptot, and ?E were significantly higher in the DIE than in the other groups. DIE also showed significantly more PMN, airspace collapse, and apoptosis than the other groups. However, no beneficial effect on lipid peroxidation was observed in DEUG group. In conclusion, eugenol avoided changes in lung mechanics, pulmonary inflammation, and alveolar collapse elicited by diesel particles. It attenuated the activation signal of caspase-3 by DEP, but apoptosis evaluated by TUNEL was avoided. Finally, it could not avoid oxidative stress as indicated by malondialdehyde. PMID:22194320

Zin, Walter A; Silva, Ana G L S; Magalhães, Clarissa B; Carvalho, Giovanna M C; Riva, Douglas R; Lima, Crystianne C; Leal-Cardoso, Jose H; Takiya, Christina M; Valença, Samuel S; Saldiva, Paulo H N; Faffe, Débora S

2012-03-01

54

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

PubMed Central

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

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

55

DNA damage response induced by HZE particles in human cells  

NASA Astrophysics Data System (ADS)

Convincing evidences indicate that high-linear energy transfer (LET) ionizing radiation (IR) induced complex DNA lesions are more difficult to repair than isolated DNA lesions induced by low-LET IR; this has been associated with the increased RBE for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in high energy charged-particle irradiated human cells. We have employed an in situ method to directly monitor induction and repair of clustered DNA lesions at the single-cell level. We showed, consistent with biophysical modeling, that the kinetics of loss of clustered DNA lesions was substantially compromised in human fibroblasts. The unique spatial distribution of different types of DNA lesions within the clustered damages determined the cellular ability to repair these damages. Importantly, examination of metaphase cells derived from HZE particle irradiated cells revealed that the extent of chromosome aberrations directly correlated with the levels of unrepaired clustered DNA lesions. In addition, we used a novel organotypic human lung three-dimensional (3D) model to investigate the biological significance of unrepaired DNA lesions in differentiated lung epithelial cells. We found that complex DNA lesions induced by HZE particles were even more difficult to be repaired in organotypic 3D culture, resulting enhanced cell killing and chromosome aberrations. Our data suggest that DNA repair capability in differentiated cells renders them vulnerable to DSBs, promoting genome instability that may lead to carcinogenesis. As the organotypic 3D model mimics human lung, it opens up new experimental approaches to explore the effect of radiation in vivo and will have important implications for evaluating radiation risk in human tissues.

Chen, David; Aroumougame, Asaithamby

56

Coxsackievirus-induced acute neonatal central nervous system disease model  

PubMed Central

Coxsackievirus B (CVB) is a significant pathogen that causes pediatric central nervous system disease with acute syndromes commonly. The onset of its infection was abrupt, and after recovery there usually will be severe mental sequelae. The disease model for research was not established by the way of natural infection, although there are various investigations about the CVB-induced central nervous system (CNS) diseases. Thus, we have established an acute neonatal CNS disease mice model by CVB orally infecting. This model imitated the natural infection route and focuses the onset of CNS disease, inducing severe infection and lesion in the hippocampus and cortex regions, and the stability of the model was demonstrated. A pathology score system was developed for quantitative pathology analysis, which standardizes the CNS pathology analysis by statistics analysis. By this model, the track of CVB penetrating the blood brain barrier in vivo has been captured. One of the experimental strains CVB3/Macocy, as a new variant, was isolated, and its genomic RNA was cloned. According to its nucleotide sequence, we have characterized its genomic structure and defined its genotype. Based on the sequence, some mutations which do not change the CVB-induced CNS damage have been found. The model is an effective tool for studies on CVB-induced CNS diseases. PMID:24696707

Wang, Lulu; Dong, Changyuan; Chen, Dong-E; Song, Zhen

2014-01-01

57

MHD-Induced Alpha Particle Loss in TFTR  

SciTech Connect

MHD-induced increases in alpha particle loss to the wall were observed for both coherent modes and transient reconnection events using an array of scintillator detectors near the wall of Tokamak Fusion Test Reactor (TFTR). The magnitude of the coherent MHD-induced alpha loss as seen by these detectors was normally comparable to the MHD-quiescent first-orbit or toroidal-field ripple loss, but the magnitude of the alpha loss during reconnection events was up to 1000 times higher than this for a short time. Modeling suggest that the coherent MHD loss mechanism will be even less significant for future reactor-scale deuterium-tritium tokamaks due to the smaller ratio of the alpha gyroradius to minor radius.

Darrow, D.S.; Fredrickson, E.D.; Taylor, G.; White, R.B.; Zweben, S.J.; von Goeler, S.

1999-03-01

58

Ion-beam-induced-charge characterisation of particle detectors  

NASA Astrophysics Data System (ADS)

Ion-beam-induced-charge collection (IBIC) in a nuclear microprobe has been used to characterise detectors for the measurement of particles over a median energy range (100 keV-1 MeV). Three standard detector devices have been studied: a PIPS detector with a buried (ion-implanted) junction structure, a Schottky barrier junction device and a PN-junction photodiode. A 2.0 MeV focussed helium ion beam was used to probe the active area of each device with a spatial resolution ˜1-2 ?m, to quantify the thickness of the dead layer, the charge collection response and the reduction in charge collection efficiency induced by ion-beam damage.

Yang, C.; Jamieson, D. N.; Hearne, S. M.; Pakes, C. I.; Rout, B.; Gauja, E.; Dzurak, A. J.; Clark, R. G.

2002-05-01

59

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...

60

Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease  

PubMed Central

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

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

2012-01-01

61

Pathogenesis of Chlamydia induced pelvic inflammatory disease  

PubMed Central

Further research is necessary to elucidate the pathogenesis of chlamydial PID. It is hoped that these endeavours will eventually lead to a vaccine to prevent not only chlamydia infection, but also chlamydia associated infertility, ectopic pregnancy, and chronic pelvic pain. In the meantime we need to develop strategies to prevent primary and secondary chlamydia infection and its sequelae. Recently, Scholes et. al demonstrated that a population based approach to identify and test women at high risk for cervical C trachomatis infection effectively reduced risk of PID. Hopefully, through the use of public health measures, we can see similar decreases of chlamydia associated genital tract disease worldwide. ??? PMID:10448337

Cohen, C. R.; Brunham, R. C.

1999-01-01

62

Heavy charged-particle induced lesions in rabbit cerebral cortex  

SciTech Connect

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.

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

1988-02-01

63

Drug induced lung disease--amiodarone in focus.  

PubMed

More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lung disease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lung disease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication) of this medication. The incidence of amiodarone-induced lung disease is approximately 5-7%. PMID:25546981

Vasi?, Nada R; Milenkovi?, Branislava A; Pešut, Dragica P; Stevi?, Ruža S; Jovanovi?, Dragana M

2014-01-01

64

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

PubMed

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

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

65

Surface acoustic wave-induced precise particle manipulation in a trapezoidal glass microfluidic channel  

E-print Network

, particle alignment with only one IDT active was realized. A finite element method simulation was usedSurface acoustic wave-induced precise particle manipulation in a trapezoidal glass microfluidic.1088/0960-1317/22/2/025018 Surface acoustic wave-induced precise particle manipulation in a trapezoidal glass microfluidic channel L

66

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

SciTech Connect

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.

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

67

Insights into amyloid-?-induced mitochondrial dysfunction in Alzheimer disease  

Microsoft Academic Search

Amyloid-? has long been implicated in the pathogenesis of Alzheimer disease. The focus was initially on the extracellular fibrillar deposits of amyloid-? but more recently has shifted to intracellular oligomeric forms of amyloid-?. Unfortunately, the mechanism(s) by which either extracellular or intracellular amyloid-? induces neuronal toxicity remains unclear. That said, a number of recent studies indicate that mitochondria might be

Xinglong Wang; Bo Su; George Perry; Mark A. Smith; Xiongwei Zhu

2007-01-01

68

GPi pallidotomy for Parkinson's disease with drug-induced psychosis  

Microsoft Academic Search

Levodopa-induced psychosis may seriously threaten the ability of patients with Parkinson's disease (PD) to continue leading an independent life. A retrospective assessment of the therapeutic effects of the globus pallidus internus (GPi) pallidotomy on the activities of daily living (ADL) of seven PD patients presenting with mild or moderate degrees of psychosis was carried out. Their scores according to the

Kazumichi Yamada; Satoshi Goto; Yukitaka Ushio

2003-01-01

69

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

PubMed Central

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

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

70

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

PubMed

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

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

71

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

PubMed

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

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

72

Hypoxia and Hypoxia Inducible Factors: Diverse Roles in Liver Diseases  

PubMed Central

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

Nath, Bharath; Szabo, Gyongyi

2011-01-01

73

A novel particle separation method based on induced-charge electro-osmotic flow and polarizability of dielectric particles.  

PubMed

A new microfluidic method of particle separation was proposed and studied theoretically in this paper. This method is based on the induced charge electro-osmotic flow (ICEOF) and polarizability of dielectric particles. In this method, a pair of metal plates is embedded on the side channel walls to create a region of circulating flows under applied electric field. When a dielectric particle enters this region, the vortices produced by ICEOF around the particle will interact with the circulating flows produced by the metal plates. Such hydrodynamic interaction influences the particle's trajectory, and may result in the particle being trapped in the flow circulating zone or passing through this flow circulating zone. Because the hydrodynamic interaction is sensitive to the applied electric field, and the polarizability and the size of the particles, separation of different particles can be realized by controlling these parameters. Comparing with electrophoresis and dielectrophoresis methods, this strategy presented in this paper is simple and sensitive. PMID:25043290

Zhang, Fang; Li, Dongqing

2014-10-01

74

Visual phenomena induced by cosmic rays and accelerated particles  

NASA Technical Reports Server (NTRS)

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.

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

1972-01-01

75

Ejection of particles placed on a thin film by laser-induced forward transfer  

NASA Astrophysics Data System (ADS)

Laser-induced forward transfer (LIFT) was applied to eject the particles placed on a thin film. The behavior of the fluorescent particles in the gas phase was observed by a two-dimensional laser-induced fluorescence (2D-LIF) technique. The behavior of emissive particles was also imaged. The speed of the particles was in the order of few hundreds m/s, and changed with ablation conditions. The fastest speed was around 280 m/s.

Nakata, Yoshiki; Okada, Tatsuo; Maeda, Mitsuo

2001-06-01

76

Bacterial lipopolysaccharides as inducers of disease resistance in tobacco.  

PubMed Central

The cell wall component of Pseudomonas solanacearum that induces disease resistance in tobacco was highly heat stable at neutral or alkaline pH but highly labile at acid pH. Activity was unaffected by nucleases and proteases but destroyed by a mixture of beta-glycosidases. Washing of bacterial cell walls released a lipopolysaccharide (LPS) fraction with high inducer activity. Purified LPS, extracted by a variety of procedures from whole cells, isolated cell walls, and culture filtrates of both smooth and rough forms of P. solanacearum, induced disease resistance in tobacco at concentrations as low as 50 microgram/ml. The LPS from the non-plant pathogens Escherichia coli B, E. coli K, and Serratia marcescens was also active. Cell wall protein, free phospholipid, and nucleic acids were not necessary for activity. Moreover, since LPS from rough forms was active, the O-specific polysaccharide of the LPS was not required for activity. Hydrolysis of the remaining core-lipid A linkage or deacylation of lipid A destroyed inducer activity. When injected into tobacco leaves, purified LPS attached to tobacco mesophyll cell walls and induced ultrastructural changes in the host cell similar to those induced by attachment of whole heat-killed bacteria. Images PMID:21613

Graham, T L; Sequeira, L; Huang, T S

1977-01-01

77

Particles induce apical plasma membrane enlargement in epithelial lung cell line depending on particle surface area dose  

Microsoft Academic Search

BACKGROUND: Airborne particles entering the respiratory tract may interact with the apical plasma membrane (APM) of epithelial cells and enter them. Differences in the entering mechanisms of fine (between 0.1 ?m and 2.5 ?m) and ultrafine ( ? 0.1 ?m) particles may be associated with different effects on the APM. Therefore, we studied particle-induced changes in APM surface area in

Christina Brandenberger; Barbara Rothen-Rutishauser; Fabian Blank; Peter Gehr; Christian Mühlfeld

2009-01-01

78

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...

79

Interleukin-35 induces regulatory B cells that suppress autoimmune disease.  

PubMed

Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune disease, and increased numbers of Breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4(+) T cells to regulatory T (Treg) cells. The mechanisms mediating the induction and development of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and promotes their conversion to a Breg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12R?2 KO mice) produced less Breg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12R?2 and IL-27R? subunits. As IL-35 also induced the conversion of human B cells into Breg cells, these findings suggest that IL-35 may be used to induce autologous Breg and IL-35(+) Breg cells and treat autoimmune and inflammatory disease. PMID:24743305

Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M; Mahdi, Rashid M; Dolinska, Monika B; Sergeev, Yuri V; Wingfield, Paul T; Kim, Sung-Hye; Egwuagu, Charles E

2014-06-01

80

Particle flow control by induced dipolar interaction of superparamagnetic microbeads  

Microsoft Academic Search

Magnetic particles diluted in liquid agglomerate in rod-like particle arrays if an external homogeneous magnetic field is\\u000a applied. This work introduces a method to specifically exploit particle–particle interaction to obtain flow control of magnetic\\u000a particles without changing the motion state of the carrier liquid. Experiments show the possibility to uncouple the particle\\u000a flux from the motion state of liquid. We

A. Weddemann; F. Wittbracht; A. Auge; A. Hütten

2011-01-01

81

Lactobacillus GG in inducing and maintaining remission of Crohn's disease  

PubMed Central

Background Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn's disease and ulcerative colitis. Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission. The aim of this randomized, placebo-controlled trial was to determine the effect of oral Lactobacillus GG (L. GG) to induce or maintain medically induced remission. Methods Eleven patients with moderate to active Crohn's disease were enrolled in this trial to receive either L. GG (2 × 109 CFU/day) or placebo for six months. All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated. The primary end point was sustained remission, defined as freedom from relapse at the 6 months follow-up visit. Relapse was defined as an increase in CDAI of >100 points. Results 5/11 patients finished the study, with 2 patients in each group in sustained remission. The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group (p = 0.5). Conclusion In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD. PMID:15113451

Schultz, Michael; Timmer, Antje; Herfarth, Hans H; Sartor, R Balfour; Vanderhoof, Jon A; Rath, Heiko C

2004-01-01

82

Virus-like particles associated with banana bunchy top disease contain small single-stranded DNA  

Microsoft Academic Search

Virus-like particles were purified from banana plants with banana bunchy top disease. These particles were isometric with a diameter of 18 to 20 nm and a density of 1.28 to 1-30 g\\/ml in caesium sulphate. Associated with these particles were an ssDNA of about 1 kb and one major protein of Mr 20100. DsDNA was synthe- sized from nucleic acid

Robert M. Harding; Thomas M. Burns; James L. Dale

1991-01-01

83

Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice  

Microsoft Academic Search

To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL\\/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2?\\/?) and wild-type mice were exposed to low-dose DEP for 7 h\\/day, 5 days\\/week, for 8 weeks. Nrf2?\\/? mice exposed to low-dose DEP showed significantly increased airway

Ying Ji Li; Hajime Takizawa; Arata Azuma; Tadashi Kohyama; Yasuhiro Yamauchi; Satoru Takahashi; Masayuki Yamamoto; Tomoyuki Kawada; Shoji Kudoh; Isamu Sugawara

2008-01-01

84

Interstitial Lung Disease Induced by Drugs and Radiation  

Microsoft Academic Search

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

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

2004-01-01

85

Lipoprotein particle subclasses, cardiovascular disease and HIV infection  

Microsoft Academic Search

ObjectiveTo study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART (viral suppression [VS]).

Daniel A. Duprez; Lewis H. Kuller; Russell Tracy; James Otvos; David A. Cooper; Jennifer Hoy; Jacqueline Neuhaus; Nicholas I. Paton; Nina Friis-Moller; Fiona Lampe; Angelike P. Liappis; James D. Neaton

2009-01-01

86

Excitation of high-n toroidicity-induced shear Alfven eigenmodes by energetic particles and fusion alpha particles in tokamaks  

SciTech Connect

The stability of high-n toroidicity-induced shear Alfven eigenmodes (TAE) in the presence of fusion alpha particles or energetic ions in tokamaks is investigated. The TAE modes are discrete in nature and thus can easily tap the free energy associated with energetic particle pressure gradient through wave particle resonant interaction. A quadratic form is derived for the high-n TAE modes using gyro-kinetic equation. The kinetic effects of energetic particles are calculated perturbatively using the ideal MHD solution as the lowest order eigenfunction. The finite Larmor radius (FLR) effects and the finite drift orbit width (FDW) effects are included for both circulating and trapped energetic particles. It is shown that, for circulating particles, FLR and FDW effects have two opposite influences on the stability of the high-n TAE modes. First, they have the usual stabilizing effects by reducing the wave particle interaction strength. Second, they also have destabilizing effects by allowing more particles to resonate with the TAE modes. It is found that the growth rate induced by the circulating alpha particles increase linearly with toroidal mode number n for small {kappa}{sub {theta}}{rho}{sub {alpha}}, and decreases as 1/n for {kappa}{sub {theta}}{rho}{sub {alpha}} {much_gt} 1. The maximum growth rate is obtained at {kappa}{sub {theta}}{rho}{sub {alpha}} on the order of unity and is nearly constant for the range of 0.7 < {upsilon}{sub {alpha}}/{upsilon}{sub A} < 2.5. On the other hand, the trapped particle response is dominated by the precessional drift resonance. The bounce resonant contribution is negligible. The growth rate peaks sharply at the value of {kappa}{sub {theta}}{rho}{sub {alpha}} such that the precessional drift resonance occurs for the most energetic trapped particles. The maximum growth rate due to the energetic trapped particles is comparable to that of circulating particles.

Fu, G.Y.; Cheng, C.Z.

1992-07-01

87

Excitation of high-n toroidicity-induced shear Alfven eigenmodes by energetic particles and fusion alpha particles in tokamaks  

SciTech Connect

The stability of high-n toroidicity-induced shear Alfven eigenmodes (TAE) in the presence of fusion alpha particles or energetic ions in tokamaks is investigated. The TAE modes are discrete in nature and thus can easily tap the free energy associated with energetic particle pressure gradient through wave particle resonant interaction. A quadratic form is derived for the high-n TAE modes using gyro-kinetic equation. The kinetic effects of energetic particles are calculated perturbatively using the ideal MHD solution as the lowest order eigenfunction. The finite Larmor radius (FLR) effects and the finite drift orbit width (FDW) effects are included for both circulating and trapped energetic particles. It is shown that, for circulating particles, FLR and FDW effects have two opposite influences on the stability of the high-n TAE modes. First, they have the usual stabilizing effects by reducing the wave particle interaction strength. Second, they also have destabilizing effects by allowing more particles to resonate with the TAE modes. It is found that the growth rate induced by the circulating alpha particles increase linearly with toroidal mode number n for small {kappa}{sub {theta}}{rho}{sub {alpha}}, and decreases as 1/n for {kappa}{sub {theta}}{rho}{sub {alpha}} {much gt} 1. The maximum growth rate is obtained at {kappa}{sub {theta}}{rho}{sub {alpha}} on the order of unity and is nearly constant for the range of 0.7 < {upsilon}{sub {alpha}}/{upsilon}{sub A} < 2.5. On the other hand, the trapped particle response is dominated by the precessional drift resonance. The bounce resonant contribution is negligible. The growth rate peaks sharply at the value of {kappa}{sub {theta}}{rho}{sub {alpha}} such that the precessional drift resonance occurs for the most energetic trapped particles. The maximum growth rate due to the energetic trapped particles is comparable to that of circulating particles.

Fu, G.Y.; Cheng, C.Z.

1992-07-01

88

Electric-field-induced capillary attraction between like-charged particles at liquid interfaces  

Microsoft Academic Search

Nanometre- and micrometre-sized charged particles at aqueous interfaces are typically stabilized by a repulsive Coulomb interaction. If one of the phases forming the interface is a nonpolar substance (such as air or oil) that cannot sustain a charge, the particles will exhibit long-ranged dipolar repulsion; if the interface area is confined, mutual repulsion between the particles can induce ordering and

M. G. Nikolaides; A. R. Bausch; M. F. Hsu; A. D. Dinsmore; M. P. Brenner; C. Gay; D. A. Weitz

2002-01-01

89

Energetic-Particle-Induced Geodesic Acoustic Mode Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543, USA  

E-print Network

Energetic-Particle-Induced Geodesic Acoustic Mode G. Y. Fu* Princeton Plasma Physics Laboratory Understanding of energetic particle physics in tokamaks is of fundamental importance for burning plasmas. Recent, Princeton, New Jersey 08543, USA (Received 24 June 2008; published 30 October 2008) A new energetic particle

90

Laser-induced incandescence measurements of particles in aeroengine exhausts  

NASA Astrophysics Data System (ADS)

Laser Induced Incandescence (LII) has been demonstrated as a non-intrusive technique for measurement of particle concentration in the exhausts of aero-engines on sea level test beds as part of a European Union collaborative program (AEROJET) aimed at replacing gas sampling rakes behind development engines with non-intrusive instrumentation. Currently emissions of CO, NOx, unburned hydrocarbon, and smoke from aero-engines must be shown to be less than internationally specified limits. Measurements are made on development engines on sea level test beds by applying a number of standard analytical methods to extracted exhaust gas samples. The hardware required for exhaust gas sampling is heavy and complex and is expensive to build and install. As a result, only the minimum number of emissions tests are conducted during an engine development program, and emissions data is only available to combustion engineers late in the program. Hence, there is a need for more versatile and less costly non-intrusive measurement techniques. Molecular species can be measured using Fourier Transform Infrared (FTIR) spectroscopy, while LII is a promising smoke measuring technique. The development of an LII system specifically designed for exhaust applications is described.

Black, John D.

1999-09-01

91

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 ...

92

Experimental particle acceleration by water evaporation induced by shock waves  

NASA Astrophysics Data System (ADS)

Shock waves are commonly generated during volcanic eruptions. They induce sudden changes in pressure and temperature causing phase changes. Nevertheless, their effects on flowfield properties are not well understood. Here we investigate the role of gas expansion generated by shock wave propagation in the acceleration of ash particles. We used a shock tube facility consisting of a high-pressure (HP) steel autoclave (450 mm long, 28 mm in internal diameter), pressurized with Ar gas, and a low-pressure tank at atmospheric conditions (LP). A copper diaphragm separated the HP autoclave from a 180 mm tube (PVC or acrylic glass) at ambient P, with the same internal diameter of the HP reservoir. Around the tube, a 30 cm-high acrylic glass cylinder, with the same section of the LP tank (40 cm), allowed the observation of the processes occurring downstream from the nozzle throat, and was large enough to act as an unconfined volume in which the initial diffracting shock and gas jet expand. All experiments were performed at Pres/Pamb ratios of 150:1. Two ambient conditions were used: dry air and air saturated with steam. Carbon fibers and glass spheres in a size range between 150 and 210 ?m, were placed on a metal wire at the exit of the PVC tube. The sudden decompression of the Ar gas, due to the failure of the diaphragm, generated an initial air shock wave. A high-speed camera recorded the processes between the first 100 ?sec and several ms after the diaphragm failure at frame rates ranging between 30,000 and 50,000 fps. In the experiments with ambient air saturated with steam, the high-speed camera allowed to visualize the condensation front associated with the initial air shock; a maximum velocity of 788 m/s was recorded, which decreases to 524 m/s at distance of 0.5 ±0.2 cm, 1.1 ms after the diaphragm rupture. The condensation front preceded the Ar jet front exhausting from the reservoir, by 0.2-0.5 ms. In all experiments particles velocities following the initial condensation front exhibited large accelerations, with velocity varying from few tens of m/s up to 479 (±0.5) m/s, at distances of 1.5 (±0.3) cm and in times of 0.1 ms. This process preceded the appearance of the Ar front. Our first results suggest that the evaporation of moisture induced by compression waves associated with the air shock is able to accelerate particles (ca.100s microns in size) efficiently, at short distances. This process could have broader implications in active volcanic areas where shock waves are generated, for the damage that may follow.

Scolamacchia, T.; Alatorre Ibarguengoitia, M.; Scheu, B.; Dingwell, D. B.; Cimarelli, C.

2010-12-01

93

Treg Inducing Adjuvants for Therapeutic Vaccination Against Chronic Inflammatory Diseases  

PubMed Central

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

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

2013-01-01

94

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 obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy

95

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

E-print Network

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

Zhao, Huimin

96

Thalidomide induces mucosal healing in Crohn's disease: Case report  

PubMed Central

Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract that is defined by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-?) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-? properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn’s disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn’s disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximab after three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response. PMID:22174554

Leite, Márcio Rios; Santos, Sandra Sousa; Lyra, André Castro; Mota, Jaciane; Santana, Genoile Oliveira

2011-01-01

97

Cacao liquor proanthocyanidins inhibit lung injury induced by diesel exhaust particles.  

PubMed

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 microg/body). Dietary supplementation with 1.0 percent CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules. PMID:18547470

Yasuda, A; Takano, H; Osakabe, N; Sanbongi, C; Fukuda, K; Natsume, M; Yanagisawa, R; Inoue, K; Kato, Y; Osawa, T; Yoshikawa, T

2008-01-01

98

Alpha-particle-induced soft errors in dynamic memories  

Microsoft Academic Search

A new physical soft error mechanism in dynamic RAM's and CCD's is the upset of stored data by the passage of alpha particles through the memory array area. The alpha particles are emitted by the radioactive decay of uranium and thorium which are present in parts-per-million levels in packaging materials. When an alpha particle penetrates the die surface, it can

T. C. May; M. H. Woods

1979-01-01

99

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

NASA Astrophysics Data System (ADS)

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.

