Estudio comparativo entre una prueba rápida y RT-PCR tiempo real en el diagnóstico de influenza AH1N1 2009 Comparative study of a rapid testing with real time RT-PCR for diagnosis of influenza AH1N1 2009

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Luz Araceli Castro-Cárdenas

2011-08-01

Full Text Available OBJETIVO: Comparar la prueba QuickVue Influenza A+B empleando como estándar la RT-PCR tiempo real para influenza AH1N1 2009. MATERIAL Y MÉTODOS: Estudio retrospectivo-comparativo de 135 muestras de vías respiratorias de individuos sintomáticos para influenza procesadas de mayo 2009 a octubre 2010.Las pruebas citadas se realizaron simultáneamente. Se utilizó el software Confidence Interval Analysis 2000. RESULTADOS: Sensibilidad 62.96; especificidad 94.44; valor predictivo negativo 62.9; valor predictivo positivo 94.44; razón de probabilidad positiva 11.33 y razón de probabilidad negativa 0.39. Se calcularon intervalos de confianza a 95. DISCUSIÓN: Los valores obtenidos concuerdan con otros estudios donde la sensibilidad fluctúa de 50 a 70 y especificidad entre 90 y 95 por ciento. La prueba QuickVue Influenza A+B es rápida, simple y de menor costo que el RT-PCR tiempo real, útil para identificar el tipo de virus en brotes de influenza de una población determinadaOBJECTIVE: Compare QuickVue Influenza A+B test with real-time RT-PCR for the diagnosis of influenza AH1N1 2009. MATERIAL AND METHODS: Retrospective-comparative study of 135 respiratory specimens from individuals with symptoms of influenza processed from May 2009 to October 2010.The above mentioned tests were performed simultaneously. For statistic analysisthe softwareof Confidence IntervalAnalysis 2000 was used. RESULTS: The parameters obtained were: sensitivity 62.96; specificity 94.44; negative predictive value 62.9; positive predictive value 94.44; positive likelihood ratio 11.33; negative likelihood ratio 0.39. Confidence intervals to 95,were calculated to all of the above data. DISCUSSION: The test QuickVue InfluenzaA+B is a rapid,simple test,with lower cost than real-time RT-PCR useful for identifying the type of virus outbreaks of influenza in a given population.It correlates well with more specific test and similar reports.

Cell lineage in vascularized bone transplantation.

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Willems, Wouter F; Larsen, Mikko; Friedrich, Patricia F; Bishop, Allen T

2014-01-01

The biology behind vascularized bone allotransplantation remains largely unknown. We aim to study cell traffic between donor and recipient following bone auto-, and allografting. Vascularized femoral transplantation was performed with arteriovenous bundle implantation and short-term immunosuppression. Twenty male Piebald Virol Glaxo (PVG; RT1(c) ) rats received isotransplants from female PVG (RT1(c) ) rats and 22 male PVG rats received allografts from female Dark Agouti rats (DA, RT1(a) ), representing a major histocompatibility mismatch. Both groups were randomly analyzed at 4 or 18 weeks. Bone remodeling areas (inner and outer cortical samples) were labeled and laser capture microdissected. Analysis of sex-mismatch genes by real-time reverse transcription-polymerase chain reaction provided the relative Expression Ratio (rER) of donor (female) to recipient (male) cells. The rER was 0.456 ± 0.266 at 4 weeks and 0.749 ± 0.387 at 18 weeks (p = 0.09) in allotransplants. In isotransplants, the rER was 0.412 ± 0.239 and 0.467 ± 0.252 at 4 and 18 weeks, respectively (p = 0.21). At 4 weeks, the rER at the outer cortical area of isotransplants was significantly lower in isotransplants as compared with allotransplants (0.247 ± 0.181 vs. 0.549 ± 0.184, p = 0.007). Cells in the inner and outer cortical bone remodeling areas in isotransplants were mainly donor derived (rER 0.5) at 18 weeks. Applying novel methodology, we describe detailed cell traffic in vascularized bone transplants, elaborating our comprehension on bone transplantation. Copyright © 2013 Wiley Periodicals, Inc.

Cytokines affecting CD4+T regulatory cells in transplant tolerance. II. Interferon gamma (IFN-γ) promotes survival of alloantigen-specific CD4+T regulatory cells.

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Nomura, Masaru; Hodgkinson, Suzanne J; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine; Plain, Karren M; Boyd, Rochelle; Hall, Bruce M

2017-06-01

CD4 + T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4 + T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4 + T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts. If cultures with specific-donor alloantigen are supplemented by supernatant from ConA activated lymphocytes the tolerance transferring cells survive, suggesting these cells depend on cytokines for their survival. In this study, we found addition of rIFN-γ to MLC with specific-donor alloantigen maintained the capacity of tolerant CD4 + T cells to transfer alloantigen-specific tolerance and their ability to suppress PVG allograft rejection mediated by co-administered naïve CD4 + T cells. IFN-γ suppressed the in vitro proliferation of tolerant CD4 + T cells. Tolerant CD4 + CD25 + T cells did not proliferate in MLC to PVG stimulator cells with no cytokine added, but did when IFN-γ was present. IFN-γ did not alter proliferation of tolerant CD4 + CD25 + T cells to third-party Lewis. Tolerant CD4 + CD25 + T cells' expression of IFN-γ receptor (IFNGR) was maintained in culture when IFN-γ was present. This study suggested that IFN-γ maintained tolerance mediating alloantigen-specific CD4 + CD25 + T cells. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Searching for Roots. Pärt: Symphony No. 1, "Polyphonic" / Guy S. Rickards

Index Scriptorium Estoniae

Rickards, Guy S.

1997-01-01

Uuest heliplaadist "Searching for Roots. Pärt: Symphony No. 1, "Polyphonic". Nekrolog, Op. 3; Tubin: Symphony No. 11; Tüür: Searching for Roots. Insula deserta. Zeitraum. Royal Stockholm Philharmonic Orchestra / Paavo Järvi. Virgin Classics VC5 45212-2 (72 min.:DDD)

AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: implications for myocardial differentiation and regional identity.

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Thomas, Penny S; Rajderkar, Sudha; Lane, Jamie; Mishina, Yuji; Kaartinen, Vesa

2014-06-15

BMP signaling plays an essential role in second heart field-derived heart and arterial trunk development, including myocardial differentiation, right ventricular growth, and interventricular, outflow tract and aortico-pulmonary septation. It is mediated by a number of different BMP ligands, and receptors, many of which are present simultaneously. The mechanisms by which they regulate morphogenetic events and degree of redundancy amongst them have still to be elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in anterior second heart field-derived cell development, and compared it with that of BmpR1a. By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1 plays an essential role in arterial pole morphogenesis, identifying defects in outflow tract wall and cushion morphology that preceded a spectrum of septation defects from double outlet right ventricle to common arterial trunk in mutants. Its absence caused dysregulation in gene expression important for myocardial differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2). Although these defects resemble to some degree those in the equivalent Bmpr1a mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1 locus only partially restored septation in Acvr1 mutants. These data show that both BmpR1a and AcvR1 are needed for normal heart development, in which they play some non-redundant roles, and refine our understanding of the genetic and morphogenetic processes underlying Bmp-mediated heart development important in human congenital heart disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Can low-dose irradiation of donor hearts before transplantation inhibit graft vasculopathy?

International Nuclear Information System (INIS)

Shirasawa, Bungo; Hamano, Kimikazu; Ito, Hiroshi; Gohra, Hidenori; Katho, Tomoe; Fujimura, Yoshihiko; Esato, Kensuke

1999-01-01

This experimental study was conducted to histopathologically determine whether the low-dose irradiation of donor hearts before transplantation can inhibit graft vasculopathy. Immediately after donor F 344 rat hearts were removed, they were treated with a single dose of radiation using 7.5 Gy, 15 Gy, or no radiation (control group). The F 344 hearts were transplanted into Lewis rats heterotopically, and cyclosporine A was injected intramuscularly for 20 days after transplantation in all groups. The hearts were harvested 90 days after transplantation, and examined for intimal thickening using elastica van Gieson staining. Severe intimal thickening was observed in both the irradiated groups, the percent intimal area of the coronary arteries was significantly increased in both these groups, to 34.3±12.9 in the 7.5 Gy group and 37.0±8.9 in the 15 Gy group, compared with 23.1±9.8 in the control group (p<0.01). In conclusion, these findings show that low-dose irradiation to donor hearts before transplantation does not inhibit graft vasculopathy. (author)

Development and implementation of the quality control panel of RT-PCR and real-time RT-PCR for avian influenza A (H5N1 surveillance network in mainland China

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Wang Wei

2011-03-01

Full Text Available Abstract Background Reverse transcription PCR (RT-PCR and real time RT-PCR (rRT-PCR have been indispensable methods for influenza surveillance, especially for determination of avian influenza. The movement of testing beyond reference lab introduced the need of quality control, including the implementation of an evaluation system for validating personal training and sample proficiency testing. Methods We developed a panel with lysates of seasonal influenza virus (H1N1, H3N2 and B, serials of diluted H5N1 virus lysates, and in-vitro transcribed H5 hemaglutinin (HA and an artificial gene RNAs for RT-PCR and rRT-PCR quality control assessment. The validations of stability and reproducibility were performed on the panel. Additionally, the panel was implemented to assess the detection capability of Chinese human avian influenza networks. Results The panel has relatively high stability and good reproducibility demonstrated by kappa's tests. In the implementation of panel on Chinese human avian influenza networks, the results suggested that there were a relatively low number of discrepancies for both concise and reproducibility in Chinese avian influenza virus net works. Conclusions A quality control panel of RT-PCR and real-time RT-PCR for avian influenza A (H5N1 surveillance network was developed. An availably statistical data, which are used to assess the detection capability of networks on avian influenza virus (H5N1, can be obtained relatively easily through implementation of the panel on networks.

Grafting and Poisson Structure in (2+1)-Gravity with Vanishing Cosmological Constant

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Meusburger, C.

2006-09-01

We relate the geometrical construction of (2+1)-spacetimes via grafting to phase space and Poisson structure in the Chern-Simons formulation of (2+1)-dimensional gravity with vanishing cosmological constant on manifolds of topology mathbb{R} × S_g, where S g is an orientable two-surface of genus g>1. We show how grafting along simple closed geodesics λ is implemented in the Chern-Simons formalism and derive explicit expressions for its action on the holonomies of general closed curves on S g .We prove that this action is generated via the Poisson bracket by a gauge invariant observable associated to the holonomy of λ. We deduce a symmetry relation between the Poisson brackets of observables associated to the Lorentz and translational components of the holonomies of general closed curves on S g and discuss its physical interpretation. Finally, we relate the action of grafting on the phase space to the action of Dehn twists and show that grafting can be viewed as a Dehn twist with a formal parameter θ satisfying θ2 = 0.

Structural Evolution of the R-T Phase Boundary in KNN-Based Ceramics

KAUST Repository

Lv, Xiang

2017-10-04

Although a rhombohedral-tetragonal (R-T) phase boundary is known to substantially enhance the piezoelectric properties of potassium-sodium niobate ceramics, the structural evolution of the R-T phase boundary itself is still unclear. In this work, the structural evolution of R-T phase boundary from -150 °C to 200 °C is investigated in (0.99-x)K0.5Na0.5Nb1-ySbyO3-0.01CaSnO3-xBi0.5K0.5HfO3 (where x=0~0.05 with y=0.035, and y=0~0.07 with x=0.03) ceramics. Through temperature-dependent powder X-ray diffraction (XRD) patterns and Raman spectra, the structural evolution was determined to be Rhombohedral (R, <-125 °C) → Rhombohedral+Orthorhombic (R+O, -125 °C to 0 °C) → Rhombohedral+Tetragonal (R+T, 0 °C to 150 °C) → dominating Tetragonal (T, 200 °C to Curie temperature (TC)) → Cubic (C, >TC). In addition, the enhanced electrical properties (e.g., a direct piezoelectric coefficient (d33) of ~450±5 pC/N, a conversion piezoelectric coefficient (d33*) of ~580±5 pm/V, an electromechanical coupling factor (kp) of ~0.50±0.02, and TC~250 °C), fatigue-free behavior, and good thermal stability were exhibited by the ceramics possessing the R-T phase boundary. This work improves understanding of the physical mechanism behind the R-T phase boundary in KNN-based ceramics and is an important step towards their adoption in practical applications. This article is protected by copyright. All rights reserved.

TRPC1 expression and distribution in rat hearts

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W. Niu

2009-12-01

Full Text Available Transient receptor potential canonical (TRPC proteins have been identified as a family of plasma membrane calcium-permeable channels. TRPC proteins can be activated by various stimuli and act as cellular sensors in mammals. Stretch-activated ion channels (SACs have been proposed to underlie cardiac mechano-electric feedback (MEF, although the molecular entity of SAC remains unknown. There is evidence suggesting that transient receptor potential canonical 1 (TRPC1 is a stretch-activated ion channel. As a non-selective cation channel, TRPC1 may cause stretch-induced depolarization and arrhythmia and thus may contribute to the MEF of the heart. In this study, we examined the expression patterns of TRPC1 in detail at both the mRNA and protein levels in rat hearts.We isolated total RNA from the left and right atria, and the left and right ventricles, and detected TRPC1 mRNA in these tissues using reverse-transcriptase polymerase chain reaction (RT-PCR. To study the protein localization and targeting, we performed immunohistochemistry and immunofluorescence labeling with the antibody against TRPC1. TRPC1 was detected in the cardiomyocytes of the ventricle and atrium at both the mRNA and protein levels. The cell membrane and Ttubule showed strong fluorescence labeling in the ventricular myocytes. Purkinje cells, the endothelial cells and smooth muscle cells of the coronary arterioles also displayed TRPC1 labeling. No TRPC1 was detected in fibroblasts. In conclusion, TRPC1 is widely expressed in the rat heart, including in working cells, Purkinje cells and vascular cells, suggesting that it plays an important role in the heart. The specific distribution pattern offered a useful insight into its function in adult rat ventricular cells. Further investigations are needed to clarify the role of TRPC1 in regulating cardiac activity, including cardiac MEF.

Effect of donor fasting on survival of pancreas and heart grafts after warm ischemia.

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Nishihara, M; Sumimoto, R; Asahara, T; Fukuda, Y; Southard, J H; Dohi, K

1996-09-01

Livers from fasted animals are believed to be more vulnerable to ischemic injury than those from fed donors. However, we have recently shown the opposite: livers from fasted rats were more tolerant to ischemic injury. Indeed, the survival rate of 60 min warm ischemic damaged livers increased from 0 to 90% if donor rats were fasted for three days. In this study, we examined how donor fasting affects the outcome of pancreas and heart preservation. BN rats were used as both donors and recipients, and recipients of pancreatic grafts were rendered diabetic prior to transplantation. Pancreatic or heart grafts were subjected to 90 min or 25 min of warm ischemia and were transplanted into the right side of the necks of recipients rats. The viability rate of hearts transplanted from fed donors into fed recipients was only about 11% (1/9) after transplantation. However, the viability rate with fasted donors was 75% (6/8). The rate of successful pancreatic grafting from fed donors into fed recipients was 28.6% (2/7), and that from fasted donors to fed recipients was 41.7% (5/12). These results confirm that the nutritional status of the donor is an important factor in the outcome of not only liver, but also pancreas and heart preservation during transplantation, although the effect of fasting on pancreatic graft is marginal.

The effect of reverse triiodothyronine (rT3) treatment on the plasma levels of iodothyronines in growing Japanese quails

International Nuclear Information System (INIS)

Niezgoda, J.; Wronska-Fortuna, D.; Sechman, A.; Bobek, S.; Sowa, J.

1994-01-01

It has been established that 3.3',5-triiodothyronine (T 3 ) acts hipermetabolically, whereas 3'3.5'-triiodothyronine (reverse T 3 , rT 3 ) acts hypometabolically. The normal ratio of T 3 to rT 3 in domestic flows fluctuates around 10. Since the excess of T 3 may promote catabolic processes and lower weight gain, the aim of this experiment was to find the optimal ratio of T 3 :rT 3 in blood plasma which corresponds with the greatest weight gain in Japanese quail. Reverse T 3 was given in drinking water (1 μg rT 3 /ml) for 3, 10, 20 or 30 days. It has been found that T 3 /rT 3 ratio of about 5, after 20 days of rT 3 administration, stimulated the weight gain of Japanese quail of both sexes from 7 to 44% with more pronounced effect in female birds. (author). 26 refs, 4 figs, 1 tab

Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts

Energy Technology Data Exchange (ETDEWEB)

Peng, Yin [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Zhao, Shaomin [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States); School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069 (China); Song, Langying [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Wang, Manyuan [School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069 (China); Jiao, Kai, E-mail: kjiao@uab.edu [Department of Genetics, The University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

2013-11-29

Highlights: •SERTAD1 interacts with SMAD1. •Sertad1 is expressed in mouse embryonic hearts. •SERTAD1 is localized in both cytoplasm and nucleus of cardiomyocytes. •SERTAD1 enhances expression of BMP target cardiogenic genes as a SMAD1 co-activator. -- Abstract: Despite considerable advances in surgical repairing procedures, congenital heart diseases (CHDs) remain the leading noninfectious cause of infant morbidity and mortality. Understanding the molecular/genetic mechanisms underlying normal cardiogenesis will provide essential information for the development of novel diagnostic and therapeutic strategies against CHDs. BMP signaling plays complex roles in multiple cardiogenic processes in mammals. SMAD1 is a canonical nuclear mediator of BMP signaling, the activity of which is critically regulated through its interaction partners. We screened a mouse embryonic heart yeast two-hybrid library using Smad1 as bait and identified SERTAD1 as a novel interaction partner of SMAD1. SERTAD1 contains multiple potential functional domains, including two partially overlapping transactivation domains at the C terminus. The SERTAD1-SMAD1 interaction in vitro and in mammalian cells was further confirmed through biochemical assays. The expression of Sertad1 in developing hearts was demonstrated using RT-PCR, western blotting and in situ hybridization analyses. We also showed that SERTAD1 was localized in both the cytoplasm and nucleus of immortalized cardiomyocytes and primary embryonic cardiomyocyte cultures. The overexpression of SERTAD1 in cardiomyocytes not only enhanced the activity of two BMP reporters in a dose-dependent manner but also increased the expression of several known BMP/SMAD regulatory targets. Therefore, these data suggest that SERTAD1 acts as a SMAD1 transcriptional co-activator to promote the expression of BMP target genes during mouse cardiogenesis.

SheppHeartCABG trial-comprehensive early rehabilitation after coronary artery bypass grafting

DEFF Research Database (Denmark)

Hojskov, Ida Elisabeth; Moons, Philip; Hansen, Niels Viggo

2017-01-01

rehabilitation. The SheppHeartCABG trial will investigate the effect of early comprehensive rehabilitation in early phase rehabilitation versus usual care. The aim of this paper is to present the protocol for the SheppHeartCABG trial. METHODS/ANALYSIS: SheppHeartCABG is an investigator-initiated randomised...... clinical superiority trial with blinded outcome assessment, employing 1:1 central randomisation to rehabilitation plus usual care versus usual care alone. On the basis of a sample size calculation, 326 patients undergoing coronary artery bypass grafting will be included from two clinical sites. All...... patients receive usual care and patients allocated to the experimental intervention follow 4 weeks rehabilitation consisting of an exercise programme, psycho-educative consultations and a compact mindfulness programme. The primary outcome is physical function measured by the 6-min walk test. The secondary...

Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

Science.gov (United States)

Melikian, George L; Rhee, Soo-Yon; Taylor, Jonathan; Fessel, W Jeffrey; Kaufman, David; Towner, William; Troia-Cancio, Paolo V; Zolopa, Andrew; Robbins, Gregory K; Kagan, Ron; Israelski, Dennis; Shafer, Robert W

2012-05-01

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice

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Laurie L. Baggio

2017-11-01

Conclusions: GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.

NASA SPoRT GOES-R Proving Ground Activities

Science.gov (United States)

Stano, Geoffrey T.; Fuell, Kevin K.; Jedloec, Gary J.

2010-01-01

The NASA Short-term Prediction Research and Transition (SPoRT) program is a partner with the GOES-R Proving Ground (PG) helping prepare forecasters understand the unique products to come from the GOES-R instrument suite. SPoRT is working collaboratively with other members of the GOES-R PG team and Algorithm Working Group (AWG) scientists to develop and disseminate a suite of proxy products that address specific forecast problems for the WFOs, Regional and National Support Centers, and other NOAA users. These products draw on SPoRT s expertise with the transition and evaluation of products into operations from the MODIS instrument and the North Alabama Lightning Mapping Array (NALMA). The MODIS instrument serves as an excellent proxy for the Advanced Baseline Imager (ABI) that will be aboard GOES-R. SPoRT has transitioned and evaluated several multi-channel MODIS products. The true and false color products are being used in natural hazard detection by several SPoRT partners to provide better observation of land features, such as fires, smoke plumes, and snow cover. Additionally, many of SPoRT s partners are coastal offices and already benefit from the MODIS sea surface temperature composite. This, along with other surface feature observations will be developed into ABI proxy products for diagnostic use in the forecast process as well as assimilation into forecast models. In addition to the MODIS instrument, the NALMA has proven very valuable to WFOs with access to these total lightning data. These data provide situational awareness and enhanced warning decision making to improve lead times for severe thunderstorm and tornado warnings. One effort by SPoRT scientists includes a lightning threat product to create short-term model forecasts of lightning activity. Additionally, SPoRT is working with the AWG to create GLM proxy data from several of the ground based total lightning networks, such as the NALMA. The evaluation will focus on the vastly improved spatial

Dynamo transformation of the collisional R-T in a weakly ionized ...

Indian Academy of Sciences (India)

where the interstellar neutrals undergo charge exchange collisions with ions in the solar wind [1]. ... regime of magnetically confined torroidal plasma. The author refutes their ... rate ´7К-М µ for the usual collisional R-T is given as. 7К-М g v Дp.

Development and characterization of radioimmunoassay methods for the measurement of iodothyronines (T4, T3 and rT3)

International Nuclear Information System (INIS)

Russo, E.M.K.; Vieira, J.G.H.; Barros Maciel, R.M. de; Fonseca, R.M.G.

1982-01-01

The experience acquired in the development of radioimmunoassay for T 4 , T 3 and rT 3 in unextrated serum is described. Antisera were produced in rabbits using iodothyronines conjugated to bovine serum albumin: the antisera selected provided the development of sensitive and specific radioassay methods. Stable high activity T 3 , T 4 and rT 3 tracers were prepared by iodination of 3,5 T 2 , T 3 and 3,3' T 2 by the chloramine-T method, and purified by column chromatography on Sephadex G25. Binding of those iodothyronines to endogenous serum proteins was blocked by including 8-aniline-1-naphtalene sulphonic acid (ANSA) in the T 4 and T 3 assays and thymerosal in the rT 3 assay. Normal values were defined in 46 healthy euthyroid adults of both sexes: T 4 = 7,1 +- 1,3μg/dl; T 3 = 139 +- 35ng/dl and rT 3 = 18,0 +- 7,9ng/dl. (Author) [pt

CHARACTERIZING THE ROLE OF THE NELL1 GENE IN CARDIOVASCULAR DEVELOPMENT

Energy Technology Data Exchange (ETDEWEB)

Liu, L. Y.; Culiat, C.

2007-01-01

Nell1{sup 6R} is a chemically-induced point mutation in a novel cell-signaling gene, Nell1, which results in truncation of the protein and degradation of the Nell16R transcript. Earlier studies revealed that loss of Nell1 function reduces expression of numerous extracellular matrix (ECM) proteins required for differentiation of bone and cartilage precursor cells, thereby causing severe skull and spinal defects. Since skeletal and cardiovascular development are closely linked biological processes, this research focused on: a) examining Nell16R mutant mice for cardiovascular defects, b) determining Nell1 expression in fetal and adult hearts, and c) establishing how ECM genes affected by Nell1 infl uence heart development. Structural heart defects in Nell16R mutant fetuses were analyzed by heart length and width measurements and standard histological methods (haematoxylin and eosin staining). Nell1 expression was assayed in fetal and adult hearts using reverse transcription polymerase chain reaction (RT-PCR). A comprehensive bioinformatics analysis using public databases (Stanford SOURCE Search, Integrated Cartilage Gene Database, Mouse Genome Informatics, and NCBI UniGene) was undertaken to investigate the relationship between cardiovascular development and each of twentyeight genes affected by Nell1. Nell1-defi cient mice have signifi cantly enlarged hearts (particularly the heart width), dramatically reduced blood fl ow out of the heart and unexpanded lungs. Isolation of total RNAs from hearts of adult (control and heterozygote) and fetal (control and homozygous mutant) mice have been completed and RT-PCR assays are in progress. The bioinformatics analysis showed that the majority of genes with reduced expression in Nell1-defi cient mice are normally expressed in the heart (79%; 22/28), blood vessels (71%; 20/28) and bone marrow (61%; 17/28). Moreover, mouse mutations in seven of these genes (Col15a1, Osf-2, Bmpr1a, Pkd1, Mfge8, Ptger4, Col5a1) manifest

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

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Qin E-de

2010-06-01

Full Text Available Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009 influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis.

Mesenchymal stem cells improve mouse non-heart-beating liver graft survival by inhibiting Kupffer cell apoptosis via TLR4-ERK1/2-Fas/FasL-caspase3 pathway regulation

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Yang Tian

2016-10-01

Full Text Available Abstract Background Liver transplantation is the optimal treatment option for end-stage liver disease, but organ shortages dramatically restrict its application. Donation after cardiac death (DCD is an alternative approach that may expand the donor pool, but it faces challenges such as graft dysfunction, early graft loss, and cholangiopathy. Moreover, DCD liver grafts are no longer eligible for transplantation after their warm ischaemic time exceeds 30 min. Mesenchymal stem cells (MSCs have been proposed as a promising therapy for treatment of certain liver diseases, but the role of MSCs in DCD liver graft function remains elusive. Methods In this study, we established an arterialized mouse non-heart-beating (NHB liver transplantation model, and compared survival rates, cytokine and chemokine expression, histology, and the results of in vitro co-culture experiments in animals with or without MSC infusion. Results MSCs markedly ameliorated NHB liver graft injury and improved survival post-transplantation. Additionally, MSCs suppressed Kupffer cell apoptosis, Th1/Th17 immune responses, chemokine expression, and inflammatory cell infiltration. In vitro, PGE2 secreted by MSCs inhibited Kupffer cell apoptosis via TLR4-ERK1/2-caspase3 pathway regulation. Conclusion Our study uncovers a protective role for MSCs and elucidates the underlying immunomodulatory mechanism in an NHB liver transplantation model. Our results suggest that MSCs are uniquely positioned for use in future clinical studies owing to their ability to protect DCD liver grafts, particularly in patients for whom DCD organs are not an option according to current criteria.

Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

International Nuclear Information System (INIS)

Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

1985-01-01

To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

Development of a novel real-time RT-PCR assay to detect Seneca Valley virus-1 associated with emerging cases of vesicular disease in pigs.

Science.gov (United States)

Fowler, Veronica L; Ransburgh, Russell H; Poulsen, Elizabeth G; Wadsworth, Jemma; King, Donald P; Mioulet, Valerie; Knowles, Nick J; Williamson, Susanna; Liu, Xuming; Anderson, Gary A; Fang, Ying; Bai, Jianfa

2017-01-01

Seneca Valley virus 1 (SVV-1) can cause vesicular disease that is clinically indistinguishable from foot-and-mouth disease, vesicular stomatitis and swine vesicular disease. SVV-1-associated disease has been identified in pigs in several countries, namely USA, Canada, Brazil and China. Diagnostic tests are required to reliably detect this emerging virus, and this report describes the development and evaluation of a novel real-time (r) reverse-transcription (RT) PCR assay (rRT-PCR), targeting the viral polymerase gene (3D) of SVV-1. This new assay detected all historical and contemporary SVV-1 isolates examined (n=8), while no cross-reactivity was observed with nucleic acid templates prepared from other vesicular disease viruses or common swine pathogens. The analytical sensitivity of the rRT-PCR was 0.79 TCID 50 /ml and the limit of detection was equivalent using two different rRT-PCR master-mixes. The performance of the test was further evaluated using pig nasal (n=25) and rectal swab samples (n=25), where concordant results compared to virus sequencing were generated for 43/50 samples. The availability of this assay, will enable laboratories to rapidly detect SVV-1 in cases of vesicular disease in pigs, negated for notifiable diseases, and could enable existing knowledge gaps to be investigated surrounding the natural epidemiology of SVV-1. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of heat shock transcription factor 1(HSF1)-upregulated macrophage in ameliorating pressure overload-induced heart failure in mice.

Science.gov (United States)

Du, Peizhao; Chang, Yaowei; Dai, Fangjie; Wei, Chunyan; Zhang, Qi; Li, Jiming

2018-08-15

In order to explore the role of macrophages in HSF1-mediated alleviation of heart failure, mice model of pressure overload-induced heart failure was established using transverse aortic constriction (TAC). Changes in cardiac function and morphology were studied in TAC and SHAM groups using ultrasonic device, tissue staining, electron microscopy, real-time quantitative polymerase chain reaction (RT-QPCR), and Western blotting. We found that mice in the TAC group showed evidence of impaired cardiac function and aggravation of fibrosis on ultrasonic and histopathological examination when compared to those in the SHAM group. The expressions of HSF1, LC3II/LC3I, Becline-1 and HIF-1, as well as autophagosome formation in TAC group were greater than that in SHAM group. On sub-group analyses in the TAC group, improved cardiac function and alleviation of fibrosis was observed in the HSF1 TG subgroup as compared to that in the wild type subgroup. Expressions of LC3II/LC3I, Becline-1 and HIF-1, too showed an obvious increase; and increased autophagosome formation was observed on electron microscopy. Opposite results were observed in the HSF1 KO subgroup. These results collectively suggest that in the pressure overload heart failure model, HSF1 promoted formation of macrophages by inducing upregulation of HIF-1 expression, through which heart failure was ameliorated. Copyright © 2018 Elsevier B.V. All rights reserved.

Når det er svært at være ung i DK

DEFF Research Database (Denmark)

Nielsen, Jens Christian; Sørensen, Niels Ulrik; Ozmec, Martha Nina

I rapporten Når det er svært at være ung i DK – unges trivsel og mistrivsel i tal offentliggør Center for Ungdomsforskning resultaterne af en stor videnskabelig spørgeskemaundersøgelse om trivsel og mistrivsel blandt 15-24-årige unge i Danmark. Rapporten indgår i det treårige forskningsprojekt Når...... det er svært at være ung i DK, som Center for Ungdomsforskning udfører med støtte fra Egmont Fonden. Rapporten bygger på telefoninterviews med 3.481 unge, der udgør et repræsentativt udsnit af alle 15-24-årige unge i Danmark. I rapporten forfølges de unges trivsel og mistrivsel gennem to spor: 1) Et...

Genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease

Science.gov (United States)

Scott, Robert A.; Freitag, Daniel F.; Li, Li; Chu, Audrey Y.; Surendran, Praveen; Young, Robin; Grarup, Niels; Stancáková, Alena; Chen, Yuning; V.Varga, Tibor; Yaghootkar, Hanieh; Luan, Jian'an; Zhao, Jing Hua; Willems, Sara M.; Wessel, Jennifer; Wang, Shuai; Maruthur, Nisa; Michailidou, Kyriaki; Pirie, Ailith; van der Lee, Sven J.; Gillson, Christopher; Olama, Ali Amin Al; Amouyel, Philippe; Arriola, Larraitz; Arveiler, Dominique; Aviles-Olmos, Iciar; Balkau, Beverley; Barricarte, Aurelio; Barroso, Inês; Garcia, Sara Benlloch; Bis, Joshua C.; Blankenberg, Stefan; Boehnke, Michael; Boeing, Heiner; Boerwinkle, Eric; Borecki, Ingrid B.; Bork-Jensen, Jette; Bowden, Sarah; Caldas, Carlos; Caslake, Muriel; Cupples, L. Adrienne; Cruchaga, Carlos; Czajkowski, Jacek; den Hoed, Marcel; Dunn, Janet A.; Earl, Helena M.; Ehret, Georg B.; Ferrannini, Ele; Ferrieres, Jean; Foltynie, Thomas; Ford, Ian; Forouhi, Nita G.; Gianfagna, Francesco; Gonzalez, Carlos; Grioni, Sara; Hiller, Louise; Jansson, Jan-Håkan; Jørgensen, Marit E.; Jukema, J. Wouter; Kaaks, Rudolf; Kee, Frank; Kerrison, Nicola D.; Key, Timothy J.; Kontto, Jukka; Kote-Jarai, Zsofia; Kraja, Aldi T.; Kuulasmaa, Kari; Kuusisto, Johanna; Linneberg, Allan; Liu, Chunyu; Marenne, Gaëlle; Mohlke, Karen L.; Morris, Andrew P.; Muir, Kenneth; Müller-Nurasyid, Martina; Munroe, Patricia B.; Navarro, Carmen; Nielsen, Sune F.; Nilsson, Peter M.; Nordestgaard, Børge G.; Packard, Chris J.; Palli, Domenico; Panico, Salvatore; Peloso, Gina M.; Perola, Markus; Peters, Annette; Poole, Christopher J.; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Salomaa, Veikko; Sánchez, María-José; Sattar, Naveed; Sharp, Stephen J.; Sims, Rebecca; Slimani, Nadia; Smith, Jennifer A.; Thompson, Deborah J.; Trompet, Stella; Tumino, Rosario; van der A, Daphne L.; van der Schouw, Yvonne T.; Virtamo, Jarmo; Walker, Mark; Walter, Klaudia; Abraham, Jean E.; Amundadottir, Laufey T.; Aponte, Jennifer L.; Butterworth, Adam S.; Dupuis, Josée; Easton, Douglas F.; Eeles, Rosalind A.; Erdmann, Jeanette; Franks, Paul W.; Frayling, Timothy M.; Hansen, Torben; Howson, Joanna M. M.; Jørgensen, Torben; Kooner, Jaspal; Laakso, Markku; Langenberg, Claudia; McCarthy, Mark I.; Pankow, James S.; Pedersen, Oluf; Riboli, Elio; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schunkert, Heribert; Vollenweider, Peter; O'Rahilly, Stephen; Deloukas, Panos; Danesh, John; Goodarzi, Mark O.; Kathiresan, Sekar; Meigs, James B.; Ehm, Margaret G.; Wareham, Nicholas J.; Waterworth, Dawn M.

2016-01-01

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to inform development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in 6 genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing, and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr;rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and lower T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomised controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. PMID:27252175

Exogenous modulation of TGF-β1 influences TGF-βR-III-associated vascularization during wound healing in irradiated tissue

International Nuclear Information System (INIS)

Wehrhan, F.; Schultze-Mosgau, S.; Grabenbauer, G.G.; Roedel, F.; Amann, K.

2004-01-01

Background and purpose: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)β isoforms following surgery in irradiated graft beds. Altered levels of TGF-β 1 are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-β receptor-III (TGF-βR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-β 1 treatment on TGF-βR-III-associated vascularization in the transition area between irradiated graft bed and graft. Material and methods: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n=16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 μg anti-TGF-β 1 into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-βR-III and E-selection expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. Results: A significantly higher expression of TGF-βR-III was seen in the irradiated and anti-TGF-β 1 -treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-βR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-β 1 -treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher

Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease.