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

2014-04-01

100

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

PubMed Central

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

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

2006-01-01

101

Adenovirus Particles that Display the Plasmodium falciparum Circumsporozoite Protein NANP Repeat Induce Sporozoite-Neutralizing Antibodies in Mice  

PubMed Central

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

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

2011-01-01

102

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

NASA Astrophysics Data System (ADS)

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.

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

2013-01-01

103

Co-Cr-Mo Alloy Particles Induce Tumor Necrosis Factor Alpha Production in MLO-Y4 Osteocytes: A Role for Osteocytes in Particle Induced Inflammation  

PubMed Central

Wear debris-induced osteolysis is purportedly the limiting problem affecting the long term results of joint arthroplasty. Pathogenic effects of wear debris in peri-implant cells such as macrophages, osteoblasts and osteoclasts have been well studied. In contrast, the affects of wear-debris on osteocytes, which make up over 90% of all bone cells, remains unknown. We hypothesized that metal implant debris can induce the proinflammatory response in osteocytes. This study demonstrated the effects of cobalt-chromium-molybdenum alloy (Co-Cr-Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. Co-Cr-Mo alloy particle treatment significantly (p<0.05) up-regulated tumor necrosis factor alpha (TNF?) gene expression after 3 and 6 hr and TNF? protein production after 24 hr, but down-regulated interleukin-6 (IL-6) gene expression after 6 hr. Co-Cr-Mo alloy particle treatment also induced osteocyte apoptosis after 24 hr. This apoptotic effect was partially (40%) dependent on TNF?. Therefore, our results suggest that osteocytes play a role in particle induced inflammation and bone resorption following total hip arthroplasty by inducing pro-inflammatory cytokines and inducing osteocyte apoptosis. PMID:19497395

Kanaji, Arihiko; Caicedo, Marco S.; Virdi, Amarjit S.; Sumner, D. Rick; Hallab, Nadim J.; Sena, Kotaro

2009-01-01

104

Screening for asbestos-induced diseases in Finland.  

PubMed

Screening for asbestos-induced diseases in Finland was carried out in 1990-1992 as a part of the Asbestos Program of the Finnish Institute of Occupational Health. The aim of the present study was to find the workers who had developed an asbestos-induced disease in certain occupations. Examination of active or retired workers included a personal interview on work history and asbestos exposure, and a chest X-ray. The target group for the screening comprised workers under 70 years of age who had worked at least for 10 years in construction, 1 year in a shipyard or in the manufacture of asbestos products. A preliminary questionnaire was sent to 54,409 workers, 18,943 of whom finally participated in the screening examination. The mean age of the workers was 53 years; 95% were employed in construction, 2% in shipyards, and 3% in the asbestos industry. The criteria for a positive screening result were (1) a radiographic finding clearly indicating lung fibrosis (at least ILO category 1/1), (2) a radiographic finding indicating mild lung fibrosis (ILO category 1/0) with unilateral or bilateral pleural plaques, (3) marked abnormalities of the visceral pleura (marked adhesions with or without pleural thickening), or (4) bilateral pleural plaques. The positive cases totalled 4,133 (22%) and were sent for further investigation. In addition to the screening, information on the presence of asbestos in the work environment, prevention of asbestos exposure, as well as on the health effects of asbestos exposure and smoking were given to the participating workers. The screening acted as a preliminary survey to prompt further national follow-up of asbestos-induced diseases among the workers who have been exposed to asbestos. This article presents the material, methods, and overall results of the screening. PMID:8876791

Koskinen, K; Rinne, J P; Zitting, A; Tossavainen, A; Kivekäs, J; Reijula, K; Roto, P; Huuskonen, M S

1996-09-01

105

Mineralogical and geochemical aspects of mineral-induced disease  

SciTech Connect

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.

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

106

Advances in metal-induced oxidative stress and human disease.  

PubMed

Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), glutathione (GSH), carotenoids, flavonoids, and other antioxidants) are capable of chelating metal ions reducing thus their catalytic activity to form ROS. A novel therapeutic approach to suppress oxidative stress is based on the development of dual function antioxidants comprising not only chelating, but also scavenging components. Parodoxically, two major antioxidant enzymes, superoxide dismutase (SOD) and catalase contain as an integral part of their active sites metal ions to battle against toxic effects of metal-induced free radicals. The aim of this review is to provide an overview of redox and non-redox metal-induced formation of free radicals and the role of oxidative stress in toxic action of metals. PMID:21414382

Jomova, Klaudia; Valko, Marian

2011-05-10

107

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

PubMed Central

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

McGinnes, Lori W.; Morrison, Trudy G.

2014-01-01

108

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

E-print Network

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.

Seishi Enomoto; Olga Fuksi?ska; Zygmunt Lalak

2014-12-23

109

Passing particle toroidal precession induced by electric field in a tokamak  

SciTech Connect

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.

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

110

Animal models of beryllium-induced lung disease  

SciTech Connect

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.

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

1996-10-01

111

Animal models of beryllium-induced lung disease.  

PubMed Central

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 micrograms Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving > or = 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 micrograms (-300 micrograms 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. PMID:8933044

Finch, G L; Hoover, M D; Hahn, F F; Nikula, K J; Belinsky, S A; Haley, P J; Griffith, W C

1996-01-01

112

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

PubMed

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

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

2015-03-01

113

Charged particle-induced noise in camera systems  

Microsoft Academic Search

When a camera system is operated in a flux of charged particles, it will generate transient signals. The charged particles will impinge on the focal plane array and generate tracks of ionized electron-hole pairs. The charge tracks will diffuse, and some of the charge will be collected as signal and the rest will recombine. Bremsstrahlung radiation will be generated in

Carl Christian Liebe

2001-01-01

114

Particle Trapping at Planet-Induced Gap Edges and Vortices  

NASA Astrophysics Data System (ADS)

We use numerical simulations to perform a systematic study on the dynamics of dust particles in protoplanetary disks under the influence of a planet in disks. Dust particles in viscous disks (representing turbulent regions in disks) and inviscid hydro disks (``dead zone'') have been simulated separately using our newly developed Two-Fluids FARGO and ATHENA+Particle codes. For inviscid 3-D disks, we found that a low mass planet (8 M_earth) open almost unnoticeable gaps in gas which can still lead to significant dust piling up at gap edges. Sharp gap edges carved out by a massive planet are unstable to the formation of vortices, which can efficiently trap particles with a wide range of sizes(at least 4 orders of magnitude in our cases). Thus gaps and vortices in particle disks should be very common if there are planets in the``dead zones''. For viscous disks, the dust features are significantly smoothed out by the parameterized turbulent diffusion, and small dust particles can follow the accreting gas flowing to the inner disk. Thus, the so-called ``dust filtration'' mechanism by the gap edges can differentiate big and small dust particles. MHD simulations are developed to understand the gap opening and particle concentration in realistic turbulent disks.

Zhu, Zhaohuan; Stone, James; Rafikov, Roman; Bai, Xuening; Espaillat, Catherine

2013-07-01

115

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

PubMed Central

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

2008-01-01

116

[Drug-induced interstitial lung diseases : Often forgotten].  

PubMed

Drug-induced interstitial lung diseases (DILD) are probably more common than diagnosed. Due to their potential reversibility, increased vigilance towards DILD is appropriate also from the radiologist's point of view, particularly as these diseases regularly exhibit radiological correlates in high-resolution computed tomography (HRCT) of the lungs.Based on personal experience typical relatively common manifestations of DILD are diffuse alveolar damage (DAD), eosinophilic pneumonia (EP), hypersensitivity pneumonitis (HP), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). These patterns are presented based on case studies, whereby emphasis is placed on the clinical context. This is to highlight the relevance of interdisciplinary communication and discussion in the diagnostic field of DILD as it is a diagnosis of exclusion or of probability in most cases.Helpful differential diagnostic indications for the presence of DILD, such as an accompanying eosinophilia or increased attenuation of pulmonary consolidations in amiodarone-induced pneumopathy are mentioned and the freely available online database http://www.pneumotox.com is presented. PMID:25446693

Poschenrieder, F; Stroszczynski, C; Hamer, O W

2014-12-01

117

MOLECULAR CARCINOGENESIS 52:726738 (2013) Reduction of Inflammatory Bowel Disease-Induced  

E-print Network

MOLECULAR CARCINOGENESIS 52:726­738 (2013) Reduction of Inflammatory Bowel Disease-Induced Tumor of sEH in inflammatory bowel disease (IBD) and its induced carcinogenesis. In the present study- ment for IBD. � 2012 Wiley Periodicals, Inc. Key words: inflammatory bowel disease; carcinogenesis

Hammock, Bruce D.

118

Filler particles used in dental biomaterials induce production and release of inflammatory mediators in vitro.  

PubMed

Although dental composites are in extensive use today, little is known about the biological effects of the filler particles. As composite materials are gradually broken down in the aggressive environment of the oral cavity, the filler particles may leak and induce toxic effects on the surrounding tissue and cells. The aim of this study was to elucidate possible adverse biological effects of commonly used dental filler particles; bariumaluminiumsilica (BaAlSi) and bariumaluminiumfluorosilica (BaAlFSi) with mean size of 1 microm. BEAS-2B cells were used as a model system. Particle morphology, mean particle size in solution, and particle surface charge were determined by scanning electron microscopy and Malvern zetasizer technology, respectively. Enzyme-linked immunosorbent assay was used to detect secretion of cytokine and chemokine (IL-8 and IL-6) and quantitative PCR for detection of gene activity. Both types of particle increased the release of IL-6 and IL-8 in a dose-dependent manner. BaAlFSi particles induced a more marked IL-8 response compared to BaAlSi particles, whereas no significant difference was observed for the IL-6 response. Mechanistic studies using specific inhibitors and activators indicated that cyclic AMP-dependent protein kinase A is partly involved in the observed IL-8 response. In conclusion, we consider dental filler particles to have potential to induce adverse biological response in cell cultures. PMID:18759324

Ansteinsson, Vibeke E; Samuelsen, Jan Tore; Dahl, Jon E

2009-04-01

119

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

E-print Network

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 ...

Simo, I. Ruiz

120

Characterization of nuclear physics targets using Rutherford backscattering and particle induced x-ray emission  

E-print Network

Rutherford backscattering and particle induced x-ray emission have been utilized to precisely characterize targets used in nuclear fission experiments. The method allows for a fast and non destructive determination of target thickness, homogeneity and element composition.

Th. Rubehn; G. J. Wozniak; L. Phair; L. G. Moretto; Kin M. Yu

1996-09-23

121

Aloe vera Induced Biomimetic Assemblage of Nucleobase into Nanosized Particles  

PubMed Central

Aim Biomimetic nano-assembly formation offers a convenient and bio friendly approach to fabricate complex structures from simple components with sub-nanometer precision. Recently, biomimetic (employing microorganism/plants) synthesis of metal and inorganic materials nano-particles has emerged as a simple and viable strategy. In the present study, we have extended biological synthesis of nano-particles to organic molecules, namely the anticancer agent 5-fluorouracil (5-FU), using Aloe vera leaf extract. Methodology The 5-FU nano- particles synthesized by using Aloe vera leaf extract were characterized by UV, FT-IR and fluorescence spectroscopic techniques. The size and shape of the synthesized nanoparticles were determined by TEM, while crystalline nature of 5-FU particles was established by X-ray diffraction study. The cytotoxic effects of 5-FU nanoparticles were assessed against HT-29 and Caco-2 (human adenocarcinoma colorectal) cell lines. Results Transmission electron microscopy and atomic force microscopic techniques confirmed nano-size of the synthesized particles. Importantly, the nano-assembled 5-FU retained its anticancer action against various cancerous cell lines. Conclusion In the present study, we have explored the potential of biomimetic synthesis of nanoparticles employing organic molecules with the hope that such developments will be helpful to introduce novel nano-particle formulations that will not only be more effective but would also be devoid of nano-particle associated putative toxicity constraints. PMID:22403622

Chauhan, Arun; Zubair, Swaleha; Sherwani, Asif; Owais, Mohammad

2012-01-01

122

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

NASA Astrophysics Data System (ADS)

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.

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

1993-04-01

123

Modeling Huntington’s Disease with Induced Pluripotent Stem Cells  

PubMed Central

Huntington’s disease (HD) causes severe motor dysfunction, behavioral abnormalities, cognitive impairment and death. Investigations into its molecular pathology have primarily relied on murine tissues; however, the recent discovery of induced pluripotent stem cells (iPSCs) has opened new possibilities to model neurodegenerative disease using cells derived directly from patients, and therefore may provide a human-cell-based platform for unique insights into the pathogenesis of HD. Here, we will examine the practical implementation of iPSCs to study HD, such as approaches to differentiate embryonic stem cells (ESCs) or iPSCs into medium spiny neurons, the cell type most susceptible in HD. We will explore the HD-related phenotypes identified in iPSCs and ESCs and review how brain development and neurogenesis may actually be altered early, before the onset of HD symptoms, which could inform the search for drugs that delay disease onset. Finally, we will speculate on the exciting possibility that ESCs or iPSCs might be used as therapeutics to restore or replace dying neurons in HD brains. PMID:23459227

Kaye, Julia A.

2013-01-01

124

Diesel exhaust particles induce endothelial dysfunction in apoE ?\\/? mice  

Microsoft Academic Search

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?\\/? mice with slight atherosclerosis and from normal

Christian S. Hansen; Majid Sheykhzade; Peter Møller; Janne Kjaergaard Folkmann; Ole Amtorp; Thomas Jonassen; Steffen. Loft

2007-01-01

125

Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice  

PubMed Central

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

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

126

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...

127

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...

128

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

E-print Network

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 it is extremely difficult to measure air flow around an insect at a free flight situation, the tested fire ant

Gui, Lichuan

129

Alpha and beta particle induced scintillations in liquid and solid neon  

Microsoft Academic Search

Scintillations induced by alpha and beta particles in liquid and solid neon are studied and their light yield measured. Charged particle scintillation in neon is primarily in the extreme ultraviolet (EUV). We detect this EUV light by converting it to blue using a wavelength shifting fluor and detecting the blue light with a photomultiplier tube. It is observed that liquid

R. A. Michniak; R. Alleaume; D. N. McKinsey; J. M. Doyle

2002-01-01

130

Flow-induced orientation of non-spherical particles: Effect of aspect ratio and medium rheology  

Microsoft Academic Search

The flow-induced orientation of spheroidal particles in viscoelastic fluids is studied by means of rheo-optical methods and flow microscopy. Using suitable model systems a wide range of rotational Péclet and Weissenberg numbers have been covered, providing a systematic and global picture of the various orientational transitions. The effects of particle size and aspect ratio have been considered separately. Increasing the

D. Z. Gunes; R. Scirocco; J. Mewis; J. Vermant

2008-01-01

131

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

PubMed

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

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

132

Two-dimensional soot-particle sizing by time-resolved laser-induced incandescence  

NASA Astrophysics Data System (ADS)

The evaluation of the temporal decay of the laser-induced incandescence (LII) signal from soot particles is introduced as a technique to obtain two-dimensional distributions of particle sizes and is applied to a laminar diffusion flame. This novel approach to soot sizing exhibits several theoretical and technical advantages compared with the established combination of elastic scattering and LII, especially as it yields absolute sizes of primary particles without requiring calibration.

Will, Stefan; Schraml, Stephan; Leipertz, Alfred

1995-11-01

133

Continuous-flow particle and cell separations in a serpentine microchannel via curvature-induced dielectrophoresis  

Microsoft Academic Search

Particle and cell separations are critical to chemical and biomedical analyses. This study demonstrates a continuous-flow\\u000a electrokinetic separation of particles and cells in a serpentine microchannel through curvature-induced dielectrophoresis.\\u000a The separation arises from the particle size-dependent cross-stream dielectrophoretic deflection that is generated by the\\u000a inherent electric field gradients within channel turns. Through the use of a sheath flow to focus

Junjie Zhu; Robert Cameron Canter; Gyunay Keten; Pallavi Vedantam; Tzuen-Rong J. Tzeng; Xiangchun Xuan

134

Turbulence-induced preferential concentration of solid particles in microgravity conditions  

Microsoft Academic Search

A box of near-isotropic, particle-laden turbulence was flown aboard NASA's reduced gravity aircraft in order to measure the\\u000a turbulence-induced preferential concentration of solid particles in microgravity. Three particle sets of Stokes numbers based\\u000a on the fluid Kolmogorov time scale of approximately 0.5, 5, and 50 were tested for relative amounts of preferential concentration.\\u000a Eight fans in each corner of a

T. Fallon; C. B. Rogers

2002-01-01

135

Comparison of the performance of particle filter algorithms applied to tracking of a disease epidemic.  

PubMed

We present general methodology for sequential inference in nonlinear stochastic state-space models to simultaneously estimate dynamic states and fixed parameters. We show that basic particle filters may fail due to degeneracy in fixed parameter estimation and suggest the use of a kernel density approximation to the filtered distribution of the fixed parameters to allow the fixed parameters to regenerate. In addition, we show that "seemingly" uninformative uniform priors on fixed parameters can affect posterior inferences and suggest the use of priors bounded only by the support of the parameter. We show the negative impact of using multinomial resampling and suggest the use of either stratified or residual resampling within the particle filter. As a motivating example, we use a model for tracking and prediction of a disease outbreak via a syndromic surveillance system. Finally, we use this improved particle filtering methodology to relax prior assumptions on model parameters yet still provide reasonable estimates for model parameters and disease states. PMID:25016201

Sheinson, Daniel M; Niemi, Jarad; Meiring, Wendy

2014-09-01

136

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

PubMed

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

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

2014-08-01

137

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

PubMed Central

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

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

2012-01-01

138

DRIFT-INDUCED PERPENDICULAR TRANSPORT OF SOLAR ENERGETIC PARTICLES  

SciTech Connect

Drifts are known to play a role in galactic cosmic ray transport within the heliosphere and are a standard component of cosmic ray propagation models. However, the current paradigm of solar energetic particle (SEP) propagation holds the effects of drifts to be negligible, and they are not accounted for in most current SEP modeling efforts. We present full-orbit test particle simulations of SEP propagation in a Parker spiral interplanetary magnetic field (IMF), which demonstrate that high-energy particle drifts cause significant asymmetric propagation perpendicular to the IMF. Thus in many cases the assumption of field-aligned propagation of SEPs may not be valid. We show that SEP drifts have dependencies on energy, heliographic latitude, and charge-to-mass ratio that are capable of transporting energetic particles perpendicular to the field over significant distances within interplanetary space, e.g., protons of initial energy 100 MeV propagate distances across the field on the order of 1 AU, over timescales typical of a gradual SEP event. Our results demonstrate the need for current models of SEP events to include the effects of particle drift. We show that the drift is considerably stronger for heavy ion SEPs due to their larger mass-to-charge ratio. This paradigm shift has important consequences for the modeling of SEP events and is crucial to the understanding and interpretation of in situ observations.

Marsh, M. S.; Dalla, S.; Kelly, J.; Laitinen, T., E-mail: mike.s.marsh@gmail.com [Jeremiah Horrocks Institute, University of Central Lancashire, Preston, PR1 2HE (United Kingdom)

2013-09-01

139

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

SciTech Connect

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}.

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

140

Effect of induced electric field on migration of a charged porous particle.  

PubMed

The effect of ambient fluid flow on a charged porous spherical particle suspended in an aqueous medium is analyzed. The porous particle is ion permeable and fluid penetrable. The induced electric field due to the polarization of the particle's electric double layer and counterion condensation leads to a hindrance effect on particle migration by producing an electric force. The influence of this retardation force on the hydrodynamics of the particle is studied through the Nernst-Planck equations, which are coupled with the Stokes-Brinkman equation. The interactions of the double-layer polarization, shielding effect, electroosmosis of unbalanced ions and fluid convection are analyzed. The settling velocity and fluid collection efficiency of the charged aggregate is determined. We have studied the electrokinetics for a wide range of fixed charge density and permeability of the particle with no assumption made on the thickness of the double layer relative to the dimension of the particle. PMID:25374308

Gopmandal, Partha P; Bhattacharyya, S; Barman, Bhanuman

2014-11-01

141

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

PubMed Central

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

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

142

Virus-Like Particle-Induced Protection Against MRSA Pneumonia Is Dependent on IL-13 and Enhancement of Phagocyte Function  

PubMed Central

The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c+ cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G+ or CD11c+ cells. Early IL-13 production associated with VLP-induced CD11c+ cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13–dependent mechanisms. PMID:22642909

Rynda-Apple, Agnieszka; Dobrinen, Erin; McAlpine, Mark; Read, Amanda; Harmsen, Ann; Richert, Laura E.; Calverley, Matthew; Pallister, Kyler; Voyich, Jovanka; Wiley, James A.; Johnson, Ben; Young, Mark; Douglas, Trevor; Harmsen, Allen G.

2013-01-01

143

Molecular Basis of Asbestos-Induced Lung Disease  

PubMed Central

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

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

2013-01-01

144

Enhanced homologous recombination is induced by alpha-particle radiation in somatic cells of Arabidopsis thaliana  

NASA Astrophysics Data System (ADS)

Almost 9 percent of cosmic rays which strike the earth's atmosphere are alpha particles. As one of the ionizing radiations (IR), its biological effects have been widely studied. However, the plant genomic instability induced by alpha-particle radiation was not largely known. In this research, the Arabidopsis thaliana transgenic for GUS recombination substrate was used to evaluate the genomic instability induced by alpha-particle radiation (3.3MeV). The pronounced effects of systemic exposure to alpha-particle radiation on the somatic homologous recombination frequency (HRF) were found at different doses. The 10Gy dose of radiation induced the maximal HRF which was 1.9-fold higher than the control. The local radiation of alpha-particle (10Gy) on root also resulted in a 2.5-fold increase of somatic HRF in non-radiated aerial plant, indicating that the signal(s) of genomic instability was transferred to non-radiated parts and initiated their genomic instability. Concurrent treatment of seedlings of Arabidopsis thaliana with alpha-particle and DMSO(ROS scavenger) both in systemic and local radiation signifi- cantly suppressed the somatic HR, indicating that the free radicals produced by alpha-particle radiation took part in the production of signal of genomic instability rather than the signal transfer. Key words: alpha-particle radiation, somatic homologous recombination, genomic instability

Bian, Po; Liu, Ping; Wu, Yuejin

145

On the effect of induced electro-osmosis on a cylindrical particle next to a surface.  

PubMed

The effect of induced electro-osmosis on a cylindrical particle positioned next to a planar surface (wall) is studied theoretically both under the thin double layer approximation utilizing the Smoluchowski slip velocity approximation and under thick electric double layer conditions by solving the Poisson-Nernst-Planck (PNP) equations. The imposed, undisturbed electric field is parallel to the planar surface. The induced hydrodynamic and electrostatic forces are calculated as functions of the particle's and the medium's dielectric constants and the distance between the particle and the surface. The resultant force acting on the particle is directed normal to and away from the wall. The presence of such a repulsive force may adversely affect the interactions between macromolecules suspended in solution and wall-immobilized molecules and may be significant to near-wall particle imaging velocimetry (PIV) in electrokinetic flows. PMID:17311434

Zhao, Hui; Bau, Haim H

2007-03-27

146

Buckling-induced jamming in channel flow of particle rafts  

NASA Astrophysics Data System (ADS)

We report on observations of the flow of plastic particles floating on the surface of water in a rectangular channel. The system is driven by moving one wall of the channel at a constant velocity. The opposite side of the channel is open, and the particles are pushed into a region free of material. During the flow, video of the particle motions is captured, and the average force on the pushing wall is measured. We have studied particle shapes that are both circular disks and rectangular bars. We find that when the rectangular bars form a layer at the side walls of the channel (whether or not the central region is filled with disks or additional rectangular bars), the system exhibits sudden increases and decreases in the average force on the driving wall. This behavior is consistent with the existence of jamming in the system. We report on the shape and velocity dependence of these force fluctuations, and the evidence that buckling of the rectangular blocks at the wall is responsible for generating the jamming dynamics.

Kuo, Chin-Chang; Dennin, Michael

2013-03-01

147

Synchronization of particle motion induced by mode coupling in a two-dimensional plasma crystal.  

PubMed

The kinematics of dust particles during the early stage of mode-coupling induced melting of a two-dimensional plasma crystal is explored. It is found that the formation of the hybrid mode causes the particle vibrations to partially synchronize at the hybrid frequency. Phase- and frequency-locked hybrid particle motion in both vertical and horizontal directions (hybrid mode) is observed. The system self-organizes in a rhythmic pattern of alternating in-phase and antiphase oscillating chains of particles. The spatial orientation of the synchronization pattern correlates well with the directions of the maximal increment of the shear-free hybrid mode. PMID:25353905

Couëdel, L; Zhdanov, S; Nosenko, V; Ivlev, A V; Thomas, H M; Morfill, G E

2014-05-01

148

Synchronization of particle motion induced by mode coupling in a two-dimensional plasma crystal  

NASA Astrophysics Data System (ADS)

The kinematics of dust particles during the early stage of mode-coupling induced melting of a two-dimensional plasma crystal is explored. It is found that the formation of the hybrid mode causes the particle vibrations to partially synchronize at the hybrid frequency. Phase- and frequency-locked hybrid particle motion in both vertical and horizontal directions (hybrid mode) is observed. The system self-organizes in a rhythmic pattern of alternating in-phase and antiphase oscillating chains of particles. The spatial orientation of the synchronization pattern correlates well with the directions of the maximal increment of the shear-free hybrid mode.