Science.gov (United States)

Lu, Qiyu; Sun, Yi; Duan, Yuyin; Li, Bin; Xia, Jianming; Yu, Songhua; Zhang, Guimin

2018-03-16

Valvular heart disease is a leading cause of cardiovascular mortality, especially in China. More than a half of valvular heart diseases are caused by acute rheumatic fever. microRNA is involved in many physiological and pathological processes. However, the miRNA profile of the rheumatic valvular heart disease is unknown. This research is to discuss microRNAs and their target gene pathways involved in rheumatic heart valve disease. Serum miRNA from one healthy individual and four rheumatic heart disease patients were sequenced. Specific differentially expressed miRNAs were quantified by Q-PCR in 40 patients, with 20 low-to-moderate rheumatic mitral valve stenosis patients and 20 severe mitral valve stenosis patients. The target relationship between certain miRNA and predicted target genes were analysis by Luciferase reporter assay. The IL-1β and IL1R1 expression levels were analyzed by immunohistochemistry and western blot in the mitral valve from surgery of mitral valve replacement. The results showed that 13 and 91 miRNAs were commonly upregulated or downregulated in all four patients. Nine miRNAs, 1 upregulated and 8 downregulated, that had a similar fold change in all 4 patients were selected for quantitative PCR verification. The results showed similar results from miRNA sequencing. Within these 9 tested miRNAs, hsa-miR-205-3p and hsa-miR-3909 showed a low degree of dispersion between the members of each group. Hsa miR-205-3p and hsa-miR-3909 were predicted to target the 3'UTR of IL-1β and IL1R1 respectively. This was verified by luciferase reporter assays. Immunohistochemistry and Western blot results showed that the mitral valve from rheumatic valve heart disease showed higher levels of IL- 1β and IL1R1 expression compared with congenital heart valve disease. This suggested a difference between rheumatic heart valve disease and other types of heart valve diseases, with more inflammatory responses in the former. In the present study, by next generation

Quantitation of TGF-beta1 mRNA in porcine mesangial cells by comparative kinetic RT/PCR: comparison with ribonuclease protection assay and in situ hybridization.

Science.gov (United States)

Ceol, M; Forino, M; Gambaro, G; Sauer, U; Schleicher, E D; D'Angelo, A; Anglani, F

2001-01-01

Gene expression can be examined with different techniques including ribonuclease protection assay (RPA), in situ hybridisation (ISH), and quantitative reverse transcription-polymerase chain reaction (RT/PCR). These methods differ considerably in their sensitivity and precision in detecting and quantifying low abundance mRNA. Although there is evidence that RT/PCR can be performed in a quantitative manner, the quantitative capacity of this method is generally underestimated. To demonstrate that the comparative kinetic RT/PCR strategy-which uses a housekeeping gene as internal standard-is a quantitative method to detect significant differences in mRNA levels between different samples, the inhibitory effect of heparin on phorbol 12-myristate 13-acetate (PMA)-induced-TGF-beta1 mRNA expression was evaluated by RT/PCR and RPA, the standard method of mRNA quantification, and the results were compared. The reproducibility of RT/PCR amplification was calculated by comparing the quantity of G3PDH and TGF-beta1 PCR products, generated during the exponential phases, estimated from two different RT/PCR (G3PDH, r = 0.968, P = 0.0000; TGF-beta1, r = 0.966, P = 0.0000). The quantitative capacity of comparative kinetic RT/PCR was demonstrated by comparing the results obtained from RPA and RT/PCR using linear regression analysis. Starting from the same RNA extraction, but using only 1% of the RNA for the RT/PCR compared to RPA, significant correlation was observed (r = 0.984, P = 0.0004). Moreover the morphometric analysis of ISH signal was applied for the semi-quantitative evaluation of the expression and localisation of TGF-beta1 mRNA in the entire cell population. Our results demonstrate the close similarity of the RT/PCR and RPA methods in giving quantitative information on mRNA expression and indicate the possibility to adopt the comparative kinetic RT/PCR as reliable quantitative method of mRNA analysis. Copyright 2001 Wiley-Liss, Inc.

PpRT1: the first complete gypsy-like retrotransposon isolated in Pinus pinaster.

Science.gov (United States)

Rocheta, Margarida; Cordeiro, Jorge; Oliveira, M; Miguel, Célia

2007-02-01

We have isolated and characterized a complete retrotransposon sequence, named PpRT1, from the genome of Pinus pinaster. PpRT1 is 5,966 bp long and is closely related to IFG7 gypsy retrotransposon from Pinus radiata. The long terminal repeats (LTRs) have 333 bp each and show a 5.4% sequence divergence between them. In addition to the characteristic polypurine tract (PPT) and the primer binding site (PBS), PpRT1 carries internal regions with homology to retroviral genes gag and pol. The pol region contains sequence motifs related to the enzymes protease, reverse transcriptase, RNAseH and integrase in the same typical order known for Ty3/gypsy-like retrotransposons. PpRT1 was extended from an EST database sequence indicating that its transcription is occurring in pine tissues. Southern blot analyses indicate however, that PpRT1 is present in a unique or a low number of copies in the P. pinaster genome. The differences in nucleotide sequence found between PpRT1 and IFG7 may explain the strikingly different copy number in the two pine species genome. Based on the homologies observed when comparing LTR region among different gypsy elements we propose that the highly conserved LTR regions may be useful to amplify other retrotransposon sequences of the same or close retrotransposon family.

Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

DEFF Research Database (Denmark)

Dimitrijevic, Ivan; Edvinsson, Lars; Chen, Qingwen

2009-01-01

expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. METHODS: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina...... pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro...

Optimization of cellulose acrylate and grafted 4-vinylpyridine and 1-vinylimidazole synthesis

Directory of Open Access Journals (Sweden)

Bojanić Vaso

2010-01-01

Full Text Available Optimization of cellulose acrylate synthesis by reaction with sodium cellulosate and acryloyl chloride was carried out. Optimal conditions for conducting the synthesis reaction of cellulose acrylate were as follows: the molar ratio of cellulose/potassium-t-butoxide/acryloyl chloride was 1:3:10 and the optimal reaction time was 10 h. On the basis of elemental analysis with optimal conditions for conducting the reaction of cellulose acrylate, the percentage of substitution of glucose units in cellulose Y = 80.7%, and the degree of substitution of cellulose acrylate DS = 2.4 was determined. The grafting reaction of acrylate vinyl monomers onto cellulose in acetonitrile with initiator azoisobutyronitrile (AIBN in a nitrogen atmosphere was performed, by mixing for 5 h at acetonitrile boiling temperature. Radical copolymerization of synthesized cellulose acrylate and 4-vinylpyridine, 1-vinylimidazole, 1-vinyl-2-pyrrolidinone and 9-vinylcarbazole, cellulose-poly-4-vinylpyridine (Cell-PVP, cellulose-poly-1- vinylimidazole (Cell-PVIm and cellulose-poly-1-vinyl-2-pyrrolidinone (Cell-P1V2P and cellulose-poly-9-vinylcarbazole (Cell-P9VK were synthesized. Acrylate cellulose and cellulose grafted copolymers were confirmed by IR spectroscopy, based on elementary analysis and the characteristics of grafted copolymers of cellulose were determined. The mass share of grafted copolymers, X, the relationship of derivative parts/cellulose vinyl group, Z, and the degree of grafting copolymers of cellulose (mass% were determined. In reaction of methyl iodide and cellulose-poly-4-vinylpyridine (Cell-PVP the cellulose-1-methyl-poly-4-vinylpyridine iodide (Cell-1-Me-PVPJ was synthesized. Cellulose acrylate and grafted copolymers were obtained with better thermal, electrochemical and ion-emulation properties for bonding of noble metals Au, Pt, Pd from water solutions. The synthesis optimization of cellulose acrylate was applied as a model for the synthesis of grafted

Optimal temporal windows and dose-reducing strategy for coronary artery bypass graft imaging with 256-slice CT

Energy Technology Data Exchange (ETDEWEB)

Lu, Kun-Mu [Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Shih Lin District, Taipei 111, Taiwan. (China); Lee, Yi-Wei [Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Guan, Yu-Xiang [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Chen, Liang-Kuang [Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Shih Lin District, Taipei 111, Taiwan. (China); School of Medicine, Fu Jen Catholic University, Taipei, Taiwan (China); Law, Wei-Yip, E-mail: m002325@ms.skh.org.tw [Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Shih Lin District, Taipei 111, Taiwan. (China); Su, Chen-Tau, E-mail: m005531@ms.skh.org.tw [Department of Radiology, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Shih Lin District, Taipei 111, Taiwan. (China); School of Medicine, Fu Jen Catholic University, Taipei, Taiwan (China)

2013-12-11

Objective: To determine the optimal image reconstruction windows in the assessment of coronary artery bypass grafts (CABGs) with 256-slice computed tomography (CT), and to assess their associated optimal pulsing windows for electrocardiogram-triggered tube current modulation (ETCM). Methods: We recruited 18 patients (three female; mean age 68.9 years) having mean heart rate (HR) of 66.3 beats per minute (bpm) and a heart rate variability of 1.3 bpm for this study. A total of 36 CABGs with 168 segments were evaluated, including 12 internal mammary artery (33.3%) and 24 saphenous vein grafts (66.7%). We reconstructed 20 data sets in 5%-step through 0–95% of the R–R interval. The image quality of CABGs was assessed by a 5-point scale (1=excellent to 5=non-diagnostic) for each segment (proximal anastomosis, proximal, middle, distal course of graft body, and distal anastomosis). Two reviewers discriminated optimal reconstruction intervals for each CABG segment in each temporal window. Optimal windows for ETCM were also evaluated. Results: The determined optimal systolic and diastolic reconstruction intervals could be divided into 2 groups with threshold HR=68. The determined best reconstruction intervals for low heart rate (HR<68) and high heart rate (HR>68) were 76.0±2.5% and 45.0±0% respectively. Average image quality scores were 1.7±0.6 with good inter-observer agreement (Kappa=0.79). Image quality was significantly better for saphenous vein grafts versus arterial grafts (P<0.001). The recommended windows of ETCM for low HR, high HR and all HR groups were 40–50%, 71–81% and 40–96% of R-R interval, respectively. The corresponding dose savings were about 60.8%, 58.7% and 22.7% in that order. Conclusions: We determined optimal reconstruction intervals and ETCM windows representing a good compromise between radiation and image quality for following bypass surgery using a 256-slice CT.

A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

OpenAIRE

Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

2010-01-01

Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same a...

Data of evolutionary structure change: 1PVDB-2NXWA [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1PVDB-2NXWA 1PVD 2NXW B A SEITLGKYLFERLKQVNVNTVFGLPGDFNLSLLDKIYEV...DAAARYSSTLGVAAVTYGAGAFNMVNAVAGAYAEKSPVVVISGAPGTTEGGL---LLDTQFQVFKEITVAQARLDDPAKAPAEIARVLGAARAQSRPVYLEIPRNMVNAEVE------PVG-DDPAWPVD...indel> 0 1PVD B 1PVD...rmsd> 1.6578389406204224 1 1PVD... B 1PVDB EQHPR-YGGVY

Permanent atrial fibrillation in heart failure patients as another condition with increased reverse triiodothyronine concentration.

Science.gov (United States)

Jakowczuk, Maciej; Zalas, Dominika; Owecki, Maciej

2016-09-01

To fully investigate the thyroid hormonal function in patients with the most common arrhythmia - atrial fibrillation. 120 patients (aged 55-85 yrs) with symptoms of congestive heart failure exacerbation and no other concomitant disorders (inclusion criteria: normal cardiac troponin T at admission and 12 hours after, normal renal, hepatic and respiratory function; exclusion criteria: inflammatory state, history of myocardial infarction). Depending on the presence of permanent atrial fibrillation (PAF), patients were divided into two groups: PAF (34 females, 26 males) and regular sinus heart rhythm (43 females, 17 males), the groups did not differ in terms of heart rate, blood pressure, presence of overt/subclinical thyroid dysfunction, and medical therapy used. In all subjects thyroid stimulating hormone, free thyroxine, free triiodothyronine, reverse triiodothyronine were measured; echocardiography was performed. PAF group showed higher FT4 and rT3 (1.41 vs. 1.27 ng/dl, p=0.0007; 0.61 vs. 0.32 ng/ml, p<0.0001, respectively). With ROC curve analysis the biochemical thyroid related factor of the highest prognostic value for PAF occurrence (with the highest sensitivity and specificity: 77% and 72%, respectively) was rT3 with the cut-off of above 0.3 ng/ml. Also, a positive correlation between rT3 levels and left ventricular posterior wall diameter was observed (Spearman's correlation coefficient 0.33, p=0.0093). PAF is another condition where an increase in rT3 is observed. rT3 concentration above 0.3 ng/ml may be a novel biochemical sign associated with the presence of PAF in patients with chronic heart failure.

Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft's Function and Predict Survival after Liver Transplantation.

Directory of Open Access Journals (Sweden)

Daniele Nicolini

Full Text Available The reduction of insulin-like growth factor 1 (IGF-1 plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT.From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years, and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated.All patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1, and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p65 years or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320 and 30 (r = -0.3894, p = 0.0368 was found. After multivariate analysis, early (within 15 days IGF-1 normalization [Exp(b = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate.IGF-1 postoperative levels are correlated with the graft's quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT.

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

Science.gov (United States)

González-Guerra, José Luis; Castilla-Cortazar, Inma; Aguirre, Gabriel A; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E; García-Villalón, Ángel Luis

2017-01-01

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

Directory of Open Access Journals (Sweden)

José Luis González-Guerra

Full Text Available Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R. In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides; carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation.

Science.gov (United States)

Liu, Qi; Liu, Xing; Gao, Jinlan; Shi, Xiuyan; Hu, Xihua; Wang, Shusen; Luo, Yang

2013-01-01

DOC-1R (deleted in oral cancer-1 related) is a novel putative tumor suppressor. This study investigated DOC-1R antitumor activity and the underlying molecular mechanisms. Cell phenotypes were assessed using flow cytometry, BrdU incorporation and CDK2 kinase assays in DOC-1R overexpressing HeLa cells. In addition, RT-PCR and Western blot assays were used to detect underlying molecular changes in these cells. The interaction between DOC-1R and CDK2 proteins was assayed by GST pull-down and immunoprecipitation-Western blot assays. The data showed that DOC-1R overexpression inhibited G1/S phase transition, DNA replication and suppressed CDK2 activity. Molecularly, DOC-1R inhibited CDK2 expression at the mRNA and protein levels, and there were decreased levels of G1-phase cyclins (cyclin D1 and E) and elevated levels of p21, p27, and p53 proteins. Meanwhile, DOC-1R associated with CDK2 and inhibited CDK2 activation by obstructing its association with cyclin E and A. In conclusion, the antitumor effects of DOC-1R may be mediated by negatively regulating G1 phase progression and G1/S transition through inhibiting CDK2 expression and activation.

Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival.

Science.gov (United States)

Butts, Ryan J; Savage, Andrew J; Nietert, Paul J; Kavarana, Minoo; Moussa, Omar; Burnette, Ali L; Atz, Andrew M

2014-12-01

A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log-rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p HLA matching at the C locus or the DQ locus

Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

Science.gov (United States)

Hughes, Robert N; Hancock, Nicola J

2016-01-01

To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males. Copyright © 2015 Elsevier Inc. All rights reserved.

Costo-efectividad en la detección de influenza H1N1: datos clínicos versus pruebas rápidas Cost-effectiveness in the detection of influenza H1N1: clinical data versus rapid tests

Directory of Open Access Journals (Sweden)

Jorge González-Canudas

2011-01-01

Full Text Available OBJETIVO: Evaluar el desempeño de los datos clínicos y la prueba rápida (PR en el diagnóstico de influenza H1N1, y analizar el costo-beneficio que representa el uso de esta herramienta diagnóstica. MÉTODOS: Se aplicó la PR a pacientes que acudieron a cuatro hospitales en la ciudad de México con sintomatología similar a influenza (SSI durante el período octubre y noviembre de 2009. Se comparó el desempeño diagnóstico de la SSI más la PR contra el de la reacción en cadena de la polimerasa en transcripción reversa en tiempo real (rRT-PCR. La rRT-PCR fue procesada en un laboratorio de referencia y cegado al resultado de la PR. Además, se llevó a cabo una evaluación económica a partir de la cual se estimó el impacto presupuestal relacionado con la utilización de la PR RESULTADOS: Se incluyó a 78 pacientes, de los cuales 39 fueron positivos para influenza H1N1 y 6 para influenza A estacional, de acuerdo al resultado de la rRT-PCR. La SSI mostró una sensibilidad de 96% y una especificidad de 21%, la PR de 76% y 82% y el conjunto de SSI más PR de 96% y 100%, respectivamente. El Cociente de Verosimilitud positivo de la SSI-cefalea fue de 31,5 y el de SSI-odinofagia fue de 330. El uso de PR mostró un ahorro de US$ 12,6 por cada caso sospechoso. CONCLUSIONES: El uso de la PR como auxiliar en el diagnóstico de influenza H1N1 incrementa la certeza y reduce el costo promedio por paciente sospechoso e infectado.OBJECTIVE: Evaluate the performance of clinical data and the rapid influenza diagnostic test (RIDT in diagnosing influenza H1N1, and analyze the cost-benefit of using this diagnostic tool. METHODS: The RIDT was used for patients who came to four hospitals in Mexico City with an influenza-like illness (ILI in October and November 2009. The diagnostic performance of the ILI clinical data and the RIDT was compared to that of the real-time reverse transcription polymerase chain reaction (rRT-PCR test. The rRT-PCR test was

[miR-497 suppresses proliferation of human cervical carcinoma HeLa cells by targeting cyclin E1].

Science.gov (United States)

Han, Jiming; Huo, Manpeng; Mu, Mingtao; Liu, Junjun; Zhang, Jing

2014-06-01

To evaluate the effect of miR-497 on proliferation of human cervical carcinoma HeLa cells and target relationship between miR-497 and cyclin E1 (CCNE1). Pre-miR-497 sequences were synthesized and cloned into pcDNATM6.2-GW to construct recombinant plasmid pcDNATM6.2-GW-pre-miR-497 and identified by real-time quantitative PCR (qRT-PCR). In addition, sequences of the wild-type CCNE1 (WT-CCNE1) and mutant CCNE1 (MT-CCNE1) were respectively cloned into pmirGLO vectors. MTT assay was used to explore the impact of miR-497 on the proliferation of HeLa cells. Furthermore, the target effect of miR-497 on the CCNE1 was identified by dual-luciferase reporter assay system, qRT-PCR and Western blotting. The recombinant plasmids pcDNATM6.2-GW-pre-miR-497 and pmirGLO-WT-CCNE1, pmirGLO-MT-CCNE1 were successfully constructed, and the miR-497 expression level in HeLa cells transfected with pre-miR-497 was significantly higher than that in the neg-miR group (PHeLa cells (PHeLa cells with pre-miR-497 transfection (PHeLa cells transfected with pre-miR-497 (PHeLa cells could suppress cell proliferation by targeting CCNE1.

The RNA binding protein HuR does not interact directly with HIV-1 reverse transcriptase and does not affect reverse transcription in vitro

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Gronenborn Angela M

2010-05-01

Full Text Available Abstract Background Lemay et al recently reported that the RNA binding protein HuR directly interacts with the ribonuclease H (RNase H domain of HIV-1 reverse transcriptase (RT and influences the efficiency of viral reverse transcription (Lemay et al., 2008, Retrovirology 5:47. HuR is a member of the embryonic lethal abnormal vision protein family and contains 3 RNA recognition motifs (RRMs that bind AU-rich elements (AREs. To define the structural determinants of the HuR-RT interaction and to elucidate the mechanism(s by which HuR influences HIV-1 reverse transcription activity in vitro, we cloned and purified full-length HuR as well as three additional protein constructs that contained the N-terminal and internal RRMs, the internal and C-terminal RRMs, or the C-terminal RRM only. Results All four HuR proteins were purified and characterized by biophysical methods. They are well structured and exist as monomers in solution. No direct protein-protein interaction between HuR and HIV-1 RT was detected using NMR titrations with 15N labeled HuR variants or the 15N labeled RNase H domain of HIV-1 RT. Furthermore, HuR did not significantly affect the kinetics of HIV-1 reverse transcription in vitro, even on RNA templates that contain AREs. Conclusions Our results suggest that HuR does not impact HIV-1 replication through a direct protein-protein interaction with the viral RT.

Coronary artery bypass grafting on the beating heart using the Octopus method

NARCIS (Netherlands)

Thijssens, K. M.; Rodrigus, I. E.; Amsel, B. J.; de Hert, S. G.; Moulijn, A. C.

2000-01-01

STUDY OBJECTIVE: To study the usefulness and effectiveness of off-pump coronary bypass grafting with the Octopus heart stabilizing device. METHOD: The files of thirty-one patients undergoing coronary artery bypass with the aid of the Octopus heart stabilizing device between April 1996 and October

Urine and serum microRNA-1 as novel biomarkers for myocardial injury in open-heart surgeries with cardiopulmonary bypass.

Science.gov (United States)

Zhou, Xian; Mao, Anqiong; Wang, Xiaobin; Duan, Xiaoxia; Yao, Yi; Zhang, Chunxiang

2013-01-01

MicroRNA-1 (miR-1) is a cardio-specific/enriched microRNA. Our recent studies have revealed that serum and urine miR-1 could be a novel sensitive biomarker for acute myocardial infarction. Open-heart surgeries with cardiopulmonary bypass (CPB) are often accompanied with surgery injury and CPB-associated injury on the hearts. However, the association of miR-1 and these intra-operative and post-operative cardiac injures is unknown. The objective of this study was to test the hypothesis that urine and serum miR-1 might be a novel biomarker for myocardial injuries in open-heart surgeries with CPB. Serum and urine miR-1 levels in 20 patients with elective mitral valve surgery were measured at pre-surgery, pre-CPB, 60 min post-CBP, and 24h post-CBP. Serum cardiac troponin-I (cTnI) was used as a positive control biomarker for cardiac injury. Compared with these in pre-operative and pre-CPB groups, the levels of miR-1 in serum and urine from patients after open-heart surgeries and CPB were significant increased at all observed time points. A similar pattern of serum cTnI levels and their strong positive correlation with miR-1 levels were identified in these patients. The results suggest that serum and urine miR-1 may be a novel sensitive biomarker for myocardial injury in open-heart surgeries with CPB.

Access to Heart Transplantation: A Proper Analysis of the Competing Risks of Death and Transplantation Is Required to Optimize Graft Allocation.

Science.gov (United States)

Cantrelle, Christelle; Legeai, Camille; Latouche, Aurélien; Tuppin, Philippe; Jasseron, Carine; Sebbag, Laurent; Bastien, Olivier; Dorent, Richard

2017-08-01

Heart allocation systems are usually urgency-based, offering grafts to candidates at high risk of waitlist mortality. In the context of a revision of the heart allocation rules, we determined observed predictors of 1-year waitlist mortality in France, considering the competing risk of transplantation, to determine which candidate subgroups are favored or disadvantaged by the current allocation system. Patients registered on the French heart waitlist between 2010 and 2013 were included. Cox cause-specific hazards and Fine and Gray subdistribution hazards were used to determine candidate characteristics associated with waitlist mortality and access to transplantation. Of the 2053 candidates, 7 variables were associated with 1-year waitlist mortality by the Fine and Gray method including 4 candidate characteristics related to heart failure severity (hospitalization at listing, serum natriuretic peptide level, systolic pulmonary artery pressure, and glomerular filtration rate) and 3 characteristics not associated with heart failure severity but with lower access to transplantation (blood type, age, and body mass index). Observed waitlist mortality for candidates on mechanical circulatory support was like that of others. The heart allocation system strongly modifies the risk of pretransplant mortality related to heart failure severity. An in-depth competing risk analysis is therefore a more appropriate method to evaluate graft allocation systems. This knowledge should help to prioritize candidates in the context of a limited donor pool.

miR-371, miR-138, miR-544, miR-145, and miR-214 could modulate Th1/Th2 balance in asthma through the combinatorial regulation of Runx3.

Science.gov (United States)

Qiu, Yu-Ying; Zhang, Ying-Wei; Qian, Xiu-Fen; Bian, Tao

2017-01-01

Asthma is tightly related to the imbalance of Th1/Th2 cells, and Runx3 plays a pivotal role in the differentiation of T helper cells. The present study aimed to investigate dysregulated microRNAs that may target Runx3 in CD4 + T cells from asthmatic patients and reveal Runx3 function in Th1/Th2 balance regulation. We detected the levels of Th1- and Th2-related cytokines by ELISA and analyzed the differentiation marker gene of T helper cells by qRT-PCR. Results indicated that an imbalance of Th1/Th2 cells was present in our asthmatic subject. Runx3 expression was reduced in the CD4 + T cells from asthmatic patients. Overexpression of Runx3 could restore the Th1/Th2 balance. After performing microRNA microarray assay, we found a series of microRNAs that were considerably altered in the CD4 + T cells from asthmatic patients. Among these upregulated microRNAs, eight microRNAs that may target Runx3 were selected by bioinformatics prediction. Five microRNAs, namely miR-371, miR-138, miR-544, miR-145, and miR-214, were confirmed by qRT-PCR and selected as candidate microRNAs. Luciferase reporter assay showed that these five microRNAs could directly target the 3'-UTR of Runx3. However, only simultaneous inhibition of these five microRNAs could alter the expression of Runx3. Most importantly, only simultaneous inhibition could improve the Th1/Th2 balance. Thus, we suggest that miR-371, miR-138, miR-544, miR-145, and miR-214 can modulate the Th1/Th2 balance in asthma by regulating Runx3 in a combinatorial manner.

Ion exchange fiber by radiation grafting, 1

International Nuclear Information System (INIS)

Fujiwara, Kunio

1990-01-01

Radiation grafting is gaining attention as a method for producing high performance materials. This method can be applied to add functions to existing polymer plastics. The author participated in the research program on the production of ion exchange fiber by radiation grafting and its applicability at the Japan Atomic Energy Research Institute, Takasaki Radiation Chemistry Research Establishment. Consequently, it was clarified that it was possible to introduce the cation exchange group, represented by sulfonic and carboxyl groups, and the anion exchange group, represented by the quarternary ammonium group, to polypropylene fiber available on the market. The ion exchange capacity was able to be controlled by the degree of grafting, i.e. approximately up to 3 meq/g in both strong acid and strong base and approximately up to 5 meq/g in weak acid were obtained. The adsorption performance of ammonia, a representative malodorous substance, was also studied using test cation exchange fiber. The adsorption rate of H type strong acid cation exchange fiber was great, due to the H type having neutral reaction, and the adsorption capacity matched the ion exchange capacity. Although the Cu and Ni types features coordinated adsorption and their adsorption rates were from 1/2 to 1/3 of that of the H type, their adsorption capacities showed increase along with the metal adsorbed. (author)

Appropriate control time constant in relation to characteristics of the baroreflex vascular system in 1/R control of the total artificial heart.

Science.gov (United States)

Mizuta, Sora; Saito, Itsuro; Isoyama, Takashi; Hara, Shintaro; Yurimoto, Terumi; Li, Xinyang; Murakami, Haruka; Ono, Toshiya; Mabuchi, Kunihiko; Abe, Yusuke

2017-09-01

1/R control is a physiological control method of the total artificial heart (TAH) with which long-term survival was obtained with animal experiments. However, 1/R control occasionally diverged in the undulation pump TAH (UPTAH) animal experiment. To improve the control stability of the 1/R control, appropriate control time constant in relation to characteristics of the baroreflex vascular system was investigated with frequency analysis and numerical simulation. In the frequency analysis, data of five goats in which the UPTAH was implanted were analyzed with first Fourier transform technique to examine the vasomotion frequency. The numerical simulation was carried out repeatedly changing baroreflex parameters and control time constant using the elements-expanded Windkessel model. Results of the frequency analysis showed that the 1/R control tended to diverge when very low frequency band that was an indication of the vasomotion frequency was relative high. In numerical simulation, divergence of the 1/R control could be reproduced and the boundary curves between the divergence and convergence of the 1/R control varied depending on the control time constant. These results suggested that the 1/R control tended to be unstable when the TAH recipient had high reflex speed in the baroreflex vascular system. Therefore, the control time constant should be adjusted appropriately with the individual vasomotion frequency.

Characterization of V1R receptor (ora) genes in Lake Victoria cichlids.

Science.gov (United States)

Ota, Tomoki; Nikaido, Masato; Suzuki, Hikoyu; Hagino-Yamagishi, Kimiko; Okada, Norihiro

2012-05-15

Although olfaction could play a crucial role in underwater habitats by allowing fish to sense a variety of nonvolatile chemical signals, the importance of olfaction in species-rich cichlids is still controversial. In particular, examining whether cichlids rely on olfaction for reproduction is of primary interest to understand the mechanisms of speciation. In the present study, we explored the V1R (also known as ora) genes, which are believed to encode reproductive pheromone receptors in fish, in the genomes of Lake Victoria cichlids. By screening a bacterial artificial chromosome library, we identified all six intact V1R genes (V1R1 to V1R6) that have been reported in other teleost fish. Furthermore, RT-PCR and in situ hybridization analyses showed that all of the V1R genes were expressed in the olfactory epithelium, indicating that these receptors are functional in cichlids. These observations indicate that cichlids use V1R-mediated olfaction in some ways for their social behaviors. Copyright © 2012 Elsevier B.V. All rights reserved.

Performance of a commercial assay for the diagnosis of influenza A (H1N1 infection in comparison to the Centers for Disease Control and Prevention protocol of real time RT-PCR

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María G Barbás

2012-03-01

Full Text Available At the time of influenza A (H1N1 emergency, the WHO responded with remarkable speed by releasing guidelines and a protocol for a real-time RT-PCR assay (rRT-PCR. The aim of the present study was to evalúate the performance of the "Real Time Ready Influenza A/H1N1 Detection Set" (June 2009-Roche kit in comparison to the CDC reference rRT-PCR protocol. The overall sensitivity of the Roche assay for detection of the Inf A gene in the presence or absence of the H1 gene was 74.5 %. The sensitivity for detecting samples that were only positive for the Inf A gene (absence of the H1 gene was 53.3 % whereas the sensitivity for H1N1-positive samples (presence of the Inf A gene and any other swine gene was 76.4 %. The specificity of the assay was 97.1 %. A new version of the kit (November 2009 is now available, and a recent evaluation of its performance showed good sensitivity to detect pandemic H1N1 compared to other molecular assays.Durante la pandemia de influenza A (H1N1, la OMS recomendó algoritmos y protocolos de detección del virus mediante RT-PCR en tiempo real. El objetivo del presente estudio fue evaluar el desempeño del equipo que comercializa la empresa Roche, Real Time Ready Influenza A/H1N1 Detection Set (junio de 2009, en comparación con el protocolo de RT-PCR en tiempo real de los CDC. La sensibilidad global del ensayo de Roche para la detección del gen Inf A en presencia o ausencia del gen H1 fue 74,5 %. La sensibilidad para la detección de muestras positivas solo para el gen Inf A (ausencia del gen H1 fue 53,3 % y la sensibilidad para la detección de muestras positivas para H1N1 (presencia del gen Inf A y cualquier otro gen porcino fue 76,4 %. La especificidad fue 97,1 %. Existe una nueva versión del equipo (noviembre 2009 que, según se ha descrito, presenta buena sensibilidad en comparación con otros ensayos moleculares para detectar H1N1 pandémica.

Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

Directory of Open Access Journals (Sweden)

Toshiki Hirakawa

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs, the expression of insulin-like growth factor-1 (IGF1 and IGF1 receptor (IGF1R was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9 was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2 and hypoxia (1% O2. IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

Performance Evaluation of the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit: Comparison with the Roche COBAS® AmpliPrep/COBAS TaqMan® HIV-1 Test Ver.2.0 for Quantification of HIV-1 Viral Load in Indonesia.

Science.gov (United States)

Kosasih, Agus Susanto; Sugiarto, Christine; Hayuanta, Hubertus Hosti; Juhaendi, Runingsih; Setiawan, Lyana

2017-08-08

Measurement of viral load in human immunodeficiency virus type 1 (HIV-1) infected patients is essential for the establishment of a therapeutic strategy. Several assays based on qPCR are available for the measurement of viral load; they differ in sample volume, technology applied, target gene, sensitivity and dynamic range. The Bioneer AccuPower® HIV-1 Quantitative RT-PCR is a novel commercial kit that has not been evaluated for its performance. This study aimed to evaluate the performance of the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit. In total, 288 EDTA plasma samples from the Dharmais Cancer Hospital were analyzed with the Bioneer AccuPower® HIV-1 Quantitative RT-PCR kit and the Roche COBAS? AmpliPrep/COBAS® TaqMan® HIV-1 version 2.0 (CAP/CTM v2.0). The performance of the Bioneer assay was then evaluated against the Roche CAP/CTM v2.0. Overall, there was good agreement between the two assays. The Bioneer assay showed significant linear correlation with CAP/CTM v2.0 (R2=0.963, plaboratories.

High specific radioactivity (1R,2S)-4-[18F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

International Nuclear Information System (INIS)

Langer, Oliver; Valette, Heric; Dolle, Frederic; Halldin, Christer; Loc'h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-01-01

The radiolabeled catecholamine analogue (1R,2S)-6-[ 18 F]fluorometaraminol (6-[ 18 F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[ 18 F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[ 18 F]fluorometaraminol (4-[ 18 F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/μmol). In the present study, we demonstrate in rats that 4-[ 18 F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[ 18 F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[ 18 F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[ 18 F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[ 18 F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[ 18 F]FMR is a promising alternative to 6-[ 18 F]FMR for myocardial neuronal mapping with PET in humans

C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.

Science.gov (United States)

Krijnen, Paul A J; Kupreishvili, Koba; de Vries, Margreet R; Schepers, Abbey; Stooker, Wim; Vonk, Alexander B A; Eijsman, Leon; Van Hinsbergh, Victor W M; Zeerleder, Sacha; Wouters, Diana; van Ham, Marieke; Quax, Paul H A; Niessen, Hans W M

2012-01-01

Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Expanding arch aneurysm causing a "kink" in a Bentall graft and heart failure.

Science.gov (United States)

Al-Mohaissen, Maha A; Skarsgard, Peter; Khoo, Clarence; Virani, Sean A; Munt, Brad; Leipsic, Jonathon; Ignaszewski, Andrew

2012-07-01

Marfan syndrome is associated with a high incidence of aortic root aneurysm and life-threatening aortic dissection. With the successful use of surgical aortic root replacement, dissection-related mortality has been significantly reduced. We present the case of a patient with Marfan syndrome who presented with heart failure secondary to an unusual graft-related complication 14 years after a Bentall procedure. Investigations revealed a supra-aortic stenosis resulting from a kink in the Bentall graft caused by pressure from an expanding aortic arch aneurysm. The patient underwent surgery with improvement in his ejection fraction and heart failure symptoms.

Structural Evolution of the R-T Phase Boundary in KNN-Based Ceramics

KAUST Repository

Lv, Xiang; Wu, Jiagang; Xiao, Dingquan; Zhu, Jianguo; Zhang, Xixiang

2017-01-01

, the structural evolution of R-T phase boundary from -150 °C to 200 °C is investigated in (0.99-x)K0.5Na0.5Nb1-ySbyO3-0.01CaSnO3-xBi0.5K0.5HfO3 (where x=0~0.05 with y=0.035, and y=0~0.07 with x=0.03) ceramics. Through temperature-dependent powder X-ray diffraction

6,6'-(1E,1'E-((1R,2R-1,2-Diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilylethynylphenol

Directory of Open Access Journals (Sweden)

David Díaz Díaz

2013-03-01

Full Text Available Functionalizable salen derivative, 6,6'-(1E,1'E-((1R,2R-1,2-diphenylethane-1,2-diylbis(azan-1-yl-1-ylidenebis(methan-1-yl-1-ylidenebis(2-tert-butyl-4-((trimethylsilyl ethyn-ylphenol (3, was synthesized by condensation between (1R,2R-1,2-diphenylethane-1,2-diamine (2 and 3-tert-butyl-2-hydroxy-5-((trimethylsilylethynyl benzaldehyde (1 under refluxing conditions. The title compound was characterized by 1H-NMR, 13C-NMR, FT-IR, high-resolution mass spectrometry, optical rotation and melting point determination.