Couëdel, L.; Zhdanov, S.; Nosenko, V.; Ivlev, A. V.; Thomas, H. M.; Morfill, G. E.

2014-05-01

149

Energetic particle-induced enhancements of stratospheric nitric acid  

NASA Technical Reports Server (NTRS)

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.

Aikin, Arthur C.

1994-01-01

150

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

NASA Astrophysics Data System (ADS)

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.

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

2015-01-01

151

Pollutant particles induce arginase II in human bronchial epithelial cells  

EPA Science Inventory

Exposure to particulate matter (PM) is associated with adverse pulmonary effects, including induction and exacerbation of asthma. Recently arginase was shown to play an important role in the pathogenesis of asthma. In this study, we hypothesized that PM exposure would induce ar...

152

Induced healing of aneurysmal bone cysts by demineralized bone particles  

Microsoft Academic Search

Two cases of induced healing of aneurysmal bone cyst (ABC) following intralesional implantation of a bone paste made of autogeneic bone marrow and allogeneic bone powder are reported. The calcaneum in one case and the superior pubic ramus in the other were blown out by an ABC and would have required extensive surgery. Via a minimal exposure, the cyst was

C. Delloye; P. Nayer; J. Malghem; H. Noel

1996-01-01

153

Inhibitory effects of luteolin on titanium particle-induced osteolysis in a mouse model.  

PubMed

Wear particles liberated from the surfaces of an implanted prosthesis are associated with peri-implant osteolysis and subsequent aseptic loosening. In the latter wear particle-induced inflammation and osteoclastogenesis have been identified as critical factors, and their inhibition as important steps in the treatment of affected patients, such as those undergoing total hip replacement. In this study the ability of luteolin to inhibit both titanium (Ti) particle-induced osteoclastogenesis in vitro and osteolysis in a murine calvaria Ti particle-induced model of osteolysis was examined. The results showed that luteolin, a highly potent and efficient inhibitor of tumor necrosis factor ? (TNF-?) and interleukin-6 expression, inhibited Ti particle-induced inflammatory cytokine release, osteoclastogenesis, and bone resorption in bone marrow macrophages. Microcomputed tomography and histological analyses showed that the Ti particles caused significant bone resorption and increased TRAP(+) multinuclear osteoclasts in the murine calvarial model of osteolysis, whereas this was not the case in the luteolin treatment group, in which osteolytic suppression was accompanied by a decrease in both TNF-? production and serum levels of the osteoclast marker the C-terminal telopeptide fragment of type I collagen. These results support the use of luteolin as a natural compound in the prevention and treatment of aseptic loosening after total replacement arthroplasty. PMID:22583904

Shin, Dong-Kyu; Kim, Mi-Hyung; Lee, Sang-Han; Kim, Tae-Ho; Kim, Shin-Yoon

2012-09-01

154

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

PubMed

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

Li, Jinbing; Wang, Xiaoyong

2015-02-01

155

Foot and mouth disease (FMD) virus: Quantification of whole virus particles during the vaccine manufacturing process by size exclusion chromatography  

Microsoft Academic Search

Foot and mouth disease (FMD) is a highly infectious viral disease that affects cattle, sheep, goats and swine causing severe economic losses worldwide. The efficacy of inactivated vaccines is critically dependent on the integrity of foot and mouth disease virus (FMDV) particles. The recommended method to quantify the active ingredient of vaccines is the 140S quantitative sucrose density gradient analysis.

Marcelo A. Spitteler; Ignacio Fernández; Erika Schabes; Alejandro Krimer; Emmanuel G. Régulier; Mariela Guinzburg; Eliana Smitsaart; M. Susana Levy

2011-01-01

156

Wave induced transport and mixing of buoyant particles  

NASA Astrophysics Data System (ADS)

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.

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

2014-05-01

157

A disease marker for aspirin-induced chronic urticaria.  

PubMed

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

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

2014-01-01

158

Physiological and morphological responses induced by ?-particle radiation on Arabidopsis thaliana embryos.  

PubMed

Alpha (a)-particle radiation has been thoroughly studied in the occupational and residential environments, but biological mechanisms induced by a-particle radiation on plants are not clearly understood. In this study, radiation effects were examined using different total doses (1, 10, 100 Gy, respectively) of 241Am, a-particle on Arabidopsis embryos. No significant difference in the germination percentage was observed between the 3 levels of doses and the control. Germination speed and root length were increased by treatment with the 1-Gy dose of a-particles, and decreased by treatment with 10- and 100-Gy doses. Moreover, the bending degree of roots increased with radiation dose, and the roots showed an "S" shape when treated with the 100-Gy dose. Root bending under the 100-Gy dose was inhibited by scavengers of reactive oxygen species (ROS). Root gravitropism and root length may respond to the consistency of ROS induced by irradiation. Further analysis of the physiological effects revealed that an increase in a-particle radiation intensity enhanced the activity of catalase and the content of malondialdehyde, but superoxide dismutase activity was reduced by treatment with 100-Gy radiation of a-particles, suggesting that the high linear energy transfer of a-particles may cause a relatively high level of membrane lipid preoxidation and high accumulation of ROS. ROS showed both physiological and morphological responses following exposure to ?-particle radiation in Arabidopsis embryos. PMID:25501166

Ren, J; Liu, L; Jin, X L; Fu, S L; Ding, Z C

2014-01-01

159

Comparison of Particle Size Measurements with Laser-Induced Incandescence, Mass Spectroscopy, and Scanning Mobility Particle Sizing in a Laminar Premixed Ethylene\\/Air Flame  

Microsoft Academic Search

Particle size distribution functions (PSDF) and mean particle sizes have been determined in a laminar premixed ethylene\\/air flame with three different experimental approaches: photo-ionization mass spectrometry (PIMS), scanning mobility particle sizing (SMPS), and laser-induced incandescence (LII). The main goal of this investigation was the cross-validation of these three methods used at our institute for the determination of particle sizes in

R. Stirn; T. Gonzalez Baquet; S. Kanjarkar; W. Meier; K. P. Geigle; H. H. Grotheer; C. Wahl; M. Aigner

2009-01-01

160

Sorbent behaviour in circulating fluidized bed combustors: Relevance of thermally induced fractures to particle size dependence  

Microsoft Academic Search

The particle size dependence of the performance of various limestones and dolostones in capturing SO2 in fluidized bed combustors was determined and explained in terms of the occurrence of thermally induced fractures (TIFs). Data were obtained in a bench-scale fluidized bed reactor, a pilot-scale down-fired combustor and a 30 MW(e) circulating fluidized bed combustor (CFBC). Finer particle size fractions (100

Sarma V. Pisupati; Ronald S. Wasco; Joel L. Morrison; Alan W. Scaroni

1996-01-01

161

The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.  

PubMed

Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson's disease-like pathology. To begin to address how DEP may exert CNS effects, microglia and neuron-glia cultures were treated with either nanometer-sized DEP (< 0.22 ?M; 50 ?g/mL), ultrafine carbon black (ufCB, 50 ?g/mL), or DEP extracts (eDEP; from 50 ?g/mL DEP), and the effect of microglial activation and dopaminergic (DA) neuron function was assessed. All three treatments showed enhanced ameboid microglia morphology, increased H2 O2 production, and decreased DA uptake. Mechanistic inquiry revealed that the scavenger receptor inhibitor fucoidan blocked DEP internalization in microglia, but failed to alter DEP-induced H2 O2 production in microglia. However, pre-treatment with the MAC1/CD11b inhibitor antibody blocked microglial H2 O2 production in response to DEP. MAC1(-/-) mesencephalic neuron-glia cultures were protected from DEP-induced loss of DA neuron function, as measured by DA uptake. These findings support that DEP may activate microglia through multiple mechanisms, where scavenger receptors regulate internalization of DEP and the MAC1 receptor is mandatory for both DEP-induced microglial H2 O2 production and loss of DA neuron function. PMID:23470120

Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E; Johnson, Jo Anne; McGraw, Constance; Block, Michelle L

2013-06-01

162

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...

163

Oncoprotein Akt/PKB induces trophic effects in murine models of Parkinson's disease  

E-print Network

Oncoprotein Akt/PKB induces trophic effects in murine models of Parkinson's disease Vincent Ries an established role in the treatment of human neurodegenerative diseases. One impediment has been the diffi, neurons affected in Parkinson's disease, by adeno-associated virus 1 trans- duction with a gene encoding

Burke, Robert E

164

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...

165

Particle-induced amorphization of complex ceramics. Final report  

SciTech Connect

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?

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

1998-08-01

166

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

NASA Astrophysics Data System (ADS)

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.

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

2015-01-01

167

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

PubMed

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

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

1980-01-30

168

Electric-field-induced capillary attraction between like-charged particles at liquid interfaces  

NASA Astrophysics Data System (ADS)

Nanometre- and micrometre-sized charged particles at aqueous interfaces are typically stabilized by a repulsive Coulomb interaction. If one of the phases forming the interface is a nonpolar substance (such as air or oil) that cannot sustain a charge, the particles will exhibit long-ranged dipolar repulsion; if the interface area is confined, mutual repulsion between the particles can induce ordering and even crystallization. However, particle ordering has also been observed in the absence of area confinement, suggesting that like-charged particles at interfaces can also experience attractive interactions. Interface deformations are known to cause capillary forces that attract neighbouring particles to each other, but a satisfying explanation for the origin of such distortions remains outstanding. Here we present quantitative measurements of attractive interactions between colloidal particles at an oil-water interface and show that the attraction can be explained by capillary forces that arise from a distortion of the interface shape that is due to electrostatic stresses caused by the particles' dipolar field. This explanation, which is consistent with all reports on interfacial particle ordering so far, also suggests that the attractive interactions might be controllable: by tuning the polarity of one of the interfacial fluids, it should be possible to adjust the electrostatic stresses of the system and hence the interparticle attractions.

Nikolaides, M. G.; Bausch, A. R.; Hsu, M. F.; Dinsmore, A. D.; Brenner, M. P.; Gay, C.; Weitz, D. A.

2002-11-01

169

Particle-induced indentation of the alveolar epithelium caused by surface tension forces  

PubMed Central

Physical contact between an inhaled particle and alveolar epithelium at the moment of particle deposition must have substantial effects on subsequent cellular functions of neighboring cells, such as alveolar type-I, type-II pneumocytes, alveolar macrophage, as well as afferent sensory nerve cells, extending their dendrites toward the alveolar septal surface. The forces driving this physical insult are born at the surface of the alveolar air-liquid layer. The role of alveolar surfactant submerging a hydrophilic particle has been suggested by Gehr and Schürch's group (e.g., Respir Physiol 80: 17–32, 1990). In this paper, we extended their studies by developing a further comprehensive and mechanistic analysis. The analysis reveals that the mechanics operating in the particle-tissue interaction phenomena can be explained on the basis of a balance between surface tension force and tissue resistance force; the former tend to move a particle toward alveolar epithelial cell surface, the latter to resist the cell deformation. As a result, the submerged particle deforms the tissue and makes a noticeable indentation, which creates unphysiological stress and strain fields in tissue around the particle. This particle-induced microdeformation could likely trigger adverse mechanotransduction and mechanosensing pathways, as well as potentially enhancing particle uptake by the cells. PMID:20634359

Kojic, M.; Tsuda, A.

2010-01-01

170

A Disease Marker for Aspirin-Induced Chronic Urticaria  

PubMed Central

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

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

2014-01-01

171

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

SciTech Connect

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.

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

172

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

NASA Astrophysics Data System (ADS)

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.

Hussain, S.; Marchand, R.

2014-07-01

173

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...

174

Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium  

PubMed Central

Wear particles generated with use of total joint replacements incite a chronic macrophage-mediated inflammatory reaction, which leads to implant failure. Macrophage activation may be polarized into two states, with an M1 proinflammatory state dominating an alternatively activated M2 anti-inflammatory state. We hypothesized that IL-4, an activator of M2 macrophages, could modulate polyethylene (PE) particle-induced osteolysis in an experimental murine model. Four animal groups included (a) calvarial saline injection with harvest at 14 days (b) single calvarial injection of PE particles subcutaneously (SC) without IL-4 (c) PE particles placed as in (b), then IL-4 given SC for 14 consecutive days and (d) PE particles as in (b) then IL-4 beginning 7 days after particle injection for 7 days. The calvarial bone volume to total tissue volume was measured using microCT and histomorphometry. Calvaria were cultured for 24 h to assess release of RANKL, OPG, TNF-?, and IL-1ra and isolation and identification of M1 and M2 specific proteins. MicroCT and histomorphometric analysis showed that bone loss was significantly decreased following IL-4 administration to PE treated calvaria for both 7 and 14 days. Western blot analysis showed an increased M1/M2 ratio in the PE treated calvaria, which decreased with addition of IL-4. Cytokine analysis showed that the RANKL/OPG ratio and TNF-?/IL-1ra ratio decreased in PE-treated calvaria following IL-4 addition for 14 days. IL-4 delivery mitigated PE particle-induced osteolysis through macrophage polarization. Modulation of macrophage polarization is a potential treatment strategy for wear particle induced periprosthetic osteolysis. PMID:23225668

Rao, Allison J.; Nich, Christophe; Dhulipala, Lakshmi S.; Gibon, Emmanuel; Valladares, Roberto; Zwingenberger, Stefan; Smith, R. Lane; Goodman, Stuart B.

2014-01-01

175

Marek's disease virus induces Th-2 activity during cytolytic infection  

Technology Transfer Automated Retrieval System (TEKTRAN)

Marek’s disease (MD) is a lymphoproliferative disease of chickens that is caused by a highly cell-associated oncogenic alpha-herpesvirus, Marek’s disease virus (MDV). The role of cytokines and other related proteins in MD pathogenesis and immunity is poorly understood. The aim of this study was to...

176

PINK1-induced mitophagy promotes neuroprotection in Huntington's disease.  

PubMed

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by aberrant expansion of CAG repeat in the huntingtin gene. Mutant Huntingtin (mHtt) alters multiple cellular processes, leading to neuronal dysfunction and death. Among those alterations, impaired mitochondrial metabolism seems to have a major role in HD pathogenesis. In this study, we used the Drosophila model system to further investigate the role of mitochondrial damages in HD. We first analyzed the impact of mHtt on mitochondrial morphology, and surprisingly, we revealed the formation of abnormal ring-shaped mitochondria in photoreceptor neurons. Because such mitochondrial spheroids were previously detected in cells where mitophagy is blocked, we analyzed the effect of PTEN-induced putative kinase 1 (PINK1), which controls Parkin-mediated mitophagy. Consistently, we found that PINK1 overexpression alleviated mitochondrial spheroid formation in HD flies. More importantly, PINK1 ameliorated ATP levels, neuronal integrity and adult fly survival, demonstrating that PINK1 counteracts the neurotoxicity of mHtt. This neuroprotection was Parkin-dependent and required mitochondrial outer membrane proteins, mitofusin and the voltage-dependent anion channel. Consistent with our observations in flies, we demonstrated that the removal of defective mitochondria was impaired in HD striatal cells derived from HdhQ111 knock-in mice, and that overexpressing PINK1 in these cells partially restored mitophagy. The presence of mHtt did not affect Parkin-mediated mitochondrial ubiquitination but decreased the targeting of mitochondria to autophagosomes. Altogether, our findings suggest that mitophagy is altered in the presence of mHtt and that increasing PINK1/Parkin mitochondrial quality control pathway may improve mitochondrial integrity and neuroprotection in HD. PMID:25611391

Khalil, B; El Fissi, N; Aouane, A; Cabirol-Pol, M-J; Rival, T; Liévens, J-C

2015-01-01

177

Light flash phenomena induced by HzE particles  

NASA Technical Reports Server (NTRS)

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.

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

1980-01-01

178

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...

179

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...

180

Environmentally induced epigenetic transgenerational inheritance of disease susceptibility.  

PubMed

Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure-specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed with regard to disease etiology. PMID:24657180

Nilsson, Eric E; Skinner, Michael K

2015-01-01

181

Purification, characterization and serological detection of virus-like particles associated with banana bunchy top disease in Australia  

Microsoft Academic Search

Isometric virus-like particles, 18 nm in diameter, have been isolated from banana (Musa spp.) affected by bunchy top disease in Australia. Banana bunchy top disease-associated virus-like particles (BBTV) banded as a single component with buoyant density of 1-28 to 1.29 g\\/ml in Cs2SO4 and sedimented at about 46S in isokinetic sucrose density gradients. The A260\\/.42S 0 of purified preparations was

John E. Thomas; Ralf G. Dietzgen

1991-01-01

182

Fluid-Induced Propulsion of Rigid Particles in Wormlike Micellar Solutions  

E-print Network

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.

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

2014-02-20

183

Induced velocities of grains embedded in a turbulent gas. [test particle theory application to protostellar clouds  

NASA Technical Reports Server (NTRS)

A theory is presented for the dynamics of dust particles in an incompressible turbulent fluid. Grain-gas coupling occurs through friction forces that are proportional to the mean grain velocity relative to the gas. This test particle theory is applied to the case of Kolmogoroff spectrum in a protostellar cloud. The mean turbulence induced grain velocity and the mean turbulent relative velocity of two grains are calculated. Whereas the former should determine the dust scale height, grain-grain collisions are influenced by the latter. For a reasonable strength of turbulence, the mean induced relative velocity of two particles turns out to be at least as large as the corresponding terminal velocity difference during gravitational settling.

Voelk, H. J.; Morfill, G.; Roeser, S.; Jones, F. C.

1978-01-01

184

Particle irradiation induces FGF2 expression in normal human lens cells.  

PubMed

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. PMID:11025644

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

2000-11-01

185

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

PubMed

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

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

2014-03-01

186

Alpha particle induced gamma yields in uranium hexafluoride  

NASA Astrophysics Data System (ADS)

Fluorine has a relatively large (?,n) production cross-section in the MeV range, the energy range of interest for special nuclear materials. In the uranium fuel cycle enriched UF6 in particular is a reasonably prolific source of (?,n) neutrons because along with 235U, 234U becomes enriched and it has a relatively short half-life. This enables the mass content of storage cylinders containing UF6 to be verified by neutron counting methods. In association with such measurements high resolution gamma-ray spectrometry (HRGS) measurements using a high-purity Ge detector are often undertaken to determine the 235U enrichment based off the intensity of the direct 186 keV line. The specific (?,n) neutron production, neutrons per second per gram of U, is sensitive to the relative isotopic composition, particularly the 234U concentration, and the traditional gross neutron counting approach is needed to quantitatively interpret the data. In addition to F(?,n) neutrons, ?-induced reaction ?-rays are generated, notably at 110, 197, 582, 891, 1236 and 1275 keV. If one could observe 19F(?,x?) gamma-lines in the HRGS spectra the thought was that perhaps the ?-activity could be estimated directly, and in turn the 234U abundance obtained. For example, by utilizing the ratio of the detected 197-186 keV full energy peaks. However, until now there has been no readily available estimate of the expected strength of the reaction gamma-rays nor any serious consideration as to whether they might be diagnostic or not. In this work we compute the thick target yields of the chief reaction gamma-rays in UF6 using published thin target data. Comparisons are made to the neutron production rates to obtain ?/n estimates, and also to the 235U decay line at 186 keV which we take as a fiducial line. It is shown that the reaction gamma-rays are produced but are far too weak for practical safeguards purposes. Now that the underlying numerical data is readily available however, it can be used to support neutron and gamma production calculations in other fluorine compounds, for example impure plutonium reference materials where fluorine may be present only at the parts per million by weight level yet still present a serious nuisance addition to the neutron production rate.

Croft, Stephen; Swinhoe, Martyn T.; Miller, Karen A.

2013-01-01

187

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

PubMed

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

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

188

Mechanism of production of light complex particles in nucleon-induced reactions  

E-print Network

The Improved Quantum Molecular Dynamics (ImQMD) model incorporated with the statistical decay model is successful in describing emission of nucleons in the intermediate energy spallation reactions, but not good enough in describing productions of light complex particles, i.e. $d$, $t$, $^3$He and $^4$He. To improve the description on emission of light complex particles, a phenomenological mechanism called surface coalescence and emission is introduced into 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.

Dexian Wei; Ning Wang; Li Ou

2014-02-10

189

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

E-print Network

: Jan 25, 2013 Abstract: Subdural hematoma (SDH) usually occurs secondary to trauma, in bleeding; Hyperthyroidism; Graves disease. Introduction Subdural hematoma (SDH) usually occurs secondary to trauma

Carr, Leslie

190

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

PubMed

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

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

2011-01-15

191

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

PubMed Central

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

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

192

Fast Particle Finite Orbit Width and Larmor Radius E ects on Low-n Toroidicity induced Alfv en Eigenmode Excitation  

E-print Network

Fast Particle Finite Orbit Width and Larmor Radius E ects on Low-n Toroidicity induced Alfv en 451 Princeton, NJ 08543-0451 January 13, 1999 The e ects of nite drift orbit width FOW and nite Larmor !c is particle cy- clotron frequency by following the particle drift orbit and thus fully retains

193

Fast Particle Finite Orbit Width and Larmor Radius Effects on Lown Toroidicity induced Alfv'en Eigenmode Excitation  

E-print Network

Fast Particle Finite Orbit Width and Larmor Radius Effects on Low­n Toroidicity induced Alfv.O. Box 451 Princeton, NJ 08543­0451 (January 13, 1999) The effects of finite drift orbit width (FOW­kinetic equation (! ø ! c , where ! c is particle cy­ clotron frequency) by following the particle drift orbit

194

Neurobiology of Disease Oxytocin Reverses Amphetamine-Induced Deficits in Social  

E-print Network

Neurobiology of Disease Oxytocin Reverses Amphetamine-Induced Deficits in Social Bonding: Evidence exposure to the commonly abused psychostimulant amphetamine (AMPH) inhibits the formation of partner: addiction; amphetamine; dopamine; oxytocin; social bonding Introduction Drug addiction has devastating

McQuade, D. Tyler

195

HIF Prolyl Hydroxylase Inhibitors Prevent Neuronal Death Induced by Mitochondrial Toxins: Therapeutic Implications for Huntington's Disease and Alzheimer's Disease  

PubMed Central

Abstract Mitochondrial dysfunction is a central feature of a number of acute and chronic neurodegenerative conditions, but clinically approved therapeutic interventions are only just emerging. Here we demonstrate the potential clinical utility of low molecular weight inhibitors of the hypoxia inducible factor prolyl-4-hydroxylases (HIF PHDs) in preventing mitochondrial toxin-induced cell death in mouse striatal neurons that express a “knock-in” mutant Huntingtin allele. Protection from 3-nitropropionic acid (3-NP, a complex II inhibitor)-induced toxicity by HIF PHD inhibition occurs without rescue of succinate dehydrogenase activity. Although HIF-1? mRNA is dramatically induced by mutant huntingtin, HIF-1? depletion by short interfering RNAs (siRNA) does not affect steady-state viability or protection from 3-NP-induced death by HIF PHD inhibitors in these cells. Moreover, 3-NP-induced complex II inhibition in control or mutant striatal neurons does not lead to activation of HIF-dependent transcription. HIF PHD inhibition also protects cortical neurons from 3-NP-induced cytotoxicity. Protection of cortical neurons by HIF PHD inhibition correlates with enhanced VEGF but not PGC-1? gene expression. Together, these findings suggest that HIF PHD inhibitors are promising candidates for preventing cell death in conditions such as Huntington's disease and Alzheimer's disease that are associated with metabolic stress in the central nervous system. Antioxid. Redox Signal. 12, 435–443. PMID:19659431

Niatsetskaya, Zoya; Basso, Manuela; Speer, Rachel E.; McConoughey, Stephen J.; Coppola, Giovanni; Ma, Thong C.

2010-01-01

196

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

PubMed

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

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

2013-09-01

197

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

NASA Astrophysics Data System (ADS)

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.

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

2013-09-01

198

Curvature-induced dielectrophoresis for continuous separation of particles by charge in spiral microchannels  

PubMed Central

The separation of particles from a heterogeneous mixture is critical in chemical and biological analyses. Many methods have been developed to separate particles in microfluidic devices. However, the majority of these separations have been limited to be size based and binary. We demonstrate herein a continuous dc electric field driven separation of carboxyl-coated and noncoated 10 ?m polystyrene beads by charge in a double-spiral microchannel. This method exploits the inherent electric field gradients formed within the channel turns to manipulate particles by dielectrophoresis and is thus termed curvature-induced dielectrophoresis. The spiral microchannel is also demonstrated to continuously sort noncoated 5 ?m beads, noncoated 10 ?m beads, and carboxyl-coated 10 ?m beads into different collecting wells by charge and size simultaneously. The observed particle separation processes in different situations are all predicted with reasonable agreements by a numerical model. This curvature-induced dielectrophoresis technique eliminates the in-channel microelectrodes and obstacles that are required in traditional electrode- and insulator-based dielectrophoresis devices. It may potentially be used to separate multiple particle targets by intrinsic properties for lab-on-a-chip applications. PMID:21792385

Zhu, Junjie; Xuan, Xiangchun

2011-01-01

199

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

NASA Astrophysics Data System (ADS)

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.

Li, Bin; Zhang, Jizong; Ge, Haixiong

2013-01-01

200

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

PubMed Central

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

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

2014-01-01

201

Polyethylene particle-induced bone resorption in substance P-deficient mice.  

PubMed

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening. PMID:17401694

Wedemeyer, C; Neuerburg, C; Pfeiffer, A; Heckelei, A; von Knoch, F; Hilken, G; Brankamp, J; Henschke, F; von Knoch, M; Löer, F; Saxler, G

2007-04-01

202

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

PubMed Central

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

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

203

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

NASA Astrophysics Data System (ADS)

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.

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

204

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 ...

205

Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease  

Microsoft Academic Search

INTRODUCTION: Mechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-? (TNF-?) and interleukin-8 (IL-8) in patients without lung disease. METHODS: Patients without lung disease and submitted to mechanical ventilation admitted to

Roselaine Pinheiro de Oliveira; Marcio Pereira Hetzel; Mauro dos Anjos Silva; Daniele Dallegrave; Gilberto Friedman

2010-01-01

206

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

PubMed

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

Lee, Chen-Chen; Kang, Jaw-Jou

2002-12-01

207

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

Microsoft Academic Search

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

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

2011-01-01

208

[Methodologic aspects of theories on trauma-induced disease].  

PubMed

The authors have summarized the materials on the theory of trauma disease from the standpoint of methodological principle of determinism. The appearance of a new type of association in functioning self-regulating systems is shown which are characterized by cyclic pattern in the form of interaction of processes of different direction. It was noted that different technical approaches to studying the trauma disease should not hide their methodological unity based upon principles and laws of dialectical materialism. PMID:3232292

Lytkin, M I; Petlenko, V P

1988-08-01

209

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

PubMed

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

Busquets, Maria Antònia; Sabaté, Raimon; Estelrich, Joan

2014-01-01

210

Flux induced growth of sub-Kelvin nano-particles by organic vapor  

NASA Astrophysics Data System (ADS)

New particle formation (NPF) in the atmosphere strongly influences the concentration of atmospheric aerosol, and therefore its impact on climate. New particle formation is a two-stage process consisting of homogeneous nucleation of thermodynamically stable clusters followed by growth of these clusters to a detectable size (> 3 nm). Due to the large coagulation rate of clusters smaller than 3 nm with the pre-existing aerosol population, for new particle formation to take place, these clusters need to grow sufficiently fast before being removed by coagulation. While some previous modeling and field studies have indicated that condensation of low-volatility organic vapor may play an important role in the initial growth of the clusters, it is suggested that due to the small size of the clusters, the strong Kelvin effect may prevent typical ambient organics from condensing on these clusters. Here we show that the particle number flux induced by the heterogeneous nucleation of organics vapor can effectively grow clusters substantially smaller than the Kelvin diameter, traditionally considered as the minimum size of particles that can be grown through condensation. Including this flux can lead to a factor of 10 or higher increases in the predicted rates of new particle formation and the production of cloud condensation nuclei.

Wang, J.; McGraw, R. L.; Kuang, C.

2011-12-01

211

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

NASA Astrophysics Data System (ADS)

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.

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

2014-03-01

212

A Lagrangian particle model to predict the airborne spread of foot-and-mouth disease virus  

NASA Astrophysics Data System (ADS)

Airborne spread of bioaerosols in the boundary layer over a complex terrain is simulated using a Lagrangian particle model, and applied to modelling the airborne spread of foot-and-mouth disease (FMD) virus. Two case studies are made with study domains located in a hilly region in the northwest of the Styrian capital Graz, the second largest town in Austria. Mountainous terrain as well as inhomogeneous and time varying meteorological conditions prevent from application of so far used Gaussian dispersion models, while the proposed model can handle these realistically. In the model, trajectories of several thousands of particles are computed and the distribution of virus concentration near the ground is calculated. This allows to assess risk of infection areas with respect to animal species of interest, such as cattle, swine or sheep. Meteorological input data like wind field and other variables necessary to compute turbulence were taken from the new pre-operational version of the non-hydrostatic numerical weather prediction model LMK ( Lokal-Modell-Kürzestfrist) running at the German weather service DWD ( Deutscher Wetterdienst). The LMK model provides meteorological parameters with a spatial resolution of about 2.8 km. To account for the spatial resolution of 400 m used by the Lagrangian particle model, the initial wind field is interpolated upon the finer grid by a mass consistent interpolation method. Case studies depict a significant influence of local wind systems on the spread of virus. Higher virus concentrations at the upwind side of the hills and marginal concentrations in the lee are well observable, as well as canalization effects by valleys. The study demonstrates that the Lagrangian particle model is an appropriate tool for risk assessment of airborne spread of virus by taking into account the realistic orographic and meteorological conditions.

Mayer, D.; Reiczigel, J.; Rubel, F.

213

Recombinant nucleocapsid-like particles from dengue-2 induce functional serotype-specific cell-mediated immunity in mice.  

PubMed

The interplay of different inflammatory cytokines induced during dengue virus infection plays a role in either protection or increased disease severity. In this sense, vaccine strategies incorporating whole virus are able to elicit both functional and pathological responses. Therefore, an ideal tetravalent vaccine candidate against dengue should be focused on serotype-specific sequences. In the present work, a new formulation of nucleocapsid-like particles (NLPs) obtained from the recombinant dengue-2 capsid protein was evaluated in mice to determine the level of protection against homologous and heterologous viral challenge and to measure the cytotoxicity and cytokine-secretion profiles induced upon heterologous viral stimulation. As a result, a significant protection rate was achieved after challenge with lethal dengue-2 virus, which was dependent on CD4(+) and CD8(+) cells. In turn, no protection was observed after heterologous challenge. In accordance, in vitro-stimulated spleen cells from mice immunized with NLPs from the four dengue serotypes showed a serotype-specific response of gamma interferon- and tumour necrosis factor alpha-secreting cells. A similar pattern was detected when spleen cells from dengue-immunized animals were stimulated with the capsid protein. Taking these data together, we can assert that NLPs constitute an attractive vaccine candidate against dengue. They induce a functional immune response mediated by CD4(+) and CD8(+) cells in mice, which is protective against viral challenge. In turn, they are potentially safe due to two important facts: induction of serotype specific cell-mediated immunity and lack of induction of antiviral antibodies. Further studies in non-human primates or humanized mice should be carried out to elucidate the usefulness of the NLPs as a potential vaccine candidate against dengue disease. PMID:22398317

Gil, Lázaro; Bernardo, Lídice; Pavón, Alequis; Izquierdo, Alienys; Valdés, Iris; Lazo, Laura; Marcos, Ernesto; Romero, Yaremis; Guzmán, María G; Guillén, Gerardo; Hermida, Lisset

2012-06-01

214

Ebola Virus VP40Induced Particle Formation and Association with the Lipid Bilayer  

Microsoft Academic Search

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

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

2001-01-01

215

Laser-Induced Breakdown Spectroscopy for the Analysis of Cobalt–Chromium Orthopaedic Wear Debris Particles  

Microsoft Academic Search

Laser-induced breakdown spectroscopy (LIBS) is investigated for the quantitative analysis of individual cobalt-chromium wear par- ticles generated in vivo from human artié cial knee joints. As imple- mented, the LIBS technique provided a measurement of the abso- lute chromium and cobalt masses for individual wear particles, which enabled calculation of chromium-to-cobalt mass ratios and the equivalent spherical diameter on a

E. A. Mokhbat; D. W. Hahn

2002-01-01

216

Polyethylene Particle-Induced Bone Resorption in Substance P-Deficient Mice  

Microsoft Academic Search

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed\\u000a in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact\\u000a of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based\\u000a on ultrahigh molecular weight polyethylene

C. Wedemeyer; C. Neuerburg; A. Pfeiffer; A. Heckelei; F. von Knoch; G. Hilken; J. Brankamp; F. Henschke; M. von Knoch; F. Löer; G. Saxler

2007-01-01

217

Calculation of radiation-induced DNA damage from photons and tritium beta-particles  

Microsoft Academic Search

Radiation-induced damage in nucleosomal DNA was modelled by Monte Carlo means. An atomistic representation of DNA with a first\\u000a hydration shell was used. DNA single- and double-strand break (SSB and DSB) yields were calculated for 137Cs photons, x-rays and tritium beta-particles. Monte Carlo-generated electron tracks for liquid water were used to model energy\\u000a deposition. Chemical evolution of a track and

V. V. Moiseenko; R. N. Hamm; A. J. Waker; W. V. Prestwich

2001-01-01

218

Diesel Exhaust Particles Enhance Antigen-induced Airway Inflammation and Local Cytokine Expression in Mice  

Microsoft Academic Search

Previous experimental studies have suggested that nasal instillation of diesel exhaust particles (DEP) can enhance nasal IgE response and cytokine production. However, there is no experimental evi- dence for the relation of DEP to allergic asthma. We investigated the effects of DEP inoculated in- tratracheally on antigen-induced airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin production in mice.

HIROHISA TAKANO; TOSHIKAZU YOSHIKAWA; TAKAMICHI ICHINOSE; YUICHI MIYABARA; KOICHI IMAOKA; MASARU SAGAI

1997-01-01

219

Shear-induced particle rotation and its effect on electrorheological and dielectric properties in cellulose suspension  

NASA Astrophysics Data System (ADS)

Electrorheological (ER) and dielectric properties under high electric fields were measured simultaneously on hydroxypropylcellulose suspension. When measuring these properties as a function of frequency of the electric field, we found a positive peak in each spectrum of the ER effect and the first-order dielectric permittivity while a negative one in the spectrum of the third-order dielectric permittivity with these peak frequencies nearly equal to (shearrate)/4? . Referring to the well-known results for the particle rotation in the sheared suspension, it is suggested that the observed peaks are due to shear-induced particle rotation and the rotation occurs even under high electric field. On the basis of these results, effects of the particle rotation on the ER and the dielectric properties are discussed.

Misono, Y.; Negita, K.

2004-12-01

220

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

PubMed Central

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

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

221

Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis.  

PubMed

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

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

222

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

NASA Astrophysics Data System (ADS)

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.

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

2014-01-01

223

Polyethylene wear particles induce TLR 2 upregulation in the synovial layer of mice.  

PubMed

A cellular and receptor mediated response to ultra-high-molecular-weight-polyethylene (UHMWPE) wear particles results in a release of proinflammatory cytokines and induces an inflammatory reaction causing osteolysis in total joint replacement. This investigation offers insight into the toll-like receptor (TLR) mediated activation by polyethylene wear particles in the synovial layer of mice. We hypothesized that, similar to recent in vitro results, UHMWPE particles lead to an upregulation of TLR 1 and 2 and TLR 4 in vivo in the synovial tissue of mice as well. Therefore, UHMWPE particles were generated in a common knee simulator according to the ISO standard, separated by acid digestion and determined by scanning electron microscopy. Endotoxin was removed using a method based on ultracentrifugation. A particle suspension (50 ?l; 0.1 vol./vol.%) was injected into the left knee joint of female Balb/c mice (n = 8). In a control group, phosphate-buffered saline was injected into the left knee of Balb/c mice (n = 8). The mice were sacrificed after 7 days. Immunohistochemical staining was performed with TLR 1, 2 and 4 polyclonal antibodies for Balb/c mice and evaluated by light microscopy. The particle-stimulated group showed a thickened synovial layer, an increased cellular infiltration and a TLR 2-upregulation in the synovial layer compared to the control group. An increased expression of TLR 1 and TLR 4 could not be demonstrated. These results indicate a mainly TLR 2-induced inflammation to polyethylene wear debris in the synovial layer of mice. PMID:24249629

Paulus, A C; Frenzel, J; Ficklscherer, A; Roßbach, B P; Melcher, C; Jansson, V; Utzschneider, S

2014-02-01

224

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

PubMed

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

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

1969-04-01

225

What is Alzheimer's Disease? Alzheimer's disease is a form of brain degeneration in which abnormal particles called neurofibrillary  

E-print Network

What is Alzheimer's Disease? Alzheimer's disease is a form of brain degeneration in which abnormal fact and remember it 30 minutes, or a day later, a skill we refer to as "memory". Who Gets Alzheimer's disease? The two main categories of Alzheimer's disease (AD) are familial and sporadic. Familial Alzheimer

Contractor, Anis

226

Exploiting the Wall-Induced Non-inertial Lift in Electrokinetic Flow for a Continuous Particle Separation by Size.  

PubMed

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

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

2015-01-13

227

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

PubMed Central

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

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

2012-01-01

228

[Radiation-induced meningioma: the changing pattern of the disease].  

PubMed

In this country radiation-induced meningiomas were usually associated with low-dose irradiation of the scalp of immigrants from North Africa, given as part of the treatment of tinea capitis. An Ashkenazi patient developed meningiomas 15 years after high-dose irradiation for a benign lesion in the parasellar region. The accumulating literature about high-dose radiation-induced meningiomas is reviewed and attention is drawn to the ever increasing number of meningiomas observed in immigrants from the former Soviet Union. PMID:9153891

Sviri, G; Sahar, A; Feinsod, M

1997-02-16

229

Rosuvastatin-Induced Arrest in Progression of Renal Disease  

Microsoft Academic Search

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

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

2004-01-01

230

Dopamine-Induced Nonmotor Symptoms of Parkinson's Disease  

PubMed Central

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

Park, Ariane; Stacy, Mark

2011-01-01

231

Dopamine-induced nonmotor symptoms of Parkinson's disease.  

PubMed

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

Park, Ariane; Stacy, Mark

2011-01-01

232

Drug-induced impulse control disorders in Parkinson's disease.  

PubMed

Dopamine replacement treatment with excessive or aberrant dopamine receptor stimulation can cause behavioral disturbances in Parkinson's disease, comprising dopamine dysregulation syndrome, punding, and impulse control disorders. Common impulse control disorders are compulsive buying, pathological gambling, binge eating, hypersexuality, and compulsive reckless driving. PMID:21560063

Reiff, J; Jost, W H

2011-05-01

233

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

PubMed

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. PMID:20858930

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

2010-10-22

234

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

NASA Astrophysics Data System (ADS)

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.

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

2010-10-01

235

Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases  

PubMed Central

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 meeting was the eighth in a series of transatlantic conferences first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit (1979), that have fostered long-standing collaborations between researchers in the fields of mineralogy, cell and molecular biology, pathology, toxicology, and environmental/occupational health. Results The goal of this meeting, which was largely supported by a conference grant from the NHLBI, was to assemble a group of clinical and basic research scientists who presented and discussed new data on the mechanistic effects of inhaled particulates on the onset and development of morbidity and mortality in the lung and cardiovascular system. Another outcome of the meeting was the elucidation of a number of host susceptibility factors implicated in adverse health effects associated with inhaled pathogenic particulates. Conclusion New models and data presented supported the paradigm that both genetic and environmental (and occupational) factors affect disease outcomes from inhaled particulates as well as cardiopulmonary responses. These future studies are encouraged to allow the design of appropriate strategies for prevention and treatment of particulate-associated morbidity and mortality, especially in susceptible populations. PMID:17537262

Mossman, Brooke T; Borm, Paul J; Castranova, Vincent; Costa, Daniel L; Donaldson, Kenneth; Kleeberger, Steven R

2007-01-01

236

Strontium ranelate inhibits titanium-particle-induced osteolysis by restraining inflammatory osteoclastogenesis in vivo.  

PubMed

Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900 mg kg(-1) day(-1)) by gavage for 14 days. After 14 days, the calvaria were collected for micro-computed tomography (?CT), histological and molecular analysis. The results of ?CT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-? and interleukin-1? in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening. PMID:25078426

Liu, Xing; Zhu, Shijun; Cui, Jingfu; Shao, Hongguo; Zhang, Wen; Yang, Huilin; Xu, Yaozeng; Geng, Dechun; Yu, Long

2014-11-01

237

Adenosine A2A Receptor Activation Prevents Wear Particle-Induced Osteolysis  

PubMed Central

Prosthesis loosening, associated with wear-particle–induced inflammation and osteoclast-mediated bone destruction, is a common cause for joint implant failure, leading to revision surgery. Adenosine A2A receptors (A2AR) mediate potent anti-inflammatory effects in many tissues and prevent osteoclast differentiation. We tested the hypothesis that an A2AR agonist could reduce osteoclast-mediated bone resorption in a murine calvaria model of wear-particle–induced bone resorption. C57Bl/6 and A2A knockout (A2ARKO) mice received ultrahigh-molecular weight polyethylene particles (UHMWPE) and were treated daily with either saline or the A2AR agonist CGS21680. After 2 weeks, micro-computed tomography of calvaria demonstrated that CGS21680 reduced particle-induced bone pitting and porosity in a dose-dependent manner, increasing cortical bone and bone volume compared to control mice. Histological examination demonstrated diminished inflammation after treatment with CGS21680. In A2AKO mice, CGS21680 did not affect osteoclast-mediated bone resorption or inflammation. Levels of bone-resorption markers receptor activator of nuclear factor-kB (RANK), RANK ligand (RANKL), cathepsin K, CD163, and osteopontin were reduced following CGS21680 treatment, together with a reduction in osteoclasts. Secretion of interleukin 1? (IL-1?) and TNF? was significantly decreased, whereas IL-10 was markedly increased in bone by CGS21680. These results in mice suggest that site-specific delivery of an adenosine A2AR agonist could enhance implant survival, delaying or eliminating the need for revision arthroplastic surgery. PMID:22623741

Mediero, Aránzazu; Frenkel, Sally R.; Wilder, Tuere; He, Wenjie; Mazumder, Amitabha; Cronstein, Bruce N.

2012-01-01

238

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

PubMed

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

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

239

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

SciTech Connect

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.

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

240

LDL particle size and number compared with LDL cholesterol and risk categorization in end-stage renal disease patients  

PubMed Central

Background Few studies have been conducted that make comparisons between traditional measures of cholesterol and cholesterol subfractions, and only one study has compared low-density lipoprotein cholesterol (LDL-C) particle number, LDL-C particle size and LDL-C among end-stage renal disease (ESRD) patients. The purpose of this study was to examine the relationships between cholesterol measures and differences in risk stratification when using ATP-III guidelines compared with cholesterol particle number and size in ESRD patients. Methods ESRD patients (n=1,092) from clinics associated with the Central Texas Nephrology Associates were recruited to participate in this study. Results LDL particle size categorized more patients at-risk when compared with LDL-C, non-HDL-C and triglycerides. Pearson correlation coefficients revealed a strong significant correlation between LDL-C and LDL particle number (r2=0.908, p=0.0001) and a significant correlation between LDL particle number and LDL particle size (r2=?0.290, p=0.0001). A significant but weak correlation existed between LDL-C and LDL particle size (r2=0.107, p=0.0001). A significant correlation existed between LDL particle number and triglycerides (r2=0.335, p=0.0001) and a significant inverse relationship between LDL particle size and triglycerides (r2=?0.500, p=0.0001). Conclusions Our study seems to suggest that using LDL particle size may help to identify those who would not be considered at-risk using LDL-C, non-HDL-C or triglycerides alone, and can be used as a further screening measure that may be more predictive of coronary heart disease outcomes. PMID:21360474

Bowden, Rodney G.; Wilson, Ronald L.; Beaujean, A. Alexander

2015-01-01

241

Modeling fundamental plasma transport and particle-induced emission in a simplified Test Cell  

NASA Astrophysics Data System (ADS)

This work involves the modeling of fundamental plasma physics processes occurring within environments that are similar to that of the discharge and plume regions of electric propulsion devices such as Hall effect thrusters. The research is conducted as a collaborative effort with the Plasma & Space Propulsion Laboratory at the University of California, Los Angeles (UCLA), as part of the University of Michigan/AFRL Center for Excellence in Electric Propulsion (MACEEP). Transport physics, such as particle-particle collisions and particle-induced electron emission, are simulated within the UCLA experimental facility and its representative electric propulsion environment. Simulation methods employed include the direct simulation Monte Carlo (DSMC) and particle-in-cell (PIC) techniques for the kinetic simulation of charged, rarefied species on high-performance computing architectures. Momentum- (MEX) and charge-exchange (CEX) collision cross-section models for Xe and Xe+, both total and differential, are successfully validated at collision energies of ˜1.5 keV within the novel facility. Heavy-species collisional transport models are validated and the importance of scattering anisotropy in this collision-dominated environment is shown. The theory of particle-induced electron emission (PIE) is then investigated in the context of the relevant energies and environments of the UCLA facility and electric propulsion devices and diagnostics. Reduced, semi-empirical models for total yield and emitted electron energy distribution functions that are easily implemented in a DSMC-PIC code are developed for the simulation of secondary-electron emission due to low-energy ions and high-energy atoms, even in the case of incomplete target-material information. These models are important for the characterization of electric propulsion devices due to the problematic nature of low-temperature plasma diagnostic techniques in which the emission of electrons is physically indistinguishable from the collection of ions.

Giuliano, Paul Nicholas

242

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

PubMed Central

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

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

2011-01-01

243

Protein kinase C-? mediates lung injury induced by diesel exhaust particles.  

PubMed

Recently, we reported that diesel exhaust particles (DEPs) disrupt tight junctions (TJs) in alveolar epithelial cells (AECs) via an increase in reactive oxygen species (ROS). In this study, we investigated the role of protein kinase C (PKC)-? activation in DEP-induced lung injury. C57/bl6 mice were instilled intratracheally with 50 ?l of saline containing 100 ?g of DEPs or titanium dioxide (TiO2). Twenty-four hours later, bronchoalveolar lavage was performed to assess neutrophil counts and protein concentrations. In addition, in vitro experiments were performed in primary rat and human AECs exposed to DEPs (50 ?g/cm(2)) for 3 hours. Transepithelial electrical conductance was measured, and TJ protein association was analyzed by immunoprecipitation. To determine whether the overexpression of antioxidants prevented DEP-induced lung injury, AECs and mice were infected with adenoviruses containing catalase and manganese superoxide dismutase (MnSOD) plasmids. In vivo, the overexpression of catalase and MnSOD prevented DEP-induced neutrophil recruitment. The inhibition of PKC-? activation also prevented DEP-induced neutrophil recruitment in vivo. In vitro, DEPs activated PKC-? in AECs, but not in alveolar macrophages. Using a specific myristolated PKC-? pseudosubstrate pepetide (PKC-? ps), we showed that PKC-? mediated the DEP-induced dissociation of occludin and zonula occludin-1 (ZO1) in rat and human AECs. In addition, the overexpression of constitutively active PKC-? induced the dissociation of occludin and ZO1 in AECs. DEP-induced TJ disruption occurs via PKC-?. TJ disruption seems to be in part responsible for DEP-induced lung injury. PMID:23221045

Caraballo, Juan C; Borcherding, Jennifer; Thorne, Peter S; Comellas, Alejandro P

2013-03-01

244

Bifrontal ECT for drug-induced psychosis in Parkinson's disease.  

PubMed

Psychosis has been documented to occur during treatment for idiopathic Parkinson's disease (PD). This case report describes an elderly male who developed psychosis during the course of treatment for idiopathic PD. He was treated with clozapine but experienced significant adverse effects without clinical improvement. He was prescribed bifrontal electroconvulsive therapy (BF-ECT). Here, we report the efficacy of BF-ECT in treating psychosis and motor symptoms in PD, without producing cognitive side effects in an elderly male. PMID:21772651

Muralidharan, K; Thimmaiah, R; Chakraborty, V; Jain, S

2011-04-01

245

Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology  

Microsoft Academic Search

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

Gregg L. Semenza

2001-01-01

246

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

PubMed

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

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

2015-01-01

247

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

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

248

An experimental facility for measurement of charged particle continua arising from neutron induced reactions  

NASA Astrophysics Data System (ADS)

A facility to measure neutron-induced charged-particle continua using beams of 25-60 MeV is described. The heart of the facility consists of the production and collimation of a neutron beam into a scattering chamber containing the target and three independent detector telescopes. Each telescope contains three elements and provides good particle identification for p, d, t, 3He, and ?. While " E- ?E" displays are used to identify energetic particles, a time-of-flight versus pulse-height scheme is used to identify low-energy alphas (from 3-8 MeV) that stop in the first element. Good timing and energy resolution obtained with this system allow the simultaneous measurement of hydrogen and helium isotopes with a wide range of energies: from about 3-60 MeV. Corrections to measured spectra relevant to this set-up are discussed. This facility has been used to obtain extensive data on neutron-induced reactions on tissue-resident elements such as carbon, nitrogen and oxygen.

Subramanian, T. S.; Romero, J. L.; Brady, F. P.

1980-08-01

249

Is delayed genomic instability specifically induced by high-LET particles?  

NASA Astrophysics Data System (ADS)

Ionizing radiation can induce a large variety of damages in the DNA. The processing or repair of this damage occurs in the first minutes up to several hours after irradiation. Afterwhile the remaining lesions are fixed in an irreparable state. However, in recent years, data have accumulated to suggest that genomic instability can manifest in the progeny of irradiated cells leading to accumulation of damage through cell generations. Different biological endpoints were described: delayed cell death, delayed mutations, de novo chromosomal instability. The question regarding the ability of sparsely ionizing X-or ?-rays to induce such phenomenon is still unclear for normal cells. In most of the reports, high linear energy transfer (LET) particles are able to induce genomic instability but not low-LET particles. The mechanisms underlying this phenomenon are still unknown. In human fibroblasts irradiated by heavy ions in a large range of LETs, we showed that the chromosomal instability is characterized by telomeric associations (TAS) involving specific chromosomes. The same instability is observed during the senescence process and during the first passages after viral transfection. The specific chromosomal instability that we observed after irradiation would not be a direct consequence of irradiation but would be a natural phenomenon occurring after many cell divisions. The effect of the irradiation would lie on the bypass of the senescence process that would permit cells with end to end fusions to survive and be transmitted through cell generations, accumulating chromosome rearrangements and chromosome imbalances. Research on molecular mechanisms of chromosomal instability is focused on the role of telomeres in end to end fusions. Such observations could contribute to understand why chromosomal instability is not a dose dependant phenomenon. Why high-LET particles would be so potent in inducing delayed instability? The answer might lie in the study of primary effects of ionizing radiations (X-rays, ?-rays and heavy ions). Cell survival studies showed that K-shell ionizations could be the primary physical events responsible of cell death. The quality of the DNA damages and gene mutations high-LET induced could be the keyhole leading to the great efficiency of these particles.