Effect Of IGF-1 On Expression Of Gh Receptor, IGF-1, IGF-1 ...

African Journals Online (AJOL)

... and the skin expression of growth hormone receptor (GHR), insulin-like growth factor1 (IGF-1), insulin-like growth factor receptor (IGF- R), KAP3.2 and KAP6-1 mRNA were measured by RT-PCR. The results indicated that IGF-1 could degrade GHR gene expression, have no effect of IGF-1 and IGF-1R gene expression, ...

Graft copolymers of polypropylene films. 1. radiation induced grafting of mixed monomers. Vol. 3

International Nuclear Information System (INIS)

El-Salmawi, K.M.; El-Naggar, A.M.; Said, H.M.; Zahran, A.H.

1996-01-01

Radiation graft copolymerization of co monomer mixtures of acrylic acid (AAC), and styrene (S) onto polypropylene (PP) film by mutual method has been investigated. The effects of different factors that may affect the grafting yield such as inhibitor concentration (Mohr's salt), solvent composition (MeOH and H 2 O), radiation dose and dose rate were considered. It was found that the role of Mohr's salt is very effective when the ratio of AAC in the co monomer mixtures was at lower values. However, the addition of 1.25 Wt% of Mohr's salt reduced the homo polymer formation and enhances the grafting process. Graft copolymerization in presence of solvent mixture composed of methanol and water was found to afford higher grafting than in pure methanol regardless of the composition of the co monomer mixture used. However, the highest degree of grafting was obtained at a solvent composition of 20% H 2 O:80%MeOH and a co monomer mixture of 20%AAC:80%sty. An attempt was made to determine each PAAC and PS fractions in the total graft yield obtained. Two methods of analysis based on using the reactivity ratios reported in literature, elemental analysis and IR spectroscopy. The determination of poly (acrylic acid) and polystyrene fractions by elemental analysis is believed more accurate than these by reactivity ratio. The precise results obtained by elemental analysis with respect to the chemical structure of known polymer prepared under identical conditions. The results obtained by IR measurements go well with that obtained with the reactivity ratio methods. 5 figs., 3 tabs

MicroRNA-124 (MiR-124 Inhibits Cell Proliferation, Metastasis and Invasion in Colorectal Cancer by Downregulating Rho-Associated Protein Kinase 1(ROCK1

Directory of Open Access Journals (Sweden)

Liqing Zhou

2016-05-01

Full Text Available Background/Aims: MiR-124 inhibits neoplastic transformation, cell proliferation, and metastasis and downregulates Rho-associated protein kinase (ROCK1 in Colorectal Cancer (CRC. The aim of this study was to further investigate the roles and interactions of ROCK1 and miR-124 and the effects of knockdown of ROCK1and MiR-124 in human Colorectal Cancer (CRC. Methods: Three Colorectal cancer cell lines (HCT116, HT29 and SW620 and one Human Colonic Mucosa Epithelial cell line (NCM460 were studied. The protein expression of ROCK1 was examined by Western-blot and qRT-PCR were performed to examine the expression levels of ROCK1 mRNA and miR-124. Furthermore, We performed transfection of cancer cell line (SW620 with pre-miR-124(mimics, anti-miR-124(inhibitor, ROCK1 siRNA and the control, then observed the affects of ROCK1 protein expression by westen-blot, cell proliferation by EDU (5-ethynyl-2'deoxyuridine assay and expression levels of ROCK1mRNA by qRT-PCR . A soft agar formation assay, Migration and invasion assays were used to determine the effect of regulation of miR-124 and ROCK1, and survivin on the transformation and invasion capability of colorectal cancer cell. Results: MiR-124 expression was significantly downregulated in CRC cell lines compare to normal (P 0.05. ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (P Conclusions: In conclusion, our results demonstrated that miR-124 not only promoted cancer cell hyperplasia and significantly associated with CRC metastasis and progression, but also downregulated ROCK1 protein expression. More importantly, increased ROCK1 expression or inhibited miR-124 expression may constitute effective new therapeutic strategies for the treatment of renal cancer in the future.

SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

Directory of Open Access Journals (Sweden)

Tao Shen

2014-01-01

Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.

Science.gov (United States)

Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

2004-12-01

Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.

Disruption of CTCF at the miR-125b1 locus in gynecological cancers

International Nuclear Information System (INIS)

Soto-Reyes, Ernesto; Herrera, Luis A; González-Barrios, Rodrigo; Cisneros-Soberanis, Fernanda; Herrera-Goepfert, Roberto; Pérez, Víctor; Cantú, David; Prada, Diddier; Castro, Clementina; Recillas-Targa, Félix

2012-01-01

In cancer cells, transcriptional gene silencing has been associated with genetic and epigenetic defects. The disruption of DNA methylation patterns and covalent histone marks has been associated with cancer development. Until recently, microRNA (miRNA) gene silencing was not well understood. In particular, miR-125b1 has been suggested to be an miRNA with tumor suppressor activity, and it has been shown to be deregulated in various human cancers. In the present study, we evaluated the DNA methylation at the CpG island proximal to the transcription start site of miR-125b1 in cancer cell lines as well as in normal tissues and gynecological tumor samples. In addition, we analyzed the association of CTCF and covalent histone modifications at the miR-125b1 locus. To assess the DNA methylation status of the miR-125b1, genomic DNA was transformed with sodium bisulfite, and then PCR-amplified with modified primers and sequenced. The miR-125b1 gene expression was analyzed by qRT-PCR using U6 as a control for constitutive gene expression. CTCF repressive histone marks abundance was evaluated by chromatin immunoprecipitation assays. The disruption of CTCF in breast cancer cells correlated with the incorporation of repressive histone marks such H3K9me3 and H3K27me3 as well as with aberrant DNA methylation patterns. To determine the effect of DNA methylation at the CpG island of miR-125b1 on the expression of this gene, we performed a qRT-PCR assay. We observed a significant reduction on the expression of miR-125b1 in cancer cells in comparison with controls, suggesting that DNA methylation at the CpG island might reduce miR-125b1 expression. These effects were observed in other gynecological cancers, including ovarian and cervical tumors. A reduction of miR-125b1 expression in cancers, correlated with methylation, repressive histone marks and loss of CTCF binding at the promoter region

High specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

Energy Technology Data Exchange (ETDEWEB)

Langer, Oliver; Valette, Heric; Dolle, Frederic E-mail: dolle@dsvidf.cea.fr; Halldin, Christer; Loc' h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-04-01

The radiolabeled catecholamine analogue (1R,2S)-6-[{sup 18}F]fluorometaraminol (6-[{sup 18}F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[{sup 18}F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/{mu}mol). In the present study, we demonstrate in rats that 4-[{sup 18}F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[{sup 18}F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[{sup 18}F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[{sup 18}F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[{sup 18}F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[{sup 18}F]FMR is a promising alternative to 6-[{sup 18}F]FMR for myocardial neuronal mapping with PET in humans.

Graft copolymers of polypropylene films. 1. radiation induced grafting of mixed monomers. Vol. 3

Energy Technology Data Exchange (ETDEWEB)

El-Salmawi, K M; El-Naggar, A M; Said, H M; Zahran, A H [Radiation Chemistry Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, (Egypt)

1996-03-01

Radiation graft copolymerization of co monomer mixtures of acrylic acid (AAC), and styrene (S) onto polypropylene (PP) film by mutual method has been investigated. The effects of different factors that may affect the grafting yield such as inhibitor concentration (Mohr`s salt), solvent composition (MeOH and H{sub 2} O), radiation dose and dose rate were considered. It was found that the role of Mohr`s salt is very effective when the ratio of AAC in the co monomer mixtures was at lower values. However, the addition of 1.25 Wt% of Mohr`s salt reduced the homo polymer formation and enhances the grafting process. Graft copolymerization in presence of solvent mixture composed of methanol and water was found to afford higher grafting than in pure methanol regardless of the composition of the co monomer mixture used. However, the highest degree of grafting was obtained at a solvent composition of 20% H{sub 2} O:80%MeOH and a co monomer mixture of 20%AAC:80%sty. An attempt was made to determine each PAAC and PS fractions in the total graft yield obtained. Two methods of analysis based on using the reactivity ratios reported in literature, elemental analysis and IR spectroscopy. The determination of poly (acrylic acid) and polystyrene fractions by elemental analysis is believed more accurate than these by reactivity ratio. The precise results obtained by elemental analysis with respect to the chemical structure of known polymer prepared under identical conditions. The results obtained by IR measurements go well with that obtained with the reactivity ratio methods. 5 figs., 3 tabs.

Meniscal allograft transplantation. Part 1: systematic review of graft biology, graft shrinkage, graft extrusion, graft sizing, and graft fixation.

Science.gov (United States)

Samitier, Gonzalo; Alentorn-Geli, Eduard; Taylor, Dean C; Rill, Brian; Lock, Terrence; Moutzouros, Vasilius; Kolowich, Patricia

2015-01-01

To provide a systematic review of the literature regarding five topics in meniscal allograft transplantation: graft biology, shrinkage, extrusion, sizing, and fixation. A systematic literature search was conducted using the PubMed (MEDLINE), ScienceDirect, and EBSCO-CINAHL databases. Articles were classified only in one topic, but information contained could be reported into other topics. Information was classified according to type of study (animal, in vitro human, and in vivo human) and level of evidence (for in vivo human studies). Sixty-two studies were finally included: 30 biology, 3 graft shrinkage, 11 graft extrusion, 17 graft size, and 6 graft fixation (some studies were categorized in more than one topic). These studies corresponded to 22 animal studies, 22 in vitro human studies, and 23 in vivo human studies (7 level II, 10 level III, and 6 level IV). The principal conclusions were as follows: (a) Donor cells decrease after MAT and grafts are repopulated with host cells form synovium; (b) graft preservation alters collagen network (deep freezing) and causes cell apoptosis with loss of viable cells (cryopreservation); (c) graft shrinkage occurs mainly in lyophilized and gamma-irradiated grafts (less with cryopreservation); (d) graft extrusion is common but has no clinical/functional implications; (e) overall, MRI is not superior to plain radiograph for graft sizing; (f) graft width size matching is more important than length size matching; (g) height appears to be the most important factor influencing meniscal size; (h) bone fixation better restores contact mechanics than suture fixation, but there are no differences for pullout strength or functional results; and (i) suture fixation has more risk of graft extrusion compared to bone fixation. Systematic review of level II-IV studies, Level IV.

L'essentiel de la RT 2012 obligations et mise en oeuvre de la réglementation thermique

CERN Document Server

Leblond, Philippe

2004-01-01

Issue du Grenelle de l’environnement, la réglementation thermique 2012 (RT 2012) a pour objectif de limiter les consommations énergétiques des bâtiments et leurs émissions de gaz à effet de serre. Depuis le 1er janvier 2013, tous les dossiers de permis de construire doivent être conformes aux exigences de résultats et de moyens imposées par la RT 2012. Ils devront indiquer notamment : • la valeur de deux coefficients : Bbiomax, le besoin bioclimatique maximal admissible, et Cepmax, la consommation conventionnelle maximale des bâtiments pour les usages en chauffage, ventilation et refroidissement ; • la valeur de la Ticréf, la température conventionnelle intérieure de référence ; • un certain nombre d’exigences de moyens, comme le respect de la surface et l’ouverture minimales des baies, ou l’obligation d’utiliser les énergies renouvelables. Cet ouvrage didactique et complet décrypte les textes de la RT 2012 et fournit sous forme de guide pratique une méthode simple adaptable ...

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

Science.gov (United States)

Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

2013-01-01

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

Table 1. Primer sequences used for real-time qRT-PCR analysis of ...

Indian Academy of Sciences (India)

User

TGTCCCAGTAAACCGCTC. GAATCCAGCACGATACCAGT. Figure 1. Expression analysis of candidate CsActin and CsFbox genes by qRT-PCR in response to 4°C treatment. The y-axis indicates Cq values, and error bars represent standard deviations of the mean values of four replicates. Rt, roots; St, stems; Le, leaves; Fl ...

Fabrication of TiO_2 nanorod assembly grafted rGO (rGO@TiO_2-NR) hybridized flake-like photocatalyst

International Nuclear Information System (INIS)

Lv, Kangle; Fang, Shun; Si, Lingling; Xia, Yang; Ho, Wingkei; Li, Mei

2017-01-01

Highlights: • TiO_2 nanorod assembly grafted with GO hybrid was successfully fabricated. • TiO_2 nanorods can reduce the aggregation of TiO_2 nanoparticles on graphene. • This unique structure facilitates the injection of electron from TiO_2 to graphene. - Abstract: To efficiently separate the photo-generated electron–hole pairs of TiO_2 hybrid, anatase TiO_2 nanorod assembly grafted reduced graphene oxides (rGO@TiO_2-NR) hybrid was successfully fabricated using potassium titanium oxalate (PTO) and graphene oxides (GO) as starting materials and diethylene glycol (DEG) as reductant. The effect of GO content on the structure and photocatalytic activity of rGO@TiO_2-NR composite was systematically studied. Results show that, in the absence of GO, only TiO_2 microsphere assembly is obtained from TiO_2 nanorods. The presence of GO results in the formation of a flake-like TiO_2-nanorod-assembled grafted rGO hybrid. The photocatalytic activity of rGO@TiO_2-NR composite increases first and then decreases with increase in the amount of GO from 0 wt.% to 10 wt.%. The hybridized S4 sample prepared with 4 wt.% GO possesses the highest photocatalytic activity with a constant rate of 0.039 min"−"1 in the photocataytic degradation of Brilliant X-3B dye (X3B); this sample was enhanced more than three times when compared with pure TiO_2 sample (0.012 min"−"1). The enhanced photocatalytic activity of the rGO@TiO_2-NR hybrid was attributed to the strong interaction between TiO_2 nanorods and rGO. The unique hierarchical structure of 1D nanorod assembly TiO_2–rGO flakes facilitates the injection and transfer of photo-generated electrons from TiO_2 to graphene, thus retarding the recombination of electron–hole pairs and enhancing the photocatalytic activity. The enlarged BET surface areas, not only increasing the number of active sites, but also facilitating the adsorption of the dye, and improved light-harvesting ability also contribute to the enhanced photoreactivity

SPoRT's Participation in the GOES-R Proving Ground Activity

Science.gov (United States)

Jedlovec, Gary; Fuell, Kevin; Smith, Matthew; Stano, Geoffrey; Molthan, Andrew

2011-01-01

The next generation geostationary satellite, GOES-R, will carry two new instruments with unique atmospheric and surface observing capabilities, the Advanced Baseline Imager (ABI) and the Geostationary Lightning Mapper (GLM), to study short-term weather processes. The ABI will bring enhanced multispectral observing capabilities with frequent refresh rates for regional and full disk coverage to geostationary orbit to address many existing and new forecast challenges. The GLM will, for the first time, provide the continuous monitoring of total lightning flashes over a hemispherical region from space. NOAA established the GOES-R Proving Ground activity several years ago to demonstrate the new capabilities of these instruments and to prepare forecasters for their day one use. Proving Ground partners work closely with algorithm developers and the end user community to develop and transition proxy data sets representing GOES-R observing capabilities. This close collaboration helps to maximize refine algorithms leading to the delivery of a product that effectively address a forecast challenge. The NASA Short-term Prediction Research and Transition (SPoRT) program has been a participant in the NOAA GOES-R Proving Ground activity by developing and disseminating selected GOES-R proxy products to collaborating WFOs and National Centers. Established in 2002 to demonstrate the weather and forecasting application of real-time EOS measurements, the SPoRT program has grown to be an end-to-end research to operations activity focused on the use of advanced NASA modeling and data assimilation approaches, nowcasting techniques, and unique high-resolution multispectral data from EOS satellites to improve short-term weather forecasts on a regional and local scale. Participation in the Proving Ground activities extends SPoRT s activities and taps its experience and expertise in diagnostic weather analysis, short-term weather forecasting, and the transition of research and experimental

Autoradiography study and SPECT imaging of reporter gene HSV1-tk expression in heart

Energy Technology Data Exchange (ETDEWEB)

Lan Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, 430022 (China)], E-mail: LXL730724@hotmail.com; Liu Ying; He Yong; Wu Tao; Zhang Binqing; Gao Zairong; An Rui [Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, 430022 (China); Zhang Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, Hubei Province, 430022 (China)], E-mail: zhyx1229@163.com

2010-04-15

Aim: To demonstrate the feasibility and optimal conditions of imaging herpes simplex virus 1-thymidine kinase (HSV1-tk) gene transferred into hearts with {sup 131}I-2'-fluoro-2'-deoxy-1-{beta}-D-arabinofuranosyl-5-iodouracil ({sup 131}I-FIAU) using autoradiography (ARG) and single photon emission computed tomography (SPECT) in animal models. Methods: HSV1-tk inserted into adenovirus vector (Ad5-tk) and adenovirus (Ad5-null) was prepared. Rats or rabbits were divided into a study group receiving intramyocardial injection of Ad5-tk, and a control group receiving Ad-null injection. In the study group of rats, two sets of experiments, time-course study and dose-dependence study, were performed. In time-course experiments, rats were injected with {sup 131}I-FIAU on Days 1, 2, 3, 5 and 7, after transfection of 1x10{sup 8} pfu Ad5-tk, to study the feasibility and suitable time course for reporter gene imaging. In dose-dependence study, various titers of Ad5-tk (5x10{sup 8}, 1x10{sup 8}, 5x10{sup 7} and 1x10{sup 7} pfu) were used to determine the threshold and optimal viral titer needed for detection of gene expression. The gamma counts of hearts were measured. The rat myocardium was analyzed by ARG and reverse transcriptase-polymerase chain reaction (RT-PCR). SPECT whole-body planar imaging and cardiac tomographic imaging were performed in the rabbit models. Results: From the ARG images, rats injected with Ad5-tk showed significant {sup 131}I-FIAU activity in the anterolateral wall compared with background signals seen in the control Ad5-null rats. In time-course study, the highest radioactivity in the focal myocardium could be seen on Day 1, and then progressively declined with time. In dose-dependence study, the level of {sup 131}I-FIAU accumulation in the transfected myocardium declined with the decrease of Ad viral titers. From the ARG analysis and gamma counting, the threshold viral titer was 5x10{sup 7} pfu, and the optimal Ad titer was 1x10{sup 8} pfu

Therapeutic effect of 15-deoxyspergualin on acute graft rejection detected by 31P nuclear magnetic resonance spectrography, and its effect on rat heart transplantation

International Nuclear Information System (INIS)

Suzuki, S.; Kanashiro, M.; Watanabe, H.; Amemiya, H.

1988-01-01

We investigated the effect of 15-deoxyspergualin (DSG) on graft rejection, starting administration at the onset of rejection and on the induction of immunologic unresponsiveness. Hearts from WKAH rats were transplanted into the neck of ACI rats. The energy metabolism of the grafted hearts was followed by 31 P nuclear magnetic resonance spectroscopy. The day that energy metabolism started to fall was defined as the onset of rejection, and intraperitoneal administration of DSG was initiated at 5 mg/kg/day for 15 days from this day. The grafted heart arrested in 2 of 10 rats 9 and 11 days after transplantation, respectively, but the remaining 8 recovered from rejection and 5 of them showed evidence of immunologic unresponsiveness. Of 10 rats treated with DSG from the day of transplantation, only 1 rat showed evidence of unresponsiveness. The initiation of DSG treatment from the onset of rejection resulted in a higher percentage of induction of unresponsiveness. Therefore, DSG was considered to specifically inhibit lymphocyte clone expansion at the onset of rejection. Spleen cells obtained from recipients 7-10 days after the end of DSG treatment were administered to syngeneic ACI rats grafted with WKAH hearts. Graft survival was significantly prolonged, but long-term unresponsiveness could not be transferred. However, immunologic unresponsiveness could be adoptively transferred in 3 of 5 rats receiving spleen cells from syngeneic rats that had recovered from rejection after DSG treatment and had acquired long-term unresponsiveness. These results suggest that suppressor cells are resistant to DSG and are spared and participate in the maintenance of immunologic unresponsiveness

Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

Directory of Open Access Journals (Sweden)

Sydney X Lu

Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

The value of research : telling the R&T story

Science.gov (United States)

2009-07-01

The Federal Highway Administration (FHWA) plays a leadership role in shaping and executing a National Research and Technology (R&T) program. The agency also acts as a convener; collaborations with State, industry, and academic partners provide the fo...

Increased diagnostic contribution of heart rate variability at 0.1Hz paced breathing

Czech Academy of Sciences Publication Activity Database

Jurák, Pavel; Halámek, Josef; Somers, V. K.; Nykodým, J.; Leinveber, P.; Fráňa, P.; Eisenberger, M.; Kára, T.

2005-01-01

Roč. 4, č. 1 (2005), s. 95 [World Congress on Heart Disease - New Trends in Research, Diagnosis and Treatment /12./. 16.07.2005-19.07.2005, Vancouver] R&D Projects: GA ČR(CZ) GA102/05/0402 Keywords : paced breathing * HRV * ICD Subject RIV: FS - Medical Facilities ; Equipment

The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

DEFF Research Database (Denmark)

Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael

2007-01-01

The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological...... effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] Ang......II) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains...

Reproductive number and serial interval of the first wave of influenza A(H1N1pdm09 virus in South Africa.

Directory of Open Access Journals (Sweden)

Brett N Archer

Full Text Available Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks. We characterize the transmissibility of influenza A(H1N1pdm09 (hereafter pH1N1 in South Africa during 2009 by estimating the serial interval (SI, the initial effective reproductive number (initial R(t and the temporal variation of R(t.We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value. We apply a likelihood-based method (method 1 for simultaneous estimation of initial R(t and the SI; estimate initial R(t from SI distributions established from prior field studies (method 2; and the Wallinga and Teunis method (method 3 to model the temporal variation of R(t.12,360 confirmed pH1N1 cases were reported in the central registry. During the period of exponential growth of the epidemic (June 21 to August 3, 2009, we simultaneously estimate a mean R(t of 1.47 (95% CI: 1.30-1.72 and mean SI of 2.78 days (95% CI: 1.80-3.75 (method 1. Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases. Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial R(t of 1.43 (95% CI: 1.38-1.49 (method 2. The mean R(t peaked at 2.91 (95% CI: 0.85-2.91 on June 21, as the epidemic commenced, and R(t>1 was sustained until August 22 (method 3.Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa. Estimations using the likelihood-based method are in agreement with field findings.

Changes in heart rate and heart rate variability during transportation of horses by road and air.

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Ohmura, Hajime; Hobo, Seiji; Hiraga, Atsushi; Jones, James H

2012-04-01

To determine the influence of transportation by road and air on heart rate (HR) and HR variability (HRV) in horses. Animals-6 healthy horses. ECG recordings were obtained from horses before (quarantine with stall rest [Q]; 24 hours) and during a journey that included transportation by road (RT; 4.5 hours), waiting on the ground in an air stall (W; 5.5 hours), and transportation by air (AT; 11 hours); HR was determined, and HRV indices of autonomic nervous activity (low-frequency [LF; 0.01 to 0.07 Hz] and high-frequency [HF; 0.07 to 0.6 Hz] power) were calculated. Mean ± SD HRs during Q, RT, W, and AT were 38.9 ± 1.5 beats/min, 41.7 ± 5.6 beats/min, 41.5 ± 4.3 beats/min, and 48.8 ± 5.6 beats/min, respectively; HR during AT was significantly higher than HR during Q. The LF power was significantly higher during Q (3,454 ± 1,087 milliseconds(2)) and AT (3,101 ± 567 milliseconds(2)) than it was during RT (1,824 ± 432 milliseconds(2)) and W (2,072 ± 616 milliseconds(2)). During Q, RT, W, and AT, neither HF powers (range, 509 to 927 milliseconds(2)) nor LF:HF ratios (range, 4.1 to 6.2) differed significantly. The HR during RT was highly correlated with LF power (R(2) = 0.979), and HR during AT was moderately correlated with the LF:HF ratio (R(2) = 0.477). In horses, HR and HRV indices during RT and AT differed, suggesting that exposure to different stressors results in different autonomic nervous influences on HR.

Epidemiology of Human Parechovirus Type1 in Clinical Samples from Children with Gastroenteritis Using RT-PCR

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Dabirmanesh B

2011-03-01

Full Text Available Background and Objectives: Human parechovirus type-1 (HPeV-1 is a genus of picornaviridea with a single stranded positive sense RNA genome. In general it seems to be responsible for more gastrointestinal and respiratory syndromes and less responsible for central nervous system (CNS symptoms. Since there is no accurate information about diagnosis and epidemiology of HPeV-1 in Iran and it is very important to distinguish between viral and bacterial diarrhea to decrease the unnecessary use of antibiotics, this study aimed at rapid detection and epidemiology of HPeV-1 in stool samples from children with gastroenteritis using specific RT-PCR. Methods: Viral RNA was isolated from 472 stool samples from children (under 4 years old with diarrhea; CDNA was prepared and amplified using specific primers from 5′untranslated region (5′ UTR of HPeV-1 genome by nested RT-PCR. Amplified DNA product was electrophoresed on 1% agarose gel and a single band of 265 bp was obtained. Data were analyzed by SPSS software. We also performed a comparison between the cell culture (Vero and RT-PCR method for HPeV1 detection.Results: Out of 472 samples examined during two years, 112 samples were HpeV-1 positive (23.7%. The results showed that the prevalence of this virus was in children under one year (6-12 months old with diarrhea (p=0.036 in spring and autumn (p<0.001. Boys had more positive cases than the girls (p<0.001. Out of 20 samples which were found positive by HPeV1 RT-PCR only three of them showed CPE on Vero Cells after a week.Conclusion: The results revealed that RT-PCR is a more practical and sensitive technique for HPeV-1 detection directly from clinical samples, which is valuable for epidemiology. Also, the rapid detection of HPeV1 by RT-PCR can decrease both the unnecessary use of antibiotics and the costs in clinical practice

Cardiac Bmi1(+) cells contribute to myocardial renewal in the murine adult heart.

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Valiente-Alandi, Iñigo; Albo-Castellanos, Carmen; Herrero, Diego; Arza, Elvira; Garcia-Gomez, Maria; Segovia, José C; Capecchi, Mario; Bernad, Antonio

2015-10-26

The mammalian adult heart maintains a continuous, low cardiomyocyte turnover rate throughout life. Although many cardiac stem cell populations have been studied, the natural source for homeostatic repair has not yet been defined. The Polycomb protein BMI1 is the most representative marker of mouse adult stem cell systems. We have evaluated the relevance and role of cardiac Bmi1 (+) cells in cardiac physiological homeostasis. Bmi1 (CreER/+);Rosa26 (YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy. After tamoxifen (TM) induction, yellow fluorescent protein (YFP) is expressed under the control of Rosa26 regulatory sequences in Bmi1 (+) cells. These cells and their progeny were tracked by FACS, immunofluorescence and RT-qPCR techniques from 5 days to 1 year. FACS analysis of non-cardiomyocyte compartment from TM-induced Bmi1-YFP mice showed a Bmi1 (+)-expressing cardiac progenitor cell (Bmi1-CPC: B-CPC) population, SCA-1 antigen-positive (95.9 ± 0.4 %) that expresses some stemness-associated genes. B-CPC were also able to differentiate in vitro to the three main cardiac lineages. Pulse-chase analysis showed that B-CPC remained quite stable for extended periods (up to 1 year), which suggests that this Bmi1 (+) population contains cardiac progenitors with substantial self-maintenance potential. Specific immunostaining of Bmi1-YFP hearts serial sections 5 days post-TM induction indicated broad distribution of B-CPC, which were detected in variably sized clusters, although no YFP(+) cardiomyocytes (CM) were detected at this time. Between 2 to 12 months after TM induction, YFP(+) CM were clearly identified (3 ± 0.6 % to 6.7 ± 1.3 %) by immunohistochemistry of serial sections and by flow cytometry of total freshly isolated CM. B-CPC also contributed to endothelial and smooth muscle (SM) lineages in vivo. High Bmi1 expression identifies a non-cardiomyocyte resident cardiac population (B-CPC) that contributes to the main lineages of the heart in

Initial mass function in R-associations CMaR1, Mon R1 and Mon R2 from radiodata

International Nuclear Information System (INIS)

Pyatunina, T.B.

1985-01-01

Results of search for compact radiosources in R-associations CMa R1 and Mon R1 carried out with the radiotelescope RATAN-600 at the 7.6-cm wavelength are given. The number of sources found in the association Mon R1 is approximately equal to the expected number of background extragalactic radiosources. In the association CMa R1 seven radiosources of small angular diameter with the flux greater than 30 mJy are found, two of which probably are background sources. A comparison of optical and radiodata on the association CMa R1 and previously published data on the association Mon R2 make it possible to estimate the initial mass function for associations under study: xi(M) infinity Msup(-2.7+-0.7) for stars with M approximately 10Msub(Sun)

Used mixed oxide fuel reprocessing at RT-1 plant

Energy Technology Data Exchange (ETDEWEB)

Kolupaev, D.; Logunov, M.; Mashkin, A.; Bugrov, K.; Korchenkin, K. [FSUE PA ' Mayak' , 30, Lenins str, Ozersk, 460065 (Russian Federation); Shadrin, A.; Dvoeglazov, K. [ITCP ' PRORYV' , 2/8 Malaya Krasmoselskay str, Moscow, 107140 (Russian Federation)

2016-07-01

Reprocessing of the mixed uranium-plutonium spent nuclear fuel of the BN-600 reactor was performed at the RT-1 plant twice, in 2012 and 2014. In total, 8 fuel assemblies with a burn-up from 73 to 89 GW day/t and the cooling time from 17 to 21 years were reprocessed. The reprocessing included the stages of dissolution, clarification, extraction separation of U and Pu with purification from the fission products, refining of uranium and plutonium at the relevant refining cycles. Dissolution of the fuel composition of MOX used nuclear fuel (UNF) in nitric acid solutions in the presence of fluoride ion has occurred with the full transfer of actinides into solution. Due to the high content of Pu extraction separation of U and Pu was carried out on a nuclear-safe equipment designed for the reprocessing of highly enriched U spent nuclear fuel and Pu refining. Technological processes of extraction, separation and refining of actinides proceeded without deviations from the normal mode. The output flow of the extraction outlets in their compositions corresponded to the regulatory norms and remained at the level of the compositions of the streams resulting from the reprocessing of fuel types typical for the RT-1 plant. No increased losses of Pu into waste have been registered during the reprocessing of BN-600 MOX UNF an compare with VVER-440 uranium UNF reprocessing. (authors)

Investigating perioperative heart migration during robot-assisted coronary artery bypass grafting interventions.

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Linte, Cristian A; Cho, Daniel S; Wedlake, Chris; Moore, John; Chen, Elvis; Bainbridge, Daniel; Patel, Rajni; Peters, Terry; Kiaii, Bob B

2011-09-01

: For robot-assisted coronary artery bypass graft interventions, surgeons typically use a preoperative thoracic computed tomography scan of the patient to plan the procedure. However, the cardiac anatomy is prone to changes induced perioperatively in the effort to access the heart and surgical targets, which, in turn, may invalidate the initial plan. This article presents a method to estimate the perioperative heart migration, information which can be further exploited to refine the preoperative surgical plan. : Tracked transesophageal ultrasound images of four patients' hearts were acquired at each stage in the procedure: before lung deflation, after lung deflation, and after both lung deflation and CO2 thoracic insufflation. Anatomic features of interest-the mitral and aortic valves-were identified from each dataset, and their movement between the different procedure stages was recorded and used to estimate the global heart displacement. Moreover, the local morphology of the features of interest was investigated to provide insight on the extent of the deformation the heart has undergone during the workflow. : The study suggested that the heart does undergo substantial displacement-on the order of 10 to 15 mm in each direction (axial, coronal, and sagittal) after lung deflation and CO2 thoracic insufflation. However, no significant differences (P > 0.1) were observed in the morphologic characteristics of the features of interest across the multiple workflow stages, suggesting that local deformations occur at a much smaller scale compared with the global migration. : The quantification of the perioperatively induced changes is critical to track the displacement of the heart and surgical targets. The recorded migration patterns should not be ignored but rather be used to update the surgical plan to better suit the intraoperative environment.

GOES-R Proving Ground Activities at the NASA Short-Term Prediction Research and Transition (SPoRT) Center

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Molthan, Andrew

2011-01-01

SPoRT is actively involved in GOES-R Proving Ground activities in a number of ways: (1) Applying the paradigm of product development, user training, and interaction to foster interaction with end users at NOAA forecast offices national centers. (2) Providing unique capabilities in collaboration with other GOES-R Proving Ground partners (a) Hybrid GOES-MODIS imagery (b) Pseudo-GLM via regional lightning mapping arrays (c) Developing new RGB imagery from EUMETSAT guidelines

Inhibition of EGFR or IGF-1R signaling enhances radiation response in head and neck cancer models but concurrent inhibition has no added benefit

International Nuclear Information System (INIS)

Raju, Uma; Molkentine, David P; Valdecanas, David R; Deorukhkar, Amit; Mason, Kathryn A; Buchholz, Thomas A; Meyn, Raymond E; Ang, Kie-Kian; Skinner, Heath

2015-01-01

Interaction between the epidermal growth factor receptor (EGFR) and the insulin-like growth factor receptor (IGF-1R) has been well established in many cancer types. We investigated the effects of cetuximab (EGFR antibody) and IMC-A12 (IGF-1R antibody) on the response of head and neck squamous cell carcinoma (HNSCC) to radiation therapy (RT). The effects of cetuximab and IMC-A12 on cell viability and radiosensitivity were determined by clonogenic cell survival assay. Formation of nuclear γ-H2AX and 53BP1 foci was monitored by immunofluorescence. Alterations in target signaling were analyzed by Western blots. In vivo tumor growth delay assay was performed to determine the efficacy of triple therapy with IMC-A12, cetuximab, and RT. In vitro data showed that cetuximab differentially affected the survival and the radiosensitivity of HNSCC cells. Cetuximab suppressed DNA repair that was evident by the prolonged presence of nuclear γ-H2AX and 53BP1 foci. IMC-A12 did not have any effect on the cell survival. However, it increased the radiosensitivity of one of the cell lines. EGFR inhibition increased IGF-1R expression levels and also the association between EGFR and IGF-1R. Addition of IMC-A12 to cetuximab did not increase the radiosensitivity of these cells. Tumor xenografts exhibited enhanced response to RT in the presence of either cetuximab or IMC-A12. Concurrent treatment regimen failed to further enhance the tumor response to cetuximab and/or RT. Taken together our data suggest that concomitant inhibition of both EGFR and IGF-1R pathways did not yield additional therapeutic benefit in overcoming resistance to RT

Significance of changes of levels of plasma proBNP1-76 in patients with chronic pulmonary heart disease

International Nuclear Information System (INIS)

Li Guizhong; Xu Hua; Cao Jun; Jiang Wei; Pang Yongzheng; Tang Chaoshu

2003-01-01

Objective: To investigate the significance of the changes levels of plasma proBNP 1-76 in patients with COPD and chronic pulmonary heart disease. Methods: Plasma proBNP 1-76 levels were determined with radioimmunoassay in patients with CHPD (n=23), COPD (n=24) and 32 controls. Results: The concentrations of plasma proBNP 1-76 in patients with chronic obstructive pulmonary disease were significantly increased (vs controls, p 1-76 (r=0.541, p 1-76 , right inferior pulmonary artery diameter, right ventricle out flow tract diameter and right ventricle anterior wall thickness in patients with chronic pulmonary heart disease were increased significantly (vs COPD patients and controls, p 1-76 (r=0.477, p 1-76 is an early marker of right ventricular hypertrophy and right ventricular dysfunction, measurement of which is useful in the management of patients with chronic pulmonary heart disease in daily practice

The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through IGF1R-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets

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Hu, Wei-Syun; Ting, Wei-Jen; Chiang, Wen-Dee; Pai, Peiying; Yeh, Yu-Lan; Chang, Chung-Ho; Lin, Wan-Teng; Huang, Chih-Yang

2015-01-01

The prevalence of obesity is high in older adults. Alcalase potato protein hydrolysate (APPH), a nutraceutical food, might have greater benefits and be more economical than hypolipidemic drugs. In this study, serum lipid profiles and heart protective effects were evaluated in high fat diet (HFD) induced hyperlipidemia in aging rats treated with APPH (15, 45 and 75 mg/kg/day) and probucol (500 mg/kg/day). APPH treatments reduced serum triacylglycerol (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels to the normal levels expressed in the control group. Additionally, the IGF1R-PI3K-Akt survival pathway was reactivated, and Fas-FADD (Fas-associated death domain) induced apoptosis was inhibited by APPH treatments (15 and 45 mg/kg/day) in HFD aging rat hearts. APPH (75 mg/kg/day) rather than probucol (500 mg/kg/day) treatment could reduce serum lipids without affecting HDL expression. The heart protective effect of APPH in aging rats with hyperlipidemia was through lowering serum lipids and enhancing the activation of the compensatory IGF1R-PI3K-Akt survival pathway. PMID:25950762

Amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole

International Nuclear Information System (INIS)

Saidov, D.K.; Rakhmonov, R.O.; Khodzhiboev, Yu.; Kukaniev, M.A.; Bandaev, S.