Testard, Isabelle; Sabatier, Laure

1998-12-01

250

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

NASA Astrophysics Data System (ADS)

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.

Yan, Zijie

2011-12-01

251

A Case of Venlafaxine-Induced Interstitial Lung Disease  

PubMed Central

A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD. PMID:25237379

Oh, Serim; Kim, Hyera; Kim, Minjung; Choi, Sun Ha; Seo, Hyewon; Park, Tae-In

2014-01-01

252

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle  

NASA Technical Reports Server (NTRS)

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, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

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

2003-01-01

253

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle  

NASA Astrophysics Data System (ADS)

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, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

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

254

Effect of vitamin C and iron chelation on diesel exhaust particle and carbon black induced oxidative damage and cell adhesion molecule expression in human endothelial cells.  

PubMed

Exposure to particulate matter is associated with oxidative stress and risk of cardiovascular diseases. We investigated if vitamin C and desferrioxamine (iron chelator) altered the levels of oxidative stress and expression of cell adhesion molecules upon exposure to diesel exhaust particles (DEP) and carbon black in cultured human umbilical vein endothelial cells (HUVECs). We found that the particles were only slightly cytotoxic in the high concentration ranges. Particle-induced intracellular reactive oxygen species (ROS) production was attenuated by vitamin C administration or iron chelation and particularly when combined (p<0.001). Only desferrioxamine protected the DNA from oxidative damage in terms of strand breaks and formamidopyrimidine DNA glycosylase sensitive sites induced by carbon black (p<0.01). Carbon black and small sized DEP generated from an Euro4 engine increased the surface expression of VCAM-1 and ICAM-1, whereas DEP from an engine representing an old combustion type engine (SRM2975) with larger particles did not affect the expression of cell adhesion molecules. These effects were also attenuated by desferrioxamine but not vitamin C. The study shows that exposure to carbon black and DEP in HUVECs can generate both oxidative stress and expression of cell surface adhesion molecules and that these effects can in part be attenuated by vitamin C and desferrioxamine. PMID:21421028

Frikke-Schmidt, Henriette; Roursgaard, Martin; Lykkesfeldt, Jens; Loft, Steffen; Nøjgaard, Jacob Klenø; Møller, Peter

2011-06-24

255

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

PubMed Central

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

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

2012-01-01

256

[Mania with psychotic feature induced by the use of pramipexole in Parkinson's disease: a case report].  

PubMed

Parkinson's disease, a neurodegenerative disorder characterized by movement abnormalities, is frequently complicated by psychiatric syndromes. Psychiatric symptoms may be the direct result of PD, its co-morbid pathologies, or occur as a side effect of its pharmacotherapy. Pramipexole, like other dopamine agonists for treating Parkinson's disease , has a tendency to induce psychotic and manic symptoms due to central dopaminergic stimulation. In this article, mania with psychotic feature induced by the use of dopamine agonists which is not observed frequently in the literature will be discussed. PMID:25219695

Meriç, Ceren; Pirdo?an, Efruz; Günday Toker, Ömür; Tekin, Atilla; Bak?m, Bahad?r; Çelik, Selime

2014-01-01

257

Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease  

Microsoft Academic Search

Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease. T.A.R. Seemungal, R. Harper-Owen, A. Bhowmik, D.J. Jeffries, J.A. Wedzicha. #ERS Journals Ltd 2000. ABSTRACT: Common colds are associated with exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at

T. A. R. Seemungal; R. Harper-Owen; A. Bhowmik; D. J. Jeffries; J. A. Wedzicha

2000-01-01

258

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

PubMed Central

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

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

259

Oncogene-Induced Senescence as a New Mechanism of Disease: The Paradigm of Erdheim–Chester Disease  

PubMed Central

Erdheim–Chester disease (ECD) is a rare form of systemic histiocytosis characterized by the diffuse infiltration of tissues by lipid-laden macrophages. As the clinical course and prognosis are highly influenced by site of disease involvement, ECD course ranges from asymptomatic to life threatening, with a reported global 5-year mortality of 30–40%. Whether ECD is an inflammatory or clonal disease in its nature has long been debated. The disease is characterized by a network of pro-inflammatory cyto/chemokines responsible for the recruitment and activation of histiocytes into ECD lesions, similarly to what reported in Langerhans cell histiocytosis (LCH). Growing evidence supports a central role of the oncogenic BRAFV600E mutation in histiocytosis pathogenesis, and suggests oncogene-induced senescence (OIS), a major protective mechanism against oncogenic events characterized by cell-cycle arrest and the induction of pro-inflammatory molecules, as the possible link between the oncogenic mutation and the observed inflammation. Indeed, ECD recapitulates in vivo the molecular events associated with OIS, i.e., cell-cycle arrest and a potent local inflammatory response. Accordingly, the infiltration of different tissues by macrophages and the inflammatory local and systemic effects observed in ECD likely represent a drawback of OIS. Therefore, these findings delineate a new conception of OIS as a new pathogenic mechanism intrinsically responsible for disease development. PMID:24982657

Cavalli, Giulio; Biavasco, Riccardo; Borgiani, Bruno; Dagna, Lorenzo

2014-01-01

260

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

Microsoft Academic Search

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

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

261

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

USGS Publications Warehouse

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.

Jayanetti, S.; Mayanovic, R.A.; Anderson, A.J.; Bassett, W.A.; Chou, I.-M.

2001-01-01

262

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

NASA Astrophysics Data System (ADS)

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.

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

2007-04-01

263

Intra-tumor distribution of metallofullerene using micro-particle induced X-ray emission (PIXE).  

PubMed

To clarify the intra tumor distribution of gadlinium containing fullerene (Gd@C82), micro particle induced X-ray emission (Micro-PIXE) analysis were performed. The tumor bearing BALB/c mice were injected Gd@C82 and subcutaneous tumors were taken from 48h after the intravenous injection. Using the Micro-PIXE method, we could visualize Gd intra tumor distribution. Therefore our results indicate the possibility that Micro-PIXE is useful technique for imaging the bioditribution of Gd, and Gd@C82 is potentially useful Gd carrier for NCT. PMID:24491681

Yamamoto, Yohei; Yamamoto, Tetsuya; Horiguchi, Yukichi; Shirakawa, Makoto; Satoh, Takahiro; Koka, Masashi; Nagasaki, Yukio; Nakai, Kei; Matsumura, Akira

2014-06-01

264

Experimental Study of the Cross Sections of {alpha}-Particle Induced Reactions on 209Bi  

SciTech Connect

Alpha particle induced reactions for generation of 211At used in therapeutic nuclear medicine and possible contaminants were investigated with the stacked foil activation technique on natural bismuth targets up to E{alpha}=39 MeV. Excitation functions for the reactions 209Bi({alpha},2n)211At, 209Bi({alpha},3n)210At, 209Bi({alpha},x) 210Po obtained from direct alpha emission measurements and gamma spectra from decay products are compared with earlier literature values. Thick target yields have been deduced from the experimental cross sections.

Hermanne, A. [Cyclotron Department, Vrije Universiteit Brussel, Laarbeeklaan 103, B1090 Brussels (Belgium); Tarkanyi, F.; Takacs, S.; Szucs, Z. [Atomki, Hungarian Academy of Sciences, Bem Ter, H4001 Debrecen (Hungary)

2005-05-24

265

Involvement of superoxide and nitric oxide on airway inflammation and hyperresponsiveness induced by diesel exhaust particles in mice  

Microsoft Academic Search

We previously demonstrated that chronic intratracheal instillation of diesel exhaust particles (DEP) induces airway inflammation and hyperresponsiveness in the mouse, and that these effects were partially reversed by the administration of superoxide dismutase (SOD). In the present study, we have investigated the involvement of superoxide in DEP-induced airway response by analyzing the localization and activity of two enzymes: (1) a

Heung-Bin Lim; Takamichi Ichinose; Yuichi Miyabara; Hirohisa Takano; Yoshito Kumagai; Nobuhiro Shimojyo; J. L Devalia; Masaru Sagai

1998-01-01

266

Comparative pathology: radiation-induced coronary artery disease in man and animals.  

PubMed

The occurrence of coronary artery disease following mediastinal radiation for malignancies has long been debated. However, the development of coronary pathology in young individuals following radiation who lack risk factors for atherosclerosis is highly suggestive of a cause-and-effect relationship. By far the most convincing pathologic changes are adventitial scarring and medial atrophy with severe intimal atherosclerotic disease consisting of necrotic core, fibrous tissue, and calcification. Initial clinical studies in patients with coronary atherosclerosis treated with intraluminal radiation following stenting hold great promise in the treatment and prevention of restenosis. There are little or no data, however, on long-term effects of intra-coronary radiation therapy in man. Therefore, it may be important to study the chronic effects of radiation in animal models in order to predict what is likely to occur in humans. We evaluated the effects of varying doses (0.15-23.0 microCi of 32P) of beta-particle-emitting radioactive stents in pig coronary arteries at 1 and 6 months. At 1 month, there were dose-dependent changes in the morphology of the intima and media. High activities (>3 microCi) caused medial necrosis with fibrin deposition in the media and intima, with interspersed red cells most marked in regions surrounding the stent struts. Only rare smooth muscle cells (SMCs) and inflammatory cells were seen away from the stent struts. In the intermediate (1 microCi) stent activity group, the neointima was expanded by SMCs and a proteoglycan-rich matrix with focal endothelialization of the luminal surface. Neovascular capillaries and extravascular red cells were present adjacent to stent struts. At low activities (<0.5 microCi), the neointima was significantly smaller than control stents and consisted of SMCs and matrix with complete endothelialization of the luminal surface. The neointimal cell density of the media and intima decreased with increasing doses of radiation. In pigs 6 months after radioactive stenting (activities ranging from 0.5-12 microCi 32P), >3.0 microCi radioactive stents induced marked neointimal thickening, with changes similar to atherosclerosis, consisting of necrotic debris containing cholesterol clefts surrounded by macrophage collections, fibrosis, and focal calcification. There was increased adventitial thickening in the radiated vs non-radiated arteries. The intermediate stent activity (1.0 microCi) also showed greater neointimal thickening (vs control stents) and consisted mostly of SMCs in a proteoglycan-rich matrix. At <1.0 microCi, there were minimal differences seen between radiated and control non-radiated stented arteries. The media was unevenly injured in all stent activities and varied from less than to significantly greater than controls. These data suggest that radiation-induced coronary atherosclerosis seen in man is partially simulated in normal porcine coronary arteries 6 months following high-dose beta-particle-emitting radioactive stent placement. There is greater fibrosis and thickness of the adventitia and focal attenuation of the media in man and severe luminal narrowing in pig coronary arteries treated with high doses of radiation. Only long-term clinical follow up and careful autopsy studies will determine if endoluminal or intra-arterial radiation is a viable means of reducing restenosis in man. PMID:10406688

Virmani, R; Farb, A; Carter, A J; Jones, R M

1998-01-01

267

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

PubMed Central

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

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

1969-01-01

268

Effect of electric-field-induced capillary attraction on the motion of particles at an oil-water interface.  

PubMed

Here, we investigate experimentally and theoretically the motion of spherical glass particles of radii 240-310 microm attached to a tetradecane-water interface. Pairs of particles, which are moving toward each other under the action of lateral capillary force, are observed by optical microscopy. The purpose is to check whether the particle electric charges influence the particle motion, and whether an electric-field-induced capillary attraction could be detected. The particles have been hydrophobized by using two different procedures, which allow one to prepare charged and uncharged particles. To quantify the hydrodynamic viscous effects, we developed a semiempirical quantitative approach, whose validity was verified by control experiments with uncharged particles. An appropriate trajectory function was defined, which should increase linearly with time if the particle motion is driven solely by the gravity-induced capillary force. The analysis of the experimental results evidences for the existence of an additional attraction between two like-charged particles at the oil-water interface. This attraction exceeds the direct electrostatic repulsion between the two particles and leads to a noticeable acceleration of their motion. PMID:18060167

Boneva, Mariana P; Christov, Nikolay C; Danov, Krassimir D; Kralchevsky, Peter A

2007-12-28

269

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

NASA Astrophysics Data System (ADS)

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.

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

2014-10-01

270

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

SciTech Connect

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.

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

271

Biological dose estimation of UVA laser microirradiation utilizing charged particle-induced protein foci  

PubMed Central

The induction of localized DNA damage within a discrete nuclear volume is an important tool in DNA repair studies. Both charged particle irradiation and laser microirradiation (LMI) systems allow for such a localized damage induction, but the results obtained are difficult to compare, as the delivered laser dose cannot be measured directly. Therefore, we revisited the idea of a biological dosimetry based on the microscopic evaluation of irradiation-induced Replication Protein A (RPA) foci numbers. Considering that local dose deposition is characteristic for both LMI and charged particles, we took advantage of the defined dosimetry of particle irradiation to estimate the locally applied laser dose equivalent. Within the irradiated nuclear sub-volumes, the doses were in the range of several hundreds of Gray. However, local dose estimation is limited by the saturation of the RPA foci numbers with increasing particle doses. Even high-resolution 4Pi microscopy did not abrogate saturation as it was not able to resolve single lesions within individual RPA foci. Nevertheless, 4Pi microscopy revealed multiple and distinct 53BP1- and ?H2AX-stained substructures within the lesion flanking chromatin domains. Monitoring the local recruitment of the telomere repeat-binding factors TRF1 and TRF2 showed that both proteins accumulated at damage sites after UVA–LMI but not after densely ionizing charged particle irradiation. Hence, our results indicate that the local dose delivered by UVA–LMI is extremely high and cannot be accurately translated into an equivalent ionizing radiation dose, despite the sophisticated techniques used in this study. PMID:20167590

Splinter, J.; Jakob, B.; Lang, M.; Yano, K.; Engelhardt, J.; Hell, S. W.; Chen, D. J.; Durante, M.; Taucher-Scholz, G.

2010-01-01

272

Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status.  

PubMed

Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of ?H2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1Gy (211)At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles. PMID:24769180

Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena; Lindegren, Sture; Jensen, Holger; Bäck, Tom; Swanpalmer, John; Elmroth, Kecke

2014-04-21

273

Application of human induced pluripotent stem cells for modeling and treating neurodegenerative diseases.  

PubMed

The advent of human induced pluripotent stem cells (hiPSCs), reprogrammed in vitro from both healthy and disease-state human somatic cells, has triggered an enormous global research effort to realize personalized regenerative medicine for numerous degenerative conditions. hiPSCs have been generated from cells of many tissue types and can be differentiated in vitro to most somatic lineages, not only for the establishment of disease models that can be utilized as novel drug screening platforms and to study the molecular and cellular processes leading to degeneration, but also for the in vivo cell-based repair or modulation of a patient's disease profile. hiPSCs derived from patients with the neurodegenerative diseases amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease and multiple sclerosis have been successfully differentiated in vitro into disease-relevant cell types, including motor neurons, dopaminergic neurons and oligodendrocytes. However, the generation of functional iPSC-derived neural cells that are capable of engraftment in humans and the identification of robust disease phenotypes for modeling neurodegeneration still require several key challenges to be addressed. Here, we discuss these challenges and summarize recent progress toward the application of iPSC technology for these four common neurodegenerative diseases. PMID:24815224

Payne, Natalie L; Sylvain, Aude; O'Brien, Carmel; Herszfeld, Daniella; Sun, Guizhi; Bernard, Claude C A

2015-01-25

274

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

SciTech Connect

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.

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

2011-05-25

275

M-FISH analysis shows that complex chromosome aberrations induced by alpha -particle tracks are cumulative products of localized rearrangements.  

PubMed

Complex chromosome aberrations are characteristically induced after exposure to low doses of densely ionizing radiation, but little is understood about their formation. To address this issue, we irradiated human peripheral blood lymphocytes in vitro with 0.5 Gy densely ionizing alpha-particles (mean of 1 alpha-particle/cell) and analyzed the chromosome aberrations produced by using 24-color multiplex fluorescence in situ hybridization (M-FISH). Our data suggest that complex formation is a consequence of direct nuclear alpha-particle traversal and show that the likely product of illegitimate repair of damage from a single alpha-particle is a single complex exchange. From an assessment of the "cycle structure" of each complex exchange we predict alpha-particle-induced damage to be repaired at specific localized sites, and complexes to be formed as cumulative products of this repair. PMID:12205292

Anderson, Rhona M; Stevens, David L; Goodhead, Dudley T

2002-09-17

276

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

NASA Astrophysics Data System (ADS)

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.

Hui, Katrina; Lin, Guang; Pan, Wenxiao

2013-01-01

277

Mineral particles of varying composition induce differential chemokine release from epithelial lung cells: importance of physico-chemical characteristics.  

PubMed

Presently, little is known about the potential health effects of mineral particles other than asbestos and quartz. In this study, a human epithelial lung cell line (A549), primary human small airway epithelial cells (SAECs) and primary rat type 2 (T2) cells were exposed to stone quarry particles of two size fractions (<10 and <2.5 microm) from nine different rock samples. The ability to induce the release of chemokines from lung cells was investigated and compared with the particles' mineral and element composition and the amount of soluble elements. The stone particles induced the release of only low levels of interleukin (IL)-8 from A549 cells. In contrast, some of the other particles induced the release of high levels of macrophage inflammatory protein (MIP)-2 from T2 cells, and high levels of IL-8 from SAECs. Differences in particle surface area could account for differences in activity between the <10 and <2.5 microm fractions of six out of the nine rock samples. For two samples the <2.5 microm fraction was most active and for one sample the <10 microm fraction was most active. Content of the mineral plagioclase displayed a strong, negative correlation with the potential to induce MIP-2, whereas the mineral pyroxene was positively correlated with MIP-2 induction. However, neither plagioclase nor pyroxene content was sufficient to explain differences in bioactivity between the particles. No statistically significant correlation was found between the amounts of total or soluble elements and MIP-2 release. In conclusion, the results suggest that mineral particles with a high content of plagioclase have a low potential to induce a pro-inflammatory response. However, a particular mineral or element responsible for eliciting strong increases in chemokine release could not be identified. Thus, at present it appears that analysing mineral and element content is insufficient to predict stone particle bioactivity, and that biological testing is a necessity. PMID:15640311

Ovrevik, J; Myran, T; Refsnes, M; Låg, M; Becher, R; Hetland, R B; Schwarze, P E

2005-04-01

278

Fructose Induced Endotoxemia in Pediatric Nonalcoholic Fatty Liver Disease  

PubMed Central

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

Patel, Shivani S.; Sun, Xiaoyan; Song, Ming; Mannery, Yanci O.; McClain, Craig J.; Vos, Miriam B.

2014-01-01

279

Exercise-induced Signals for Vascular Endothelial Adaptations: Implications for Cardiovascular Disease  

PubMed Central

This article reviews recent advances in our understanding of hemodynamic signals, external/compressive forces, and circulating factors that mediate exercise training-induced vascular adaptations, with particular attention to the roles of these signals in prevention and treatment of endothelial dysfunction and cardiovascular (CV) diseases. PMID:22844545

Jenkins, Nathan T.; Martin, Jeffrey S.; Laughlin, M. Harold; Padilla, Jaume

2012-01-01

280

Animal Models of Cigarette Smoke-Induced Chronic Obstructive Lung Disease  

Microsoft Academic Search

Recent years have seen an explosion of animal models of cigarette smoke-induced chronic obstructive lung disease (COPD). Almost all of these have concentrated on the induction and prevention of emphysema. Neutrophils and neutrophil elastase, macrophages and macrophage-derived metalloproteases, lymphocytes, TNF-?, and oxidants have all been shown to play a role in the pathogenesis of emphysema in animal models, and interventions

A. Churg; J. Wright

2007-01-01

281

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

PubMed Central

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

2014-01-01

282

Increased response to visual feedback of drug-induced dyskinetic movements in advanced Parkinson's disease  

E-print Network

movements during visually guided manual tracking? Two major types of involuntary movements in PD, action's disease during manual tracking with and without visual feedback. Six inpatients at the DepartmentIncreased response to visual feedback of drug-induced dyskinetic movements in advanced Parkinson

Miall, Chris

283

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...

284

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 ...

285

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...

286

AN EPIZOOTIC OF ADENOVIRUS-INDUCED HEMORRHAGIC DISEASE IN CAPTIVE BLACK-TAILED DEER (ODOCOILEUS HEMIONUS)  

Microsoft Academic Search

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,

Walter M. Boyce; Leslie W. Woods; M. Kevin Keel; N. James MacLachlan; Charles O. Porter; Howard D. Lehmkuhl

287

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...

288

SHORT COMMUNICATION Development of diet-induced fatty liver disease in  

E-print Network

SHORT COMMUNICATION Development of diet-induced fatty liver disease in the aging mouse and age on liver morphology and biochemistry was characterized, while evaluating the potential of 15 min) to suppress lipid accumulation in the liver. Following a 36-week protocol (animals 43 weeks of age

289

Correlation between lipid peroxidation-induced TBARS level and disease severity in obsessive–compulsive disorder  

Microsoft Academic Search

Oxidative stress is thought to play an important role in several neuropsychiatric diseases including obsessive–compulsive disorder (OCD). Thiobarbituric acid reacting substances (TBARS) are products formed as a result of free radical induced lipid peroxidation in the human body. Our study investigated the correlation between TBARS and the clinical severity of OCD as indicated by the Yale Brown Obsessive Compulsive Scale

Sutirtha Chakraborty; Om Prakash Singh; Anindya Dasgupta; Nikhiles Mandal; Harendra Nath Das

2009-01-01

290

Targeted Cytoplasmic Irradiation with Alpha Particles Induces Mutations in Mammalian Cells  

NASA Astrophysics Data System (ADS)

Ever since x-rays were shown to induce mutation in Drosophila more than 70 years ago, prevailing dogma considered the genotoxic effects of ionizing radiation, such as mutations and carcinogenesis, as being due mostly to direct damage to the nucleus. Although there was indication that alpha particle traversal through cellular cytoplasm was innocuous, the full impact remained unknown. The availability of the microbeam at the Radiological Research Accelerator Facility of Columbia University made it possible to target and irradiate the cytoplasm of individual cells in a highly localized spatial region. By using dual fluorochrome dyes (Hoechst and Nile Red) to locate nucleus and cellular cytoplasm, respectively, thereby avoiding inadvertent traversal of nuclei, we show here that cytoplasmic irradiation is mutagenic at the CD59 (S1) locus of human-hamster hybrid (AL) cells, while inflicting minimal cytotoxicity. The principal class of mutations induced are similar to those of spontaneous origin and are entirely different from those of nuclear irradiation. Furthermore, experiments with radical scavenger and inhibitor of intracellular glutathione indicated that the mutagenicity of cytoplasmic irradiation depends on generation of reactive oxygen species. These findings suggest that cytoplasm is an important target for genotoxic effects of ionizing radiation, particularly radon, the second leading cause of lung cancer in the United States. In addition, cytoplasmic traversal by alpha particles may be more dangerous than nuclear traversal, because the mutagenicity is accomplished by little or no killing of the target cells.

Wu, Li-Jun; Randers-Pehrson, Gerhard; Xu, An; Waldren, Charles A.; Geard, Charles R.; Yu, Zengliang; Hei, Tom K.

1999-04-01

291

Effect of temperature and iron-oxide nano-particle inclusions on the ultrasound vaporization pressure of perfluorocarbon droplets for disease detection and therapy  

E-print Network

Iron-Oxide Nano-particle inclusions on the Ultrasound Vaporization Pressure of Perfluorocarbon Droplets for Disease DetectionIron-Oxide Nano-particle inclusions on the Ultrasound Vaporization Pressure of Perfluorocarbon Droplets for Disease Detectioniron oxide nanoparticle loaded emulsions36. 2.3.2 Acoustic droplet vaporization and microbubble detection.

Amirriazi, Seyed Saleh

2009-01-01

292

Swainsonine-induced high mountain disease in calves.  

PubMed

Swainsonine, an indolizidine alkaloid in the locoweeds (certain species of the Astragalus and Oxytropis genera), was fed to young Holstein bull calves in their milk at high elevation (3090 m), and the incidence of high mountain disease (HMD) was compared with locoweed-fed and control calves. Five of 5 calves fed swainsonine and 5 of 5 calves fed fresh Oxytropis sericea showed outward signs of HMD, which included edema under the jaws, throat area and brisket and gross and microscopic lesions of HMD and locoweed poisoning. Grossly there were HMD lesions, including congestion of the liver, right ventricular hypertrophy, and dilatation and excessive fluid in the thoracic and abdominal cavities. Microscopically, the severe centrilobular lesions in the liver, edema of the pulmonary artery, severe edema and/or fibrosis of the roof of the right atrium were suggestive of HMD. The mild to moderate neurovisceral cytoplasmic foamy vacuolation of selected tissues and cerebellar neuroaxonal dystrophy in all calves fed swainsonine and locoweed were indicative of locoweed poisoning. In control calves, 1 of 6 showed equally severe outward, gross, and microscopic lesions of HMD, but none had any lesions indicative of locoweed poisoning. The ratio of right ventricle to left ventricle wall weights were significantly higher (P = 0.033) for the swainsonine-fed calves (1.4) and the locoweed-fed calves (1.3) compared to the controls (0.9). Scores indicating the severity of HMD from observations prior to necropsy were significantly higher for the swainsonine and locoweed-fed calves compared to controls (P = 0.032).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1907051

James, L F; Panter, K E; Broquist, H P; Hartley, W J

1991-06-01

293

Microvascular Lesions by Estrogen-Induced ID3: Its Implications in Cerebral and Cardiorenal Vascular Disease.  

PubMed

Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered when cerebral, coronary, or glomerular arterioles grow inappropriately as a result of abnormal cell proliferation. The risk factor(s) and molecular mechanisms responsible for microvascular lesion formation are largely unknown. Although controversial, both animal and epidemiological studies have shown that estrogen increases the risk of stroke which may be due to microvascular lesions. Since microvascular diseases are characterized by excessive vessel growth, it is plausible that estrogen-induced neovascularization contributes to the growth of microvascular lesions. We present evidence for how ID3 overexpression in endothelial cells contributes to the development of an estrogen-induced neovascular phenotype with an additional focus on Pyk2 kinase. Our data showed that ID3 overexpression increased neovascularization, cell migration, and spheroid growth of human cerebral microvascular endothelial cells, hCMEC/D3. ID3-overexpressing cells showed significant estrogen-induced G2/M phase transition. Estrogen treatment increased both ID3 phosphorylation; total protein that was inhibited by tamoxifen, and Pyk2-mediated estrogen-induced ID3 mRNA expression. These findings suggest that Pyk2 signals ID3 expression and ID3 is necessary for estrogen-induced neovascularization in hCMEC/D3 cells. A better understanding of how microvascular lesions depend on ID3 may open new avenues for prevention and treatment of neurological diseases. PMID:25129100

Das, Jayanta K; Felty, Quentin

2015-03-01

294

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

E-print Network

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.

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

2014-07-26

295

Analysing the influence of different street vegetation on traffic-induced particle dispersion using microscale simulations.  

PubMed

Urban vegetation can be viewed as compensation to the environmental drawbacks of urbanisation. However, its ecosystem function is not well-known and, for urban planning, vegetation is mainly considered as an element of urban design. This article argues that planning practice needs to re-examine the impact of vegetation cover in the urban fabric given our evaluation of vegetation's effects on air quality, including the dispersion of traffic-induced particles at street level. Using the three-dimensional microclimate model ENVI-met®, we evaluate these effects regarding the height-to-width ratio of streets flanked by buildings and the vertical and horizontal density of street vegetation. Our results reveal vegetation's effect on particle dispersion through its influence on street ventilation. In general, vegetation was found to reduce wind speed, causing inhibition of canyon ventilation and, consequently, an increase in particle concentrations. Vegetation was also found to reduce wind speed at crown-height and to disrupt the flow field in close vicinity to the canopy. With increasing height-to-width ratio of street canyons, wind speed reduction increases and the disturbance of the flow impacts across a canyon's entire width. We also found that the effect is more pronounced in configurations with poor ventilation, such as the low wind speed, perpendicular inflow direction, and in deep canyons cases. PMID:21924543

Wania, Annett; Bruse, Michael; Blond, Nadège; Weber, Christiane

2012-02-01

296

Human-induced pluripotent stem cells pave the road for a better understanding of motor neuron disease.  

PubMed

While motor neuron diseases are currently incurable, induced pluripotent stem cell research has uncovered some disease-relevant phenotypes. We will discuss strategies to model different aspects of motor neuron disease and the specific neurons involved in the disease. We will then describe recent progress to investigate common forms of motor neuron disease: amyotrophic lateral sclerosis, hereditary spastic paraplegia and spinal muscular atrophy. PMID:24821704

Winner, Beate; Marchetto, Maria C; Winkler, Jürgen; Gage, Fred H

2014-09-15

297

Protection against titanium particle-induced inflammatory osteolysis by the proteasome inhibitor bortezomib in vivo.  

PubMed

Wear particle-induced vascularized granulomatous inflammation and subsequent inflammatory osteolysis is the most common cause of aseptic loosening after total joint replacement (TJR); however, the precise mechanism by which this occurs is unclear. This study investigates the effects of the proteasome inhibitor bortezomib (Bzb) on the expression of key biochemical markers of bone metabolism and vascularised granulomatous tissues, such as receptor activator of nuclear factor-?B ligand (RANKL), osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor-associated factor 6 (TRAF6). In addition, the effect of Bzb on apoptosis of CD68+ cells was examined. A total of 32 female BALB/C mice were randomly divided into four groups. After implantation of calvaria bone from syngeneic littermates, titanium (Ti) particles were injected into established air pouches for all mice (excluding negative controls) to provoke inflammatory osteolysis. Subsequently, Bzb was administered at a ratio of 0, 0.1, or 0.5 mg/kg on day 1, 4, 8, and 11 post-surgery to alleviate this response. All of the air pouches were harvested 14 days after the surgical procedure and were processed for molecular and histological analysis. The results demonstrated that Ti injection elevated the expression of RANKL, OPG, VEGF, and TRAF6 at both the gene and protein levels, increased counts of infiltrated cells and thickness of air pouch membranes, and elevated the apoptosis index (AI) of CD68+ cells. Bzb treatment significantly improved Ti particle-induced implanted bone osteolysis, attenuated vascularised granulomatous tissues and elevated AI of CD68+ cells. Therefore, the proteasome pathway may represent an effective therapeutic target for the prevention and treatment of aseptic loosening. PMID:22391745

Mao, Xin; Pan, Xiaoyun; Zhao, Song; Peng, Xiaochun; Cheng, Tao; Zhang, Xianlong

2012-08-01

298

Expression of ORF A1 of infectious bursal disease virus results in the formation of virus-like particles  

Microsoft Academic Search

A recombinant vaccinia virus inducibly expressing ORF A1 of infectious bursal disease virus (IBDV) has been constructed and characterized. Cells infected with this recombinant virus express the IBDV poly- protein, which is proteolytically processed to give mature VP2, VP3, and VP4 polypeptides. An elec- tron microscopy study revealed that the cytoplasm of cells infected with the recombinant virus contains abundant

A. Ferna; C. Risco; S. Marti; J. P. Albar; J. F. Rodri; Estructura de Macromole

299

Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity  

PubMed Central

Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)–enriched aromatic fraction in O2•? generation, decrease of membrane potential (??m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)–sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ??m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ??m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ??m are mediated by adsorbed chemicals rather than the particles themselves. PMID:15471724

Xia, Tian; Korge, Paavo; Weiss, James N.; Li, Ning; Venkatesen, M. Indira; Sioutas, Constantinos; Nel, Andre

2004-01-01

300

The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis.  

PubMed

The detection of peptides from the calcitonin (CT) family in the periarticular tissue of loosened implants has raised hopes of opening new regenerative therapies in the process of aseptic loosening, which remains the major cause of early implant failure in endoprosthetic surgery. We have previously shown the roles of ?-calcitonin gene-related peptide (?-CGRP) and the CALCA gene which encodes ?-CGRP/CT in this process. To uncover the role of direct calcitonin receptor (CTR) mediated signalling, we studied particle-induced osteolysis (PIO) in a murine calvaria model with a global deletion of the CTR (CTR-KO) using ?CT analysis and histomorphometry. As expected, CTR-KO mice revealed reduced bone volume compared to wild-type (WT) controls (p<0.05). In CTR-KO mice we found significantly higher RANKL (receptor activator of NF-?B ligand) expression in the particle group than in the control group. The increase in osteoclast numbers by the particles was twice as high as the increase of osteoclasts in the WT mice (400 vs. 200%). Changes in the eroded surface and actual osteolysis due to ultrahigh-molecular-weight polyethylene particles were similar in WTs and CTR-KOs. Taken together, our findings strengthen the relevance of the OPG/RANK/RANKL system in the PIO process. CTR seems to have an effect on osteoclast differentiation in this context. As there were no obvious changes of the amount of PIO in CTR deficiency, regenerative strategies in aseptic loosening of endoprosthetic implants based on peptides arising from the CT family should rather focus on the impact of ?-CGRP. PMID:25486133

Neuerburg, Carl; Wedemeyer, Christian; Goedel, Jan; Schlepper, Rüdiger; Hilken, Gero; Schwindenhammer, Benjamin; Schilling, Arndt Friedrich; Jäger, Marcus; Kauther, Max Daniel

2015-03-01

301

Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNF?.  

PubMed

In contrast to the well-understood inflammatory pathway driven by TNF?, by which implant-derived particles induce bone resorption, little is known about the process in which loosening is generated as a result of force-induced mechanical stimulus at the bone-implant interface. Specifically, there is no knowledge as to what cells or signaling pathways couple mechanical stimuli to bone resorption in context of loosening. We hypothesized that different stimuli, i.e., fluid flow versus wear particles, act through different cytokine networks for activation and localization of osteoclasts. By using an animal model in which osteoclasts and bone resorption were induced by fluid pressure or particles, we were able to detect distinct differences in osteoclast localization and inflammatory gene expression between fluid pressure and titanium particles. Fluid pressure recruits and activates osteoclasts with bone marrow contact away from the fluid pressure exposure zone, whereas titanium particles recruit and activate osteoclasts in areas in direct contact to particles. Fluid pressure induced weaker expression of the selected inflammatory related genes, although the eventual degree of osteoclast induction was similar in both models. Using TNF?Ra (4 mg/kg) (Enbrel) and dexamethasone (2 mg/kg) as specific and more general suppressors of inflammation we showed that the TNF?Ra failed to generate statistically impaired osteoclast generation while dexamethasone was much more potent. These results demonstrate that fluid pressure induces osteoclasts at a different localization than titanium particles by a molecular pathway less associated with TNF? and the innate system, which open up for other pathways controlling pressure induced osteoclastogenesis. PMID:22095724

Nilsson, Anna; Norgård, Maria; Andersson, Göran; Fahlgren, Anna

2012-04-01

302

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...

303

A Review on Chemical-Induced Inflammatory Bowel Disease Models in Rodents  

PubMed Central

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

Randhawa, Puneet Kaur; Singh, Kavinder; Singh, Nirmal

2014-01-01

304

Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis*  

PubMed Central

The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD. PMID:24626274

Dias, Olívia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, André Nathan; Athanazio, Rodrigo Abensur; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

2014-01-01

305

Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice  

PubMed Central

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

Nemmar, Abderrahim; Subramaniyan, Deepa; Ali, Badreldin H.

2012-01-01

306

Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles in mice.  

PubMed

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 (15 µg/animal) every 2(nd) 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) 1 h 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

Nemmar, Abderrahim; Subramaniyan, Deepa; Ali, Badreldin H

2012-01-01

307

Airway resistance, inflammation and oxidative stress following exposure to diesel exhaust particle in angiotensin II-induced hypertension in mice.  

PubMed

Exposure to particulate matter is a risk factor for respiratory and cardiovascular diseases. However, the mechanisms underlying these effects are not well understood. Here, we compared the impact of diesel exhaust particles (DEP) on airway resistance, inflammation and oxidative stress in normal mice, or mice made hypertensive by implanting osmotic minipump infusing angiotensin II. On day 13 after the onset of infusion, angiotensin II induced significant increase in heart rate (P<0.05) and systolic blood pressure (P<0.0001). On the same day, mice were intratracheally instilled with either DEP (15 ?g/mouse) or saline. Twenty-four hour later, the measurement of airway reactivity to methacholine (0-10mg/ml) in vivo by a forced oscillation technique showed a significant and dose dependent increase in airway resistance in normotensive mice exposed to DEP compared to those exposed to saline. In hypertensive mice, there was no difference in airway resistance in DEP versus saline exposed mice. However, following exposure to DEP, airway resistance significantly increased in normotensive versus hypertensive mice. Bronchoalveolar lavage (BAL) fluid analysis showed a significant increase in macrophage numbers in normotensive mice exposed to DEP compared to those exposed to saline, and to hypertensive mice exposed to DEP. Neutrophil numbers were significantly increased in both normotensive and hypertensive mice exposed to DEP compared with their respective control groups. Superoxide dismutase activity was significantly decreased following DEP exposure in both normotensive and hypertensive mice compared to their respective controls. However, total proteins, a marker for increase of epithelial permeability, and malondialdehyde, a reflection of lipid peroxidation, were only increased in normotensive mice exposed to DEP. Therefore, our data suggest that DEP do not aggravate airway resistance and inflammation in angiotensin II-induced hypertensive mice. On the contrary, at the dose of DEP and time point investigated, airway resistance, inflammation and oxidative stress are increased in normotensive compared to hypertensive mice. PMID:22214961

Nemmar, Abderrahim; Subramaniyan, Deepa; Zia, Shaheen; Yasin, Javed; Ali, Badreldin H

2012-02-26

308

Evaluation of hydrophobic and hydrophilic kaolin particle films for peach crop, arthropod and disease management.  

PubMed

Hydrophobic and/or hydrophilic kaolin particle film treatments to peach (Prunus persica (L) Batsch) trees were evaluated for crop and pest management capabilities in six studies from 1997 to 2000. Unsprayed control and standard treatments, the latter consisting of a commercial pesticide program, were included for comparison. Treatments in initial studies were applied via handgun, which resulted in a uniform and heavy deposit of kaolin after the first application. In contrast, treatments in subsequent studies used airblast equipment, which provided a uniform but less dense coverage, even after multiple applications. Results showed that both formulations of kaolin provided control of oriental fruit moth (Grapholita molesta (Busck)), plum curculio (Conotrachelus nenuphar (Herbst)) and Japanese beetle (Popillia japonica Newman) that was comparable with or better than the standard pesticide program. Effective management of late season catfacing insects (tarnished plant bugs Lygus lineolaris (Palisot de Beauvois) and stinkbugs Acrosternum hilare (Say), Euschistus servus (Say), and E tristigmus (Say)) and leafrollers (undetermined species) was also observed, although kaolin applications significantly increased phytophagous mite (Panonychus ulmi (Koch)) levels. In contrast to arthropod management, kaolin failed to control either peach scab (Cladosporium carpophilum (Von Thumen)) or rusty spot (Podosphaera leucotricha (Ell and Ev) ES Salmon) in any of the 4 years of the study. However, hydrophobic kaolin provided effective brown rot (Monilinia fructicola (G Winter) Honey) control when applied via handgun, and partial control when applied via airblast; hydrophilic kaolin failed to provide any control. These results suggest that hydrophobicity and deposit density may be important factors for effective disease management. The application of kaolin significantly delayed fruit maturation, increased fruit size and increased soluble solids relative to the standard. This effect, attributed to a reduction in plant stress, also resulted in increased fruit number and yield on young trees, indicating that an accentuated beneficial response from kaolin applications may be possible. PMID:15593071

Lalancette, Norman; Belding, Robert D; Shearer, Peter W; Frecon, Jerome L; Tietjen, William H

2005-01-01

309

Periodontal Disease and Bisphosphonates Induce Osteonecrosis of the Jaws in the Rat  

PubMed Central

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

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

310

particles  

NASA Astrophysics Data System (ADS)

We explore a facile and nontoxic hydrothermal route for synthesis of a Cu2ZnSnS4 nanocrystalline material by using l-cysteine as the sulfur source and ethylenediaminetetraacetic acid (EDTA) as the complexing agent. The effects of the amount of EDTA, the mole ratio of the three metal ions, and the hydrothermal temperature and time on the phase composition of the obtained product have been systematically investigated. The addition of EDTA and an excessive dose of ZnCl2 in the hydrothermal reaction system favor the generation of kesterite Cu2ZnSnS4. Pure kesterite Cu2ZnSnS4 has been synthesized at 180°C for 12 h from the reaction system containing 2 mmol of EDTA at 2:2:1 of Cu/Zn/Sn. It is confirmed by Raman spectroscopy that those binary and ternary phases are absent in the kesterite Cu2ZnSnS4 product. The kesterite Cu2ZnSnS4 material synthesized by the hydrothermal process consists of flower-like particles with 250 to 400 nm in size. It is revealed that the flower-like particles are assembled from single-crystal Cu2ZnSnS4 nanoflakes with ca. 20 nm in size. The band gap of the Cu2ZnSnS4 nanocrystalline material is estimated to be 1.55 eV. The films fabricated from the hierarchical Cu2ZnSnS4 particles exhibit fast photocurrent responses under intermittent visible-light irradiation, implying that they show potentials for use in solar cells and photocatalysis.

Xia, Yu; Chen, Zhihong; Zhang, Zhengguo; Fang, Xiaoming; Liang, Guozheng

2014-05-01

311

Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease  

PubMed Central

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a ‘vicious cycle’ of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets. © 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd PMID:24817420

Ji, Bing; Genever, Paul G; Patton, Ronald J; Fagan, Michael J

2014-01-01

312

Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease.  

PubMed

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets. PMID:24817420

Ji, Bing; Genever, Paul G; Patton, Ronald J; Fagan, Michael J

2014-11-01

313

Staphylococcus ?-toxin promotes mouse allergic skin disease by inducing mast cell degranulation  

PubMed Central

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

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

314

SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease  

PubMed Central

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

2014-01-01

315

Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.  

PubMed

Parkinson's disease is the second most common neurodegenerative movement disorder; however, its etiology remains elusive. Nevertheless, in vivo observations have concluded that oxidative stress is one of the most common causes in the pathogenesis of Parkinson's disease. It is known that mitochondria play a crucial role in reactive oxygen species-mediated pathways, and several gene products that associate with mitochondrial function are the subject of Parkinson's disease research. The PTEN-induced kinase 1 (PINK1) protects cells from mitochondrial dysfunction and is linked to the autosomal recessive familial form of the disease. PINK1 is a key player in many signaling pathways engaged in mitophagy, apoptosis, or microglial inflammatory response and is induced by oxidative stress. Several proteins participate in mitochondrial networks, and they are associated with PINK1. The E3 ubiquitin ligase Parkin, the protease presenilin-associated rhomboid-like serine protease, the tyrosine kinase c-Abl, the protein kinase MARK2, the protease HtrA2, and the tumor necrosis factor receptor-associated protein 1 (TRAP1) provide different steps of control in protection against oxidative stress. Furthermore, environmental toxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, have been identified as contributors to parkinsonism by increasing oxidative stress in dopaminergic neurons. The present review discusses the mechanisms and effects of oxidative stress, the emerging concept of the impact of environmental toxins, and a possible neuroprotective role of the antioxidant astaxanthin in various neurodegenerative disorders with particular emphasis in Parkinson's disease. PMID:24522549

Gaki, Georgia S; Papavassiliou, Athanasios G

2014-06-01

316

Regulation of low-density lipoprotein particle size distribution in NIDDM and coronary disease: importance of serum triglycerides  

Microsoft Academic Search

Summary  An increase of low-density lipoprotein triglycerides (LDL-Tg) was found to be an independent coronary artery disease (CAD) risk factor for non-insulin-dependent diabetic (NIDDM) patients in a recent prospective study. We examined the composition and size of LDL particles in 50 NIDDM men with angiographically verified CAD (NIDDM+ CAD+) and in 50 NIDDM men without CAD (NIDDM+ CAD–) as compared to

S. LahdenperÄ; M. SyvÄnne; J. Kahri; M.-R. Taskinen

1996-01-01

317

Exposure to metal welding fume particles and risk for cardiovascular disease in Denmark: a prospective cohort study  

Microsoft Academic Search

ObjectivesTo study welding fume particles in relation to cardiovascular diseases.MethodsIn 1986, 10 059 male metal workers in 75 welding companies were sent a questionnaire about their welding experience and lifestyle (83.3% response rate). Of these, 5866 were available for analysis and had ever welded at baseline. Information on exposure to welding fumes after 1986 was obtained by individual linkage to

Else Ibfelt; Jens Peter Bonde; Johnni Hansen

2010-01-01

318

Shear-induced reaction-limited aggregation kinetics of Brownian particles at arbitrary concentrations  

E-print Network

The aggregation of interacting Brownian particles in sheared concentrated suspensions is an important issue in colloid and soft matter science per se. Also, it serves as a model to understand biochemical reactions occurring in vivo where both crowding and shear play an important role. We present an effective medium approach within the Smoluchowski equation with shear which allows one to calculate the encounter kinetics through a potential barrier under shear at arbitrary colloid concentrations. Experiments on a model colloidal system in simple shear flow support the validity of the model in the range considered. By generalizing Kramers' rate theory to the presence of collective hydrodynamics, our model explains the significant increase in the shear-induced reaction-limited aggregation kinetics upon increasing the colloid concentration.

Alessio Zaccone; Daniele Gentili; Hua Wu; Massimo Morbidelli

2010-04-13

319

Light induced ferromagnetism of nanocrystalline CuCr2Se4 particles  

NASA Astrophysics Data System (ADS)

A novel method to synthesize ternary chalcogenide nanoparticles was developed with microwaveassisted polyol reaction in this study. Copper chloride, chromium acetate and metallic selenium were used as precursors with stoichiometric ratios in poly ethylene glycol. Magnetic moment of CuCr2Se4 nanoparticles was measured from 300 to 750 K with external magnetic field of 500 Oe in argon atmosphere and Curie temperature was calculated as 445 K. Nanocrystalline CuCr2Se4 particles were dispersed in the matrix of light transparent resin so as to investigate light induced effect on the magnetic properties. Light illumination in an external magnetic field increased the magnetization and increment of magnetization ( ?J) to initial magnetization ( J) showed a maximum at 250 Gauss.

Kim, D.; Chung, K. C.; Choi, C. J.

2013-06-01

320

Evaluation of Nigerian animal feeds by particle-induced X-ray emission.  

PubMed

There is need to evaluate the locally available animal feeds in Nigeria so as to be able to combine them in acceptable proportions to the animals to achieve the desired growth rate. The technique of particle-induced X-ray emission (PIXE) was employed for the evaluation of these locally available animal feeds, which include Panicum maximum (Guinea grass), Cynodon plectostachyum (grass), Leucaena leucephala (legume), Calopogonium mucunoides (legume), Gliricidia sepium (legume), Euphorbia polychrome (legume), Pueraria phaseloides (legume), and Centrosema pubescens (legume). The proton beam delivered by the 2.5-MV AN 2,000 Van de Graaff accelerator at the International Centre for Theoretical Physics Laboratori Nazionali di Legnaro (LNL), Padova, Italy was used for the PIXE measurements. Twenty-one different elements were detected at various concentrations and their nutritional effects on different animals are discussed. PMID:16217142

Olabanji, S O; Olubunmi, P; Ceccato, D; Buoso, M C; De Poli, M; Moschini, G

2005-11-01

321

Excitation function of (3)He-particle induced nuclear reactions on natural palladium.  

PubMed

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

Al-Abyad, M; Tárkányi, F; Ditrói, F; Takács, S

2014-12-01

322

The merits of particle induced X-ray emission in revealing painting techniques  

NASA Astrophysics Data System (ADS)

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.

Neelmeijer, C.; Mäder, M.

2002-04-01

323

Nuclear physics of cosmic ray interaction with semiconductor materials: Particle-induced soft errors from a physicist's perspective  

Microsoft Academic Search

The key issues of cosmic-ray-induced soft-error rates, SER (also referred to as single-event upset, SEU, rates) in microelectronic devices are discussed from the viewpoint of fundamental atomic and nuclear interactions between high-energy particles and semiconductors. From sea level to moderate altitudes, the cosmic ray spectrum is dominated by three particle species: nucleons (protons and neutrons), pions, and muons. The characteristic

Henry H. K. Tang

1996-01-01

324

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...

325

Key node selection for containing infectious disease spread using particle swarm optimization  

Microsoft Academic Search

In recent years, some emerging and reemerging infectious diseases have grown into global health threats due to high human mobility. It is important to have intervention plans for containing the spread of such infectious diseases. Among various intervention strategies, screening infected people is an efficient way for evaluating the infection scale and controlling the spread of infectious diseases. Considering the

Xiuju Fu; Sonja Lim; Lipo Wang; G. Lee; S. Ma; Limsoon Wong; Gaoxi Xiao

2009-01-01

326

Methotrexate-induced Hodgkin disease in a patient with systemic lupus erythematosus.  

PubMed

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

Sliesoraitis, Sarunas; Khan, Rizwan; Rothman, Jan

2009-06-01

327

Oral Immunization with Recombinant Lactobacillus plantarum Induces a Protective Immune Response in Mice with Lyme Disease?  

PubMed Central

Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens. PMID:18632920

del Rio, Beatriz; Dattwyler, Raymond J.; Aroso, Miguel; Neves, Vera; Meirelles, Luciana; Seegers, Jos F. M. L.; Gomes-Solecki, Maria

2008-01-01

328

Thermally induced light-driven microfluidics using a MOEMS-based laser scanner for particle manipulation  

NASA Astrophysics Data System (ADS)

One key challenge in the field of microfluidics and lab-on-a-chip experiments for biological or chemical applications is the remote manipulation of fluids, droplets and particles. These can be volume elements of reactants, particles coated with markers, cells or many others. Light-driven microfluidics is one way of accomplishing this challenge. In our work, we manipulated micrometre sized polystyrene beads in a microfluidic environment by inducing thermal flows. Therefore, the beads were held statically in an unstructured microfluidic chamber, containing a dyed watery solution. Inside this chamber, the beads were moved along arbitrary trajectories on a micrometre scale. The experiments were performed, using a MOEMS (micro-opto-electro-mechanical-systems)-based laser scanner with a variable focal length. This scanner system is integrated in a compact device, which is flexibly applicable to various microscope setups. The device utilizes a novel approach for varying the focal length, using an electrically tunable lens. A quasi statically driven MOEMS mirror is used for beam steering. The combination of a tunable lens and a dual axis micromirror makes the device very compact and robust and is capable of positioning the laser focus at any arbitrary location within a three dimensional working space. Hence, the developed device constitutes a valuable extension to manually executed microfluidic lab-on-chip experiments.

Kremer, Matthias P.; Tortschanoff, Andreas

2014-03-01

329

Modeling particle-induced electron emission in a simplified plasma Test Cell  

NASA Astrophysics Data System (ADS)

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 (˜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.