2015-01-01

Present article is devoted to amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole. The reaction of new modifications of derivatives of imidazo-[2.1-B]-1.3.4-thiadiazoles-2-bromine-6-p-bromophenyl and 2-alkyl alkylene sulfonyl-6-phenyl imidazo--[2.1-B]-1.3.4-thiadiazole on Mannich with secondary and heterocyclic amines was studied.

Future of the reprocessing business at the RT-1 plant

International Nuclear Information System (INIS)

Bukharin, O.

1995-01-01

Economic viability of reprocessing operations at the RT-1 plant is provided by the contracts with nuclear utilities from Finland and Hungary. Finland will stop sending fuel to Mayak for reprocessing after 1996. Hungary will be capable to resolve the problem of spent fuel domestically some time in the future. This increases vulnerability of the reprocessing business at Mayak to future political uncertainties. (author)

A new beating-heart off-pump coronary artery bypass grafting training model

NARCIS (Netherlands)

Bouma, Wobbe; Kuijpers, Michiel; Bijleveld, Aanke; De Maat, Gijs E.; Koene, Bart M.; Erasmus, Michiel E.; Natour, Ehsan; Mariani, Massimo A.

OBJECTIVES: Training models are essential in mastering the skills required for off-pump coronary artery bypass grafting (OPCAB). We describe a new, high-fidelity, effective and reproducible beating-heart OPCAB training model in human cadavers. METHODS: Human cadavers were embalmed according to the

Molecular characterization of the Jatropha curcas JcR1MYB1 gene encoding a putative R1-MYB transcription factor

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Hui-Liang Li

2014-09-01

Full Text Available The cDNA encoding the R1-MYB transcription factor, designated as JcR1MYB1, was isolated from Jatropha curcas using rapid amplification of cDNA ends. JcR1MYB1 contains a 951 bp open reading frame that encodes 316 amino acids. The deduced JcR1MYB1 protein was predicted to possess the conserved, 56-amino acid-long DNA-binding domain, which consists of a single helix-turn-helix module and usually occurs in R1-MYBs. JcR1MYB1 is a member of the R1-MYB transcription factor subfamily. A subcellular localization study confirmed the nuclear localization of JcR1MYB1. Expression analysis showed that JcR1MYB1 transcripts accumulated in various examined tissues, with high expression levels in the root and low levels in the stem. JcR1MYB1 transcription was up-regulated by polyethylene glycol, NaCl, and cold treatments, as well as by abscisic acid, jasmonic acid, and ethylene treatment. Analysis of transgenic tobacco plants over-expressing JcR1MYB1 indicates an inportant function for this gene in salt stress.

Divergent Requirements for EZH1 in Heart Development Versus Regeneration.

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Ai, Shanshan; Yu, Xianhong; Li, Yumei; Peng, Yong; Li, Chen; Yue, Yanzhu; Tao, Ge; Li, Chuanyun; Pu, William T; He, Aibin

2017-07-07

Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Heart development was normal in Ezh1 -/- ( Ezh 1 knockout) and Ezh2 f/f ::cTNT -Cre ( Ezh 2 knockout) embryos. Ablation of both genes in Ezh1 -/- ::Ezh2 f/f ::cTNT -Cre embryos caused lethal heart malformations, including hypertrabeculation, compact myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome profiling showed that derepressed genes were upregulated in a manner consistent with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2 was dispensable. This finding was further supported by rescue experiments: cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal heart regeneration in Ezh 1 knockout. In myocardial infarction performed outside of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1 occupied and activated genes related to cardiac growth. Our work unravels divergent mechanisms of EZH1 in heart development and regeneration, which will empower efforts to overcome epigenetic barriers to heart regeneration. © 2017 American Heart Association, Inc.

Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart.

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Simon R Foster

Full Text Available G protein-coupled receptors (GPCRs are critical for cardiovascular physiology. Cardiac cells express >100 nonchemosensory GPCRs, indicating that important physiological and potential therapeutic targets remain to be discovered. Moreover, there is a growing appreciation that members of the large, distinct taste and odorant GPCR families have specific functions in tissues beyond the oronasal cavity, including in the brain, gastrointestinal tract and respiratory system. To date, these chemosensory GPCRs have not been systematically studied in the heart. We performed RT-qPCR taste receptor screens in rodent and human heart tissues that revealed discrete subsets of type 2 taste receptors (TAS2/Tas2 as well as Tas1r1 and Tas1r3 (comprising the umami receptor are expressed. These taste GPCRs are present in cultured cardiac myocytes and fibroblasts, and by in situ hybridization can be visualized across the myocardium in isolated cardiac cells. Tas1r1 gene-targeted mice (Tas1r1(Cre/Rosa26(tdRFP strikingly recapitulated these data. In vivo taste receptor expression levels were developmentally regulated in the postnatal period. Intriguingly, several Tas2rs were upregulated in cultured rat myocytes and in mouse heart in vivo following starvation. The discovery of taste GPCRs in the heart opens an exciting new field of cardiac research. We predict that these taste receptors may function as nutrient sensors in the heart.

Epidemiology of Human Parechovirus Type1 in Clinical Samples from Children with Gastroenteritis Using RT-PCR

Directory of Open Access Journals (Sweden)

F Ghazi

2012-05-01

Full Text Available

Background and Objectives: Human parechovirus type-1 (HPeV-1 is a genus of picornaviridea with a single stranded positive sense RNA genome. In general it seems to be responsible for more gastrointestinal and respiratory syndromes and less responsible for central nervous system (CNS symptoms. Since there is no accurate information about diagnosis and epidemiology of HPeV-1 in Iran and it is very important to distinguish between viral and bacterial diarrhea to decrease the unnecessary use of antibiotics, this study aimed at rapid detection and epidemiology of HPeV-1 in stool samples from children with gastroenteritis using specific RT-PCR.

Methods: Viral RNA was isolated from 472 stool samples from children (under 4 years old with diarrhea; CDNA was prepared and amplified using specific primers from 5^′untranslated region (5^′ UTR of HPeV-1 genome by nested RT-PCR. Amplified DNA product was electrophoresed on 1% agarose gel and a single band of 265 bp was obtained. Data were analyzed by SPSS software. We also performed a comparison between the cell culture (Vero and RT-PCR method for HPeV1 detection.

Results: Out of 472 samples examined during two years, 112 samples were HpeV-1 positive (23.7%. The results showed that the prevalence of this virus was in children under one year (6-12 months old with diarrhea (p=0.036 in spring and autumn (p<0.001. Boys had more positive cases than the girls (p<0.001. Out of 20 samples which were found positive by HPeV1 RT-PCR only three of them showed CPE on Vero Cells after a week.

Conclusion: The results revealed that RT-PCR is a more practical and sensitive technique for HPeV-1 detection directly from clinical samples, which is valuable for epidemiology. Also, the rapid

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

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Pedersen Niels C

2007-04-01

Full Text Available Abstract Background We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251 mutants with a K65R mutation in reverse transcriptase (RT, and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later. Results The early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. Conclusion This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be

Fabrication of TiO2 nanorod assembly grafted rGO (rGO@TiO2-NR) hybridized flake-like photocatalyst

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Lv, Kangle; Fang, Shun; Si, Lingling; Xia, Yang; Ho, Wingkei; Li, Mei

2017-01-01

To efficiently separate the photo-generated electron-hole pairs of TiO2 hybrid, anatase TiO2 nanorod assembly grafted reduced graphene oxides (rGO@TiO2-NR) hybrid was successfully fabricated using potassium titanium oxalate (PTO) and graphene oxides (GO) as starting materials and diethylene glycol (DEG) as reductant. The effect of GO content on the structure and photocatalytic activity of rGO@TiO2-NR composite was systematically studied. Results show that, in the absence of GO, only TiO2 microsphere assembly is obtained from TiO2 nanorods. The presence of GO results in the formation of a flake-like TiO2-nanorod-assembled grafted rGO hybrid. The photocatalytic activity of rGO@TiO2-NR composite increases first and then decreases with increase in the amount of GO from 0 wt.% to 10 wt.%. The hybridized S4 sample prepared with 4 wt.% GO possesses the highest photocatalytic activity with a constant rate of 0.039 min-1 in the photocataytic degradation of Brilliant X-3B dye (X3B); this sample was enhanced more than three times when compared with pure TiO2 sample (0.012 min-1). The enhanced photocatalytic activity of the rGO@TiO2-NR hybrid was attributed to the strong interaction between TiO2 nanorods and rGO. The unique hierarchical structure of 1D nanorod assembly TiO2-rGO flakes facilitates the injection and transfer of photo-generated electrons from TiO2 to graphene, thus retarding the recombination of electron-hole pairs and enhancing the photocatalytic activity. The enlarged BET surface areas, not only increasing the number of active sites, but also facilitating the adsorption of the dye, and improved light-harvesting ability also contribute to the enhanced photoreactivity of rGO@TiO2-NR hybrid.

Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

Science.gov (United States)

Zhao, Qiang; Zhu, Yunpeng; Xu, Zhiyun; Cheng, Zhaoyun; Mei, Ju; Chen, Xin; Wang, Xiaowei

2018-04-24

The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown. To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG. Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation. Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography. Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with

The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through IGF1R-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets

Directory of Open Access Journals (Sweden)

Wei-Syun Hu

2015-05-01

Full Text Available The prevalence of obesity is high in older adults. Alcalase potato protein hydrolysate (APPH, a nutraceutical food, might have greater benefits and be more economical than hypolipidemic drugs. In this study, serum lipid profiles and heart protective effects were evaluated in high fat diet (HFD induced hyperlipidemia in aging rats treated with APPH (15, 45 and 75 mg/kg/day and probucol (500 mg/kg/day. APPH treatments reduced serum triacylglycerol (TG, total cholesterol (TC, and low density lipoprotein (LDL levels to the normal levels expressed in the control group. Additionally, the IGF1R-PI3K-Akt survival pathway was reactivated, and Fas-FADD (Fas-associated death domain induced apoptosis was inhibited by APPH treatments (15 and 45 mg/kg/day in HFD aging rat hearts. APPH (75 mg/kg/day rather than probucol (500 mg/kg/day treatment could reduce serum lipids without affecting HDL expression. The heart protective effect of APPH in aging rats with hyperlipidemia was through lowering serum lipids and enhancing the activation of the compensatory IGF1R-PI3K-Akt survival pathway.

Early physical training and psycho-educational intervention for patients undergoing coronary artery bypass grafting. The SheppHeart randomized 2 × 2 factorial clinical pilot trial

DEFF Research Database (Denmark)

Højskov, Ida E; Moons, Philip; Hansen, Niels V

2015-01-01

BACKGROUND: Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility, pain and insufficient sleep. Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising. However......, no randomized clinical trials have tested a comprehensive rehabilitation programme consisting of both physical exercise and psycho-education in the early rehabilitation phase. AIMS: The aims of the present SheppHeart pilot randomized clinical trial were to evaluate the feasibility of patient recruitment......, patient acceptance of the intervention, safety and tolerability of the intervention. METHODS AND DESIGN: Sixty patients admitted for coronary artery bypass graft were randomized 1:1:1:1 to: 1) physical exercise plus usual care, or 2) psycho-educational intervention plus usual care, or 3) physical exercise...

Interleukin-1β regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

International Nuclear Information System (INIS)

Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

2010-01-01

Research highlights: → Levels of IL-1β are increased in the pig myocardium after infarction. → Cultured pig heart cells possess IL-1 receptors. → IL-1β increases cell proliferation of pig heart cells in-vitro. → IL-1β increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. → IL-1β may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1β is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1β on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1β. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1β resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1β plays a major role in the events of tissue remodelling in the heart. Combined with our recently published in vivo data (Meybohm et al., PLoS One

Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

Energy Technology Data Exchange (ETDEWEB)

Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

2010-09-03

Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

Isothermal (vapour + liquid) equilibrium for the binary {l_brace}1,1,2,2-tetrafluoroethane (R134) + propane (R290){r_brace} and {l_brace}1,1,2,2-tetrafluoroethane (R134) + isobutane (R600a){r_brace} systems

Energy Technology Data Exchange (ETDEWEB)

Dong Xueqiang [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Gong Maoqiong, E-mail: gongmq@mail.ipc.ac.c [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Liu Junsheng [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China); Graduate University of Chinese Academy of Sciences, Beijing 100039 (China); Wu Jianfeng, E-mail: jfwu@mail.ipc.ac.c [Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, P.O. Box 2711, Beijing 100190 (China)

2010-09-15

(Vapour + liquid) equilibrium (VLE) data for the binary systems of {l_brace}1,1,2,2-tetrafluoroethane (R134) + propane (R290){r_brace} and {l_brace}1,1,2,2-tetrafluoroethane (R134) + isobutane (R600a){r_brace} were measured with a recirculation method at the temperatures ranging from (263.15 to 278.15) K and (268.15 to 288.15) K, respectively. All of the data were correlated by the Peng-Robinson (PR) equation of state (EoS) with the Huron-Vidal (HV) mixing rules utilizing the non-random two-liquid (NRTL) activity coefficient model. Good agreement can be found between the experimental data and the correlated results. Azeotropic behaviour can be found at the measured temperature ranges for these two mixtures.

MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

Directory of Open Access Journals (Sweden)

Yi Zhu

2013-09-01

Full Text Available Background/Aims: Myocardium ischemia-reperfusion (I/R injury can be caused by imbalances in cellular metabolism. Lactate, transported by monocarboxylate transporters (MCTs, has been implicated as a mechanism in this process. The present study was designed to investigate the expression and functional role of MCTs in rat hearts during ischemia and reperfusion. Methods: Langendorff-perfused rat hearts were subjected to 20 minutes stabilization, 30 minutes of global ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting expression changes in MCT1, MCT4 during myocardial I/R injury and lactate concentration was measured. Post-ischemic left ventricular function and infract size were determined at end-point, followed by the pretreatment of D-lactate, a competitive inhibitor of MCTs. Results: MCT4 was significantly increased following global ischemia and MCT1 expression was increased during the early stages of reperfusion in isolated rat hearts, while the expression of the ancillary protein CD147 was increased during I/R injury. We determined increases in AMPK phosphorylation status, which was significantly elevated following ischemia and early reperfusion. Blocking monocarboxylate transport by competitive inhibition with D-lactate caused decreased left ventricular performance and increased infarct size. Conclusion: Increased MCT4 expression facilitates lactate extrusion during the ischemic period, while increased MCT1 may facilitate lactate transport into and out of cells simultaneously during early reperfusion, with increases in AMPK phosphorylation status during the myocardial I/R period. Lactate transport by MCTs has a profound protective effect during myocardial ischemia reperfusion injury.

Determination of taste receptor type 1 member 1 (TAS1R1) gene ...

African Journals Online (AJOL)

Jane

2011-10-10

Oct 10, 2011 ... 1Institute of Cellular and Molecular Biology, College of Life Science, Xuzhou Normal University, ... TAS1R1 and TAS1R3 form an L-amino acid sensor, ... 0.5 × TBE buffer (89 mM tris–borate, 2 mM EDTA, pH 8.3) for 2 h at.

[Flowmetric assessment of coronary bypass grafts in the conditions of artificial circulation and on the beating heart].

Science.gov (United States)

Bazylev, V V; Nemchenko, E V; Karnakhin, V A; Pavlov, A A; Mikulyak, A I

2016-01-01

Advantages and shortcomings of aortocoronary bypass grafting on the beating heart and in the conditions of artificial circulation (AC) have long been discussed. The data on patency of bypass grafts in the remote period are indicative of comparable results of operations with and without AC or advantages of using AC. In order to determine benefits of each method it is necessary to reveal intraoperative predictors of bypass grafts occlusion in the remote period. We analyzed the results of ultrasound flowmetry of the blood flow through the left internal thoracic artery during bypass grafting of the anterior descending artery with the use of AC and on the beating heart. A retrospective study included a total of 352 patients subdivided into 2 groups: Group One was composed of 120 patients undergoing surgery in the conditions of AC and Group Two comprised 232 patients subjected to similar operations on the beating heart. Blood flow was measured with the help of flowmeter VeryQ MediStim® after termination of AC and inactivation of heparin by protamine, with systolic pressure of 100-110 mm Hg. There were no statistically significant differences between the groups by the diameter and degree of stenosis of the anterior descending artery, diameter of the left internal thoracic artery. The mean volumetric blood flow velocity (Qmean) along the shunts in Group One was higher (p=0.01). No statistically significant differences by the pulsatility index (PI) between the groups were revealed (p=0.2). A conclusion was drawn that coronary bypass grafting of the anterior descending artery by the left internal thoracic artery in the conditions of artificial circulation made it possible to achieve higher volumetric velocity of blood flow through the conduit as compared with operations on the beating heart, with similar resistance index. The immediate results of the operations with the use of the both techniques did not differ.

Development of tailored real-time RT-PCR assays for the detection and differentiation of serotype O, A and Asia-1 foot-and-mouth disease virus lineages circulating in the Middle East

DEFF Research Database (Denmark)

Reid, Scott M.; Mioulet, Valerie; Knowles, Nick J.

2014-01-01

transcription polymerase chain reaction (rRT-PCR) assays using primer/probe sets designed from the VP1 coding region of the virus genomes were developed for the specific detection of serotype O, A and Asia-1 FMD viruses (FMDVs) circulating in the Middle East. These assays were evaluated using representative...... by the generic rRT-PCR diagnostic assays but negative by virus isolation and antigen-detection ELISA which would otherwise have to be serotyped by nucleotide sequencing. A similar approach could be used to develop serotyping assays for FMDV strains circulating in other regions of the world....

Fabrication of TiO{sub 2} nanorod assembly grafted rGO (rGO@TiO{sub 2}-NR) hybridized flake-like photocatalyst

Energy Technology Data Exchange (ETDEWEB)

Lv, Kangle, E-mail: lvkangle@mail.scuec.edu.cn [Department of Science and Environmental Studies, The Hong Kong Institute of Education, Taipo, N.T., Hong Kong (China); Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Fang, Shun; Si, Lingling; Xia, Yang [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China); Ho, Wingkei, E-mail: keithho@ied.edu.hk [Department of Science and Environmental Studies, The Hong Kong Institute of Education, Taipo, N.T., Hong Kong (China); Li, Mei [Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Resources and Environmental Science, South-Central University for Nationalities, Wuhan 430074 (China)

2017-01-01

Highlights: • TiO{sub 2} nanorod assembly grafted with GO hybrid was successfully fabricated. • TiO{sub 2} nanorods can reduce the aggregation of TiO{sub 2} nanoparticles on graphene. • This unique structure facilitates the injection of electron from TiO{sub 2} to graphene. - Abstract: To efficiently separate the photo-generated electron–hole pairs of TiO{sub 2} hybrid, anatase TiO{sub 2} nanorod assembly grafted reduced graphene oxides (rGO@TiO{sub 2}-NR) hybrid was successfully fabricated using potassium titanium oxalate (PTO) and graphene oxides (GO) as starting materials and diethylene glycol (DEG) as reductant. The effect of GO content on the structure and photocatalytic activity of rGO@TiO{sub 2}-NR composite was systematically studied. Results show that, in the absence of GO, only TiO{sub 2} microsphere assembly is obtained from TiO{sub 2} nanorods. The presence of GO results in the formation of a flake-like TiO{sub 2}-nanorod-assembled grafted rGO hybrid. The photocatalytic activity of rGO@TiO{sub 2}-NR composite increases first and then decreases with increase in the amount of GO from 0 wt.% to 10 wt.%. The hybridized S4 sample prepared with 4 wt.% GO possesses the highest photocatalytic activity with a constant rate of 0.039 min{sup −1} in the photocataytic degradation of Brilliant X-3B dye (X3B); this sample was enhanced more than three times when compared with pure TiO{sub 2} sample (0.012 min{sup −1}). The enhanced photocatalytic activity of the rGO@TiO{sub 2}-NR hybrid was attributed to the strong interaction between TiO{sub 2} nanorods and rGO. The unique hierarchical structure of 1D nanorod assembly TiO{sub 2}–rGO flakes facilitates the injection and transfer of photo-generated electrons from TiO{sub 2} to graphene, thus retarding the recombination of electron–hole pairs and enhancing the photocatalytic activity. The enlarged BET surface areas, not only increasing the number of active sites, but also facilitating the adsorption of

Dopexamine increases internal mammary artery blood flow following coronary artery bypass grafting.

LENUS (Irish Health Repository)

Flynn, Michael J

2012-02-03

OBJECTIVE: Vasoactive agents and inotropes influence conduit-coronary blood flow following coronary artery bypass grafting (CABG). It was hypothesized that dopexamine hydrochloride, a dopamine A-1 (DA-1) and beta(2) agonist would increase conduit-coronary blood flow. A prospective randomized double blind clinical trial was carried out to test this hypothesis. DA-1 receptors have previously been localized to human left ventricle. METHODS: Twenty-six American Society of Anaesthesiology class 2-3 elective coronary artery bypass graft patients who did not require inotropic support on separation from cardiopulmonary bypass (CPB) were studied. According to a randomized allocation patients received either dopexamine (1 microg\\/kg per min) or placebo (saline) by intravenous infusion for 15 min. Immediately prior to and at 5,10 and 15 min of infusion, blood flow through the internal mammary and vein grafts (Transit time flow probes, Transonic Ltd.), heart rate, cardiac index, mean arterial pressure and pulmonary haemodynamics were noted. The data were analysed using multivariate analysis of variance. RESULTS: Low-dose dopexamine (1 microg\\/kg per min) caused a significant increase in mammary graft blood flow compared to placebo at 15 min of infusion (P=0.028, dopexamine group left internal mammary artery (LIMA) flow of 43.3+\\/-14.2 ml\\/min, placebo group LIMA flow at 26.1+\\/-16.3 ml\\/min). Dopexamine recipients demonstrated a non-significant trend to increased saphenous vein graft flow (P=0.059). Increased heart rate was the only haemodynamic change induced by dopexamine (P=0.004, dopexamine group at 85.2+\\/-9.6 beats\\/min and placebo group at 71.1+\\/-7.6 beats\\/min after 15 min of infusion). CONCLUSION: This study demonstrates that administration of dopexamine (1 microg\\/kg per min) was associated with a significant increase in internal mammary artery graft blood flow with mild increase in heart rate being the only haemodynamic change. Low-dose dopexamine may

Studies on the properties of poly (ethylene oxide) R-150 hydrogel films formed by irradiation graft

International Nuclear Information System (INIS)

Yang Zhanshan; Zhu Nankang; Yang Shuqin; Qiang Yizhong

1999-01-01

In order to improve the mechanical properties of poly (ethylene oxide) (PEO) hydrogel film was used as wound dressing. The chemical and physical properties of the PEO R-150 graft hydrogel film formed by blends of electron beam irradiated-PEO R-150 and poly(vinyl alcohol) (PVA) were studied. The experimental results showed that the crosslinking densities of the PEO R-150 graft hydrogel increased along with the increasing of the irradiation doses and decreased with the increasing of the blend concentrations. While the PVA graft proportions did not produce obvious effects on the crosslinking density of the graft hydrogel. The crosslinking density of the graft hydrogel were obviously lower than that of the pure PVA hydrogel. The equilibrium water content of the graft hydrogel decrease as the irradiation dose and the PVA graft proportion increased; but they increased as the blend concentration increased. The equilibrium water content of the graft hydrogel was obviously higher than those of the pure PVA hydrogel. The hardness of the PVA hydrogel film increased with the irradiation dose. The hardness of the graft hydrogel decreased with the blend concentration, whereas it increased with the PVA graft proportion. The results suggest the PVA produces a main effect on the crosslinking density of the graft hydrogel, the PEO R-150 produces a main effect on the equilibrium water content of the graft hydrogel, and the both polymers have double effects on the hardness of the graft hydrogel

Radio evidence for the initial stellar mass function in the R associations CMa R1, Mon R1, Mon R2

International Nuclear Information System (INIS)

Pyatunina, T.B.

1985-01-01

The R associations CMa R1 and Mon R1 have been searched for compact 7.6-cm sources with the RATAN-600 radio telescope. The Mon R1 region shows only about the expected number of background radio galaxies; in CMa R1 seven sources of small angular size with S> or =30 mJy have been found, two of them probably background objects. Comparison with optical data for CMa R1, together with previous RATAN-600 data for Mon R2, yields an initial mass function xi(M)proportionalM/sup -2.7plus-or-minus0.7/ for the rather massive (Mroughly-equal10 M/sub sun/) stars in these associations

The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis

Directory of Open Access Journals (Sweden)

Kiessling Matthew

2004-06-01

Full Text Available Abstract Background There have been inconsistent results from case-control studies assessing the association of the PON1 Q192R polymorphism with coronary heart disease (CHD. Most studies have included predominantly men and the association in women is unclear. Since lipid levels vary between the sexes the antioxidant effect of PON1 and any genes associated with it may also vary by sex. We have examined the association of the PON1 Q192R polymorphism with CHD in a large cohort of British women and combined the results from our cohort study with those from all other published studies. Results The distribution of genotypes was the same among women with CHD and those without disease. The odds ratio (95% confidence interval of having CHD comparing those with either the QR or RR genotype to those with QQ genotype (dominant model of association was 1.03 (0.89, 1.21 and the per allele odds ratio was 0.98 (0.95, 1.01. In a meta-analysis of this and 38 other published studies (10,738 cases and 17,068 controls the pooled odds ratio for the dominant effect was 1.14 (1.08, 1.20 and for the per allele effect was 1.10 (1.06, 1.13. There was evidence of small study bias in the meta-analyses and the dominant effect among those studies with 500 or more cases was 1.05 (0.96, 1.15. Ethnicity and reporting of whether the genotyping was done blind to the participants clinical status also contributed to heterogeneity between studies, but there was no difference in effect between studies with 50% or more women compared to those with fewer women and no difference between studies of healthy populations compared to those at high risk (with diabetes, renal disease of familial hypercholesterolaemia. Conclusion There is no robust evidence that the PON1 Q192R polymorphism is associated with CHD risk in Caucasian women or men.

Correlation of immune activation with HIV-1 RNA levels assayed by real-time RT-PCR in HIV-1 Subtype C infected patients in Northern India

Science.gov (United States)

Agarwal, Atima; Sankaran, Sumathi; Vajpayee, Madhu; Sreenivas, V; Seth, Pradeep; Dandekar, Satya

2014-01-01

Background Assays with specificity and cost effectiveness are needed for the measurement of HIV-1 burden to monitor disease progression or response to anti-retroviral therapy (ART) in HIV-1 subtype C infected patients. Objectives The objective of this study was to develop and validate an affordable; one step Real-Time RT-PCR assay with high specificity and sensitivity to measure plasma HIV-1 loads in HIV-1 subtype C infected patients. Results We developed an RT-PCR assay to detect and quantitate plasma HIV-1 levels in HIV-1 subtype C infected patients. An inverse correlation between plasma viral loads (PVL) and CD4+ T-cell numbers was detected at all CDC stages. Significant correlations were found between CD8+ T-cell activation and PVL, as well as with the clinical and immunological status of the patients. Conclusions The RT-PCR assay provides a sensitive method to measure PVL in HIV-1 subtype C infected patients. Viral loads correlated with immune activation and can be used to monitor HIV care in India. PMID:17962068

LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194

Directory of Open Access Journals (Sweden)

An J

2017-11-01

Full Text Available Jihong An,* Weiling Lv,* Yongzhou Zhang Department of Clinical Pharmacy, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China *These authors contributed equally to this work Background: Chemoresistance is one of the major obstacles for cancer therapy in the clinic. Nuclear paraspeckle assembly transcript 1 (NEAT1 has been reported as an oncogene in most malignancies such as lung cancer, esophageal cancer, and gastric cancer. This study is designed to investigate the function of NEAT1 in paclitaxel (PTX resistance of ovarian cancer and its potential molecular mechanism. Patients and methods: The expressions of NEAT1 and miR-194 in ovarian cancer tissues and cells were estimated by quantitative real-time polymerase chain reaction (qRT-PCR. MTT, flow cytometry, and Western blot assays were used to assess the effect of NEAT1 on PTX resistance in PTX-resistant ovarian cancer cells. Luciferase reporter assay was applied to examine the association between NEAT1, zinc finger E-box-binding homeobox 1 (ZEB1 and miR-194. Xenograft tumor model was established to confirm the biological role of NEAT1 in PTX resistance of ovarian cancer in vivo. Results: NEAT1 was upregulated, and miR-194 was downregulated in PTX-resistant ovarian cancer tissues and cells. Functionally, NEAT1 knockdown enhanced cell sensitivity to PTX via promoting PTX-induced apoptosis in vitro. NEAT1 was identified as a molecular sponge of miR-194 to upregulate ZEB1 expression. Mechanistically, NEAT1-knockdown-induced PTX sensitivity was mediated by miR-194/ZEB1 axis. Moreover, NEAT1 knockdown improved PTX sensitivity of ovarian cancer in vivo. Conclusion: NEAT1 contributed to PTX resistance of ovarian cancer cells at least partly through upregulating ZEB1 expression by sponging miR-194, elucidating a novel regulatory pathway of chemoresistance in PTX-resistant ovarian cancer cells and providing a possible long noncoding RNA (lncRNA-targeted therapy for ovarian cancer

The Involvement of miR-23a/APAF1 Regulation Axis in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Fung Lin Yong

2014-07-01

Full Text Available Recent advances in microRNAome have made microRNAs (miRNAs a compelling novel class of biomarker in cancer biology. In the present study, the role of miR-23a in the carcinogenesis of colorectal cancer (CRC was investigated. Cell viability, apoptosis, and caspase 3/7 activation analyses were conducted to determine the potentiality of apoptosis resistance function of miR-23a in CRC. Luciferase assay was performed to verify a putative target site of miR-23a in the 3'-UTR of apoptosis protease activating factor 1 (APAF1 mRNA. The expression levels of miR-23a and APAF1 in CRC cell lines (SW480 and SW620 and clinical samples were assessed using reverse transcription-quantitative real-time PCR (RT-qPCR and Western blot. We found that the inhibition of miR-23a in SW480 and SW620 cell lines resulted in significant reduction of cell viability and promotion of cell apoptosis. Moreover, miR-23a up-regulation was coupled with APAF1 down-regulation in CRC tissue samples. Taken together, miR-23a was identified to regulate apoptosis in CRC. Our study highlights the potential application of miR-23a/APAF1 regulation axis in miRNA-based therapy and prognostication.

Multiplex RT-PCR assay for differentiating European swine influenza virus subtypes H1N1, H1N2 and H3N2.

Science.gov (United States)

Chiapponi, Chiara; Moreno, Ana; Barbieri, Ilaria; Merenda, Marianna; Foni, Emanuela

2012-09-01

In Europe, three major swine influenza viral (SIV) subtypes (H1N1, H1N2 and H3N2) have been isolated in pigs. Developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. This study describes two multiplex RT-PCRs which distinguish the haemagglutinin (HA) gene and the neuraminidase (NA) gene of the three major subtypes of SIV circulating in Europe. The HA PCR was able to identify the lineage (avian or human) of the HA of H1 subtypes. The analytical sensitivity of the test, considered to be unique, was assessed using three reference viruses. The detection limit corresponded to 1×10(-1) TCID(50)/200μl for avian-like H1N1, 1×10(0) TCID(50)/200μl for human-like H1N2 and 1×10(1) TCID(50)/200μl for H3N2 SIV. The multiplex RT-PCR was first carried out on a collection of 70 isolated viruses showing 100% specificity and then on clinical samples, from which viruses had previously been isolated, resulting in an 89% positive specificity of the viral subtype. Finally, the test was able to identify the viral subtype correctly in 56% of influenza A positive samples, from which SIV had not been isolated previously. It was also possible to identify mixed viral infections and the circulation of a reassortant strain before performing genomic studies. Copyright © 2012 Elsevier B.V. All rights reserved.

TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1.

Science.gov (United States)

Zhang, Lei; Cheng, Hailing; Yue, Yuxia; Li, Shuangzhan; Zhang, Daping; He, Ruili

Long non-coding RNAs (lncRNAs) have been revealed to participate in the pathological events associated with atherosclerosis. However, the exact role of lncRNA taurine-up-regulated gene 1 (TUG1) and its possible molecular mechanism in atherosclerosis remain unidentified. High-fat diet (HFD)-treated ApoE -/- mice were used as an in vivo model of atherosclerosis. Ox-LDL-induced macrophages and vascular smooth muscle cells (VSMCs) were employed as cell models of atherosclerosis. qRT-PCR was performed to detect the expression of TUG1 and miR-133a. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were analyzed by commercially available enzyme kits. Oil red O and hematoxylin and eosin (H&E) staining were conducted to examine atherosclerotic lesion. Luciferase reporter assay combined with RNA immunoprecipitation (RIP) was applied to confirm the interaction between TUG1, miR-133a and FGF1. Cell proliferation ability was determined by Cell Counting Kit-8 (CCK-8) assay and trypan blue dye exclusion test. Cell apoptosis was evaluated with TUNEL assay. Expression and production of inflammatory cytokines was measured with western blot and ELISA analysis. TUG1 expression was up-regulated in HFD-treated ApoE -/- mice, as well as in ox-LDL-induced RAW264.7 and MOVAS cells. TUG1 knockdown inhibited hyperlipidemia, decreased inflammatory response, and attenuated atherosclerotic lesion in HFD-treated ApoE -/- mice. TUG1 could function as a molecular sponge of miR-133a to suppress its expression. TUG1 overexpression accelerated cell growth, improved inflammatory factor expression, and inhibited apoptosis in ox-LDL-stimulated RAW264.7 and MOVAS cells, while this effect was abated after transfection with miR-133 mimic. Moreover, fibroblast growth factor 1 (FGF1) was identified as a direct target of miR-133a. Restored expression of FGF1 overturned the effect of miR-133a on cell

Comparison of the anti-cancer effect of Disulfiram and 5-Aza-CdR on pancreatic cancer cell line PANC-1.

Science.gov (United States)

Dastjerdi, Mehdi Nikbakht; Babazadeh, Zahra; Salehi, Mansour; Hashemibeni, Batool; Kazemi, Mohammad

2014-01-01

Pancreatic cancer has poor prognosis by surgical and chemotherapy when it is diagnosed, so other anti-cancerous assistant therapeutic drugs are suggested e.g. epigenetic reversal of tumor-suppressor genes on promoter hypermethylation. 5-Aza-CdR is a nucleoside analog of DNMTi but it has long-term cytotoxicity effects. This study compares the anticancer effect of 5-Aza-CdR and Disulfiram potencies on PANC-1 cell line and up-regulation of p21. PANC-1 cell line was cultured in DMEM high glucose and treated by 5-Aza-CdR with 5 and 10 μM concentration for four days and 13 μM DSF (Diulfiram) for 24 hours. MS-PCR and RT-PCR were carried out to detect the methylation pattern and estimate the mRNA expression of RASSF1A and p21 in PANC-1. MS-PCR demonstrated partial unmethylation after treatment with 5-Aza-CdR while there was no unmethylated band after DSF treatment. RT-PCR showed significant differences between re-expression of RASSF1A before and after treatment with 10 μM 5-Aza-CdR (P 0.05). The significant correlation was observed between RASSF1A re-expression and p21 up-regulation before and after treatment with 10 μM 5-Aza-CdR (P 0.05), while p21 up-regulation was significantly higher after DSF treatment (P PANC-1. DSF showed no epigenetic reversion while it affected p21 up-regulation.

Unequal distribution of RT-PCR artifacts along the E1-E2 region of Hepatitis C virus.

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Domingo-Calap, Pilar; Sentandreu, Vicente; Bracho, Maria Alma; González-Candelas, Fernando; Moya, Andrés; Sanjuán, Rafael

2009-10-01

Although viral variability studies have focused traditionally on consensus sequences, the relevance of molecular clone sequences for studying viral evolution at the intra-host level is being increasingly recognized. However, for this approach to be reliable, RT-PCR artifacts do not have to contribute excessively to the observed variability. Molecular clone sequences were obtained from an in vitro transcript to estimate the maximum error rate associated to RT-PCR for the Hepatitis C virus (HCV) E1-E2 region. On average, the frequency of RT-PCR errors was one order of magnitude lower than the level of intra-host genetic variability observed in samples from an HCV outbreak. However, RT-PCR errors were not distributed evenly along the E1-E2 region and were concentrated heavily in the hypervariable region 2 (HVR 2). Although it is concluded that RT-PCR molecular clone sequences are reliable, these results warn against extrapolation of RT-PCR error rates to different genome regions. The data suggest that the RNA sequence context or secondary structure can determine the fidelity of in vitro transcription or reverse transcription. Potentially, these factors might also modify the fidelity of the viral polymerase.

Når det er svært at være ung i DK

DEFF Research Database (Denmark)

Nielsen, Jens Christian; Sørensen, Niels Ulrik

Når det er svært at være ung i DK – viden og råd om unges trivsel og mistrivsel er afslutningen på et større forskningsprojekt om unges trivsel og mistrivsel. Hæftet præsenterer forskningsprojektets hovedkonklusioner og giver desuden en række råd og ideer til, hvordan voksne kan hjælpe unge med...... at håndtere mistrivsel. Hæftet er udarbejdet af forskerne Jens Christian Nielsen og Niels Ulrik Sørensen fra Center for Ungdomsforskning. Det er den sidste publikation i forskningsprojektet Når det er svært at være ung i DK, der fra 2008-2011 har belyst unges trivsel og mistrivsel. Projektet bygger både på en...

Detection of ROS1 Gene Rearrangement in Lung Adenocarcinoma: Comparison of IHC, FISH and Real-Time RT-PCR

OpenAIRE

Shan, Ling; Lian, Fang; Guo, Lei; Qiu, Tian; Ling, Yun; Ying, Jianming; Lin, Dongmei

2015-01-01

Aims To compare fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative real-time reverse transcription-PCR (qRT-PCR) assays for detection of ROS1 fusion in a large number of ROS1-positive lung adenocatcinoma (ADC) patients. Methods Using IHC analysis, sixty lung ADCs including 16 cases with ROS1 protein expression and 44 cases without ROS1 expression were selected for this study. The ROS1 fusion status was examined by FISH and qRT-PCR assay. Results Among 60 ca...

Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells.

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Liu, Qian; Liu, Hui; Cheng, Hepeng; Li, Yang; Li, Xiaodong; Zhu, Chaoyang

2017-01-01

Bladder cancer is a common serious disease around the world. Long noncoding RNAs (lncRNAs) have been demonstrated to participate in the development and progression of various cancers, including bladder cancer. The aim of this study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1) on proliferation and apoptosis in bladder cancer cell lines and the underlying mechanism. The levels of TUG1 were detected by quantitative real time polymerase chain reaction (qRT-PCR) in bladder cancer tissues and cells. The mRNA and protein levels of zinc finger E-box binding homeobox 2 (ZEB2) were measured by qRT-PCR and Western blot analysis, respectively. The functional targets of TUG1 were predicted by online softwares and confirmed by luciferase reporter assay. The effects of TUG1 on cell proliferation and apoptosis were examined by MTT and apoptosis assay, respectively. The expression levels of β-catenin, cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis. The levels of TUG1 and ZEB2 were significantly increased in bladder cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2 overexpression reversed the effects of TUG1 knockdown on cell proliferation and apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142 could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the Wnt/β-catenin pathway by regulating ZEB2 expression in bladder cancer cells. Downregulation of TUG1 expression inhibited proliferation and induced apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through the inactivation of Wnt/β-catenin pathway.

Når det er svært at være ung i DK

DEFF Research Database (Denmark)

Nielsen, Jens Christian; Sørensen, Niels Ulrik; Grubb, Ane

I rapporten Når det er svært at være ung i DK – unges beretninger om mistrivsel og ungdomsliv præsenteres resultaterne af et kvalitativt studie af mistrivsel og ungdomsliv blandt 15-24-årige unge i Danmark. Studiet bygger på dybdegående interviews med 33 unge fra forskellige dele af landet, der...... fortæller om deres erfaringer med diverse mistrivselsformer, som ensomhed, selvskadende adfærd og mobning, og om deres besvær med at håndtere de krav, udfordringer og muligheder, der i øvrigt præger det moderne ungdomsliv. Studiet indgår i det treårige forskningsprojekt Når det er svært at være ung i DK...

Overexpression of miR-19b Impairs Cardiac Development in Zebrafish by Targeting ctnnb1

Directory of Open Access Journals (Sweden)

Mengmeng Li

2014-07-01

Full Text Available Background: MicroRNAs are broadly accepted as crucial regulators of cardiovascular development, and dysregulation of their expression has been linked to cardiac disease. MicroRNA cluster miR-17-92 has been implicated in cardiac development and function, yet its defined mechanisms of action in this context are uncertain. Here, we focused on miR-19b, a key component of the miR-17-92 cluster proven to induce cardiomyocyte proliferation in vitro. We aimed to identify the biological significance of miR-19b in cardiac development and its underlying molecular mechanism of action in vivo. Methods: We micro-injected zebrafish embryos with different concentrations (0, 2, 4 and 8 μm of miR-19b mimics or a negative control, and assessed the embryo malformation rate, mortality rate, hatching rate and heart abnormalities at 72 hours post-fertilization (72 hpf. Results: We found that overexpression of miR-19b impacted left-right symmetry and cardiac development of zebrafish embryos, characterized by pericardial edema, slower heart rate and cardiac looping defects in a dose-dependent manner. Moreover, several important signaling molecules in the Wnt signaling pathway were abnormally expressed, suggesting that overexpression of miR-19b induces the inhibition of the Wnt signaling pathway by directly targeting ctnnb1. Interestingly, the deformed cardiac phenotype was partially rescued by treatment with the GSK3β inhibitor lithium chloride. Conclusion: Our findings suggest that miR-19b regulates laterality development and heart looping in zebrafish embryos by targeting ctnnb1.

Nuclear AMPK regulated CARM1 stabilization impacts autophagy in aged heart

International Nuclear Information System (INIS)

Li, Chen; Yu, Lu; Xue, Han; Yang, Zheng; Yin, Yue; Zhang, Bo; Chen, Mai; Ma, Heng

2017-01-01

Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart. We found that fasting could promote autophagy in young hearts but not in aged hearts. The CARM1 stabilization is markedly decrease in aged hearts, which impaired nucleus TFEB-CARM1 complex and autophagy flux. Further, S-phase kinase-associated protein 2(SKP2), responsible for CARM1 degradation, was increased in aged hearts. We further validated that AMPK dependent FoxO3 phosphorylation was markedly reduced in nucleus, the decreased nuclear AMPK-FoxO3 activity fails to suppress SKP2-E3 ubiquitin ligase. This loss of repression leads to The CARM1 level and autophagy in aged hearts could be restored through AMPK activation. Taken together, AMPK deficiency results in nuclear CARM1 decrease mediated in part by SKP2, contributing to autophagy dysfunction in aged hearts. Our results identified nuclear AMPK controlled CARM1 stabilization as a new actor that regulates cardiac autophagy. - Highlights: • AMPK-dependent CARM1 stabilization is an important nuclear mechanism in cardiac autophagy. • AMPK deficiency lead to SKP2-mediated decrease in CARM1. • AMPK–SKP2–CARM1 in the regulation of autophagy dysfunction in aged heart.

SPoRT Participation in the GOES-R and JPSS Proving Grounds

Science.gov (United States)

Jedlovec, Gary; Fuell, Kevin; Smith, Matthew

2013-01-01

For the last several years, the NASA Short-term Prediction Research and Transition (SPoRT) project at has been working with the various algorithm working groups and science teams to demonstrate the utility of future operational sensors for GOES-R and the suite of instruments for the JPSS observing platforms. For GOES-R, imagery and products have been developed from polar-orbiting sensors such as MODIS and geostationary observations from SEVIRI, simulated imagery, enhanced products derived from existing GOES satellites, and data from ground-based observing systems to generate pseudo or proxy products for the ABI and GLM instruments. The suite of products include GOES-POES basic and RGB hybrid imagery, total lightning flash products, quantitative precipitation estimates, and convective initiation products. SPoRT is using imagery and products from VIIRS, CrIS, ATMS, and OMPS to show the utility of data and products from their operational counterparts on JPSS. The products include VIIRS imagery in swath form, the GOES-POES hybrid, a suite of RGB products including the air mass RGB using water vapor and ozone channels from CrIS, and several DNB products. Over a dozen SPoRT collaborative WFOs and several National Centers are involved in an intensive evaluation of the operational utility of these products.

Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

Directory of Open Access Journals (Sweden)

Pujiao Yu

2016-01-01

Full Text Available The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs, as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation

International Nuclear Information System (INIS)

Yavari, Kamal; Taghikhani, Mohammad; Mesbah-Namin, Seyed A.; Maragheh, Mohammad Ghannadi; Babaei, Mohammad Hosein; Arfaee, Ali Jabbary; Madani, Hossein; Mirzaei, Hamid Reza

2010-01-01

Purpose. Insulin like growth factor receptor 1 (IGF-1R) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy. Material and methods. Human colon carcinoma SW480 cells were transfected with the specific small interference RNA (siRNA) expression vector (pkD-shRNA-IGF-1R-V2) designed to target IGF-1R mRNA. The expression of IGF-1R mRNA and its protein among the transfected and untransfected cells were detected by semi-quantitative RT-PCR and ELISA assay. The changes in cell radiosensitivity were examined by MTT assay. Results. Transfection of mammalian expression vector pkD containing IGF-1R siRNA was shown to reduce IGF-1R mRNA levels by up to 95%. ELISA assay detected a similar inhibition of IGF-1R protein levels in cells transfected with IGF-1R siRNA. SW480 cells transfected with the expression vector for siRNA significantly rendered cells more sensitive to radiation and the highest radiation enhancement ratio was 2.02 ± 0.08. Conclusion. These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting human IGF-1R mRNA is able to enhance colon cancer radiosensitivity. Also results indicated that, combining IGF-1R siRNA and radiation significantly enhances antitumor efficacy compared with either modality alone

Homoeologous Recombination of the V1r1-V1r2 Gene Cluster of Pheromone Receptors in an Allotetraploid Lineage of Teleosts

Directory of Open Access Journals (Sweden)

Lei Zhong

2017-11-01

Full Text Available In contrast to other olfactory receptor families that exhibit frequent lineage-specific expansions, the vomeronasal type 1 receptor (V1R family exhibits a canonical six-member repertoire in teleosts. V1r1 and V1r2 are present in no more than one copy in all examined teleosts, including salmons, which are ancient polyploids, implying strict evolutionary constraints. However, recent polyploids have not been examined. Here, we identified a young allotetraploid lineage of weatherfishes and investigated their V1r1-V1r2 cluster. We found a novel pattern that the parental V1r1-V1r2 clusters had recombined in the tetraploid genome and that the recombinant was nearly fixed in the tetraploid population. Subsequent analyses suggested strong selective pressure, for both a new combination of paralogs and homogeneity among gene duplicates, acting on the V1r1-V1r2 pair.

Development of tailored real-time RT-PCR assays for the detection and differentiation of serotype O, A and Asia-1 foot-and-mouth disease virus lineages circulating in the Middle East.

Science.gov (United States)

Reid, Scott M; Mioulet, Valerie; Knowles, Nick J; Shirazi, Nazeem; Belsham, Graham J; King, Donald P

2014-10-01

Rapid and accurate diagnosis is essential for effective control of foot-and-mouth disease (FMD). In countries where FMD is endemic, identification of the serotypes of the causative virus strains is important for vaccine selection and tracing the source of outbreaks. In this study, real-time reverse transcription polymerase chain reaction (rRT-PCR) assays using primer/probe sets designed from the VP1 coding region of the virus genomes were developed for the specific detection of serotype O, A and Asia-1 FMD viruses (FMDVs) circulating in the Middle East. These assays were evaluated using representative field samples of serotype O strains belonging exclusively to the PanAsia-2 lineage, serotype A strains of the Iran-05 lineage and serotype Asia-1 viruses from three relevant sub-groups. When RNA extracted from archival and contemporary field strains was tested using one- or two-step rRT-PCR assays, all three primer/probe sets detected the RNA from homotypic viruses and no cross-reactivity was observed with heterotypic viruses. Similar results were obtained using both single- and multiplex assay formats. Using plasmid standards, the minimum detection level of these tests was found to be lower than two copies. The results illustrate the potential of tailored rRT-PCR tools for the detection and categorization of viruses circulating in the Middle East belonging to distinct subgroups of serotypes O, A and Asia-1. These assays can also overcome the problem of serotyping samples which are found positive by the generic rRT-PCR diagnostic assays but negative by virus isolation and antigen-detection ELISA which would otherwise have to be serotyped by nucleotide sequencing. A similar approach could be used to develop serotyping assays for FMDV strains circulating in other regions of the world. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Replication-dependent 65R→K reversion in human immunodeficiency virus type 1 reverse transcriptase double mutant K65R + L74V

International Nuclear Information System (INIS)

Sharma, Prem L.; Nurpeisov, Viktoria; Lee, Kimberly; Skaggs, Sara; Di San Filippo, Christina Amat; Schinazi, Raymond F.

2004-01-01

Understanding of the mechanisms of interaction among nucleoside reverse transcriptase inhibitor (NRTI)-selected mutations in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) coding sequence is essential for the design of newer drugs and for enhancing our vision of the structure function relationship among amino acids of the polymerase domain of HIV-1. Although several nucleoside reverse transcriptase inhibitors select RT mutations K65R and L74V, the combination of 65R + 74V is rare in clinics. A novel NRTI (-)-β-D-dioxolane-guanosine (DXG) is known to select in vitro either the 65R or 74V mutant virus (Antimicrob. Agents Chemother. 44 (2000) 1783). These mutations were not selected together during repeated passaging of the HIV-1 in the presence of this drug. To analyze the impact of these RT mutations on viral replication, a double mutant containing K65R + L74V was created by site-directed mutagenesis in a pNL4-3 background. Replication kinetic assays revealed that the mutant K65R + L74V is unstable, and 65R→K reversion occurs during replication of virus in phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBM) cells in the absence of selection pressure. Replication kinetic assays in MT-2 cells demonstrated that double mutant 65R + 74V is highly attenuated for replication and the initiation of reversion is related to the increase in RT activity. Additionally, the suppression of viral replication in the presence of DXG or under suboptimal human recombinant interleukin-2 leads to minimal or no 65R→K reversion. These observations provide evidence that 65R→K reversion in the double mutant 65R + 74V is dependent on a specific rate of viral replication in a pNL4-3 background. A similar phenomenon may occur in vivo, which may have implications for treatment management strategies

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone.

Science.gov (United States)

Peterse, Elisabeth F P; Cleven, Arjen H G; De Jong, Yvonne; Briaire-de Bruijn, Inge; Fletcher, Jonathan A; Danen, Erik H J; Cleton-Jansen, Anne-Marie; Bovée, Judith V M G

2016-07-14

Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was therefore explored in this study. Expression of mediators of IGF1R signalling and phosphorylation status of IRS1 was determined in chondrosarcoma cell lines by qRT-PCR and western blot. The effect of activation and inhibition of IGF1R signalling on downstream targets was assessed by western blot. Ten chondrosarcoma cell lines were treated with OSI-906 (IGF1R and IR dual inhibitor) after which cell proliferation and migration were determined by a viability assay and the xCELLigence system, respectively. In addition, four chondrosarcoma cell lines were treated with a combination of doxorubicin and OSI-906. By immunohistochemistry, IGF1R expression levels were determined in tissue microarrays of 187 cartilage tumours and ten paraffin embedded cell lines. Mediators of IGF1R signalling are heterogeneously expressed and phosphorylated IRS1 was detected in 67 % of the tested chondrosarcoma cell lines, suggesting that IGF1R signalling is active in a subset of chondrosarcoma cell lines. In the cell lines with phosphorylated IRS1, inhibition of IGF1R signalling decreased phosphorylated Akt levels and increased IGF1R expression, but it did not influence MAPK or S6 activity. In line with these findings, treatment with IGF1R/IR inhibitors did not impact proliferation or migration in any of the chondrosarcoma cell lines, even upon stimulation with IGF1. Although synergistic effects of IGF1R/IR inhibition with doxorubicin are described for other cancers, our results demonstrate that this was not the case for chondrosarcoma. In addition, we found minimal IGF1R expression in primary tumours in contrast to the high expression detected in chondrosarcoma cell lines, even if both were derived from the

Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r.

Science.gov (United States)

Björn, Camilla; Mahlapuu, Margit; Mattsby-Baltzer, Inger; Håkansson, Joakim

2016-07-01

Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing ≥99% of microorganisms in vitro, was in the range of 3-50μg/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-α) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400μg/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. Copyright © 2016 Elsevier Inc. All rights reserved.

miR-184 and miR-150 promote renal glomerular mesangial cell aging by targeting Rab1a and Rab31.

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Liu, Xiujuan; Fu, Bo; Chen, Dapeng; Hong, Quan; Cui, Jing; Li, Jin; Bai, Xueyuan; Chen, Xiangmei

2015-08-15

The molecular mechanism of kidney aging is not well understood, but the abnormal expression of miRNAs with aging is considered to be an important contributor. miR-184 and miR-150 were screened using a miRNA microarray and qRT-PCR and found to be significantly upregulated in 24-month-old rats. Rat renal primary glomerular mesangial cells (GMCs) were isolated from 3-month and 24-month-old rats for the in vitro analysis of the roles of miR-184 and miR-150 in kidney aging. Bioinformatics analyses suggested that Rab1a and Rab31, which are associated with cell autophagy, were targeted by both miR-184 and miR-150. miR-184 and miR-150 were increased significantly in aging GMCs versus young cells, while Rab1a and Rab31 were significantly lower in aging cells. Furthermore, dual luciferase reporter assays revealed that miR-184 and miR-150 bound to the 3'-UTR of Rab1a and Rab31 mRNAs. Transfection of miR-184 and miR-150 mimics into young GMCs suppressed the expression of Rab1a and Rab31. Transfected cells showed lower autophagy activities and higher levels of cellular oxidative products, leading to the aging of young GMCs. However, miR-184 and miR-150 inhibitors promoted autophagy and reduced oxidative damage by upregulating Rab1a and Rab31 in old GMCs. In conclusion, miR-184 and miR-150 inhibited autophagy, promoting GMC aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical application of thyroid hormone in diagnosis and therapy on cardiovascular disease

International Nuclear Information System (INIS)

Wu Weiyuan; Yang Yongqing

2010-01-01

Objective: To study clinical application of sera thyroid hormone in diagnosis and therapy on cornary heart disease (CHD) heart failure, acute myocardial infarction (AMI) and pulmonary heart disease. Methods: Determined the changes of serum triiodothyronine (T 3 ), tetraiodothyronine (T 4 ), free triiodothyronine (FT 3 ), free tetraiodothyronine (FT 4 ), thyroid stimulating hormone (TSH), reverse triiodothyronine (rT 3 ) and T 3 /rT 3 levels in 150 cases patients with CHD heart failure, 86 cases patients with AMI, 103 cases patients with pulmonary heart disease and 47 cases normal controls by chemiluminescent measurement. Results: The serum levels of T 3 , T 4 , FT 3 , FT 4 , TSH, rT 3 and T 3 /rT 3 in CHD heart failure, AMI pulmonary heart disease were compared with normal controls. Serum T 4 , FT 4 and TSH levels were not different between above patients and normal controls (t=2.130, 2.214, 4.356, P 3 , FT 3 and T 3 /rT 3 were significantly decreased than those of normal controls (t=2.256, 4.416, 4.512, P 3 levels were significantly increased those of than normal controls (t=1.781, 1.813, 1.754, P>0.05). The serum T 3 , FT 3 and T 3 /rT 3 levels were significantly decreased in patient with CHD heart failure severity. But the serum rT 3 levels was significantly increased. Conclusion: The present study showed that change of serum T 3 , FT 3 and T 3 /rT 3 levels in patients with CHD heart failure, AMI and pulmonary heart disease were inpartant marker and could reflect the severity of disease and used as diagnostic or treatment indicators. (authors)

Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

Science.gov (United States)

Jabłonowska, Elżbieta; Wójcik, Kamila; Szymańska, Bożena; Omulecka, Aleksandra; Cwiklińska, Hanna; Piekarska, Anna

2014-01-01

To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1. The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed. HCV mono-infected patients, with lower grading score (G600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman's ρ = 0.586, p = 0.000001) and miR-122 (Spearman's ρ = 0.270, p = 0.014059). HMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

Renal PGC1α May Be Associated with Recovery after Delayed Graft Function.

Science.gov (United States)

Drury, Erika R; Zsengeller, Zsuzsanna K; Stillman, Isaac E; Khankin, Eliyahu V; Pavlakis, Martha; Parikh, Samir M

2018-01-01

Delayed renal graft function (DGF) contributes to the determination of length of hospitalization, risk of acute rejection, and graft loss. Existing tools aid the diagnosis of specific DGF etiologies such as antibody-mediated rejection, but markers of recovery have been elusive. The peroxisome proliferator gamma co-activator-1-alpha (PGC1α) is highly expressed in the renal tubule, regulates mitochondrial biogenesis, and promotes recovery from experimental acute kidney injury. We aimed to determine the association between renal allograft PGC1α expression and recovery from delayed graft function. We retrospectively analyzed patients undergoing renal transplantation at a single center from January 1, 2008 to June 30, 2014. PGC1α expression was assessed by immunostaining and ultrastructural characteristics by transmission electron microscopy. Of 34 patients who underwent renal biopsy for DGF within 30 days of transplant, 21 were included for analysis. Low PGC1α expression was associated with a significantly longer time on dialysis after transplant (median of 35.5 vs. 16 days, p < 0.05) and a significantly higher serum creatinine (sCr) at 4 weeks after transplantation among those who discontinued dialysis (5 vs. 1.65 mg/dL, p < 0.0001). Low PGC1α expression was not associated with higher sCr at 12 weeks after transplantation. Ultrastructural characteristics including apical membrane blebbing and necrotic luminal debris were not informative regarding clinical outcomes. These data suggest that higher PGC1α expression is associated with faster and more complete recovery from DGF. Mitochondrial biogenesis may be a therapeutic target for DGF. Larger studies are needed to validate these findings. © 2017 S. Karger AG, Basel.

Design and performance of the CDC real-time reverse transcriptase PCR swine flu panel for detection of 2009 A (H1N1) pandemic influenza virus.

Science.gov (United States)

Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

2011-07-01

Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10(-1.3 - -0.7) 50% infectious doses (ID(50)) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.

A R2R3-MYB transcription factor gene in common wheat (namely TaMYBsm1) involved in enhancement of drought tolerance in transgenic Arabidopsis.

Science.gov (United States)

Li, Meng-Jun; Qiao, Yu; Li, Ya-Qing; Shi, Zhan-Liang; Zhang, Nan; Bi, Cai-Li; Guo, Jin-Kao

2016-11-01

We isolated the TaMYBsm1 genes, encoding R2R3-type MYB proteins in common wheat, aimed to uncover the possible molecular mechanisms related to drought response. The TaMYBsm1 genes, TaMYBsm1-A, TaMYBsm1-B and TaMYBsm1-D, were isolated and analyzed from the common wheat cultivar Shimai 15. Their expression patterns under PEG 6000 and mannitol were monitored by semi-quantitative RT-PCR and β-glucuronidase (Gus) assay. The function of TaMYBsm1-D under drought stress in transgenic Arabidopsis plants was investigated, and the germination rate, water loss rate, as well as the proline and malondialdehyde (MDA) content were compared with that in wild type (WT) plants. The expression of three downstream genes (DREB2A, P5CS1 and RD29A) in TaMYBsm1-D transgenic plants was analyzed. The R2R3-MYB domains of the MYBsm1 proteins were highly conserved in plants. In addition, the TaMYBsm1 proteins were targeted to the nucleus and contained transcriptional activation domains (TADs). Gus assay and semi-quantitative RT-PCR analysis demonstrated that the TaMYBsm1 genes were up-regulated when the wheat was treated by PEG and mannitol. Compared with WT plants, the germination rates were much higher, but the water loss rates were much lower in TaMYBsm1-D overexpression plants. TaMYBsm1-D transgenic plants showed distinct higher proline contents but a lower MDA content than the WT plants. The three downstream genes were highly expressed in TaMYBsm1-D transgenic plants. We concluded from these results that TaMYBsm1 genes play an important role in plant drought stress tolerance through up-regulation of DREB2A, P5CS1 and RD29A. The increase of proline content and decrease of MDA content may also be involved in the drought response.

DGAT1 Expression Increases Heart Triglyceride Content but Ameliorates Lipotoxicity*

OpenAIRE

Liu, Li; Shi, XiaoJing; Bharadwaj, Kalyani G.; Ikeda, Shota; Yamashita, Haruyo; Yagyu, Hiroaki; Schaffer, Jean E.; Yu, Yi-Hao; Goldberg, Ira J.

2009-01-01

Intracellular lipid accumulation in the heart is associated with cardiomyopathy, yet the precise role of triglyceride (TG) remains unclear. With exercise, wild type hearts develop physiologic hypertrophy. This was associated with greater TG stores and a marked induction of the TG-synthesizing enzyme diacylglycerol (DAG) acyltransferase 1 (DGAT1). Transgenic overexpression of DGAT1 in the heart using the cardiomyocyte- specific α-myosin heavy chain (MHC) promoter led to approximately a doublin...

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1

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Qiuke Hou

2017-12-01

Full Text Available Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii verify in vitro whether occludin (OCLN and zonula occludens 1 (ZO1/TJP1 were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further

Real-time reverse transcription-polymerase chain reaction assays for identification of wild poliovirus 1 & 3.

Science.gov (United States)

Sharma, Deepa K; Nalavade, Uma P; Deshpande, Jagadish M

2015-10-01

The poliovirus serotype identification and intratypic differentiation by real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is suitable for serotype mixtures but not for intratypic mixtures of wild and vaccine poliovirus strains. This study was undertaken to develop wild poliovirus 1 and 3 (WPV1 and WPV3) specific rRT-PCR assays for use. Specific primers and probes for rRT-PCR were designed based on VP1 sequences of WPV1 and WPV3 isolated in India since 2000. The specificity of the rRT-PCR assays was evaluated using WPV1 and WPV3 of different genetic lineages, non-polio enteroviruses (NPEVs) and mixtures of wild/wild and wild/Sabin vaccine strains. The sensitivity of the assays was determined by testing serial 10-fold dilutions of wild poliovirus 1 and 3 stock suspensions of known titre. No cross-reactivity with Sabin strains, intertypic wild poliovirus isolates or 27 types of NPEVs across all the four Enterovirus species was found for both the wild poliovirus 1 and 3 rRT-PCR assays. All WPV1 and WPV3 strains isolated since 2000 were successfully amplified. The rRT-PCR assays detected 10 4.40 CCID 50 /ml of WPV1 and 10 4.00 CCID 50 /ml of WPV3, respectively either as single isolate or mixture with Sabin vaccine strains or intertypic wild poliovirus. rRT-PCR assays for WPV1 and WPV3 have been validated to detect all the genetic variations of the WPV1 and WPV3 isolated in India for the last decade. When used in combination with the current rRT-PCR assay testing was complete for confirmation of the presence of wild poliovirus in intratypic mixtures.

Downregulation of long noncoding RNA TUG1 inhibits proliferation and induces apoptosis through the TUG1/miR-142/ZEB2 axis in bladder cancer cells

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Liu Q

2017-05-01

Full Text Available Qian Liu,* Hui Liu,* Hepeng Cheng, Yang Li, Xiaodong Li, Chaoyang Zhu Department of Urology Surgery, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China *These authors contributed equally to this work Background: Bladder cancer is a common serious disease around the world. Long noncoding RNAs (lncRNAs have been demonstrated to participate in the development and progression of various cancers, including bladder cancer. The aim of this study was to investigate the effects of lncRNA taurine upregulated gene 1 (TUG1 on proliferation and apoptosis in bladder cancer cell lines and the underlying mechanism.Methods: The levels of TUG1 were detected by quantitative real time polymerase chain reaction (qRT-PCR in bladder cancer tissues and cells. The mRNA and protein levels of zinc finger E-box binding homeobox 2 (ZEB2 were measured by qRT-PCR and Western blot analysis, respectively. The functional targets of TUG1 were predicted by online softwares and confirmed by luciferase reporter assay. The effects of TUG1 on cell proliferation and apoptosis were examined by MTT and apoptosis assay, respectively. The expression levels of β-catenin, cyclinD1, and c-Myc in T24 cells were determined by Western blot analysis.Results: The levels of TUG1 and ZEB2 were significantly increased in bladder cancer tissues and cells. Knockdown of either TUG1 or ZEB2 inhibited proliferation and induced apoptosis in bladder cancer cells. Interestingly, ZEB2 overexpression reversed the effects of TUG1 knockdown on cell proliferation and apoptosis. Moreover, ZEB2 was verified as a direct target of miR-142 and miR-142 could specially bind to TUG1. In addition, downregulation of TUG1 inhibited the Wnt/β-catenin pathway by regulating ZEB2 expression in bladder cancer cells.Conclusion: Downregulation of TUG1 expression inhibited proliferation and induced apoptosis in bladder cancer cells by targeting ZEB2 mediated by miR-142 through the inactivation of Wnt

No preclinical rationale for IGF1R directed therapy in chondrosarcoma of bone

International Nuclear Information System (INIS)

Peterse, Elisabeth F. P.; Cleven, Arjen H. G.; De Jong, Yvonne; Briaire-de Bruijn, Inge; Fletcher, Jonathan A.; Danen, Erik H. J.; Cleton-Jansen, Anne-Marie; Bovée, Judith V. M. G.

2016-01-01

Chondrosarcoma is a malignant cartilage forming bone tumour for which no effective systemic treatment is available. Previous studies illustrate the need for a better understanding of the role of the IGF pathway in chondrosarcoma to determine if it can be a target for therapy, which was therefore explored in this study. Expression of mediators of IGF1R signalling and phosphorylation status of IRS1 was determined in chondrosarcoma cell lines by qRT-PCR and western blot. The effect of activation and inhibition of IGF1R signalling on downstream targets was assessed by western blot. Ten chondrosarcoma cell lines were treated with OSI-906 (IGF1R and IR dual inhibitor) after which cell proliferation and migration were determined by a viability assay and the xCELLigence system, respectively. In addition, four chondrosarcoma cell lines were treated with a combination of doxorubicin and OSI-906. By immunohistochemistry, IGF1R expression levels were determined in tissue microarrays of 187 cartilage tumours and ten paraffin embedded cell lines. Mediators of IGF1R signalling are heterogeneously expressed and phosphorylated IRS1 was detected in 67 % of the tested chondrosarcoma cell lines, suggesting that IGF1R signalling is active in a subset of chondrosarcoma cell lines. In the cell lines with phosphorylated IRS1, inhibition of IGF1R signalling decreased phosphorylated Akt levels and increased IGF1R expression, but it did not influence MAPK or S6 activity. In line with these findings, treatment with IGF1R/IR inhibitors did not impact proliferation or migration in any of the chondrosarcoma cell lines, even upon stimulation with IGF1. Although synergistic effects of IGF1R/IR inhibition with doxorubicin are described for other cancers, our results demonstrate that this was not the case for chondrosarcoma. In addition, we found minimal IGF1R expression in primary tumours in contrast to the high expression detected in chondrosarcoma cell lines, even if both were derived from the

8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

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Yan, Lifeng [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Zhou, Yong [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Yu, Shanhe [Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025 (China); Ji, Guixiang [Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042 (China); Wang, Lei [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Liu, Wei [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Gu, Aihua, E-mail: aihuagu@njmu.edu.cn [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China)

2013-11-15

Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

Design and Performance of the CDC Real-Time Reverse Transcriptase PCR Swine Flu Panel for Detection of 2009 A (H1N1) Pandemic Influenza Virus▿†‡

Science.gov (United States)

Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

2011-01-01

Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10−1.3∼−0.7 50% infectious doses (ID50) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation. PMID:21593260

miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1 cells via targeting RAF-1.

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Chao, Chen; Li, Feng; Tan, Zhiping; Zhang, Weizhi; Yang, Yifeng; Luo, Cheng

2018-01-15

Recent reports have demonstrated that RAF-1 L613V (a mutant of RAF-1) mutant mice show bone deformities similar to Noonan syndrome. It has been suggested that RAF-1 L613V might abnormally activate osteoblast differentiation of MC3T3-E1 cells. To demonstrate that RAF-1 is associated with bone deformity and that RAF-1 L613V dependent bone deformity could be inhibited by microRNA-195 (miR-195), we first investigated the amplifying influence of wild-type RAF-1 (WT) or RAF-1 L613V (L613V) on the viability and differentiation of MC3T3-E1 cells induced by bone morphogenetic protein-2 (BMP-2) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Subsequently, we investigated the blocking effect and its mechanism of miR-195 for abnormal activation of osteoblast differentiation of MC3T3-E1 cells via targeting RAF-1. RAF-1, especially RAF-1 L613V , abnormally activates osteoblast differentiation of MC3T3-E1 cells induced by BMP-2. Meanwhile, miR-195 could inhibit the cell viability and differentiation of MC3T3-E1 cells. Transfection of miR-195 largely suppressed the L613V-induced viability and osteoblast differentiation of MC3T3-E1 cells and attenuated the accelerative effect of L613V on runt-related transcription factor-2 (Runx2), Osterix (OSX), alkaline phosphatase (ALP), osteocalcin (OCN), and distal-less homeobox 5 (DLX5) osteogenic gene expressions. In addition, miR-195 decreased the expression of RAF-1 mRNA and protein by directly targeting the 3'-untranslated regions (3'-UTR) of RAF-1 mRNA in MC3T3-E1 cells. Our findings indicated that miR-195 inhibited WT and L613V RAF-1 induced hyperactive osteoblast differentiation in MC3T3-E1 cells by targeting RAF-1. miR-195 might be a novel therapeutic agent for the treatment of L613V-induced bone deformity in Noonan syndrome. Copyright © 2017. Published by

miR-101 suppresses HBV replication and expression by targeting FOXO1 in hepatoma carcinoma cell lines.