Giuliano, Paul N.; Boyd, Iain D.

2013-03-01

330

Modeling particle-induced electron emission in a simplified plasma Test Cell  

SciTech Connect

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.

Giuliano, Paul N.; Boyd, Iain D. [Department of Aerospace Engineering, University of Michigan, Ann Arbor, Michigan 48109 (United States)

2013-03-21

331

Spatial learning and memory deficits induced by exposure to iron-56-particle radiation  

NASA Technical Reports Server (NTRS)

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.

Shukitt-Hale, B.; Casadesus, G.; McEwen, J. J.; Rabin, B. M.; Joseph, J. A.

2000-01-01

332

Mechanism of vibration-induced repulsion force on a particle in a viscous fluid cell  

NASA Astrophysics Data System (ADS)

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.

Saadatmand, Mehrrad; Kawaji, Masahiro

2013-08-01

333

Mechanism of vibration-induced repulsion force on a particle in a viscous fluid cell.  

PubMed

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

Saadatmand, Mehrrad; Kawaji, Masahiro

2013-08-01

334

Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pinch  

SciTech Connect

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.

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

335

Energetic-particle-driven instabilities and induced fast-ion transport in a reversed field pincha)  

NASA Astrophysics Data System (ADS)

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.

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

336

DNA complex lesions induced by protons and alpha-particles: track structure characteristics determining linear energy transfer and particle type dependence.  

PubMed

The yield of DNA double-strand breaks (dsb) and DNA complex lesions induced by protons and alpha-particles of various energies was simulated using a Monte Carlo track structure code (MOCA15) and a simple model of the DNA molecule. DNA breaks of different complexity were analysed. The linear energy transfer (LET) and particle-type dependence of lesions of higher complexity seems to confirm the importance of clustered damage in DNA as a relevant step leading to biological endpoints such as cell inactivation. The detailed structure of proton and alpha-particle tracks was analysed to identify the main characteristics possibly responsible for such a dependence. The role of the primary ion and of its secondary electrons in inducing dsb and complex lesions is described, showing that the relative contribution of secondary electron tracks alone in inducing clustered lesions is almost negligible at high LET, but tends to dominate below = 10 keV/micron. This is consistent with the observed similar effectiveness of low-LET fast particle radiation and sparsely ionizing radiation such as x-rays. The dependence on LET and particle type is mainly due to energy deposition events of the primary ion together with short range electrons surrounding the ion track; the yield of complex lesions due to secondary electron tracks alone is substantially LET independent. The radial distributions of the energy contributing to the induction of complex lesions were analyzed and compared with the radial distributions of energy deposition of the full tracks. The results suggest that the stochastic behaviour (i.e. cluster properties) of the energy deposition pattern within a radius of a few nanometers around the ion track plays a relevant role in determining the biological radiation effectiveness. PMID:9271797

Ottolenghi, A; Merzagora, M; Paretzke, H G

1997-06-01

337

Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats  

PubMed Central

Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180?mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

Sasidharan, Suja Rani; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Ariyattu Madhavan, Chandrasekharan Nair; Agarwal, Amit

2014-01-01

338

Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats.  

PubMed

Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

Sasidharan, Suja Rani; Joseph, Joshua Allan; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Madhavan, Chandrasekharan Nair Ariyattu; Agarwal, Amit

2014-01-01

339

Structural properties of EGCG-induced, nontoxic Alzheimer's disease A? oligomers.  

PubMed

The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease ?-amyloid peptide (A?) neurotoxicity. Solution-state NMR allows probing initial EGCG-A? interactions. We show that EGCG-induced A? oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of A?. The C-terminal part of the A? peptide (residues 22-39) adopts a ?-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric A? aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development. PMID:22300765

Lopez del Amo, Juan Miguel; Fink, Uwe; Dasari, Muralidhar; Grelle, Gerlinde; Wanker, Erich E; Bieschke, Jan; Reif, Bernd

2012-08-24

340

Parkinson's disease: the treatment of drug-induced hallucinations and psychosis.  

PubMed

Drug-induced psychosis is one of the most disabling complications of advancing Parkinson's disease. It has also been one of the most difficult to treat. Clozapine was the first medication shown to be safe and effective in this setting, and it remains the standard by which newer atypical antipsychotics are measured. However, due to the small but significant risk of agranulocytosis and the need for frequent blood testing, alternatives have been sought. Risperidone, olanzapine, and quetiapine are new atypical antipsychotics that have each been proposed as an alternative to clozapine, but the literature concerning their use in Parkinson's disease is conflicted and confusing. Although quetiapine appears to be the best current choice, none of these medications have equaled clozapine's ability to safely treat drug-induced psychosis without the risk of worsening parkinsonism. PMID:11898537

Molho, E S; Factor, S A

2001-07-01

341

Disease modeling using human induced pluripotent stem cells: lessons from the liver.  

PubMed

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

Gieseck, Richard L; Colquhoun, Jennifer; Hannan, Nicholas R F

2015-01-01

342

Disease modeling using human induced pluripotent stem cells: Lessons from the liver?  

PubMed Central

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

Gieseck, Richard L.; Colquhoun, Jennifer; Hannan, Nicholas R.F.

2014-01-01

343

Effect of the recoil pressure induced by evaporation on motion of powder particles in the light field during laser cladding  

NASA Astrophysics Data System (ADS)

A model is proposed, which takes into account acceleration of powder particles by a force induced by recoil of material vapors from the irradiated region of the particle surface. Results of a numerical analysis of heat and mass transfer in the case of motion of individual stainless steel powder particles in a gas flow and in a light field of laser radiation under conditions of laser cladding are presented. Acceleration of particles is found to depend on their diameter, carrier gas velocity, powder material properties, laser radiation power, and degree of attenuation of the power density in the laser beam in the direction of its action on the substrate. The calculated results are compared with experimental data on light-propulsion acceleration of individual particles (of aluminum, aluminum oxide, and graphite) under the action of pulsed laser radiation.

Kovaleva, I. O.; Kovalev, O. B.

2012-01-01

344

Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes  

Microsoft Academic Search

A trifunctional bispecific antibody (BiLu) directed against murine CD3 and human epithelial-cell adhesion molecule (Ep- CAM) was tested for its ability to improve cell-mediated adoptive immunotherapy in a murine model of B16 melanoma cells transfected with human EpCAM. Intraperi- toneal inoculation of naive C57BL\\/6 (C57) splenocytes induced lethal graft versus host disease (GVHD) in 85% to 97% of sublethally irradiated

Shoshana Morecki; Horst Lindhofer; Elena Yacovlev; Yael Gelfand; Shimon Slavin

2006-01-01

345

Inducible mutant huntingtin expression in HN10 cells reproduces Huntington's disease-like neuronal dysfunction  

PubMed Central

Background Expansion of a polyglutamine repeat at the amino-terminus of huntingtin is the probable cause for Huntington's disease, a lethal progressive autosomal-dominant neurodegenerative disorders characterized by impaired motor performance and severe brain atrophy. The expanded polyglutamine repeat changes the conformation of huntingtin and initiates a range of pathogenic mechanisms in neurons including intracellular huntingtin aggregates, transcriptional dysregulation, energy metabolism deficits, synaptic dystrophy and ultimately neurodegeneration. It is unclear how these events relate to each other or if they can be reversed by pharmacological intervention. Here, we describe neuronal cell lines expressing inducible fragments of normal and mutant huntingtin. Results In HN10 cells, the expression of wild type and mutant huntingtin fragments was dependent on the induction time as well as on the concentration of the RheoSwitch® inducing ligand. In order to analyze the effect of mutant huntingtin expression on cellular functions we concentrated on the 72Q exon1 huntingtin expressing cell line and found that upon induction, it was possible to carefully dissect mutant huntingtin-induced phenotypes as they developed over time. Dysregulation of transcription as a result of mutant huntingtin expression showed a transcription signature replicating that reported in animal models and Huntington's disease patients. Crucially, triggering of neuronal differentiation in mutant huntingtin expressing cell resulted in the appearance of additional pathological hallmarks of Huntington's disease including cell death. Conclusion We developed neuronal cell lines with inducible expression of wild type and mutant huntingtin. These new cell lines represent a reliable in vitro system for modeling Huntington's disease and should find wide use for high-throughput screening application and for investigating the biology of mutant huntingtin. PMID:19203385

Weiss, Andreas; Roscic, Ana; Paganetti, Paolo

2009-01-01

346

Testing Drugs in Animal Models of Cigarette Smoke-induced Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

Animal models of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) provide potentially useful ways to test drug therapies, either by direct administration of the treatment of interest, or by use of genetically modified animals that mimic the actions of the drug of interest. Evaluation of the potential effects of a drug in animal models requires a long-term (generally 6-mo) smoke

Andrew Churg; Joanne L. Wright

2009-01-01

347

On Classifying Disease-Induced Patterns in the Brain Using Diffusion Tensor Images  

Microsoft Academic Search

\\u000a Diffusion tensor imaging (DTI) provides rich information about brain tissue structure especially in the white matter, which\\u000a is known to be affected in several diseases like schizophrenia. Identifying patterns of brain changes induced by pathology\\u000a is therefore crucial to clinical studies. However, the high dimensionality and complex structure of DTI make it difficult\\u000a to apply conventional linear statistical and pattern

Peng Wang; Ragini Verma

2008-01-01

348

Stat5 Is Essential for the Myelo- and Lymphoproliferative Disease Induced by TEL\\/JAK2  

Microsoft Academic Search

STAT5 is activated in a broad spectrum of human hematologic malignancies. We addressed whether STAT5 activation is necessary for the myelo- and lymphoproliferative disease induced by TEL\\/JAK2 using a genetic approach. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL\\/JAK2 develop a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5ab-deficient mice expressing TEL\\/JAK2

Juerg Schwaller; Evan Parganas; Demin Wang; Danielle Cain; Jon C. Aster; Ifor R. Williams; Chien-Kuo Lee; Rachel Gerthner; Toshio Kitamura; Julie Frantsve; Ema Anastasiadou; Mignon L. Loh; David E. Levy; James N. Ihle; D. Gary Gilliland

2000-01-01

349

Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.  

PubMed

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

Khmaladze, Ia; Kelkka, Tiina; Guerard, Simon; Wing, Kajsa; Pizzolla, Angela; Saxena, Amit; Lundqvist, Katarina; Holmdahl, Meirav; Nandakumar, Kutty Selva; Holmdahl, Rikard

2014-09-01

350

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, ...

351

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

PubMed

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

Rezvanfar, Mohammad Amin; Rezvanfar, Mohammad Ali; Shahverdi, Ahmad Reza; Ahmadi, Abbas; Baeeri, Maryam; Mohammadirad, Azadeh; Abdollahi, Mohammad

2013-02-01

352

Dipeptidyl peptidase-4 inhibition by Pterocarpus marsupium and Eugenia jambolana ameliorates streptozotocin induced Alzheimer's disease.  

PubMed

Alzheimer's disease (AD), the most common form of dementia, is characterized by the loss of normal functions of brain cells and neuronal death, ultimately leading to memory loss. Recent accumulating evidences have demonstrated the therapeutic potential of anti-diabetic agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, for the treatment of Alzheimer's disease (AD), providing opportunities to explore and test the DPP-4 inhibitors for treating this fatal disease. Prior studies determining the efficacy of Pterocarpus marsupium (PM, Fabaceae) and Eugenia jambolana (EJ, Myrtaceae) extracts for ameliorating type 2 diabetes have demonstrated the DPP-4 inhibitory properties indicating the possibility of using of these extracts even for the treating AD. Therefore, in the present study, the neuroprotective roles of PM and EJ for ameliorating the streptozotocin (STZ) induced AD have been tested in rat model. Experimentally, PM and EJ extracts, at a dose range of 200 and 400mg/kg, were administered orally to STZ induced AD Wistar rats and cognitive evaluation tests were performed using radial arm maze and hole-board apparatus. Following 30 days of treatment with the extracts, a dose- and time-dependent attenuation of AD pathology, as evidenced by decreasing amyloid beta 42, total tau, phosphorylated tau and neuro-inflammation with an increase in glucagon-like peptide-1 (GLP-1) levels was observed. Therefore, PM and EJ extracts contain cognitive enhancers as well as neuroprotective agents against STZ induced AD. PMID:24667360

Kosaraju, Jayasankar; Madhunapantula, Subbarao V; Chinni, Santhivardhan; Khatwal, Rizwan Basha; Dubala, Anil; Muthureddy Nataraj, Satish Kumar; Basavan, Duraiswamy

2014-07-01

353

Analysis of Clonostachys rosea-Induced Resistance to Tomato Gray Mold Disease in Tomato Leaves  

PubMed Central

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

Guan, Xin; Chen, Xiuling; Chen, Hongyu; Zhang, Jian; Zhang, Junfeng; Li, Jingfu; Yang, Yijun; Wang, Aoxue

2014-01-01

354

Pathogen-induced elicitin production in transgenic tobacco generates a hypersensitive response and nonspecific disease resistance.  

PubMed Central

The rapid and effective activation of disease resistance responses is essential for plant defense against pathogen attack. These responses are initiated when pathogen-derived molecules (elicitors) are recognized by the host. We have developed a strategy for creating novel disease resistance traits whereby transgenic plants respond to infection by a virulent pathogen with the production of an elicitor. To this end, we generated transgenic tobacco plants harboring a fusion between the pathogen-inducible tobacco hsr 203J gene promoter and a Phytophthora cryptogea gene encoding the highly active elicitor cryptogein. Under noninduced conditions, the transgene was silent, and no cryptogein could be detected in the transgenic plants. In contrast, infection by the virulent fungus P. parasitica var nicotianae stimulated cryptogein production that coincided with the fast induction of several defense genes at and around the infection sites. Induced elicitor production resulted in a localized necrosis that resembled a P. cryptogea-induced hypersensitive response and that restricted further growth of the pathogen. The transgenic plants displayed enhanced resistance to fungal pathogens that were unrelated to Phytophthora species, such as Thielaviopsis basicola, Erysiphe cichoracearum, and Botrytis cinerea. Thus, broad-spectrum disease resistance of a plant can be generated without the constitutive synthesis of a transgene product. PMID:9927640

Keller, H; Pamboukdjian, N; Ponchet, M; Poupet, A; Delon, R; Verrier, J L; Roby, D; Ricci, P

1999-01-01

355

Neuroprotective activity of Stereospermum suaveolens DC against 6-OHDA induced Parkinson's disease model  

PubMed Central

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

Shalavadi, M. H.; Chandrashekhar, V. M.; Avinash, S. P.; Sowmya, C.; Ramkishan, A.

2012-01-01

356

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...

357

Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice  

Microsoft Academic Search

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

Abderrahim Nemmar; Deepa Subramaniyan; Badreldin H. Ali

2012-01-01

358

The molecular basis for disease phenotype in chronic Chlamydia-induced arthritis  

PubMed Central

Genital Chlamydia trachomatis infections can elicit an inflammatory arthritis in some individuals, and recent surprising studies have demonstrated that only ocular (trachoma) strains, not genital strains, of the organism are present in the synovial tissues of patients with the disease. This observation suggests an explanation for the small proportion of genitally-infected patients who develop Chlamydia-induced arthritis. Other recent studies have begun to identify the specific chlamydial gene products that elicit the synovial inflammatory response during both active and quiescent disease, although much more study will be required to complete the understanding of that complex process of host–pathogen interaction. Several newly developed experimental methods and approaches for study of the process will enable identification of new therapeutic targets, and possibly strategies for prevention of the disease altogether. PMID:23440251

Carter, John D; Gerard, Herve C; Whittum-Hudson, Judith A; Hudson, Alan P

2013-01-01

359

Mercaptopurine-induced hepatoportal sclerosis in a patient with Crohn's disease.  

PubMed

Thiopurines play a pivotal role in the management of inflammatory bowel disease. Azathioprine and mercaptopurine have been associated with a number of liver abnormalities, including hepatitis, veno-occlusive disease, nodular regenerative hyperplasia, and peliosis hepatitis. Patients treated with azathioprine and mercaptopurine have their liver chemistry tests routinely checked due to this potential for hepatotoxicity. Hepatoportal sclerosis is a cause of non-cirrhotic portal hypertension that is increasingly being recognized; its etiopathogenesis is not well defined. We present the first case report of mercaptopurine-induced hepatoportal sclerosis leading to non-cirrhotic portal hypertension in a patient with Crohn's disease. He had been treated with mercaptopurine for five years, and his liver chemistry tests were always within normal limits. This case underscores the potential serious liver adverse events that may arise silently and go undetected during treatment with mercaptopurine, and should alert clinicians as to the potential need to discontinue mercaptopurine in this setting. PMID:22841133

Tuyama, Ana C; Krakauer, Mark; Alzaabi, Mohamed; Fiel, Maria Isabel; Legnani, Peter; Schiano, Thomas D

2013-08-01

360

Wear particles promote endotoxin tolerance in macrophages by inducing interleukin-1 receptor-associated kinase-M expression.  

PubMed

Toll-like receptors (TLRs) recognizing pathogen-associated molecular patterns (PAMP) play a role in local immunity and participate in implant-associated loosening. TLRs-mediated signaling is regulated by interleukin-1 receptor-associated kinase-M (IRAK-M). Our previous studies have proved that IRAK-M is induced by wear particles in macrophages from periprosthetic tissues. In this study, the IRAK-M-related mechanisms were further explored by lipopolysaccharide (LPS) and/or titanium (Ti) particles stimulations and small interfering RNAs (siRNAs). The protein level of IRAK-M was studied using western blotting and tumor necrosis factor-? (TNF-?), and interleukin-1? (IL-1?) levels were measured using ELISA. Results showed that in RAW264.7 cells stimulated by LPS after Ti particle pre-exposure, IRAK-M was slightly changed, compared with LPS stimulation. And levels of TNF-? and IL-1? in cultures stimulated by LPS first after Ti particle pre-exposure were lower than in the other two groups which were stimulated by LPS with or without Ti particles (p < 0.001), whereas there were no statistic differences between the later two (p > 0.05). The cytokines were lowest in Ti particles alone stimulation. After siRNAs silenced, IRAK-M-deficient cells exhibited increased expression of the cytokines in LPS stimulation after Ti particle pre-exposure and when stimulated with Ti particles alone. Our findings suggest that debris-induced IRAK-M decreases foreign body reactions, but at the same time, the over-expression of IRAK-M may also be detrimental on local intrusion of PAMPs or bacteria, negatively regulates the LPS-induced and TLRs-mediated inflammation and results in immunosuppression in periprosthetic tissue, which may predispose to implant-associated infections. PMID:22941946

Zhang, Yangchun; Yu, Shiming; Xiao, Jianhong; Hou, Changhe; Li, Ziqing; Zhang, Ziji; Zhai, Qiyi; Lehto, Matti; Konttinen, Yrjö T; Sheng, Puyi

2013-03-01

361

PI3K? deletion reduces variability in the in vivo osteolytic response induced by orthopaedic wear particles.  

PubMed

Orthopedic wear particles activate a number of intracellular signaling pathways associated with inflammation in macrophages and we have previously shown that the phosphoinositol-3-kinase (PI3K)/Akt pathway is one of the signal transduction pathways that mediates the in vitro activation of macrophages by orthopedic wear particles. Since PI3K? is primarily responsible for PI3K activity during inflammation, we hypothesized that PI3K? mediates particle-induced osteolysis in vivo. Our results do not strongly support the hypothesis that PI3K? regulates the overall amount of particle-induced osteolysis in the murine calvarial model. However, our results strongly support the conclusion that variability in the amount of particle-induced osteolysis between individual mice is reduced in the PI3K?(-/-) mice. These results suggest that PI3K? contributes to osteolysis to different degrees in individual mice and that the mice, and patients, that are most susceptible to osteolysis may be so, in part, due to an increased contribution from PI3K?. PMID:21538508

Greenfield, Edward M; Tatro, Joscelyn M; Smith, Matthew V; Schnaser, Erik A; Wu, Dianqing

2011-11-01

362

PI3K? Deletion Reduces Variability in the In Vivo Osteolytic Response Induced by Orthopaedic Wear Particles  

PubMed Central

Orthopedic wear particles activate a number of intracellular signaling pathways associated with inflammation in macrophages and we have previously shown that the phosphoinositol-3-kinase (PI3K)/Akt pathway is one of the signal transduction pathways that mediates the in vitro activation of macrophages by orthopedic wear particles. Since PI3K? is primarily responsible for PI3K activity during inflammation, we hypothesized that PI3K? mediates particle-induced osteolysis in vivo. Our results do not strongly support the hypothesis that PI3K? regulates the overall amount of particle-induced osteolysis in the murine calvarial model. However, our results strongly support the conclusion that variability in the amount of particle-induced osteolysis between individual mice is reduced in the PI3K??/? mice. These results suggest that PI3K? contributes to osteolysis to different degrees in individual mice and that the mice, and patients, that are most susceptible to osteolysis may be so, in part, due to an increased contribution from PI3K?. PMID:21538508

Greenfield, Edward M.; Tatro, Joscelyn M.; Smith, Matthew V.; Schnaser, Erik A.; Wu, Dianqing

2012-01-01

363

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 ...

364

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 ...

365

Pressure induced increase of particle size and resulting weakening of elastic stiffness of CeO2 nanocrystals  

E-print Network

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

Downs, Robert T.

366

Determination of small soot particles in the presence of large ones from time-resolved laser-induced incandescence  

NASA Astrophysics Data System (ADS)

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.

Cenker, E.; Bruneaux, G.; Dreier, T.; Schulz, C.

2015-02-01

367

Near-infrared light responsive multi-compartmental hydrogel particles synthesized through droplets assembly induced by superhydrophobic surface.  

PubMed

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

Luo, Rongcong; Cao, Ye; Shi, Peng; Chen, Chia-Hung

2014-12-01

368

Determination of small soot particles in the presence of large ones from time-resolved laser-induced incandescence  

NASA Astrophysics Data System (ADS)

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.

Cenker, E.; Bruneaux, G.; Dreier, T.; Schulz, C.

2014-11-01

369

Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats  

NASA Technical Reports Server (NTRS)

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.

Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

2002-01-01

370

Calcineurin/NFAT pathway mediates wear particle-induced TNF-? release and osteoclastogenesis from mice bone marrow macrophages in vitro  

PubMed Central

Aim: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. Methods: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-?B ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNF? was analyzed with ELISA. Results: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-? production. The TNF-? level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 ?mol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-? production much more efficiently in the PMMA group than in the Ti group (96 h). Conclusion: Calcineurin/NFAT pathway mediates wear particles-induced TNF-? release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis. PMID:24056707

Liu, Feng-xiang; Wu, Chuan-long; Zhu, Zhen-an; Li, Mao-qiang; Mao, Yuan-qing; Liu, Ming; Wang, Xiao-qing; Yu, De-gang; Tang, Ting-ting

2013-01-01

371

Nonlocal theory of energetic-particle-induced geodesic acoustic mode This article has been downloaded from IOPscience. Please scroll down to see the full text article.  

E-print Network

Nonlocal theory of energetic-particle-induced geodesic acoustic mode This article has been. Fusion 52 (2010) 095003 (13pp) doi:10.1088/0741-3335/52/9/095003 Nonlocal theory of energetic of energetic-particle (EP)-induced geodesic acoustic modes (EGAMs) by velocity space anisotropy is investigated

Zonca, Fulvio

372

Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells  

PubMed Central

Our understanding of Alzheimer’s disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer’s disease, both caused by a duplication of the amyloid-? precursor protein gene1 (APP; termed APPDp), two with sporadic Alzheimer’s disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APPDp patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-?(1–40), phospho-tau(Thr 231) and active glycogen synthase kinase-3? (aGSK-3?). Neurons from APPDp and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with ?-secretase inhibitors, but not ?-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3? levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-?, in GSK-3? activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer’s disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer’s disease, even though it can take decades for overt disease to manifest in patients. PMID:22278060

Israel, Mason A.; Yuan, Shauna H.; Bardy, Cedric; Reyna, Sol M.; Mu, Yangling; Herrera, Cheryl; Hefferan, Michael P.; Van Gorp, Sebastiaan; Nazor, Kristopher L.; Boscolo, Francesca S.; Carson, Christian T.; Laurent, Louise C.; Marsala, Martin; Gage, Fred H.; Remes, Anne M.; Koo, Edward H.; Goldstein, Lawrence S. B.

2012-01-01

373

Pink1 suppresses alpha-synuclein-induced phenotypes in a Drosophila model of Parkinson's disease.  