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Wang, Yanjing; Tian, Hui

2017-05-20

microRNAs (miRNAs) have been identified to participate in the progression of cancers and in the infection of viruses. miR-101 expression has been found to be suppressed by HBV, however, the regulatory relationship between miR-101 and HBV replication remains elusive. In this report, miR-101 was significantly downregulated in HepG2.2.15 cells with HBV expression. miR-101 overexpression dramatically suppressed HBV replication and expression. Oppositely, overexpression of FOXO1 significantly promoted HBV replication and expression. Moreover, luciferase reporter analysis, qRT-PCR analysis and western blot assay confirmed that FOXO1 was a functional target of miR-101. Furthermore, restored FOXO1 expression abolished the inhibitory effect of miR-101 overexpression on HBV replication and expression in HepG2.2.15 cells. Our data suggested that miR-101 suppressed HBV replication and expression partially by targeting FOXO1, providing new insights into the molecular mechanisms of miR-101 in HBV-host interactions and a promising therapeutic target for HBV replication. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetic resonance angiography in renal grafts. Comparison with color Doppler echography

International Nuclear Information System (INIS)

Yanagisawa, Takayoshi; Otsubo, Osamu; Nozaki, Harushige

1995-01-01

We studied relationship between magnetic resonance angiography (MRA) of renal graft and renal graft function in 14 renal transplantations (10 from living donors, 4 from cadaveric donors). MRA was performed on 0.3-T permanent magnet system (MRP 7000, HITACHI, JAPAN) using 2 dimensional time of flight technique (FOV: 350 mm 2 , RT: 60 msec, ET: 10 msec, FA: 90deg, Slice: volumes 60, thickness 4 mm, overlap 1 mm). As for parameters of renal graft function, we evaluated color doppler echography (CD) of transplanted renal artery, renal blood flow (RBF), velocity of interlobar artery (ILA) and serum creatinine level (S-Cr). CD, RBF and velocity of ILA were visualized and measured by duplex color doppler echosystem (EUB-565A, HITACHI, JAPAN). Depending on visualization of transplanted renal artery, MRA was graded into 3 groups (MA Grade 3: visualization of ILA, MA Grade 2: visualization of segmental artery and the first branch but no visualization of ILA, MA Grade 1: visualization of main renal artery only). Likewise, visualization of CD was graded into 3 groups (CD Grade 3: good visualization of arcuate artery (AA) and ILA, CD Grade 2: poor visualization of AA but good visualization of ILA, CD Grade 1: poor visualization of ILA). The MRA grading had a very significant correlation (r=0.79, p<0.001) with the CD grading. As for RBF and velocity of ILA, the RBF of MA Grade 3 group (n=8) was significantly (p<0.05) higher than the MA Grade 2 group (n=4) and the MA Grade 1 group (n=2), and the velocity of ILA of MA Grade 3 group was also higher than the above groups but not significantly. Furthermore, the S-Cr of MA Grade 3 was significantly (p<0.05) lower than the others. These results showed that MRA of renal graft had a qualitative index of renal graft function. (author)

Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

Science.gov (United States)

Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

2014-01-01

The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

A Leu to Ile but not Leu to Val change at HIV-1 reverse transcriptase codon 74 in the background of K65R mutation leads to an increased processivity of K65R+L74I enzyme and a replication competent virus

Directory of Open Access Journals (Sweden)

Crumpacker Clyde S

2011-01-01

Full Text Available Abstract Background The major hurdle in the treatment of Human Immunodeficiency virus type 1 (HIV-1 includes the development of drug resistance-associated mutations in the target regions of the virus. Since reverse transcriptase (RT is essential for HIV-1 replication, several nucleoside analogues have been developed to target RT of the virus. Clinical studies have shown that mutations at RT codon 65 and 74 which are located in β3-β4 linkage group of finger sub-domain of RT are selected during treatment with several RT inhibitors, including didanosine, deoxycytidine, abacavir and tenofovir. Interestingly, the co-selection of K65R and L74V is rare in clinical settings. We have previously shown that K65R and L74V are incompatible and a R→K reversion occurs at codon 65 during replication of the virus. Analysis of the HIV resistance database has revealed that similar to K65R+L74V, the double mutant K65R+L74I is also rare. We sought to compare the impact of L→V versus L→I change at codon 74 in the background of K65R mutation, on the replication of doubly mutant viruses. Methods Proviral clones containing K65R, L74V, L74I, K65R+L74V and K65R+L74I RT mutations were created in pNL4-3 backbone and viruses were produced in 293T cells. Replication efficiencies of all the viruses were compared in peripheral blood mononuclear (PBM cells in the absence of selection pressure. Replication capacity (RC of mutant viruses in relation to wild type was calculated on the basis of antigen p24 production and RT activity, and paired analysis by student t-test was performed among RCs of doubly mutant viruses. Reversion at RT codons 65 and 74 was monitored during replication in PBM cells. In vitro processivity of mutant RTs was measured to analyze the impact of amino acid changes at RT codon 74. Results Replication kinetics plot showed that all of the mutant viruses were attenuated as compared to wild type (WT virus. Although attenuated in comparison to WT virus

Soluble Flt-1 links microvascular disease with heart failure in CKD.

Science.gov (United States)

Di Marco, Giovana S; Kentrup, Dominik; Reuter, Stefan; Mayer, Anna B; Golle, Lina; Tiemann, Klaus; Fobker, Manfred; Engelbertz, Christiane; Breithardt, Günter; Brand, Eva; Reinecke, Holger; Pavenstädt, Hermann; Brand, Marcus

2015-05-01

Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.

Race and ethnic differences in the epidemiology and risk factors for graft failure after heart transplantation.

Science.gov (United States)

Morris, Alanna A; Kalogeropoulos, Andreas P; Zhao, Liping; Owen, Melissa; Raja Laskar, S; David Vega, J; Smith, Andrew; Butler, Javed

2015-06-01

Contemporary epidemiology of chronic graft failure (GF) after heart transplantation (HT) is not well described. Moreover, differences in the epidemiology of GF based on race/ethnicity remain poorly understood, despite clear evidence of inferior survival of ethnic minorities after HT. The incidence of GF and the population-attributable risk (PAR) of independent risk factors for GF were assessed in 15,255 patients (76% men; mean age 52 ± 12 years) who underwent primary HT from 2004 to 2012. During a median follow-up of 4.7 years (interquartile range, 2.3-7.1 years), GF developed in 2,926 patients (19.2%), corresponding to an incidence rate of 39.8/1,000 person-years (95% confidence interval, 38.4-41.3). Blacks were more likely to develop GF than Hispanics or whites, with incidence rates of 55.1, 42.2, and 36.5/1,000 person-years, respectively. After multivariable adjustment, black race was associated with a higher risk of GF (hazard ratio, 1.4; 95% confidence interval, 1.2-1.6; p differences in risk factors for GF after HT require further study. Published by Elsevier Inc.

NASA/SPoRT's GOES-R Activities in Support of Product Development, Management, and Training

Science.gov (United States)

Fuell, K. K.; Jedlovec, G.; Molthan, A.; Stano, G. T.

2012-12-01

The NASA Short-term Prediction Research and Transition (SPoRT) Center supports many activities within the GOES-R Proving Grounds (PG). These include the development of imagery from existing instrumentation as a proxy to future Advanced Baseline Imager (ABI) capabilities on GOES-R. The Moderate Resolution Imaging Spectroradiometer (MODIS) and the Visible/Infrared Imager/Radiometer Suite (VIIRS) instruments are used to provide a glimpse of the multi-spectral capabilities that will become the norm as the number of channels and data rate dramatically increase with GOES-R. The NOAA/NWS has plans to provide operational users with all ABI channels at the highest resolution. Data fusion of individual channels into composite red, green, and blue imagery products will assist the end user with this future wave of information. While increasing the efficiency in the operational use of ABI channels, these composites provide only qualitative information. Within the GOES-R PG, SPoRT and other partners are exploring ways to include quantitative information as part of the composite imagery. However, limitations in local hardware processing and/or data bandwidth for users of the GOES-R data stream are challenges to overcome. This presentation will discuss the creation of these composite images as well as possible solutions to address these processing challenges. In a similar manner the Geostationary Lightning Mapper (GLM) to be launched on GOES-R presents several data management challenges. The GLM is a pioneering instrument to quantify total lightning from a geostationary platform. The expected data frequency from the GLM is to be at a sub-minute interval. Users of such a data set may have little experience in handling such a rapid update of information. To assist users, SPoRT is working with the NWS to develop tools within the user's decision support system to allow tracking and analysis of total lightning from a storm-based perspective. This presentation will discuss the

NASA/SPoRT's GOES-R Activities in Support of Product Development, Management, and Training

Science.gov (United States)

Fuell, Kevin K.; Jedlovec, Gary; Molthan, Andrew L.; Stano, Geoffrey T.

2012-01-01

The NASA Short-term Prediction Research and Transition (SPoRT) Center supports many activities within the GOES-R Proving Grounds (PG). These include the development of imagery from existing instrumentation as a proxy to future Advanced Baseline Imager (ABI) capabilities on GOES-R. The Moderate Resolution Imaging Spectroradiometer (MODIS) and the Visible/Infrared Imager/Radiometer Suite (VIIRS) instruments are used to provide a glimpse of the multi-spectral capabilities that will become the norm as the number of channels and data rate dramatically increase with GOES-R. The NOAA/NWS has plans to provide operational users with all ABI channels at the highest resolution. Data fusion of individual channels into composite red, green, and blue imagery products will assist the end user with this future wave of information. While increasing the efficiency in the operational use of ABI channels, these composites provide only qualitative information. Within the GOES-R PG, SPoRT and other partners are exploring ways to include quantitative information as part of the composite imagery. However, limitations in local hardware processing and/or data bandwidth for users of the GOES-R data stream are challenges to overcome. This presentation will discuss the creation of these composite images as well as possible solutions to address these processing challenges. In a similar manner the Geostationary Lightning Mapper (GLM) to be launched on GOES-R presents several data management challenges. The GLM is a pioneering instrument to quantify total lightning from a geostationary platform. The expected data frequency from the GLM is to be at a sub-minute interval. Users of such a data set may have little experience in handling such a rapid update of information. To assist users, SPoRT is working with the NWS to develop tools within the user fs decision support system to allow tracking and analysis of total lightning from a storm-based perspective. This presentation will discuss the

Dynamics of heart rate variability analysed through nonlinear and linear dynamics is already impaired in young type 1 diabetic subjects.

Science.gov (United States)

Souza, Naiara M; Giacon, Thais R; Pacagnelli, Francis L; Barbosa, Marianne P C R; Valenti, Vitor E; Vanderlei, Luiz C M

2016-10-01

Autonomic diabetic neuropathy is one of the most common complications of type 1 diabetes mellitus, and studies using heart rate variability to investigate these individuals have shown inconclusive results regarding autonomic nervous system activation. Aims To investigate the dynamics of heart rate in young subjects with type 1 diabetes mellitus through nonlinear and linear methods of heart rate variability. We evaluated 20 subjects with type 1 diabetes mellitus and 23 healthy control subjects. We obtained the following nonlinear indices from the recurrence plot: recurrence rate (REC), determinism (DET), and Shanon entropy (ES), and we analysed indices in the frequency (LF and HF in ms2 and normalised units - nu - and LF/HF ratio) and time domains (SDNN and RMSSD), through analysis of 1000 R-R intervals, captured by a heart rate monitor. There were reduced values (p<0.05) for individuals with type 1 diabetes mellitus compared with healthy subjects in the following indices: DET, REC, ES, RMSSD, SDNN, LF (ms2), and HF (ms2). In relation to the recurrence plot, subjects with type 1 diabetes mellitus demonstrated lower recurrence and greater variation in their plot, inter-group and intra-group, respectively. Young subjects with type 1 diabetes mellitus have autonomic nervous system behaviour that tends to randomness compared with healthy young subjects. Moreover, this behaviour is related to reduced sympathetic and parasympathetic activity of the autonomic nervous system.

Open heart surgery after renal transplantation.

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Yamamura, Mitsuhiro; Miyamoto, Yuji; Mitsuno, Masataka; Tanaka, Hiroe; Ryomoto, Masaaki; Fukui, Shinya; Tsujiya, Noriko; Kajiyama, Tetsuya; Nojima, Michio

2014-09-01

to evaluate the strategy for open heart surgery after renal transplantation performed in a single institution in Japan. we reviewed 6 open heart surgeries after renal transplantation in 5 patients, performed between January 1992 and December 2012. The patients were 3 men and 2 women with a mean age of 60 ± 11 years (range 46-68 years). They had old myocardial infarction and unstable angina, aortic and mitral stenosis, left arterial myxoma, aortic stenosis, and native valve endocarditis followed by prosthetic valve endocarditis. Operative procedures included coronary artery bypass grafting, double-valve replacement, resection of left arterial myxoma, 2 aortic valve replacements, and a double-valve replacement. Renal protection consisted of steroid cover (hydrocortisone 100-500 mg or methylprednisolone 1000 mg) and intravenous immunosuppressant infusion (cyclosporine 30-40 mg day(-1) or tacrolimus 1.0 mg day(-1)). 5 cases were uneventful and good renal graft function was maintained at discharge (serum creatinine 2.1 ± 0.5 mg dL(-1)). There was one operative death after emergency double-valve replacement for methicillin-resistant Staphylococcus aureus-associated prosthetic valve endocarditis. Although the endocarditis improved after valve replacement, the patient died of postoperative pneumonia on postoperative day 45. careful perioperative management can allow successful open heart surgery after renal transplantation. However, severe complications, especially methicillin-resistant Staphylococcus aureus infection, may cause renal graft loss. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

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Yun Wang

2018-03-01

Full Text Available MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII. The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

Chromatographic study of the conformational behavior of graft copolymers with a broad distribution of grafting densities in dilute solutions in selective solvents for grafts

Czech Academy of Sciences Publication Activity Database

Netopilík, Miloš; Janata, Miroslav; Svitáková, Romana; Trhlíková, Olga; Berek, D.; Macova, E.; Limpouchová, Z.; Procházka, K.

2016-01-01

Roč. 39, č. 1 (2016), s. 50-58 ISSN 1082-6076 R&D Projects: GA ČR(CZ) GA13-02938S Grant - others:OPPK(XE) CZ.2.16/3.1.00/24504 Institutional support: RVO:61389013 Keywords : interaction chromatography * size exclusion chromatography * poly(4-methylstyrene)-graft-poly(2-vinylpyridine) Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.697, year: 2016

SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer.

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Chen, Xu; Wang, Ya-Wen; Gao, Peng

2018-05-09

Spindlin1 (SPIN1), a protein highly expressed in several human cancers, has been correlated with tumorigenesis and development. Alterations of drug metabolizing enzymes and drug transporters are major determinants of chemoresistance in tumor cells. However, whether the metabolizing enzymes and transporters are under the control of SPIN1 in breast cancer chemoresistance has not yet been defined. SPIN1 expression in breast cancer cells and tissues was detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Chemosensitivity assays in vitro and in vivo were performed to determine the effect of SPIN1 on Adriamycin resistance. Downstream effectors of SPIN1 were screened by microarray and confirmed by qRT-PCR and Western blot. Luciferase assay and Western blot were used to identify miRNAs regulating SPIN1. We showed that SPIN1 was significantly elevated in drug-resistant breast cancer cell lines and tissues, compared with the chemosensitive ones. SPIN1 enhanced Adriamycin resistance of breast cancer cells in vitro, and downregulation of SPIN1 by miRNA could decrease Adriamycin resistance in vivo. Mechanistically, drug metabolizing enzymes and transporter CYP2C8, UGT2B4, UGT2B17 and ABCB4 were proven to be downstream effectors of SPIN1. Notably, SPIN1 was identified as a direct target of the miR-148/152 family (miR-148a-3p, miR-148b-3p and miR-152-3p). As expected, miR-148a-3p, miR-148b-3p or miR-152-3p could increase Adriamycin sensitivity in breast cancer cells in vitro. Moreover, high expression of SPIN1 or low expression of the miR-148/152 family predicted poorer survival in breast cancer patients. Our results establish that SPIN1, negatively regulated by the miR-148/152 family, enhances Adriamycin resistance in breast cancer via upregulating the expression of drug metabolizing enzymes and drug transporter.

MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R

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Guangnan Chen

2016-02-01

Full Text Available Background/Aims: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. Methods: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR. The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. Results: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. Conclusion: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma.

Upregulation of miR-96 enhances cellular proliferation of prostate cancer cells through FOXO1.

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Benedikta S Haflidadóttir

Full Text Available Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in prostate cancer patients and correlate with WHO grade, and decreased overall survival time; patients with low levels of miR-96 lived 1.5 years longer than patients with high miR-96 levels. The therapeutic potential was further investigated in vitro, showing that ectopic levels of miR-96 enhances growth and cellular proliferation in prostate cancer cells, implying that miR-96 has oncogenic properties in this setting. We demonstrate that miR-96 expression decreases the transcript and protein levels of FOXO1 by binding to one of two predicted binding sites in the FOXO1 3'UTR sequence. Blocking this binding site completely inhibited the growth enhancement conveyed by miR-96. This finding was corroborated in a large external prostate cancer patient cohort where miR-96 expression inversely correlated to FOXO1 expression. Taken together these findings indicate that miR-96 plays a key role in prostate cancer cellular proliferation and can enhance prostate cancer progression. This knowledge might be utilized for the development of novel therapeutic tools for prostate cancer.

Modification on liquid retention property of cassava starch by radiation grafting with acrylonitrile: Pt. 1

International Nuclear Information System (INIS)

Kiatkamjornwong, S.; Nakason, C.; Chvajarempun, J.

1993-01-01

Radiation modification on liquid retention properties of native cassava starch, gelatinized at 85 o C, by graft copolymerization with acrylonitrile was carried out by mutual irradiation to gamma-rays. A thin aluminium foil was used to cover the inner wall of the reaction vessel, so that the homopolymer concentration was reduced to be less than 1.0% with a distilled water retention value of 665 g/g of the dry weight of the saponified grafted product. Confirmation of graft copolymerization and saponification reactions was made by the infrared spectrophotometric technique. The combined effect of radiation parameters in terms of an irradiation time and a dose rate to the total dose on the extent of the grafting reaction expressed in terms of grafting parameters which directly influenced liquid retention values was evaluated in conjunction with statistical analysis. (author)

LincRNA-ROR promotes metastasis and invasion of esophageal squamous cell carcinoma by regulating miR-145/FSCN1

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Shang M

2018-01-01

Full Text Available Muhe Shang, Xianghu Wang, Ying Zhang, Zhikui Gao, Tian Wang, Ran Liu Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China Background and objective: In an attempt to discover a new biomarker for early diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC, the regulation mechanism of large intergenic non-coding RNA–regulator of reprogramming (lincRNA-ROR as a microRNA (miRNA sponge was studied.Patients and methods: ROR expression in 91 pairs of ESCC tissue samples and matched adjacent tissues was quantified with real-time fluorescent quantitative polymerase chain reaction (qRT-PCR. The ROR–miRNA–mRNA regulatory network was built with 161 esophageal cancer (EC tissues and 11 adjacent tumor tissues from The Cancer Genome Atlas (TCGA database. A total of 96 cases of ESCC from TCGA database were collected for analysis on survival rates. The regulatory relationship between ROR, miR-145 and FSCN1 was verified in ESCC cells via qRT-PCR, dual luciferase reporter (DLR assay, RNA immunoprecipitation (RIP and Western blotting. The transwell method was used to detect cell migration and invasion.Results: ROR expression in ESCC tumor tissues was significantly higher than in the adjacent tissues, p<0.001. The survival rate of ESCC patients with high ROR expression levels was lower than that of patients with low ROR expression levels (p<0.001. ROR overexpression could downregulate miR-145 by up to 50% was proven by RIP, DLR assay, and qRT-PCR. Two effective binding sites of ROR to miR-145 were verified by DLR assay. One of the sites has never been cited in the literature. The Western blotting results showed that FSCN1 was a downstream target of ROR/miR-145 (p<0.05. Transwell assays were used to show that overexpression of ROR enhanced migration and invasion behavior of ESCC and miR-145 hindered these effects.Conclusion: ROR acted as a competitive

Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo

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Denis Hélène

2008-12-01

Full Text Available Abstract Background In order to determine whether human prostate can be productively infected by HIV-1 strains with different tropism, and thus represent a potential source of HIV in semen, an organotypic culture of prostate from men undergoing prostatic adenomectomy for benign prostate hypertrophy (BPH was developed. The presence of potential HIV target cells in prostate tissues was investigated using immunohistochemistry. The infection of prostate explants following exposures with HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in culture supernatants, the quantification of HIV DNA in the explants and the detection of HIV RNA+ cells in situ. Results The overall prostate characteristics were retained for 21/2 weeks in culture. Numerous potential HIV-1 target cells were detected in the prostate stroma. Whilst HIV-1 R5SF162 strain consistently productively infected prostatic T lymphocytes and macrophages, the prototypic X4IIIB strain and a primary R5X4 strain showed less efficient replication in this organ. Conclusion The BPH prostate is a site of HIV-1 R5 replication that could contribute virus to semen. A limited spreading of HIV-1 X4 and R5X4 in this organ could participate to the preferential sexual transmission of HIV-1 R5 strains.

MiR-223 suppresses cell proliferation by targeting IGF-1R.

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Cheng You Jia

Full Text Available To study the roles of microRNA-223 (miR-223 in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR-223 was by targeting IGF-1R.

Evaluation of aortocoronary bypass graft patency by reconstructed CT image

International Nuclear Information System (INIS)

Kawakita, Seizaburo; Koide, Takashi; Saito, Yoshio; Yamamoto, Tadao; Iwasaki, Tadaaki

1982-01-01

Ten patients were examined in the period of three months from January to March 1981. The patients were operated from 1 month to 7 years before CT. A bypass to the left anterior descending artery (LAD) was grafted in 10 cases, 2 to the right coronary artery (RCA), 4 to an obtuse marginal artery (OM), and 1 to a diagonal artery. Image reconstruction was performed in 10 cases by using an image analytical computer Evaluskop. Appropriate planes for reconstruction were selected by trial and error methods upon observation of CT images. When gained picture of a graft course coincided with surgical records or angiography, the work of building images was concluded. On cross section, grafts to LAD were visualized in all 10 cases: 9 in the entire course and 1 in a proximal part of the graft. Two to RCA, 4 to OM and 1 to a diagonal were also successfully visualized. Reconstruction of graft images succeeded in 9 grafts of 6 cases. The course of a graft could be pursued from the proximal to the distal end adjacent to the cardiac chamber. The picture of a bypass to LAD was visualized in 6 of 10 grafts. Two bypass to RCA could be depicted, and 1 to OM was also found. However 3 to OM and 1 to a diagonal failed to be visualized throughout their courses in reconstructed images. I think that the causes of faillure mainly depended upon the course of the graft. When a graft was running arc-like surrounding the heart chamber, it was very difficult to depict its entire length in reconstructed images, though the graft could be detected in cross sections. These preliminary studies indicated that reconstruction of CT images had some benefits for the pursuit of graft courses. (J.P.N.)

Differentiation of bone marrow cells to functional T lymphocytes following implantation of thymus grafts and thymic stroma in nude and ATxBM mice

International Nuclear Information System (INIS)

Splitter, G.A.; McGuire, T.C.; Davis, W.C.

1977-01-01

Cardiac allografts were used to compare the immunologic capacity of nude mice and adult, thymectomized, lethally irradiated, bone marrow-reconstituted (AT x BM) mice. Neither nude nor AT x BM mice were able to reject cardiac allografts of any party. However, both rejected grafts of any party following implantation of neonatal thymus or thymus from 3-week-old syngeneic mice. Irradiated syngeneic thymus grafts (800 R) were equally effective in restoring host responsiveness against allografts. In contrast, allogeneic thymus grafts restored the capacity to reject second-party heart grafts only in AT x BM mice. Second-party grafts persisted indefintely when placed on nude mice implanted with an allogeneic, unirradiated thymus graft. Third-party grafts transplanted 17 weeks after reconstitution, however, were rejected. Irradiated nude mice given normal littermate bone marrow and simultaneously grafted with second-party thymus and heart allografts also failed to reject their second-party heart grafts. The difference in ultimate capacity to respond between AT x BM and nude mice suggests that a maturational defect exists in the nude mouse environment which impedes development of precursor T lymphocytes

Adrenal hormones interact with sympathetic innervation to modulate growth of embryonic heart in oculo.

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Tucker, D C; Torres, A

1992-02-01

To allow experimental manipulation of adrenal hormone and autonomic influences on developing myocardium without alteration of hemodynamic load, embryonic rat heart was cultured in the anterior eye chamber of an adult rat. Sympathetic innervation of embryonic day 12 heart grafts was manipulated by surgical sympathectomy of one eye chamber in each host rat. Adrenal hormone exposure was manipulated by host adrenal medullectomy (MEDX) in experiment 1 and by host adrenalectomy (ADX) in experiment 2. In experiment 1, whole heart grafts were larger in MEDX than in sham-operated hosts by 8 wk in oculo (6.14 +/- 0.71 vs. 5.09 +/- 0.69 mm2 with innervation intact and 7.97 +/- 2.07 vs. 3.09 +/- 0.63 mm2 with sympathetic innervation prevented). In experiment 2, host ADX increased growth of embryonic day 12 ventricles grafted into sympathectomized eye chambers (0.69 +/- 0.10 vs. 0.44 +/- 0.04 mm2) but did not affect growth of grafts in intact eye chambers (0.85 +/- 0.09 vs. 1.05 +/- 0.15 mm2). Corticosterone replacement (4 mg/day) entirely reversed the effect of host ADX on graft growth (superior cervical ganglionectomy, 0.47 +/- 0.03 mm2; intact eye chambers, 0.90 +/- 0.91 mm2). Beating rate of grafts was not affected by adrenal hormone manipulations. These experiments indicate that the compromised growth of embryonic heart grafts placed in sympathectomized eye chambers requires exposure to adult levels of glucocorticoids during the early days after grafting. These results suggest that interactions between neural and hormonal stimulation influence cardiac growth in the in oculo culture system and during normal development.

Yogurt Feeding Induced the Prolongation of Fully Major Histocompatibility Complex-Mismatched Murine Cardiac Graft Survival by Induction of CD4+Foxp3+ Cells.

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Uchiyama, M; Yin, E; Yanagisawa, T; Jin, X; Hara, M; Matsuyama, S; Imazuru, T; Uchida, K; Kawamura, M; Niimi, M

Yogurt is a nutrient-rich food and the beneficial effects of yogurt on both health and immunomodulatory effects are well documented. In this pilot study, we investigated the effects of commercially produced yogurt R-1 on alloimmune responses in a murine cardiac transplantation model. The R-1 is produced by Meiji Co., Ltd., and contains live and active lactic acid bacteria (lactobacillus bulgaricus OLL1073R-1) mainly. CBA (H2 k ) mice underwent transplantation of a C57BL/6 (H2 b ; B6) heart and received oral administration of 1 mL, 0.1 mL, and 0.01 mL of R-1 from the day of transplantation until 7 days afterward. Additionally, we prepared one group of CBA recipients given 1 mL of R-1 sterilized by microwave for 7 days. Histological and immunohistochemical studies were performed. Naïve CBA mice rejected B6 cardiac graft acutely (median survival time [MST]: 7 days). CBA recipients given of 1 mL of R-1 had significantly prolonged B6 allograft survival (MST, 27 days). However, other doses of 0.1 mL and 0.01 mL of R-1 did not prolonged allograft survival (MSTs, 9 days and 8.5 days, respectively). Also, CBA recipients administered microwaved R-1 had no prolongation of B6 allograft (MST, 9 days). Histological and immunohistochemical studies showed the cardiac allograft from R-1-exposed CBA recipients had preserved graft and vessel structure and the number of infiltrated CD4 + , CD8 + , and Foxp3 + cells in R-1-exposed CBA recipients increased, respectively. In conclusion, our findings imply that yogurt containing active lactic acid bacteria could change alloimmune responses partially and induce the prolongation of cardiac allograft survival via CD4 + Foxp3 + regulatory cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Coronary blood flow and thallium 201 uptake in rejecting rat heart transplantations

International Nuclear Information System (INIS)

Bergsland, J.; Hwang, K.; Driscoll, R.; Carr, E.A.; Wright, J.R.; Curran-Everett, D.C.; Carroll, M.; Krasney, E.; Krasney, J.A.

1989-01-01

The effects of rejection on coronary flow (CAF) in heart allografts are unclear, although previous evidence with cardiac imaging agents indicates impaired flow during advanced rejection. The purpose of this study was to measure CAF in heterotopically placed heart grafts. Lewis rats (LEW) received grafts from either syngeneic Lewis rats (LEW/LEW group) or allogeneic ACI rats (ACI/LEW group). CAF was measured in both the transplanted and native hearts with radiolabeled microspheres. Rejection was measured histologically (grades 0 [absent] to 4+ [severe]). In addition systemic blood pressure and cardiac outputs of the native hearts were determined with microspheres. Different animals were studied during relatively early (4 days) and late (6 days) rejection. Among the 4-day animals a cyclosporine-treated group was included (ACI/LEW CyA). In 6-day rats CAF in allografts was lower (0.56 +/- .06 ml/gm/min) compared with syngeneic grafts (1.72 +/- 0.4 ml/gm/min) (p less than 0.05). The CAF in the native hearts did not differ significantly but was higher than in the grafts in both groups. Heart rates were reduced in allografts (p less than 0.05). It is interesting that arterial pressure and cardiac output were significantly lower in animals bearing allogeneic than syngeneic grafts. In rats studied at 4 days graft CAF was lower than in the native heart in both the LEW/LEW and ACI/LEW groups, but there was no significant difference in behavior between groups. The same was true for a cyclosporine-treated group. Graft heart rates were similar in all 4-day rats

Inositol-Requiring Enzyme 1-Mediated Downregulation of MicroRNA (miR)-146a and miR-155 in Primary Dermal Fibroblasts across Three TNFRSF1A Mutations Results in Hyperresponsiveness to Lipopolysaccharide.

Science.gov (United States)

Harrison, Stephanie R; Scambler, Thomas; Oubussad, Lylia; Wong, Chi; Wittmann, Miriam; McDermott, Michael F; Savic, Sinisa

2018-01-01

Tumor necrosis factor (TNF)-receptor-associated periodic fever syndrome (TRAPS) is a rare monogenic autoinflammatory disorder characterized by mutations in the TNFRSF1A gene, causing TNF-receptor 1 (TNFR1) misfolding, increased cellular stress, activation of the unfolded protein response (UPR), and hyperresponsiveness to lipopolysaccharide (LPS). Both microRNA (miR)-146a and miR-155 provide negative feedback for LPS-toll-like receptor 2/4 signaling and cytokine production, through regulation of nuclear factor kappa B (NF-κB). In this study, we hypothesized that proinflammatory cytokine signaling in TRAPS downregulates these two miRs, resulting in LPS-induced hyperresponsiveness in TRAPS dermal fibroblasts (DFs), irrespective of the underlying genetic mutation. Primary DF were isolated from skin biopsies of TRAPS patients and healthy controls (HC). TNFR1 cell surface expression was measured using immunofluorescence. DF were stimulated with LPS, interleukin (IL)-1β, thapsigargin, or TNF, with and without inositol-requiring enzyme 1 (IRE1) inhibitor (4u8C), following which miR-146a and miR-155 expression was measured by RT-qPCR. IL-1β, IL-6, and TNF secretion was measured by enzyme-linked immunosorbent assays, and baseline expression of 384 different miRs was assessed using microfluidics assays. TNFR1 was found to be expressed on the surface of HC DF but expression was deficient in all samples with TRAPS-associated mutations. HC DF showed significant dose-dependent increases in both miR-146a and miR-155 expression levels in response to LPS; however, TRAPS DF failed to upregulate either miR-146a or miR-155 under the same conditions. This lack of miR-146a and miR-155 upregulation was associated with increased proinflammatory cytokine production in TRAPS DF in response to LPS challenge, which was abrogated by 4u8C. Incubation of HC DF with IL-1β led to downregulation of miR-146a and miR-155 expression, which was dependent on IRE1 enzyme. We observed global

Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

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Blankenberg, F.G. [Div. of Pediatric Radiology, Stanford, CA (United States); Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A. [Division of Cardiovascular Medicine, Department of Medicine, Stanford, California (United States); Tait, J.F. [Dept. of Laboratory Medicine, Univ. of Washington, Seattle (United States); Post, A.M.; Strauss, H.W. [Div. of Nuclear Medicine, Stanford Univ., CA (United States)

2001-12-01

Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

International Nuclear Information System (INIS)

Blankenberg, F.G.; Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A.; Tait, J.F.; Post, A.M.; Strauss, H.W.

2001-01-01

Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

Conditional RNA interference achieved by Oct-1 POU/rtTA fusion protein activator and a modified TRE-mouse U6 promoter

International Nuclear Information System (INIS)

Fei Zhaoliang; Chen Zheng; Wang Zhugang; Fei Jian

2007-01-01

RNA interference (RNAi) is a powerful technique and is widely used to down-regulate expression of specific genes in cultured cells and in vivo. In this paper, we report our development of a new tetracycline-inducible RNAi expression using a modified TRE-mouse U6 promoter in which the distal sequence element (DSE) was replaced by the tetracycline-responsive element (TRE). The modified TRE-mouse U6 promoter can be activated by a Tet-on version tetracycline-regulated artificial activator rTetOct which was constructed by fusing the rtTA DNA binding domain with the Oct-1 POU activation domain. This rTetOct/TRE-U6 system was successfully applied to conditionally and reversibly down-regulate the expression of endogenous p53 gene in MCF7 cells, and the expression of β-defensin gene (mBin1b) either transiently expressed in COS7 cells or stably expressed in CHO cells

HMGB1 is an independent predictor of death and heart transplantation in heart failure.

Science.gov (United States)

Volz, H C; Laohachewin, D; Schellberg, D; Wienbrandt, A R; Nelles, M; Zugck, C; Kaya, Z; Katus, H A; Andrassy, M

2012-06-01

High-Mobility-Group Box 1 (HMGB1) has been established as an important mediator of myocardial inflammation and associated with progression of heart failure (HF). The aim of this study was to analyze the prognostic value of systemic HMGB1 levels in HF patients with ischemic and non-ischemic cardiomyopathy. We conducted an analysis (median follow-up time 2.5 years) of HMGB1 plasma concentration in 154 patients with systolic HF and correlated the results with disease severity and prognosis. HMGB1 in HF patients with severe symptoms (NYHA III/IV; 5.35 ng/ml; interquartile range (IQR) = 3.48-8.42 ng/ml) was significantly elevated compared with that in patients with mild symptoms (NYHA I/II; 3.37 ng/ml, IQR = 2.31-5.22 ng/ml, p < 0.0001) and with controls (3.25 ng/ml, IQR = 3.04-3.67 ng/ml, p < 0.0001). HMGB1 levels correlated with other markers of heart failure indicating an association of HMGB1 with disease severity in HF. In a univariate cox regression model for the combined endpoint of death and heart transplantation, HMGB1 proved to be a predictor at cut-off values based on HMGB1 terciles of either 3.4 or 6.1 ng/ml (p = 0.001 and p < 0.0001, respectively). In a multivariate cox regression model, which included NT-proBNP, creatinine, age, NYHA class, white blood cell count, anemia, and age, HMGB1 remained an independent predictor of the combined endpoint (hazard ratio (HR) = 2.48, 95% confidence interval (CI) = 1.06-5.83, p = 0.037 and HR = 2.48, 95% CI = 1.31-4.71, p = 0.005, respectively). Our findings demonstrate that HMGB1 plasma concentration is elevated in HF and correlates with disease severity and that is an independent predictor of the combined endpoint death and heart transplantation in HF patients.

Loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury.

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Hilary K Siddall

Full Text Available Mutations in PTEN inducible kinase-1 (PINK1 induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI by preventing mitochondrial dysfunction.Over-expressing PINK1 in HL-1 cardiac cells reduced cell death following simulated IRI (29.2±5.2% PINK1 versus 49.0±2.4% control; N = 320 cells/group P5 animals/group; P<0.05. Cardiomyocytes isolated from PINK1-/- hearts had a lower resting mitochondrial membrane potential, had inhibited mitochondrial respiration, generated more oxidative stress during simulated IRI, and underwent rigor contracture more rapidly in response to an uncoupler when compared to PINK1+/+ cells suggesting mitochondrial dysfunction in hearts deficient in PINK1.We show that the loss of PINK1 increases the heart's vulnerability to ischemia-reperfusion injury. This may be due, in part, to increased mitochondrial dysfunction. These findings implicate PINK1 as a novel target for cardioprotection.

N-acetylcysteine Ameliorates Prostatitis via miR-141 Regulating Keap1/Nrf2 Signaling.

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Wang, Liang-Liang; Huang, Yu-Hua; Yan, Chun-Yin; Wei, Xue-Dong; Hou, Jian-Quan; Pu, Jin-Xian; Lv, Jin-Xing

2016-04-01

Chronic prostatitis was the most common type of prostatitis and oxidative stress was reported to be highly elevated in prostatitis patients. In this study, we determined the effect of N-acetylcysteine (NAC) on prostatitis and the molecular mechanism involved in it. Male Sprague-Dawley rats were divided into three groups: control group (group A, n = 20), carrageenan-induced chronic nonbacterial prostatitis (CNP) model group (group B, n = 20), and carrageenan-induced CNP model group with NAC injection (group C, n = 20). Eye score, locomotion score, inflammatory cell count, cyclooxygenase 2 (COX2) expression, and Evans blue were compared in these three groups. The expression of miR-141 was determined by quantitative real-time PCR (qRT-PCR). Moreover, protein expressions of Kelch-like ECH-associated protein-1 (Keap1) and nuclear factor erythroid-2 related factor 2 (Nrf2) and its target genes were examined by Western blot. Luciferase reporter assay was performed in RWPE-1 cells transfected miR-141 mimic or inhibitor and the plasmid carrying 3'-UTR of Keap1. The value of eye score, locomotion score, inflammatory cell count, and Evans blue were significantly decreased in group C, as well as the expression of COX2, when comparing to that of group B. These results indicated that NAC relieved the carrageenan-induced CNP. Further, we found that NAC increased the expression of miR-141 and activated the Keap1/Nrf2 signaling. Luciferase reporter assay revealed that miR-141 mimic could suppress the activity of Keap1 and stimulate the downstream target genes of Nrf2. In addition, miR-141 inhibitor could reduce the effect of NAC on prostatitis. NAC ameliorates the carrageenan-induced prostatitis and prostate inflammation pain through miR-141 regulating Keap1/Nrf2 signaling.

MiR-19a targets suppressor of cytokine signaling 1 to modulate the progression of neuropathic pain.

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Wang, Conghui; Jiang, Qi; Wang, Min; Li, Dong

2015-01-01

We aimed to investigate whether miR-19a is associated with neuropathic pain and elucidate the underlying regulatory mechanism. We established a neuropathic pain model of bilateral chronic constriction injury (bCCI). Then bCCI rats were injected with mo-miR-19a, siR-SOCS1 or blank expression vector through a microinjection syringe via an intrathecal catheter on 3 day before surgery and after surgery. Behavioral tests, such as mechanical allodynia, thermal hyperalgesia and acetone induced cold allodynia, were performed to evaluate the pain threshold. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the expression of miR-19a and western blotting was carried out to measure the expression of SOCS1. miR-19a expression levels were markedly increased in neuropathic pain models. Moreover, miR-19a significantly attenuated mechanical allodynia and thermal hyperalgesia, and similar results were obtained after knockdown of SOCS1 expression. However, miR-19a markedly increased the times that the rats appeared a sign of cold allodynia, and knockdown of SOCS1 expression had similar effects. Besides, the results of bioinformatics analysis and western blotting analysis were all confirmed that SOCS1 was a direct target of miR-19a in neuropathic pain models. Our finding indicate that SOCS1 is a direct target of miR-19a in neuropathic pain rats and miR-19a may play a critical role in regulating of neuropathic pain via targeting SOCS1.

Cardiac Ablation of Rheb1 Induces Impaired Heart Growth, Endoplasmic Reticulum-Associated Apoptosis and Heart Failure in Infant Mice

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Cao, Yunshan; Tao, Lichan; Shen, Shutong; Xiao, Junjie; Wu, Hang; Li, Beibei; Wu, Xiangqi; Luo, Wen; Xiao, Qi; Hu, Xiaoshan; Liu, Hailang; Nie, Junwei; Lu, Shuangshuang; Yuan, Baiyin; Han, Zhonglin; Xiao, Bo; Yang, Zhongzhou; Li, Xinli

2013-01-01

Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure. PMID:24351823

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery.

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Costanza Emanueli

Full Text Available Exosome nanoparticles carry a composite cargo, including microRNAs (miRs. Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG surgery, we investigated if: 1 exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2 circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn, the current "gold standard" surrogate biomarker of myocardial damage.The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210, non-cardiovascular (miR-122 and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

Acoplamiento molecular y actividad antibacteriana de las tioureas (R,R-N,N´-bis(1-ciclohexiletiltiourea y (R,R-N,N´-bis(1-feniletiltiourea

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Fabían Martínez Flores

2013-05-01

Full Text Available Las tioureas, son compuestos resultantes de sustituir el átomo de oxígeno de la urea (NH2CONH2 por un átomo de azufre (NH2CSNH2. Actualmente se ha visto que las tioureas presentan diversas actividades biológicas, dentro de las que se encuentra la antimicrobiana. En el presente estudio se evaluó la actividad antibacteriana mediante acoplamiento molecular entre la enzima DNA girasa (receptor y las tioureas (R, R-N,N´-bis(1 ciclohexiletiltiourea (CYTU1 y (R,R-N,N´-bis(1-feniletiltiourea (CYTU2 como ligando en busca del posible mecanismo de acción de estos compuestos, los resultados muestran que existe interacción entre la enzima y ambas tioureas en el sitio activo. Por otro lado, también se evaluó la actividad antibacteriana frente a cepas de Sthapylococcus aureus, Escherichia coli y Pseudomonas fluorescens, mediante el método de microdilución en caldo con la adición de bromuro de 3-(4,5-dimetil-2-tiazolil-2,5-difeniltetrazolium (MTT, como parte del ensayo de viabilidad, mostrando una disminución de la misma sólo contra las bacterias gram negativas, siendo la tiourea CYTU2 la que mostró mejor actividad antibacteriana. Molecular docking and antibacterial activity thioureas (R,R-N,N´-bis(1-cyclohexyethylthiourea and (R,R-N,N´-bis(1-phenylethylthiourea Abstract Thioureas are resultant compounds of substitute the oxygen atom from urea (NH2CONH2 for a sulfur atom (NH2CSNH2. There are evidential that show the biological activity of thioureas, within which are antibacterial activity. We studied the antibacterial activity of two thioureas (R,R-N,N´-bis(1 cyclohexylethylthiourea (CYTU1 y (R,R-N,N´-bis(1 phenylethylthiourea (CYTU2 in silico using Molecular Docking between the DNA gyrase enzyme (receptor and the two thioureas (ligand. The results showed interaction between DNA girase and both thioureas on the pocket of the enzyme. By other hand, the biological activity was evaluated against the following bacterial strains: Sthapylococcus

A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells.

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Yang, Chuang; Zhang, Jing-Jing; Peng, Yun-Peng; Zhu, Yi; Yin, Ling-Di; Wei, Ji-Shu; Gao, Wen-Tao; Jiang, Kui-Rong; Miao, Yi

2017-10-19

Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting. A luciferase activity assay, real-time quantitative polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation (ChIP) were also used to identify putative downstream targets of YY1. YY1 was confirmed to regulate autophagy in pancreatic cancer cells. It was found to directly regulate the expression of miR-30a, a known modulator of autophagy-associated genes. Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of YY1. Cumulatively, our data suggest that miR-30a acts in a feedback loop to modulate the pro-autophagic activities of YY1. Thus, autophagy in pancreatic cancer cells may be regulated, in part, by a tightly coordinated YY1/miR-30a regulatory circuit. These findings provide a potential druggable target for the development of treatments for pancreatic cancer.

Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

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Khurram Shahzad

2010-01-01

Full Text Available In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

Thrombin-induced, TNFR-dependent miR-181c downregulation promotes MLL1 and NF-κB target gene expression in human microglia.

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Yin, Min; Chen, Zhiying; Ouyang, Yetong; Zhang, Huiyan; Wan, Zhigang; Wang, Han; Wu, Wei; Yin, Xiaoping

2017-06-29

Controlling thrombin-driven microglial activation may serve as a therapeutic target for intracerebral hemorrhage (ICH). Here, we investigated microRNA (miRNA)-based regulation of thrombin-driven microglial activation using an in vitro thrombin toxicity model applied to primary human microglia. A miRNA array identified 22 differential miRNA candidates. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) identified miR-181c as the most significantly downregulated miRNA. TargetScan analysis identified mixed lineage leukemia-1 (MLL1) as a putative gene target for miR-181c. qRT-PCR was applied to assess tumor necrosis factor-alpha (TNF-α), miR-181c, and MLL1 levels following thrombin or proteinase-activated receptor-4-specific activating peptide (PAR4AP) exposure. Anti-TNF-α antibodies and tumor necrosis factor receptor (TNFR) silencing were employed to test TNF-α/TNFR dependence. A dual-luciferase reporter system and miR-181c mimic transfection assessed whether mir-181c directly binds to and negatively regulates MLL1. Nuclear factor kappa-B (NF-κB)-dependent luciferase reporter assays and NF-κB target gene expression were assessed in wild-type (MLL1+) and MLL1-silenced cells. Thrombin or PAR4AP-induced miR-181c downregulation (p < 0.05) and MLL1 upregulation (p < 0.05) that were dependent upon TNF-α/TNFR. miR-181c decreased wild-type MLL1 3'-UTR luciferase reporter activity (p < 0.05), and a miR-181c mimic suppressed MLL1 expression (p < 0.05). Thrombin treatment increased, while miR-181c reduced, NF-κB activity and NF-κB target gene expression in both wild-type (MLL1+) and MLL1-silenced cells (p < 0.05). Thrombin-induced, TNF-α/TNFR-dependent miR-181c downregulation promotes MLL1 expression, increases NF-κB activity, and upregulates NF-κB target gene expression. As miR-181c opposes thrombin's stimulation of pro-inflammatory NF-κB activity, miR-181c mimic therapy may show promise in controlling thrombin

Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression.

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Xie, Chu-Hai; Cao, Yan-Ming; Huang, Yan; Shi, Qun-Wei; Guo, Jian-Hong; Fan, Zi-Wen; Li, Ju-Gen; Chen, Bin-Wei; Wu, Bo-Yi

2016-11-01

Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma.

Pärt: Collage sur B-A-C-H für Kammerorschester / Hans-Christian Dadelsen

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Dadelsen, Hans-Christian

1993-01-01

Uuest heliplaadist "Pärt: Collage sur B-A-C-H für Kammerorschester, Summa (1991) für Streichorchester, Fratres, Sinfonie Nr. 2, Festina lente, Wenn Bach Bienen gezüchtet hätte, Credo für Klavier, Chor und Orchester. Philharmonia Orchestra and Chorus, Neeme Järvi". Chandos/Koch CD 9134 (WD: 63'02")

MicroRNA-1 overexpression blunts cardiomyocyte hypertrophy elicited by thyroid hormone.

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Diniz, Gabriela Placoná; Lino, Caroline Antunes; Moreno, Camila Rodrigues; Senger, Nathalia; Barreto-Chaves, Maria Luiza Morais

2017-12-01

It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated. Neonatal rat cardiac myocytes (NRCMs) were treated with T 3 for 24 hr and Wistar rats were subjected to hyperthyroidism for 14 days combined or not with AT1R blocker. Real Time RT-PCR analysis indicated that miR-1 expression was decreased in cardiac hypertrophy in response to TH in vitro and in vivo, and this effect was unchanged by AT1R blocker. In addition, HDAC4, which is target of miR-1, was increased in NRCMs after T 3 treatment. A gain-of-function study revealed that overexpression of miR-1 prevented T 3 -induced cardiomyocyte hypertrophy and reduced HADC4 mRNA levels in NRCMs. In vivo experiments confirmed the downregulation of miR-1 in cardiac tissue from hyperthyroid animals, which was accompanied by increased HDAC4 mRNA levels. In addition, HDAC inhibitor prevented T 3 -induced cardiomyocyte hypertrophy. Our data reveal a new mechanistic insight into cardiomyocyte growth in response to TH, suggesting that miR-1 plays a role in cardiomyocyte hypertrophy induced by TH potentially via targeting HADC4. © 2017 Wiley Periodicals, Inc.

Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR.

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Shukla, Mohan K; Singh, Neeru; Sharma, Ravendra K; Barde, Pradip V

2017-07-01

The objective of this study was to demonstrate the utility of dengue virus (DENV) non structural protein 1 (NS1) based rapid diagnostic test (RDT) for use in tribal and difficult to reach areas for early dengue (DEN) diagnosis in acute phase patients and evaluate its sensitivity and specificity against DENV NS1 enzyme linked immune sorbent assay (ELISA) and real time reverse transcriptase polymerase chain reaction (qRT-PCR). The DENV NS1 RDT was used for preliminary diagnosis during outbreaks in difficult to reach rural and tribal areas. The diagnosis was confirmed by DENV NS1 ELISA in the laboratory. The samples were also tested and serotyped by qRT-PCR. The results were evaluated using statistical tests. The DENV NS1 RDT showed 99.2% sensitivity and 96.0% specificity when analyzed using DENV NS1 ELISA as standard. The specificity and sensitivity of the RDT when compared with qRT-PCR was 93.6% and 91.1%, respectively. The serotype specific evaluation showed more than 90% sensitivity and specificity for DENV-1, 2, and 3. The RDT proved a good diagnostic tool in difficult to reach rural and tribal areas. Further evaluation studies with different commercially available RDTs in different field conditions are essential, that will help clinicians and patients for treatment and programme managers for timely intervention. © 2017 Wiley Periodicals, Inc.

Transgenic overexpression of adenine nucleotide translocase 1 protects ischemic hearts against oxidative stress.

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Klumpe, Inga; Savvatis, Konstantinos; Westermann, Dirk; Tschöpe, Carsten; Rauch, Ursula; Landmesser, Ulf; Schultheiss, Heinz-Peter; Dörner, Andrea

2016-06-01

Ischemia impairs the adenine nucleotide translocase (ANT), which transports ADP and ATP across the inner mitochondrial membrane. We investigated whether ANT1 overexpression has protective effects on ischemic hearts. Myocardial infarction was induced in wild-type (WT) and heart-specific ANT1-transgenic (ANT1-TG) rats, and hypoxia was set in isolated cardiomyocytes. ANT1 overexpression reduced the myocardial infarct area and increased the survival rate of infarcted rats. Reduced ANT1 expression and increased 4-hydroxynonenal modification of ANT paralleled to impaired ANT function in infarcted WT hearts. ANT1 overexpression improved ANT expression and function. This was accompanied by reduced mitochondrial cytochrome C release and caspase-3 activation. ANT1-TG hearts suffered less from oxidative stress, as shown by lower protein carbonylation and 4-hydroxynonenal modification of ANT. ANT1 overexpression also increased cell survival of hypoxic cardiomyocytes and attenuated reactive oxygen species (ROS) production. This was linked to higher stability of mitochondrial membrane potential and lower activity of ROS detoxifying catalase. ANT1-TG cardiomyocytes also showed higher resistance against H2O2 treatment, which was independent of catalase activity. In conclusion, ANT1 overexpression compensates impaired ANT activity under oxygen-restricted conditions. It reduces ROS production and oxidative stress, stabilizes mitochondrial integrity, and increases survival, making ANT1 a component in ROS management and heart protection during ischemia. ANT1 overexpression reduces infarct size and increases survival after infarction. ANT1 overexpression compensates restricted ANT expression and function in infarcted hearts. Increased ANT1 expression enhances mitochondrial integrity. ANT1-overexpressing hearts reduce oxidative stress by decreasing ROS generation. ANT1 is a component in ROS management and heart protection.

Active inhibitor-1 maintains protein hyper-phosphorylation in aging hearts and halts remodeling in failing hearts.

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Pritchard, Tracy J; Kawase, Yoshiaki; Haghighi, Kobra; Anjak, Ahmad; Cai, Wenfeng; Jiang, Min; Nicolaou, Persoulla; Pylar, George; Karakikes, Ioannis; Rapti, Kleopatra; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

2013-01-01

Impaired sarcoplasmic reticulum calcium cycling and depressed contractility are key characteristics in heart failure. Defects in sarcoplasmic reticulum function are characterized by decreased SERCA2a Ca-transport that is partially attributable to dephosphorylation of its regulator phospholamban by increased protein phosphatase 1 activity. Inhibition of protein phosphatase 1 through activation of its endogenous inhibitor-1 has been shown to enhance cardiac Ca-handling and contractility as well as protect from pathological stress remodeling in young mice. In this study, we assessed the long-term effects of inducible expression of constitutively active inhibitor-1 in the adult heart and followed function and remodeling through the aging process, up to 20 months. Mice with inhibitor-1 had normal survival and similar function to WTs. There was no overt remodeling as evidenced by measures of left ventricular end-systolic and diastolic diameters and posterior wall dimensions, heart weight to tibia length ratio, and histology. Higher phosphorylation of phospholamban at both Ser16 and Thr17 was maintained in aged hearts with active inhibitor-1, potentially offsetting the effects of elevated Ser2815-phosphorylation in ryanodine receptor, as there were no increases in arrhythmias under stress conditions in 20-month old mice. Furthermore, long-term expression of active inhibitor-1 via recombinant adeno-associated virus type 9 gene transfer in rats with pressure-overload induced heart failure improved function and prevented remodeling, associated with increased phosphorylation of phospholamban at Ser16 and Thr17. Thus, chronic inhibition of protein phosphatase 1, through increases in active inhibitor-1, does not accelerate age-related cardiomyopathy and gene transfer of this molecule in vivo improves function and halts remodeling in the long term.

Direct STM evidence of a surface interaction between chiral modifier and pro-chiral reagent: Methylacetoacetate on R, R-tartaric acid modified Ni {1 1 1}

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Jones, T. E.; Baddeley, C. J.

2002-11-01

The asymmetric hydrogenation of methylacetoacetate to R-methyl-3-hydroxybutyrate over R, R-tartaric acid modified Ni catalysts is a well known example of heterogeneous enantioselective catalysis. Using STM, RAIRS and TPD, we investigate the adsorption of methylacetoacetate on Ni{1 1 1} and R, R-TA modified Ni{1 1 1} in order to shed light on the molecular mechanisms underlying the enantioselective catalysis. We show that methylacetoacetate adsorption can only occur in regions of low R, R-tartaric acid coverage. Once adsorption occurs, methylacetoacetate is able to locally rearrange the tartrate modifiers to produce a two-dimensional co-crystal. We consider the implications of our work in explaining the mechanism of enantioselective hydrogenation in this type of system.

Penerapan Metode Diagnosis Cepat Virus Avian Influenza H5N1 dengan Metode Single Step Multiplex RT-PCR

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Aris Haryanto

2010-12-01

Full Text Available Avian influenza (AI virus is a segmented single stranded (ss RNA virus with negative polarity andbelong to the Orthomyxoviridae family. Diagnose of AI virus can be performed using conventional methodsbut it has low sensitivity and specificity. The objective of the research was to apply rapid, precise, andaccurate diagnostic method for AI virus and also to determine its type and subtype based on the SingleStep Multiplex Reverse Transcriptase-Polymerase Chain Reaction targeting M, H5, and N1 genes. In thismethod M, H5 and NI genes were simultaneously amplified in one PCR tube. The steps of this researchconsist of collecting viral RNAs from 10 different AI samples originated from Maros Disease InvestigationCenter during 2007. DNA Amplification was conducted by Simplex RT-PCR using M primer set. Then, bysingle step multiplex RT-PCR were conducted simultaneously using M, H5 and N1 primers set. The RTPCRproducts were then separated on 1.5% agarose gel, stained by ethidum bromide and visualized underUV transilluminator. Results showed that 8 of 10 RNA virus samples could be amplified by Simplex RTPCRfor M gene which generating a DNA fragment of 276 bp. Amplification using multiplex RT-PCRmethod showed two of 10 samples were AI positive using multiplex RT-PCR, three DNA fragments weregenerated consisting of 276 bp for M gene, 189 bp for H5 gene, and 131 bp for N1. In this study, rapid andeffective diagnosis method for AI virus can be conducted by using simultaneous Single Step Multiplex RTPCR.By this technique type and subtype of AI virus, can also be determined, especially H5N1.

Notch1 Mediates Preconditioning Protection Induced by GPER in Normotensive and Hypertensive Female Rat Hearts

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Carmine Rocca

2018-05-01

Full Text Available G protein-coupled estrogen receptor (GPER is an estrogen receptor expressed in the cardiovascular system. G1, a selective GPER ligand, exerts cardiovascular effects through activation of the PI3K-Akt pathway and Notch signaling in normotensive animals. Here, we investigated whether the G1/GPER interaction is involved in the limitation of infarct size, and improvement of post-ischemic contractile function in female spontaneous hypertensive rat (SHR hearts. In this model, we also studied Notch signaling and key components of survival pathway, namely PI3K-Akt, nitric oxide synthase (NOS and mitochondrial K+-ATP (MitoKATP channels. Rat hearts isolated from female SHR underwent 30 min of global, normothermic ischemia and 120 min of reperfusion. G1 (10 nM alone or specific inhibitors of GPER, PI3K/NOS and MitoKATP channels co-infused with G1, just before I/R, were studied. The involvement of Notch1 was studied by Western blotting. Infarct size and left ventricular pressure were measured. To confirm endothelial-independent G1-induced protection by Notch signaling, H9c2 cells were studied with specific inhibitor, N-[N-(3,5 difluorophenacetyl-L-alanyl]-S-phenylglycine t-butyl ester (DAPT, 5 μM, of this signaling. Using DAPT, we confirmed the involvement of G1/Notch signaling in limiting infarct size in heart of normotensive animals. In the hypertensive model, G1-induced reduction in infarct size and improvement of cardiac function were prevented by the inhibition of GPER, PI3K/NOS, and MitoKATP channels. The involvement of Notch was confirmed by western blot in the hypertensive model and by the specific inhibitor in the normotensive model and cardiac cell line. Our results suggest that GPERs play a pivotal role in mediating preconditioning cardioprotection in normotensive and hypertensive conditions. The G1-induced protection involves Notch1 and is able to activate the survival pathway in the presence of comorbidity. Several pathological conditions

Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

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Sariñana, Joshua; Tonegawa, Susumu

2017-01-01

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222

The combinatorial PP1-binding consensus Motif (R/Kx( (0,1V/IxFxx(R/Kx(R/K is a new apoptotic signature.

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Angélique N Godet

Full Text Available BACKGROUND: Previous studies established that PP1 is a target for Bcl-2 proteins and an important regulator of apoptosis. The two distinct functional PP1 consensus docking motifs, R/Kx((0,1V/IxF and FxxR/KxR/K, involved in PP1 binding and cell death were previously characterized in the BH1 and BH3 domains of some Bcl-2 proteins. PRINCIPAL FINDINGS: In this study, we demonstrate that DPT-AIF(1, a peptide containing the AIF(562-571 sequence located in a c-terminal domain of AIF, is a new PP1 interacting and cell penetrating molecule. We also showed that DPT-AIF(1 provoked apoptosis in several human cell lines. Furthermore, DPT-APAF(1 a bi-partite cell penetrating peptide containing APAF-1(122-131, a non penetrating sequence from APAF-1 protein, linked to our previously described DPT-sh1 peptide shuttle, is also a PP1-interacting death molecule. Both AIF(562-571 and APAF-1(122-131 sequences contain a common R/Kx((0,1V/IxFxxR/KxR/K motif, shared by several proteins involved in control of cell survival pathways. This motif combines the two distinct PP1c consensus docking motifs initially identified in some Bcl-2 proteins. Interestingly DPT-AIF(2 and DPT-APAF(2 that carry a F to A mutation within this combinatorial motif, no longer exhibited any PP1c binding or apoptotic effects. Moreover the F to A mutation in DPT-AIF(2 also suppressed cell penetration. CONCLUSION: These results indicate that the combinatorial PP1c docking motif R/Kx((0,1V/IxFxxR/KxR/K, deduced from AIF(562-571 and APAF-1(122-131 sequences, is a new PP1c-dependent Apoptotic Signature. This motif is also a new tool for drug design that could be used to characterize potential anti-tumour molecules.

1/ r potential in higher dimensions

Science.gov (United States)

Chakraborty, Sumanta; Dadhich, Naresh

2018-01-01

In Einstein gravity, gravitational potential goes as 1/r^{d-3} in d non-compactified spacetime dimensions, which assumes the familiar 1 / r form in four dimensions. On the other hand, it goes as 1/r^{α }, with α =(d-2m-1)/m, in pure Lovelock gravity involving only one mth order term of the Lovelock polynomial in the gravitational action. The latter offers a novel possibility of having 1 / r potential for the non-compactified dimension spectrum given by d=3m+1. Thus it turns out that in the two prototype gravitational settings of isolated objects, like black holes and the universe as a whole - cosmological models, the Einstein gravity in four and mth order pure Lovelock gravity in 3m+1 dimensions behave in a similar fashion as far as gravitational interactions are considered. However propagation of gravitational waves (or the number of degrees of freedom) does indeed serve as a discriminator because it has two polarizations only in four dimensions.

Data of evolutionary structure change: 1R1YC-2ZLWD [Confc[Archive

Lifescience Database Archive (English)

Full Text Available 1R1YC-2ZLWD 1R1Y 2ZLW C D -VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPT...R VQLSGEEKAAVLALWDKVN--EEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSEL...ex> 2ZLW D 2ZLWD WDK

Correlation between NFATC1 gene polymorphisms and congenital heart disease in children.

Science.gov (United States)

Li, C-L; Niu, L; Fu, M-Y; Tian, J; Wang, Q-W; An, X-J

2017-08-01

To analyze the links between NFATC1 gene polymorphism and congenital heart disease in children. In the present study, we selected 85 children patients with congenital heart disease who were hospitalized from February 2013 to February 2015 as research subjects (observation group), and 92 healthy subjects as control group. Restriction fragment length polymorphism (RFLP) was used for analysis of NFATC1 gene in samples from each group. The distribution of NFATC1 genotype and allele between the observation group (children with congenital heart disease) and the control group showed no significant difference (p >0.05), but AA, GG genotypes, and allele frequency between pathological samples of children with congenital heart disease and the control group displayed significant difference (p congenital heart disease in observation group also showed a difference, i.e., homozygote (AA, GG) ratio in children with severe congenital heart disease is relatively high. There is a correlation between NFATC1 genes and the incidence of congenital heart disease in children, and a correlation between different genotypes and allele frequency and the incidence of the disease.

Development of an In-House Multiplex Nested RT-PCR Method for Detecting Acute HIV-1 Infection in High Risk Populations.

Science.gov (United States)

Liu, Zhiying; Li, Wei; Xu, Meng; Sheng, Bo; Yang, Zixuan; Jiao, Yanmei; Zhang, Tong; Mou, Danlei; Chen, Dexi; Wu, Hao

2015-01-01

The detection of acute HIV infection (AHI) among high risk populations can help reduce secondary transmission of HIV. The nucleic acid testing (NAT) can shorten the test window period by up to 7-12 days. In this study, we describe an in-house NAT based on the multiplex nested RT-PCR method to detect the HIV RNA. We also evaluated it in a high risk cohort in Beijing. Four primer pairs were designed and evaluated for the detection of different HIV-1 subtypes in group M. Multiplex RT-PCR and nested PCR were performed. The sensitivity, specialty, primers compatibility among HIV subtypes were evaluated simultaneously. In an MSM cohort in Beijing during a 3-year period, a total of 11,808 blood samples that were negative by ELISA or indeterminate by Western blot were analyzed by this multiplex nested RT-PCR with pooling strategy. The multiplex nested RT-PCR was successfully applied for the detection of at least six HIV-1 subtypes. The sensitivity was 40 copies/ml and the specificity was 100%. A total of 29 people were tested HIV-1 positive with acute infection in a MSM cohort of Beijing during a 3 years period. This multiplex nested RT-PCR provides a useful tool for the rapid detection of acute HIV-1 infection. When used in combination with the 3(rd) generation ELISA, it can improve the detection rate of HIV infection, especially in the source limited regions.

Erectile dysfunction and pcsychoemotional state in ischemic heart disease patients undergone coronary artery bypass grafting

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Ye. V. Pomeshkin

2012-01-01

Full Text Available The impact of erectile dysfunction on psychoemotional state of patients undergone coronary artery bypass graft surgery was evaluated. The International Index of Erectile Function, postcompression cavernous artery dilation test, nocturnal penile tumescence recording and psychophysiological exam were used. It was found that ischemic heart disease patients have higher incidence of associated psychoemotional and erectile dysfunctions.

Biotransformation of (-)-(1R,4S)-Menthone and (+)-(1S,4R)-Menthone by the Common Cutworm Spodoptera litura Larvae.

Science.gov (United States)

Marumoto, Shinsuke; Okuno, Yoshiharu; Hagiwara, Yuki; Miyazawa, Mitsuo

2017-08-01

Using biotransformation as a biocatalytic process has the advantage of being able to proceed under mild conditions and with high regio- and enantioselectivity. This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)-(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)-(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,3S,4S)-7-hydroxyneomenthol (1-2) and (-)-(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2 generated three enantiomers of the above metabolites, designated as 2-1 to 2-3, respectively. The C-9 position of (-)-menthone and (+)-menthone was oxidized to carboxylic acid by S. litura, which is a metabolic pathway not observed in any other example of biocatalysis.

Pre-operative high sensitive C-reactive protein predicts cardiovascular events after coronary artery bypass grafting surgery: A prospective observational study

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Balciunas Mindaugas

2009-01-01

Full Text Available C-reactive protein is a powerful independent predictor of cardiovascular events in patients with coronary artery disease. The relation between C-reactive protein (CRP concentration and in-hospital outcome, after coronary artery bypass grafting (CABG, has not yet been established. The study aims to evaluate the predictive value of pre-operative CRP for in-hospital cardiovascular events after CABG surgery. High-sensitivity CRP (hs-CRP levels were measured pre-operatively on the day of surgery in 66 patients scheduled for elective on pump CABG surgery. Post-operative cardiovascular events such as death from cardiovascular causes, ischemic stroke, myocardial damage, myocardial infarction and low output heart failure were recorded. During the first 30 days after surgery, 54 patients were free from observed events and 14 developed the following cardiovascular events: 10 (15% had myocardial damage, four (6% had low output heart failure and two (3% suffered stroke. No patients died during the follow-up period. Serum concentration of hs-CRP ≥ 3.3 mg/l (cut-off point obtained by ROC analysis was related to higher risk of post-operative cardiovascular events (36% vs 6%, P = 0.01, myocardial damage (24% vs 6%, P = 0.04 and low output heart failure (12% vs 0%, P = 0.04. Multivariate logistic regression analysis showed that hs-CRP ≥ 3.3 mg/l ( P = 0.002, O.R.: 19.3 (95% confidence interval (CI 2.9-128.0, intra-operative transfusion of red blood cells ( P = 0.04, O.R.: 9.9 (95% C.I. 1.1-85.5 and absence of diuretics in daily antihypertensive treatment ( P = 0.02, O.R.: 15.1 (95% C.I. 1.4-160.6 were independent predictors of combined cardiovascular event. Patients having hs-CRP value greater or equal to 3.3 mg/l pre-operatively have an increased risk of post-operative cardiovascular events after on pump coronary artery bypass grafting surgery.

Fetal growth restriction and the programming of heart growth and cardiac insulin-like growth factor 2 expression in the lamb.

Science.gov (United States)

Wang, Kimberley C W; Zhang, Lei; McMillen, I Caroline; Botting, Kimberley J; Duffield, Jaime A; Zhang, Song; Suter, Catherine M; Brooks, Doug A; Morrison, Janna L

2011-10-01

Reduced growth in fetal life together with accelerated growth in childhood, results in a ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in patterns of body and heart growth in early life can lead to an increased risk of cardiovascular disease in adulthood. We aimed to investigate the role of the insulin-like growth factors in heart growth in the growth-restricted fetus and lamb. Hearts were collected from control and placentally restricted (PR) fetuses at 137-144 days gestation and from average (ABW) and low (LBW) birth weight lambs at 21 days of age. We quantified cardiac mRNA expression of IGF-1, IGF-2 and their receptors, IGF-1R and IGF-2R, using real-time RT-PCR and protein expression of IGF-1R and IGF-2R using Western blotting. Combined bisulphite restriction analysis was used to assess DNA methylation in the differentially methylated region (DMR) of the IGF-2/H19 locus and of the IGF-2R gene. In PR fetal sheep, IGF-2, IGF-1R and IGF-2R mRNA expression was increased in the heart compared to controls. LBW lambs had a greater left ventricle weight relative to body weight as well as increased IGF-2 and IGF-2R mRNA expression in the heart, when compared to ABW lambs. No changes in the percentage of methylation of the DMRs of IGF-2/H19 or IGF-2R were found between PR and LBW when compared to their respective controls. In conclusion, a programmed increased in cardiac gene expression of IGF-2 and IGF-2R may represent an adaptive response to reduced substrate supply (e.g. glucose and/or oxygen) in order to maintain heart growth and may be the underlying cause for increased ventricular hypertrophy and the associated susceptibility of cardiomyocytes to ischaemic damage later in life.