PubMed

Parkinson's disease (PD) is the most prevalent human neurodegenerative movement disorder and is characterized by a selective and progressive loss of the dopaminergic neurons. Mutations in the genes parkin and PTEN-induced putative kinase 1 (PINK1) result in autosomal recessive forms of PD. It has been suggested that parkin and Pink1 function in the same pathway in Drosophila, with Pink1 acting upstream of parkin. Previous work in our laboratory has shown the ability of parkin to rescue an alpha-synuclein-induced PD-like phenotype in Drosophila. To investigate the ability of Pink1 to protect against alpha-synuclein-induced toxicity, we have performed longevity, mobility, and histological studies to determine whether Drosophila Pink1 can rescue the alpha-synuclein phenotypes. We have found that overexpression of Pink1 results in the rescue of the alpha-synuclein-induced phenotype of premature loss of climbing ability, suppression of degeneration of the ommatidial array, and the suppression of alpha-synuclein-induced developmental defects in the Drosophila eye. These results mark the first demonstration of Pink1 counteracting PD phenotypes in a protein toxicity animal model, and they show that Pink1 is able to impart protection against potentially harmful proteins such as alpha-synuclein that would otherwise result in cellular stress. PMID:19088817

Todd, Amy M; Staveley, Brian E

2008-12-01

374

Chimeric GII.4 Norovirus Virus-Like-Particle-Based Vaccines Induce Broadly Blocking Immune Responses  

PubMed Central

ABSTRACT There is currently no licensed vaccine for noroviruses, and development is hindered, in part, by an incomplete understanding of the host adaptive immune response to these highly heterogeneous viruses and rapid GII.4 norovirus molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs every 2 to 4 years. To address the problem of GII.4 antigenic variation, we tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine platforms, which incorporate antigenic determinants from multiple strains into a single genetic background, will elicit a broader immune response against contemporary and emergent strains. Here, we compare the immune response generated by chimeric VLPs to that of parental strains and a multivalent VLP cocktail. Results demonstrate that chimeric VLPs induce a more broadly cross-blocking immune response than single parental VLPs and a similar response to a multivalent GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone from one strain into the background of another is sufficient to induce a blockade response against the strain donating epitope site A. This suggests a mechanism by which population-wide surveillance of mutations in a single epitope could be used to evaluate antigenic changes in order to identify potential emergent strains and quickly reformulate vaccines against future epidemic strains as they emerge in human populations. IMPORTANCE Noroviruses are gastrointestinal pathogens that infect an estimated 21 million people per year in the United States alone. GII.4 noroviruses account for >70% of all outbreaks, making them the most clinically important genotype. GII.4 noroviruses undergo a pattern of epochal evolution, resulting in the emergence of new strains with altered antigenicity over time, complicating vaccine design. This work is relevant to norovirus vaccine design as it demonstrates the potential for development of a chimeric VLP-based vaccine platform that may broaden the protective response against multiple GII.4 strains and proposes a potential reformulation strategy to control newly emergent strains in the human population. PMID:24741081

Debbink, Kari; Lindesmith, Lisa C.; Donaldson, Eric F.; Swanstrom, Jesica

2014-01-01

375

Gravitational perturbation of the BTZ black hole induced by test particles and weak cosmic censorship in AdS spacetime  

SciTech Connect

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.

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

376

Stress-induced cardiomyopathy associated with ipratropium bromide therapy in a patient with chronic obstructive pulmonary disease.  

PubMed

Stress-induced cardiomyopathy, also known as 'broken heart syndrome' or Takotsubo cardiomyopathy, is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle, in the absence of significant coronary artery disease. We report the case of a 56-year-old male patient with chronic obstructive pulmonary disease (COPD), with stress-induced cardiomyopathy associated with the use of ipratropium bromide, administered in the context of an acute exacerbation of COPD. PMID:24680554

Melão, Filipa; Nunes, José P L; Vasconcelos, Mariana; Dias, Paula; Almeida, Pedro B; Rodrigues, Rui; Pinho, Teresa; Madureira, António; Maciel, Maria J

2014-03-01

377

Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water  

Microsoft Academic Search

Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced water.BackgroundIncreased oxidative stress in end-stage renal disease (ESRD) patients may oxidize macromolecules and consequently lead to cardiovascular events during chronic hemodialysis. Electrolyzed reduced water (ERW) with reactive oxygen species (ROS) scavenging ability may have a potential effect on reduction of hemodialysis-induced oxidative stress in ESRD patients.MethodsWe developed a

Kuo-Chin Huang; Chih-Ching Yang; Kun-Tai Lee; Chiang-Ting Chien

2003-01-01

378

Changes in plasma chemistry after drug?induced liver disease or muscle necrosis in racing pigeons (Columba livia domestica)  

Microsoft Academic Search

Changes in plasma variables as a result of liver damage induced by ethylene glycol (group A) or D?galactosamine (group B) and of muscle damage induced by doxycycline were compared.Plasma bile acid concentration was both a specific and a sensitive indicator of liver disease. Another specific, but less sensitive indicator of liver disease was 7?GT. Plasma AS AT activity was the

J. T. Lumeij; M. Meidam; J. Wolfswinkel; M. H. Van der Hage; G. M. Dorrestein

1988-01-01

379

Sulphydryl blocker induced small intestinal inflammation in rats: a new model mimicking Crohn's disease  

PubMed Central

Background—Sulphydryl compounds are essential for maintaining mucosal integrity in the gastrointestinal tract. ?Aim—To characterise a model of experimental inflammation in the small intestine induced by a sulphydryl blocker. ?Methods—Inflammation in the small intestine was induced in rats by intrajejunal administration of 0.1 ml 2% iodoacetamide. The possible amelioration of the damage induced was modulated by intragastric administration of TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl; 50 mg/100 g body weight), ketotifen (200 µg/100 g body weight) or by addition of L-NAME (NG-nitro-L-arginine methyl ester; 0.1 mg/ml) or apocynin (120 µg/ml) to the drinking water. Rats were sacrificed at various time intervals, the small intestine resected, weighed, macroscopic lesions were assessed, and mucosal generation of inflammatory mediators and nitric oxide synthase activity were determined. ?Results—Intrajejunal administration of iodoacetamide induced, after one week, multifocal mucosal erosions, ulcerations with granulomas and giant Langhans cells. At two weeks, the mucosa was almost macroscopically intact but histologically epithelial granuloma and giant cells were present. Myeloperoxidase activity was increased in the first 24 hours, one week later mucosal nitric oxide synthase activity and generation of leukotriene B4, leukotriene C4 and thromboxane B2 were increased, whereas prostaglandin E2 generation was decreased notably. Ketotifen and apocynin significantly decreased the extent of injury which was not affected by TEMPOL or L-NAME. ?Conclusions—Jejunal inflammation induced by the sulphydryl blocker, iodoacetamide, resembles the pathological changes in Crohn's disease. The protective effect of ketotifen and apocynin indicates the contribution of O2 and pro-inflammatory mediators to the pathogenesis of the damage, and may be a novel approach to the treatment of inflammatory bowel disease. ?? Keywords: iodoacetamide; TEMPOL; ketotifen; apocynin; NO synthase PMID:9378392

Rachmilewitz, D; Okon, E; Karmeli, F

1997-01-01

380

Schisandra chinensis Prevents Alcohol-Induced Fatty Liver Disease in Rats  

PubMed Central

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

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

381

Results and perspectives of the investigation of traditional and thermal stress induced thermophoresis of particles in gas in microgravity  

NASA Astrophysics Data System (ADS)

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.

Vedernikov, Andrei; Balapanov, Daniyar; Beresnev, Sergey; Queeckers, Patrick

382

Radiation-induced cardiovascular diseases: Is the epidemiologic evidence compatible with the radiobiologic data?  

SciTech Connect

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.

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

383

Chemotherapy of East Coast fever: parvaquone treatment of clinical disease induced by isolates of Theileria parva.  

PubMed

Two experiments were carried out in which parvaquone was used to treat experimentally-induced acute clinical East Coast fever infections. In the first experiment, infections with Theileria parva parva (Kiambu 5) were induced by applying infected Rhipicephalus appendiculatus ticks or by inoculation of triturated infected-tick stabilate. The character of the disease was similar with both methods of infection and following a single treatment with parvaquone at 20 mg kg-1, 5 of 7 cattle in each group recovered. All untreated control cattle died. In the second experiment, 5 stabilate isolates from different locations within East Africa, and representative of the challenge likely to be met in the field, were used. Treatment was administered in 2 X 10 mg kg-1 doses 48 h apart. The isolates used were T. p. parva (Mbita), T. p. parva (Pugu), T. p. parva (Entebbe), T. p. lawrencei (Mara) and T. p. lawrencei/(Manyara); following treatment 3/7, 6/6, 6/7, 5/7 and 6/7 animals recovered, respectively. All untreated control cattle died. There was evidence of a difference in susceptibility of isolates to treatment, and some animals showed prolonged disease episodes. The nature of the response to treatment and the problems in treating a lympho-destructive disease are discussed. PMID:6437050

Dolan, T T; Young, A S; Leitch, B L; Stagg, D A

1984-08-01

384

Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease.  

PubMed Central

Activated components of the complement system are potent mediators of inflammation that may play an important role in numerous disease states. For example, they have been implicated in the pathogenesis of inflammatory joint diseases including rheumatoid arthritis (RA). To target complement activation in immune-mediated joint inflammation, we have utilized monoclonal antibodies (mAbs) that inhibit the complement cascade at C5, blocking the generation of the major chemotactic and proinflammatory factors C5a and C5b-9. In this study, we demonstrate the efficacy of a mAb specific for murine C5 in the treatment of collagen-induced arthritis, an animal model for RA. We show that systemic administration of the anti-C5 mAb effectively inhibits terminal complement activation in vivo and prevents the onset of arthritis in immunized animals. Most important, anti-C5 mAb treatment is also highly effective in ameliorating established disease. These results demonstrate a critical role for activated terminal complement components not only in the induction but also in the progression of collagen-induced arthritis and suggest that C5 may be an attractive therapeutic target in RA. Images Fig. 1 Fig. 2 Fig. 4 PMID:7568051

Wang, Y; Rollins, S A; Madri, J A; Matis, L A

1995-01-01

385

Induced sputum-retrieved matrix metalloproteinase 9 and tissue metalloproteinase inhibitor 1 in granulomatous diseases  

PubMed Central

Matrix metalloproteinases (MMPs) capable of degrading various components of connective tissue matrices, and tissue inhibitor metalloproteinases (TIMPs) are considered important in lung parenchymal remodeling and repair processes in pulmonary diseases. Induced sputum (IS) is a reliable noninvasive method to investigate pathogenesis, pathophysiology and treatment of lung disease. This study was designed to determine whether IS-MMP9/TIMP1 levels demonstrate lung parenchymal remodeling in sarcoidosis (SA) and Crohn's disease (CRD) patients. Sputum was induced and processed conventionally in 13 SA patients, 18 CRD patients and 9 controls. Two-hundred cells were counted on Giemsa-stained cytopreps, and T lymphocytes subsets (CD4 = T helper and CD8 = T suppressor cytotoxic cells) were analysed by FACS using monoclonal antibodies.MMP-9 and TIMP-1 were measured using commercial ELISA kits. MMP-9 concentrations, but not those of TIMP-1, were significantly greater in the sputum supernatant in SA and CRD patients compared to controls (P = 0·018 and P = 0·0019, respectively). The molar ratio, MMP-9/TIMP-1, was significantly higher in SA and CRD patients compared to controls (P = 0·008 and P = 0·024, respectively). Gelatinase species having a molecular weight similar to that of MMP-9 were demonstrated by zymographic analysis. MMP-9 levels were highly correlated with the CD4/CD8 ratio and DLCO capacity in SA but less in CRD patients. MMP-9 levels in IS provide a sensitive marker for pulmonary damage. PMID:12390324

Fireman, E; Kraiem, Z; Sade, O; Greif, J; Fireman, Z

2002-01-01

386

Effect of Stem Cell Therapy on Amiodarone Induced Fibrosing Interstitial Lung Disease in Albino Rat  

PubMed Central

Background and Objectives: The fibrosing forms of interstitial lung disease (ILD) are associated with significant morbidity and mortality. ILD may be idiopathic, secondary to occupational, infection, complicate rheumatic diseases or drug induced. Efficacy of antifibrotic agents is as far as, limited and uncertain. No effective treatment was confirmed for pulmonary fibrosis except lung transplantation. The present study aimed at investigating the possible effect of human cord blood mesenchymal stem cell (MSC) therapy on fibrosing ILD. This was accomplished by using amiodarone as a model of induced lung damage in albino rat. Methods and Results: Seventeen adult male albino rats were divided into 3 groups. Rats of amiodarone group were given 30 mg/kg of amiodarone orally 6 days/ week for 6 weeks. Rats of stem cell therapy group were injected with stem cells in the tail vein following confirmation of lung damage and left for 4 weeks before sacrifice. Obstructed bronchioles, thickened interalveolar septa and thickened wall of pulmonary vessels were found and proved morphometrically. Reduced type I pneumocytes and increased area% of collagen fibers were recorded. All findings regressed on stem cell therapy. Conclusions: Cord blood MSC therapy proved definite amelioration of fibrosing interstitial lung disease provided therapy starts early in the development of the pathogenesis. PMID:24298346

Zaglool, Somaya Saad; Zickri, Maha Baligh; Abd El Aziz, Dalia Hussein; Mabrouk, Doaa; Metwally, Hala Gabr

2011-01-01

387

Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease  

PubMed Central

Inflammatory bowel disease (IBD), the most important being Crohn's disease and ulcerative colitis, results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental, and immunological factors are involved. Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses. To investigate the etiology of IBD, animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD. Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described. In this manuscript, we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis (e.g., dextran sodium sulfate-, 2,4,6-trinitrobenzene sulfonic acid-, oxazolone-, acetic acid-, and indomethacin-induced models). We also summarize some regulatory and pathogenic factors demonstrated by these models that can, hopefully, be exploited to develop future therapeutic strategies against IBD. PMID:17948932

Kawada, Mayumi; Arihiro, Atsuko; Mizoguchi, Emiko

2007-01-01

388

Correlation between lipid peroxidation-induced TBARS level and disease severity in obsessive-compulsive disorder.  

PubMed

Oxidative stress is thought to play an important role in several neuropsychiatric diseases including obsessive-compulsive disorder (OCD). Thiobarbituric acid reacting substances (TBARS) are products formed as a result of free radical induced lipid peroxidation in the human body. Our study investigated the correlation between TBARS and the clinical severity of OCD as indicated by the Yale Brown Obsessive Compulsive Scale (YBOCS). Serum TBARS was estimated in thirty nine newly diagnosed drug free OCD patients and thirty three disease free control subjects. Mean values for serum TBARS were found to be significantly higher (P < 0.001) in cases than in controls (5.85 nmol/ml and 3.90 nmol/ml with an SD of 0.56 and 0.81 respectively). A strong positive correlation (rs = 0.757, p < 0.01) between the lipid peroxidation marker TBARS and the disease severity indicator YBOCS was found among cases. Significant positive correlation was also found between TBARS and the obsessive and compulsive subscales of YBOCS. These findings were in tune with previous studies, which suggested oxidative stress induced increased free radical generation in the OCD patients. Our findings may help in understanding the development and progress of OCD and the treatment of patients of OCD in future. PMID:19272303

Chakraborty, Sutirtha; Singh, Om Prakash; Dasgupta, Anindya; Mandal, Nikhiles; Nath Das, Harendra

2009-03-17

389

Key Node Selection for Containing Infectious Disease Spread Using Particle Swarm Optimization  

E-print Network

are alert on the highly contagious disease and make necessary self-protection with masks. The prompt action is shown on evaluating the screening control over train stations in Singapore. The optimization algorithm

Wong, Limsoon

390

Interleukin-35 Induces Regulatory B Cells that Suppress CNS Autoimmune Disease  

PubMed Central

Interleukin 10-producing regulatory B-cells (Breg-cells) suppress autoimmune diseases while aberrant elevation of Breg-cells prevents sterilizing immunity, promotes carcinogenesis and cancer metastasis by converting resting CD4+ T-cells to regulatory T-cells (Tregs). It is therefore of interest to discover factors that induce Breg-cells. Here we show that IL-35 induces Breg-cells in-vivo and promotes their conversion to a unique Breg subset that produces IL-35 (IL-35+Breg). Treatment of mice with IL-35 conferred protection from uveitis and mice lacking IL-35 or defective in IL-35-signaling produced less Breg-cells and developed severe uveitis. Ex-vivo generated Breg-cells also suppressed uveitis by inhibiting pathogenic Th17/Th1 while promoting Tregs expansion. We further show that IL-35 induced the conversion of human B-cells into Breg-cells and suppressed uveitis by activating STAT1/STAT3 through IL-35-Receptor comprising IL-12R?2/IL-27R? subunits. Discovery that IL-35 converts human B-cells into Breg-cells, allows ex-vivo production of autologous Breg-cells for immunotherapy and investigating Breg/IL-35+Breg cells roles in autoimmune diseases and cancer. PMID:24743305

Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M.; Mahdi, Rashid M.; Dolinska, Monika; Sergeey, Yuri V.; Wingfield, Paul T.; Kim, Sung-Hye; Egwuagu, Charles E.

2014-01-01

391

??T cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations.  

PubMed

Most asthma exacerbations are triggered by virus infections, the majority being caused by human rhinoviruses (RV). In mouse models, ??T cells have been previously demonstrated to influence allergen-driven airways hyper-reactivity (AHR) and can have antiviral activity, implicating them as prime candidates in the pathogenesis of asthma exacerbations. To explore this, we have used human and mouse models of experimental RV-induced asthma exacerbations to examine ??T-cell responses and determine their role in the immune response and associated airways disease. In humans, airway ??T-cell numbers were increased in asthmatic vs. healthy control subjects during experimental infection. Airway and blood ??T-cell numbers were associated with increased airways obstruction and AHR. Airway ??T-cell number was also positively correlated with bronchoalveolar lavage (BAL) virus load and BAL eosinophils and lymphocytes during RV infection. Consistent with our observations of RV-induced asthma exacerbations in humans, infection of mice with allergic airways inflammation increased lung ??T-cell number and activation. Inhibiting ??T-cell responses using anti-??TCR (anti-??T-cell receptor) antibody treatment in the mouse asthma exacerbation model increased AHR and airway T helper type 2 cell recruitment and eosinophilia, providing evidence that ??T cells are negative regulators of airways inflammation and disease in RV-induced asthma exacerbations. PMID:23385428

Glanville, N; Message, S D; Walton, R P; Pearson, R M; Parker, H L; Laza-Stanca, V; Mallia, P; Kebadze, T; Contoli, M; Kon, O M; Papi, A; Stanciu, L A; Johnston, S L; Bartlett, N W

2013-11-01

392

Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells.  

PubMed

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

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

393

Search for neutrino-induced particle showers with IceCube-40  

E-print Network

We report on the search for neutrino-induced particle-showers, so-called cascades, in the IceCube-40 detector. The data for this search was collected between April 2008 and May 2009 when the first 40 IceCube strings were deployed and operational. Three complementary searches were performed, each optimized for different energy regimes. The analysis with the lowest energy threshold (2 TeV) targeted atmospheric neutrinos. A total of 67 events were found, consistent with the expectation of 41 atmospheric muons and 30 atmospheric neutrino events. The two other analyses targeted a harder, astrophysical neutrino flux. The analysis with an intermediate threshold of 25 TeV lead to the observation of 14 cascade-like events, again consistent with the prediction of 3.0 atmospheric neutrino and 7.7 atmospheric muon events. We hence set an upper limit of $E^2 \\Phi_{lim} \\leq 7.46\\times10^{-8}\\,\\mathrm{GeV sr^{-1} s^{-1} cm^{-2}}$ (90% C.L.) on the diffuse flux from astrophysical neutrinos of all neutrino flavors, applicabl...

Aartsen, M G; Ackermann, M; Adams, J; Aguilar, J A; Ahlers, M; Altmann, D; Arguelles, C; Arlen, T C; Auffenberg, J; Bai, X; Baker, M; Barwick, S W; Baum, V; Bay, R; Beatty, J J; Tjus, J Becker; Becker, K -H; BenZvi, S; Berghaus, P; Berley, D; Bernardini, E; Bernhard, A; Besson, D Z; Binder, G; Bindig, D; Bissok, M; Blaufuss, E; Blumenthal, J; Boersma, D J; Bohm, C; Bose, D; Böser, S; Botner, O; Brayeur, L; Bretz, H -P; Brown, A M; Bruijn, R; Casey, J; Casier, M; Chirkin, D; Christov, A; Christy, B; Clark, K; Classen, L; Clevermann, F; Coenders, S; Cohen, S; Cowen, D F; Silva, A H Cruz; Danninger, M; Daughhetee, J; Davis, J C; Day, M; de André, J P A M; De Clercq, C; De Ridder, S; Desiati, P; de Vries, K D; de With, M; DeYoung, T; Díaz-Vélez, J C; Dunkman, M; Eagan, R; Eberhardt, B; Eichmann, B; Eisch, J; Euler, S; Evenson, P A; Fadiran, O; Fazely, A R; Fedynitch, A; Feintzeig, J; Feusels, T; Filimonov, K; Finley, C; Fischer-Wasels, T; Flis, S; Franckowiak, A; Frantzen, K; Fuchs, T; Gaisser, T K; Gallagher, J; Gerhardt, L; Gladstone, L; Glüsenkamp, T; Goldschmidt, A; Golup, G; Gonzalez, J G; Goodman, J A; Góra, D; Grandmont, D T; Grant, D; Gretskov, P; Groh, J C; Groß, A; Ha, C; Ismail, A Haj; Hallen, P; Hallgren, A; Halzen, F; Hanson, K; Hebecker, D; Heereman, D; Heinen, D; Helbing, K; Hellauer, R; Hickford, S; Hill, G C; Hoffman, K D; Hoffmann, R; Homeier, A; Hoshina, K; Huang, F; Huelsnitz, W; Hulth, P O; Hultqvist, K; Hussain, S; Ishihara, A; Jacobi, E; Jacobsen, J; Jagielski, K; Japaridze, G S; Jero, K; Jlelati, O; Kaminsky, B; Kappes, A; Karg, T; Karle, A; Kauer, M; Kelley, J L; Kiryluk, J; Kläs, J; Klein, S R; Köhne, J -H; Kohnen, G; Kolanoski, H; Köpke, L; Kopper, C; Kopper, S; Koskinen, D J; Kowalski, M; Krasberg, M; Kriesten, A; Krings, K; Kroll, G; Kunnen, J; Kurahashi, N; Kuwabara, T; Labare, M; Landsman, H; Larson, M J; Lesiak-Bzdak, M; Leuermann, M; Leute, J; Lünemann, J; Macías, O; Madsen, J; Maggi, G; Maruyama, R; Mase, K; Matis, H S; McNally, F; Meagher, K; Merck, M; Meures, T; Miarecki, S; Middell, E; Milke, N; Miller, J; Mohrmann, L; Montaruli, T; Morse, R; Nahnhauer, R; Naumann, U; Niederhausen, H; Nowicki, S C; Nygren, D R; Obertacke, A; Odrowski, S; Olivas, A; Omairat, A; O'Murchadha, A; Palczewski, T; Paul, L; Pepper, J A; Heros, C Pérez de los; Pfendner, C; Pieloth, D; Pinat, E; Posselt, J; Price, P B; Przybylski, G T; Quinnan, M; Rädel, L; Rameez, M; Rawlins, K; Redl, P; Reimann, R; Resconi, E; Rhode, W; Ribordy, M; Richman, M; Riedel, B; Robertson, S; Rodrigues, J P; Rott, C; Ruhe, T; Ruzybayev, B; Ryckbosch, D; Saba, S M; Sander, H -G; Santander, M; Sarkar, S; Schatto, K; Scheriau, F; Schmidt, T; Schmitz, M; Schoenen, S; Schöneberg, S; Schönwald, A; Schukraft, A; Schulte, L; Schulz, O; Seckel, D; Sestayo, Y; Seunarine, S; Shanidze, R; Sheremata, C; Smith, M W E; Soldin, D; Spiczak, G M; Spiering, C; Stamatikos, M; Stanev, T; Stanisha, N A; Stasik, A; Stezelberger, T; Stokstad, R G; Stößl, A; Strahler, E A; Ström, R; Strotjohann, N L; Sullivan, G W; Taavola, H; Taboada, I; Tamburro, A; Tepe, A; Ter-Antonyan, S; Teši?, G; Tilav, S; Toale, P A; Tobin, M N; Toscano, S; Tselengidou, M; Unger, E; Usner, M; Vallecorsa, S; van Eijndhoven, N; Van Overloop, A; van Santen, J; Vehring, M; Voge, M; Vraeghe, M; Walck, C; Waldenmaier, T; Wallraff, M; Weaver, Ch; Wellons, M; Wendt, C; Westerhoff, S; Whelan, B; Whitehorn, N; Wiebe, K; Wiebusch, C H; Williams, D R; Wissing, H; Wolf, M; Wood, T R; Woschnagg, K; Xu, D L; Xu, X W; Yanez, J P; Yodh, G; Yoshida, S; Zarzhitsky, P; Ziemann, J; Zierke, S; Zoll, M

2013-01-01

394

Search for wave-induced particle precipitation from lightning and transmitter sources. Master's thesis  

SciTech Connect

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.

Lundberg, J.E.

1988-01-01

395

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...

396

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...

397

Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by non-invasive imaging  

PubMed Central

Macrophages constitute a major part of the cell response to wear particles produced at articulating and non-articulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by non-invasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/ml UHMWPE suspension, or saline alone. Reporter RAW264.7 macrophages which stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection, and at 2-day intervals. Compared to the non-operated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 ± 0.09, 2.36 ± 0.92, and 10.32 ± 7.61 fold, respectively. The values at same time points for saline injected control group were 1.08 ± 0.07, 1.14 ± 0.27, and 1.14 ± 0.35 fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all post-injection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis. PMID:20213815

Ren, Pei-Gen; Huang, Zhinong; Ma, Ting; Biswal, Sandip; Smith, Robert L.; Goodman, Stuart B.

2010-01-01

398

High sphingomyelin levels induce lysosomal damage and autophagy dysfunction in Niemann Pick disease type A.  

PubMed

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

Gabandé-Rodríguez, E; Boya, P; Labrador, V; Dotti, C G; Ledesma, M D

2014-06-01

399

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

PubMed Central

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

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

400

Prevention of House Dust Mite Induced Allergic Airways Disease in Mice through Immune Tolerance  

PubMed Central

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

Agua-Doce, Ana; Graca, Luis

2011-01-01