Growth inhibition of human pancreatic cancer cells by lipofection mediated IGF-1R antisense oligodeoxynucletides in combination with ionizing radiation

International Nuclear Information System (INIS)

Pan Yaozhen; Sun Chengyi; Wang Yuzhi

2004-01-01

Objective: To study the growth inhibition of human pancreatic cancer cells (PC-3) by lipofection-mediated and ionizing radiation improving transfection of IGF-1R antisense oligodeoxynucletides (ASON) in vitro. Methods: Colonigenicity of PC-3 cells in vitro after 60 Co γ-radiation was observed for ascertaining their radiosensitivity and optimal radiation dose was selected according to the radiation sensitivity. PC-3 cells were transfected by two ways: 1) by lipofection-mediated IGF-1R ASON combined with ionizing radiation. 2) by lipo-ASON alone without ionizing radiation. Cell growth was assessed by MTT method. The expression of IGF-1R at mRNA level was examined by RT-PCR. Flow cytometry was used to demonstrate apoptotic changes in lipo-ASON-treated cells. Results: The inhibitory efficiency of lipo-ASON combined with ionizing radiation was higher than that without ionizing radiation (P < 0.05). The apoptotic efficiency and the decreased level of IGF-1R at mRNA were significantly improved (P < 0.05). Conclusion: Lipofection-mediated and ionizing radiation-promoted transfection of IGF-1R antisense oligodeoxynucletides (ASON) significantly decreases IGF-1R at mRNA level and induces apoptosis of human pancreatic cancer cells in vitro

Synthesis, physical and chemical properties, antihypoxic activity of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-t

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V. M. Odyntsova

2018-03-01

Full Text Available Today, an increase of natural and technogenic situations leads to the disorders of the central nervous system, functional-metabolic processes, vascular diseases, in particular, acute cerebral blood flow disorders. In addition, the changes occurring on the molecular and cellular levels are in the basis of the functional violations of individual systems and the organism as a whole. Hypoxia not only complicates the disease course, but in most cases, determines its outcome. The important role in the fight against hypoxia belongs to antioxidants, which improve the circulating oxygen utilization by the body, reduce its need for the organs and tissues, which is not only expedient but necessary for the treatment of many acute and chronic pathological processes. So, the frequency of the hypoxic states and a wide range of factors causing them determine the relevance of new ways and methods finding to overcome the oxygen deficiency. The aim of this work is the purposeful search of some 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl-4-R-4H-1,2,4-triazole-3-ylthiomethyl]-4-R1-4H-1,2,4-triazole-3-thiols, the study of their physical and chemical properties and pharmacological screening of the antihypoxic activity of the obtained compounds. Materials and methods. The study of physical and chemical properties was conducted on certified and licensed modern equipment. Antihypoxic activity was studied during the modeling process of hypoxia with hypercapnia. Mexidol was used as a comparison drug in studies at a dose of 100 mg/kg. Results. As the result of the study, it was found that the synthesized compounds and the comparison drug influenced on rats’ life span differently. Compounds, the antihypoxic activity of which exceeded control have been discovered, and others’ were at the level of Mexidol. A number of compounds showed a somewhat less activity in comparison with control, and two

Optically active antifungal azoles. XII. Synthesis and antifungal activity of the water-soluble prodrugs of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone.

Science.gov (United States)

Ichikawa, T; Kitazaki, T; Matsushita, Y; Yamada, M; Hayashi, R; Yamaguchi, M; Kiyota, Y; Okonogi, K; Itoh, K

2001-09-01

1-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1: TAK-456) was selected as a candidate for clinical trials, but since its water-solubility was insufficient for an injectable formulation, the quaternary triazolium salts 2 were designed as water-soluble prodrugs. Among the prodrugs prepared, 4-acetoxymethyl-1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-1-terazolyl)phenyl]-1-imidazolidinyl]butyl]-1H-1,2,4-triazolium chloride (2a: TAK-457) was selected as an injectable candidate for clinical trials based on the results of evaluations on solubility, stability, hemolytic effect and in vivo antifungal activities.

R-ES-ONANCE--IJU-1y

Indian Academy of Sciences (India)

many life processes are periodic - from heart's beat to the leopard's spots. Let us consider the famous Lotka-Volterra mechanism (see Box 1), which ... The same book goes on to explain the action of a catalyst as resulting from a reduction of ...

Preliminary studies on 1-vinyl-2-pyrrolidone grafting onto cellulose by pre-irradiation method

Energy Technology Data Exchange (ETDEWEB)

Severich, Patrick; Dutra, Rodrigo da Costa; Kodama, Yasko, E-mail: ykodama@ipen.br, E-mail: patrick.severich@ipen.br, E-mail: rodrigo.dutra@ipen.br [Instituto de Pesquisas Energética s e Nucleares (IPEN-CNEN/SP), São Paulo, SP (Brazil)

2017-07-01

Cellulose is considered a renewable biopolymer most abundant in nature. Better functional surfaces can be Obtained by modifying cellulose. On the other hand, poly vinyl pyrrolidone, PVP, is a synthetic nontoxic, water-soluble polymer frequently used in an extensive variety of applications including several pharmaceutical applications. Grafting 1-vinyl-2-pyrrolidone, NVP, onto polymeric cellulose can be obtained by ionizing radiation. Ionizing radiation grafting can be affected by several factors as environment, solvent, monomer concentration, temperature of graft reaction. Grafting by ionizing radiation can be performed by three methods, pre-irradiation, oxidation by peroxide and simultaneous irradiation. In this study, it was used pre-irradiation method of cellulose. Paper filter without ash, NVP without purification was used in this study. Paper samples were exposed to electron beam from Dynamitron Accelerator with radiation absorbed dose of 25 kGy. Influence of NVP concentration, temperature of reaction after irradiation on degree of grafting (DG) was studied. Also, cellulose radicals of grafted paper samples was studied by electron paramagnetic resonance using a Bruker X-band ESR at room temperature just after heating reaction. Small decrease of cellulose radicals was observed with increasing reaction temperature. It was observed DG small increase with increasing concentration of monomer in solution of water ethanol 50-50 v:v and rising temperature of reaction. Further tests using simultaneous method of grafting of NVP in cellulose paper, in water:ethanol 75:25 v:v solution, induced by gamma irradiation were performed. It was observed homopolymerization forming PVP with increasing monomer concentration. (author)

Preliminary studies on 1-vinyl-2-pyrrolidone grafting onto cellulose by pre-irradiation method

International Nuclear Information System (INIS)

Severich, Patrick; Dutra, Rodrigo da Costa; Kodama, Yasko

2017-01-01

Cellulose is considered a renewable biopolymer most abundant in nature. Better functional surfaces can be Obtained by modifying cellulose. On the other hand, poly vinyl pyrrolidone, PVP, is a synthetic nontoxic, water-soluble polymer frequently used in an extensive variety of applications including several pharmaceutical applications. Grafting 1-vinyl-2-pyrrolidone, NVP, onto polymeric cellulose can be obtained by ionizing radiation. Ionizing radiation grafting can be affected by several factors as environment, solvent, monomer concentration, temperature of graft reaction. Grafting by ionizing radiation can be performed by three methods, pre-irradiation, oxidation by peroxide and simultaneous irradiation. In this study, it was used pre-irradiation method of cellulose. Paper filter without ash, NVP without purification was used in this study. Paper samples were exposed to electron beam from Dynamitron Accelerator with radiation absorbed dose of 25 kGy. Influence of NVP concentration, temperature of reaction after irradiation on degree of grafting (DG) was studied. Also, cellulose radicals of grafted paper samples was studied by electron paramagnetic resonance using a Bruker X-band ESR at room temperature just after heating reaction. Small decrease of cellulose radicals was observed with increasing reaction temperature. It was observed DG small increase with increasing concentration of monomer in solution of water ethanol 50-50 v:v and rising temperature of reaction. Further tests using simultaneous method of grafting of NVP in cellulose paper, in water:ethanol 75:25 v:v solution, induced by gamma irradiation were performed. It was observed homopolymerization forming PVP with increasing monomer concentration. (author)

Early physical training and psycho-educational intervention for patients undergoing coronary artery bypass grafting. The SheppHeart randomized 2 × 2 factorial clinical pilot trial.

Science.gov (United States)

Højskov, Ida E; Moons, Philip; Hansen, Niels V; Greve, Helle; Olsen, Dorte Bæk; Cour, Søren La; Glud, Christian; Winkel, Per; Lindschou, Jane; Egerod, Ingrid; Christensen, Anne Vinggaard; Berg, Selina Kikkenborg

2016-10-01

Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility, pain and insufficient sleep. Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising. However, no randomized clinical trials have tested a comprehensive rehabilitation programme consisting of both physical exercise and psycho-education in the early rehabilitation phase. The aims of the present SheppHeart pilot randomized clinical trial were to evaluate the feasibility of patient recruitment, patient acceptance of the intervention, safety and tolerability of the intervention. Sixty patients admitted for coronary artery bypass graft were randomized 1:1:1:1 to: 1) physical exercise plus usual care, or 2) psycho-educational intervention plus usual care, or 3) physical exercise and psycho-educational plus usual care, or 4) usual care alone during a four week period after surgery. The acceptability of trial participation was 67% during the three month recruitment period. In the physical exercise groups, patients complied with 59% of the total expected training sessions during hospitalization. Nine patients (30%) complied with >75% and nine patients (30%) complied with 50% of the planned exercise sessions. Eleven patients (42%) participated in ⩾75% of the four consultations and six patients (23%) participated in 50% of the psycho-educational programme. Comprehensive phase one rehabilitation combining physical exercise and psycho-education in coronary artery bypass graft patients shows reasonably high inclusion, feasibility and safety. © The European Society of Cardiology 2015.

1/r potential in higher dimensions

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, Sumanta [Indian Association for the Cultivation of Science, Department of Theoretical Physics, Kolkata (India); IUCAA, Pune (India); Dadhich, Naresh [IUCAA, Pune (India); Center for Theoretical Physics, New Delhi (India)

2018-01-15

In Einstein gravity, gravitational potential goes as 1/r{sup d-3} in d non-compactified spacetime dimensions, which assumes the familiar 1/r form in four dimensions. On the other hand, it goes as 1/r{sup α}, with α = (d - 2m - 1)/m, in pure Lovelock gravity involving only one mth order term of the Lovelock polynomial in the gravitational action. The latter offers a novel possibility of having 1/r potential for the non-compactified dimension spectrum given by d = 3m + 1. Thus it turns out that in the two prototype gravitational settings of isolated objects, like black holes and the universe as a whole - cosmological models, the Einstein gravity in four and mth order pure Lovelock gravity in 3m + 1 dimensions behave in a similar fashion as far as gravitational interactions are considered. However propagation of gravitational waves (or the number of degrees of freedom) does indeed serve as a discriminator because it has two polarizations only in four dimensions. (orig.)

Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence

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Sung-Hyun Park

2016-02-01

Full Text Available Abstract Background Spindle assembly checkpoint components BubR1 and Sgo1 play a key role in the maintenance of chromosomal instability during cell division. These proteins function to block the anaphase entry until all condensed chromosomes have been attached by the microtubules emanating from both spindle poles. Haplo-insufficiency of either BubR1 or SGO1 results in enhanced chromosomal instability and tumor development in the intestine. Recent studies show that spindle checkpoint proteins also have a role in slowing down the ageing process. Therefore, we want to study whether haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence in mice. Methods We took advantage of the availability of BubR1 and SGO1 knockout mice and generated primary murine embryonic fibroblasts (MEFs with mutations in either BubR1, SGO1, or both and analyzed cellular senescence of the MEFs of various genetic backgrounds. Results We observed that BubR1 +/− SGO +/− MEFs had an accelerated cellular senescence characterized by morphological changes and expressed senescence-associated β-galactosidase. In addition, compared with wild-type MEFs or MEFs with a single gene deficiency, BubR1 +/− SGO1 +/− MEFs expressed enhanced levels of p21 but not p16. Conclusions Taken together, our observations suggest that combined deficiency of BubR1 and Sgo1 accelerates cellular senescence.

Access to Heart Transplantation: A Proper Analysis of the Competing Risks of Death and Transplantation Is Required to Optimize Graft Allocation

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Christelle Cantrelle, MS

2017-08-01

Conclusions. The heart allocation system strongly modifies the risk of pretransplant mortality related to heart failure severity. An in-depth competing risk analysis is therefore a more appropriate method to evaluate graft allocation systems. This knowledge should help to prioritize candidates in the context of a limited donor pool.

Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts

International Nuclear Information System (INIS)

Vermeer, B.J.; Santerse, B.; Van De Kerckhove, B.A.; Schothorst, A.A.; Claas, F.H.

1988-01-01

The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm 2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place

Materials testing and requirements for the ERDA nuclear-powered artificial heart. Technical progress report, July 15, 1974--May 1, 1975

International Nuclear Information System (INIS)

Andrade, J.D.; Coleman, D.L.; Leigh, A.; Hufferd, W.L.

1975-01-01

Progress on the materials research and development effort for the ERDA-sponsored nuclear-powered artificial heart program is presented. Progress made during the first three years on hydrogel grafting and biological studies is summarized. Progress during the fourth year on studies of implanted artificial hearts, development of albumin surfaces, and in vitro mechanical studies is presented. (U.S.)

Vertically integrated ZnO-Based 1D1R structure for resistive switching

International Nuclear Information System (INIS)

Zhang Yang; Duan Ziqing; Li Rui; Ku, Chieh-Jen; Reyes, Pavel I; Ashrafi, Almamun; Zhong Jian; Lu Yicheng

2013-01-01

We report a ZnO-based 1D1R structure, which is formed by a vertical integration of a FeZnO/MgO switching resistor (1R) and an Ag/MgZnO Schottky diode (1D). The multifunctional ZnO and its compounds are grown through MOCVD with in situ doping. For the R element, the current ratio of the high-resistance state (HRS) over the low-resistance state (LRS) at 1 V is 2.4 × 10 6 . The conduction mechanisms of the HRS and LRS are Poole–Frenkel emission and resistive conduction, respectively. The D element shows the forward/reverse current ratio at ±1 V to be 2.4 × 10 7 . This 1D1R structure exhibits high R HRS /R LRS ratio, excellent rectifying characteristics and robust retention. (paper)

The role of percutaneous transluminal coronary angioplasty in heart transplant recipients.

Science.gov (United States)

Schnetzler, B; Drobinski, G; Dorent, R; Camproux, A C; Ghossoub, J; Thomas, D; Gandjbakhch, I

2000-06-01

Review the acute and late results of percutaneous transluminal coronary angioplasty (PTCA) in heart transplant recipients and examine the factors predictive of restenosis. Coronary graft disease (CGD) is the main factor responsible for late graft loss. Medical treatment, surgical revascularization, or retransplantation gives only suboptimal results in this regard. Therefore, PTCA has been attempted in this situation. More than 332 heart transplantations in our institution have been performed since 1992, the date of the first PTCA in our patients. We are currently in charge of 450 patients. All the characteristics, procedure-related information, and clinical outcome of patients needing PTCA were assessed by review of each patient's clinical records. All coronary angiograms were reviewed by an independent cardiologist. Since 1992, 53 coronary sites have been dilated in the course of 39 procedures in 29 patients. Indication for PTCA was asymptomatic angiographic coronary graft disease in 35 sites (64.8%), angina in 9 (16.6%), silent ischemia in 2 (3.7%), acute myocardial infarction in 1 (1.8%), and CHF in 7 (12.9%). Primary success ( 50%) was 32.5% (14/43). Mean follow-up was 1.27 year +/- 1.2 (SD). Five deaths (17. 2%) occurred in follow-up and were all in relation to coronary graft disease. Mean time separating PTCA from death was 0.9 year +/- 1.3 (SD). We also sought to look at factors predictive of restenosis. By multivariate analysis, a positive recipient's serology for cytomegalovirus (CMV) before the graft was the only factor found protective against restenosis (odds ratio 22.4; confidence interval 1.1 to 443.4). PTCA in heart transplant recipients allows a high level of primary success with a low periprocedural-complication rate. Restenosis rate seems equivalent to restenosis rate in native coronary arteries. Mortality during follow-up is increased in this population and is the consequence of a high level of coronary events. Recipient positivity for CMV before

MiR-142-3p Functions as a Potential Tumor Suppressor in Human Osteosarcoma by Targeting HMGA1

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Guoxing Xu

2014-04-01

Full Text Available Background/Aims: Mounting evidence has shown that aberrant expression of miRNAs correlates with human cancers, and that miRNAs can function as tumor suppressors or oncogenes. Here, we investigated the role and mechanism of miR-142-3p in human osteosarcoma. Methods: We used quantitative real-time RT-PCR to measure the expression of miR-142-3p in human osteosarcoma cell lines and tissues. The roles of miR-142-3p in osteosarcoma development were studied using cultured HOS, MG63 and Saos-2 cells and tumor xenograft analyses in nude mice; their target genes were also investigated. Results: We found that miR-142-3p was significantly downregulated in osteosarcoma cell lines and clinical specimens. Overexpression of miR-142-3p suppressed osteosarcoma cell proliferation, migration and invasion, whereas miR-142-3p knockdown increased these parameters. The xenograft mouse model also revealed the suppressive effect of miR-142-3p on tumor growth. High mobility group AT-hook 1 (HMGA1 was identified as a target of miR-142-3p. Downregulation of HMGA1 induced effects on osteosarcoma cell lines similar to those induced by miR-142-3p. In contrast, restoration of HMGA1 abrogated the effects induced by miR-142-3p up-regulation. Conclusion: These results indicated that miR-142-3p may function as a tumor suppressor by targeting HMGA1 in osteosarcoma.

Blockade of Vascular Adhesion Protein-1 Inhibits Lymphocyte Infiltration in Rat Liver Allograft Rejection

OpenAIRE

Martelius, Timi; Salaspuro, Ville; Salmi, Marko; Krogerus, Leena; Höckerstedt, Krister; Jalkanen, Sirpa; Lautenschlager, Irmeli

2004-01-01

Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174–5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/gro...

Comparison of RT-PCR-Dot blot hybridization based on radioisotope 32P with conventional RT-PCR and commercial ELISA Assays for blood screening of HIV-1

International Nuclear Information System (INIS)

Maria Lina R; Andi Yasmon

2011-01-01

There are many commercial ELISA and rapid test kits that have been used for blood screening; however, the kits can give false positive and negative results. Therefore, RT-PCR (Reverse Transcription Polymerase Chain Reaction) - Dot Blot Hybridization based on radioisotope 32 P (RDBR) method was developed in this research, to compare the method with the conventional RT-PCR and commercial ELISA Enzyme-Linked lmmunosorbent Assay) kit. This method is efficient for screening of large blood specimens and surveillance study. Eighty seven samples were used and serum of the samples were tested by ELISA to detect HIV-1. The HIV-l RNA genome was extracted from plasma samples and tested using the RT-PCR and RDBR methods. Of 87 samples that were tested, the rates of positive testing of the RT-PCR, the RDBR, and the ELISA were 71.26%, 74.71%, and 80.46%, respectively. The RDBR (a combination of RTPCR and dot blot hybridization) was more sensitive than conventional RT-PCR by showing 3.45% in increase number of positive specimens. The results showed that of 9 samples (10.34%) were negative RDBR and positive ELISA, while 4 samples (4.60%) were negative ELISA and positive RDBR. The two methods showed slightly difference in the results but further validation is still needed. However, RDBR has high potential as an alternative method for screening of blood in large quantities when compared to method of conventional RT-PCR and ELISA. (author)

miR-139 is up-regulated in osteoarthritis and inhibits chondrocyte proliferation and migration possibly via suppressing EIF4G2 and IGF1R

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Hu, Weihua; Zhang, Weikai; Li, Feng; Guo, Fengjing; Chen, Anmin, E-mail: chenanmin6072@126.com

2016-05-27

Osteoarthritis (OA) is one of the most progressive articular cartilage erosions. microRNAs (miRNAs) play pivotal roles in OA modulation, but the role of miR-139 in OA remains elusive. This study aims to reveal the effects and possible mechanism of miR-139 in OA and chondrocytes. The levels of miR-139 and its possible targets eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) and insulin-like growth factor 1 receptor (IGF1R) were detected by qRT-PCR in the articular cartilages of 20 OA patients and 20 non-OA patients. Human chondrocyte CHON-001 cells were transfected with miR-139 mimic or inhibitor, as well as the siRNAs of EIF4G2 and IGF1R. Cell viability by MTT assay, proliferation by colony formation assay and migration by Transwell assay were performed. Results showed that miR-139 was up-regulated, while EIF4G2 and IGF1R mRNAs down-regulated in OA cartilages (P < 0.001), and negative correlations existed between the level of miR-139 and EIF4G2 or IGF1R. Overexpression of miR-139 in CHON-001 cells suppressed both mRNA and protein levels of EIF4G2 and IGF1R, and inhibited cell viability, colony formation number and cell migration, while miR-139 inhibitor induced the opposite effects. Knockdown of EIF4G2 or IGF1R in CHON-001 cells reversed the effects of miR-139 inhibitor on cell viability, colony formation and cell migration. These results indicate that miR-139 is capable of inhibiting chondrocyte proliferation and migration, thus being a possible therapeutic target for OA. The mechanism of miR-139 in chondrocytes may be related to its regulation on EIF4G2 and IGF1R.

R-134a (1,1,1,2-Tetrafluoroethane) Inhalation Induced Reactive Airways Dysfunction Syndrome.

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Doshi, Viral; Kham, Nang; Kulkarni, Shreedhar; Kapitan, Kent; Henkle, Joseph; White, Peter

2016-01-01

R-134a (1,1,1,2-tetrafluoroethane) is widely used as a refrigerant and as an aerosol propellant. Inhalation of R-134a can lead to asphyxia, transient confusion, and cardiac arrhythmias. We report a case of reactive airways dysfunction syndrome secondary to R-134a inhalation. A 60-year-old nonsmoking man without a history of lung disease was exposed to an air conditioner refrigerant spill while performing repairs beneath a school bus. Afterward, he experienced worsening shortness of breath with minimal exertion, a productive cough, and wheezing. He was also hypoxic. He was admitted to the hospital for further evaluation. Spirometry showed airflow obstruction with an FEV1 1.97 L (45% predicted). His respiratory status improved with bronchodilators and oral steroids. A repeat spirometry 2 weeks later showed improvement with an FEV1 2.5 L (60% predicted). Six months after the incident, his symptoms had improved, but he was still having shortness of breath on exertion and occasional cough.

Determination of taste receptor type 1 member 1 (TAS1R1) gene ...

African Journals Online (AJOL)

In this article, the objective was to investigate variations in goat TAS1R1 gene and their associations with growth traits in 317 goats by PCR-SSCP and DNA sequencing methods. The results showed two novel single nucleotide polymorphisms (SNPs): HM449123:g. [T3974C, C4037T]. In detail, two different alleles, A and B, ...

26 CFR 1.414(r)-1 - Requirements applicable to qualified separate lines of business.

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2010-04-01

... lines of business. 1.414(r)-1 Section 1.414(r)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... Plans, Etc. § 1.414(r)-1 Requirements applicable to qualified separate lines of business. (a) In general. Section 414(r) prescribes the conditions under which an employer is treated as operating qualified...

Optimization of reaction parameters of radiation induced grafting of 1-vinylimidazole onto poly(ethylene-co-tetraflouroethene) using response surface method

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Nasef, Mohamed Mahmoud, E-mail: mahmoudeithar@fkkksa.utm.my [Institute of Hydrogen Economy, International Campus, Universiti Teknologi Malaysia, 54100 Kuala Lumpur (Malaysia); Aly, Amgad Ahmed; Saidi, Hamdani; Ahmad, Arshad [Institute of Hydrogen Economy, International Campus, Universiti Teknologi Malaysia, 54100 Kuala Lumpur (Malaysia)

2011-11-15

Radiation induced grafting of 1-vinylimidazole (1-VIm) onto poly(ethylene-co-tetraflouroethene) (ETFE) was investigated. The grafting parameters such as absorbed dose, monomer concentration, grafting time and temperature were optimized using response surface method (RSM). The Box-Behnken module available in the design expert software was used to investigate the effect of reaction conditions (independent parameters) varied in four levels on the degree of grafting (G%) (response parameter). The model yielded a polynomial equation that relates the linear, quadratic and interaction effects of the independent parameters to the response parameter. The analysis of variance (ANOVA) was used to evaluate the results of the model and detect the significant values for the independent parameters. The optimum parameters to achieve a maximum G% were found to be monomer concentration of 55 vol%, absorbed dose of 100 kGy, time in the range of 14-20 h and a temperature of 61 {sup o}C. Fourier transform infrared (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to investigate the properties of the obtained films and provide evidence for grafting. - Highlights: > A precursor for phosphoric acid membrane for a high temperature PEM fuel cell was prepared. > The grafting parameters for radiation induced grafting of 1-VIm onto ETFE film were optimized. > Surface response method was used to predict the degree of grafting. > The predicted value agreed well with the experimental data as indicated by a 3% deviation. > The number of the experiments and cost of radiation induced grafting were reduced.

Clinical characteristics and usage of statins in patients with stable ischemic heart disease referred for angiography or coronary artery bypass grafting

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I.V. Shklianka

2017-12-01

Full Text Available The aim – to compare the clinical characteristics and frequency of statins usage in real clinical practice in patients referred to a specialized clinic for angiography or coronary artery bypass grafting. Materials and methods. In a retrospective slice single-center study data from a primary examination of 155 patients with stable ischemic heart disease, consecutively selected for coronary artery bypass grafting surgery, were analyzed. Depending on the inclusion of statins in the list of medicinal prescriptions, patients were retrospectively divided into two groups: those who had been prescribed statins while they were initially referred to a specialized cardiac surgery center for angiography or revascularization (n = 84 and those who were not prescribed statins (n ​​= 71. Results. The studied patients’ cohort was characterized by earlier coronary events, signs of the peripheral artery atherosclerosis and other absolute indications for treatment with statins in vast majority of cases. At the same time, groups of patients who had been and had not been prescribed statins, did not differ by vast majority of demographic, clinical and instrumental characteristics, concomitant diseases and risk factors. No statin therapy was associated with higher levels of total cholesterol and interleukin-6 compared with the group of patients taking statins (total cholesterol, respectively, 4.8 versus 4.2 mmol/l (p = 0.016 and interleukin-6, respectively, 4.4 versus. 3.1 p/ml (p = 0.022. In general, statins were prescribed in 54,2 % of patients, among them high doses – in 17 patients (20.2 %, moderate – 46 patients (54.8 %, low – 21 patients (25 %. Conclusions. The obtained data show the insufficient level of ambulatory statins usage in patients with ischemic heart disease referred for myocardial revascularization and significant discrepancy between clinical characteristics and real statins usage. Therefore, there is a great need to determine the

Grafted c-kit+/SSEA1- eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses.

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Chen, Xi; Chen, Zehua; Li, Zhengya; Zhao, Chen; Zeng, Yuxiao; Zou, Ting; Fu, Caiyun; Liu, Xiaoli; Xu, Haiwei; Yin, Zheng Qin

2016-12-30

Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry. Eye-wall c-kit + /stage-specific embryonic antigen 1 (SSEA1) - cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit + /SSEA1 - cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test. Eye-wall c-kit + /SSEA1 - cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit + /SSEA1 - cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit + /SSEA1 - cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit + /SSEA1 - cells were

The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection.

Science.gov (United States)

Clerkin, Kevin J; Restaino, Susan W; Zorn, Emmanuel; Vasilescu, Elena R; Marboe, Charles C; Mancini, Donna M

2016-09-01

Antibody-mediated rejection (AMR) has been associated with increased death and cardiac allograft vasculopathy (CAV). Early studies suggested that late AMR was rarely associated with graft dysfunction, whereas recent reports have demonstrated an association with increased mortality. We investigated the timing of AMR and its association with graft dysfunction, death, and CAV. This retrospective cohort study identified all adult orthotopic heart transplant (OHT) recipients (N = 689) at Columbia University Medical Center from 2004 to 2013. There were 68 primary cases of AMR, which were stratified by early ( 1 year post-OHT) AMR. Kaplan-Meier survival analysis and modeling was performed with multivariable logistic regression and Cox proportional hazards regression. From January 1, 2004, through October 1, 2015, early AMR (median 23 days post-OHT) occurred in 43 patients and late AMR (median 1,084 days post-OHT) occurred in 25. Graft dysfunction was less common with early compared with late AMR (25.6% vs 56%, p = 0.01). Patients with late AMR had decreased post-AMR survival compared with early AMR (1 year: 80% vs 93%, 5 years: 51% vs 73%, p < 0.05). When stratified by graft dysfunction, only those with late AMR and graft dysfunction had worse survival (30 days: 79%, 1 year: 64%, 5 years: 36%; p < 0.006). The association remained irrespective of age, sex, donor-specific antibodies, left ventricular assist device use, reason for OHT, and recovery of graft function. Similarly, those with late AMR and graft dysfunction had accelerated development of de novo CAV (50% at 1 year; hazard ratio, 5.42; p = 0.009), whereas all other groups were all similar to the general transplant population. Late AMR is frequently associated with graft dysfunction. When graft dysfunction is present in late AMR, there is an early and sustained increased risk of death and rapid development of de novo CAV despite aggressive treatment. Copyright © 2016 International Society for Heart and Lung

(Vapour + liquid) equilibrium data for the {1,1-difluoroethane (R152a) + 1,1,1,3,3-pentafluoropropane (R245fa)} system at temperatures from (323.150 to 353.150) K

International Nuclear Information System (INIS)

Yang, Lixiang; Gong, Maoqiong; Guo, Hao; Dong, Xueqiang; Wu, Jianfeng

2015-01-01

Highlights: • VLE data for (R152a + R245fa) system were measured at temperatures. • The experiments were based on the static-analytic method. • VLE data were correlated using PR–vdWs and PR–HV–NRTL models. - Abstract: In this paper, (vapour + liquid) equilibrium (VLE) for the {1,1-difluoroethane (R152a) + 1,1,1,3,3-pentafluoropropane (R245fa)} system was determined by a static-analytical method at T = (323.150 to 353.150) K. Values of the VLE were correlated by the Peng–Robison equation of state (PR EoS) using two different models, the van der Waals (vdWs) mixing rule and the Huron–Vidal (HV) mixing rule involving the non-random two-liquid (NRTL) activity coefficient model. The correlated results show good agreement with the experimental values. For the two models, the maximum average absolute deviations of the vapour phase mole fraction are 0.0034 and 0.0035, respectively.

Recipient Related Prognostic Factors for Graft Survival after Kidney Transplantation. A Single Center Experience

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Alina Daciana ELEC

2012-09-01

Full Text Available Background and Aim. Advanced chronic kidney disease (CKD severely impairs life expectancy and quality of life in affected patients. Considering its benefits, renal transplantation currently represents the optimal treatment solution for end stage kidney disease patients. Pre-transplant assessment aims to maximize the graft and patient survival by identifying potential factors influencing the post-transplant outcome. The aim of this study has been to analyze recipient related prognostic factors bearing an impact on graft survival. Material and Methods. We analyzed the graft outcomes of 426 renal transplantations performed at the Clinical Institute of Urology and Renal Transplantation of Cluj-Napoca, between January 2004 and December 2008. Variables related to recipient and to potential donor/recipient prognostic factors were studied using univariate and multivariate analysis. Results. Graft survivals at 1, 3, 5 and 7 years were 94.01%, 88.37%, 82.51% and 78.10%, respectively. Chronic rejection (41.11% and death with a functioning graft (18.88% were the main causes of graft loss. In uni and multivariate analysis the recipient related variables found to influence the renal graft outcome were: peritoneal dialysis, pre transplant residual diuresis, grade I hypertension, severe iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition. The worst graft outcomes have been found for recipients on peritoneal dialysis, with anuria, hypotension, severe iliac atheromatosis, ischemic heart disease, stroke history, dyslipidemia and a poor nutritional status. Conclusion. The type of dialysis, the pre transplant residual diuresis, recipient arterial blood pressure, iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition significantly influence graft survival.

Sphingosine-1-phosphate (S1P) activates STAT3 to protect against de novo acute heart failure (AHF).

Science.gov (United States)

Deshpande, Gaurang P; Imamdin, Aqeela; Lecour, Sandrine; Opie, Lionel H

2018-03-01

Acute heart failure (AHF) is a burden disease, with high mortality and re-hospitalisations. Using an ex-vivo model of AHF, we have previously reported that sphingosine-1-phosphate (S1P) confers cardioprotection. However, the mechanisms remain to be elucidated. In the present study, we aimed to examine the role of the cardioprotective signal transducer and activator of transcription 3 (STAT3) in S1P mediated improved functional recovery in AHF. Isolated hearts from male Long-Evans rats were subjected to hypotensive AHF for 35 min followed by a recovery phase of 30 min (n ≥ 4/group). S1P (10 nM) was given during either the hypotensive or the recovery phase with/without an inhibitor of STAT3, AG490. Functional parameters were recorded throughout the experiment. Following an AHF insult, S1P, given during the recovery phase, improved the heart rate (HR) compared to the control (175.2 ± 30.7 vs. 71.6 ± 27.4 beats per minute (BPM); p S1P abolished the cardioprotective effect of S1P (42.3 ± 17.1 vs. 148.8 ± 26.4 BPM for S1P; p S1P protects in an ex-vivo rat heart model of AHF by activation of STAT3 and provide further evidence for the usage of S1P as a potential therapy in patients suffering from AHF. Copyright © 2018 Elsevier Inc. All rights reserved.

On the Composition and Neutrix Composition of the Delta Function and the Function cosh^{-1}(|x|^{1/r}+1

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Brian Fisher

2017-03-01

Full Text Available Let $F$ be a distribution in $\\mathcal{D'}$ and let $f$ be a locally summable function. The composition $F(f(x$ of $F$ and $f$ is said to exist and be equal to the distribution $h(x$ if the limit of the sequence $\\{ F_{n}(f(x\\}$ is equal to $h(x$, where $F_n(x =F(x*\\delta _n(x$ for $n=1,2, \\ldots$ and $\\{\\delta_n(x\\}$ is a certain regular sequence converging to the Dirac delta function. It is proved that the neutrix composition $ \\delta^{(s}[\\cosh^{-1} (x_+^{1/r}+1] $ exists and \\beqa \\delta^{(s}[\\cosh^{-1} (x_+^{1/r}+1] = - \\sum _{k=0} ^{M-1} \\sum_{i=0}^{kr+r} {k \\choose i}{(-1^{i+k}rc_{r,s,k} \\over (kr+rk!}\\delta ^{(k}(x, for $s =M-1,M, M+1,\\ldots$ and $r=1,2,\\ldots,$ where $$c_{r,s,k}=\\sum _{j=0}^{i} {i \\choose j}{ (-1^{kr+r-i}(2j-i^{s+1}\\over 2^{s+i+1} },$$ $M$ is the smallest integer for which $s-2r+1 < 2Mr$ and $r\\le s/(2M+2.$ Further results are also proved.

miR-644a Inhibits Cellular Proliferation and Invasion via Suppression of CtBP1 in Gastric Cancer Cells.

Science.gov (United States)

Li, Yingchao; Yan, Xiaoni; Ren, Li; Li, Yang

2018-01-19

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the metastasis of various cancers, including gastric cancer (GC). In this study, we explored the putative significance of miR-644a and its role in EMT-mediated metastasis of GC. We first detected the expression of miR-644a in a cohort of 107 GC tissues using quantitative RT-PCR. The expression of miR-644a was suppressed in GC tissues and was associated with a later clinical stage and tumor metastasis. Restoring the expression of miR-644a could significantly suppress the migration and invasion of HGC-27 and SGC-7901 cells, which might be correlated to its suppressive effect on the EMT process. We also found that carboxyl-terminal-binding protein 1 (CtBP1) was a putative target gene of miR-644a in GC and might be involved in the suppressive effect. Collectively, through targeting CtBP1-mediated suppression of the EMT process, miR-644a might suppress the tumor metastasis of GC cells.

Cannabinoid-1 receptor (CB1R) blockers as medicines: beyond obesity and cardiometabolic disorders to substance abuse/drug addiction with CB1R neutral antagonists.

Science.gov (United States)

Janero, David R

2012-03-01

Addiction to chemical substances with abuse potential presents medical needs largely unsolved by extant therapeutic strategies. Signal transmission through the cannabinoid-1 receptor (CB1R) in the central nervous system (CNS) modulates neurotransmitters/neuronal pathways contributing to the rewarding properties and hedonic effects of certain nondrug stimuli (e.g., food) and many prototypical addictive drugs, promoting excessive intake and its pathological consequences. Typical CB1R antagonists/inverse agonists reduce the rewarding effects and normalize behavioral phenotypes associated with food and abused drugs, but carry an unacceptable adverse-event profile that may reflect, at least partly, their intrinsic ability to alter basal homeostatic CB1R signaling in the CNS and elicit a negative efficacy response. Alternatively, peripherally biased CB1R inverse agonists with limited CNS permeability and putative CB1R neutral antagonists expressing modest (if any) inverse-agonist efficacy are garnering attention for treating obesity and related cardiometabolic complications with a potentially enhanced benefit-to-risk profile. This mini-review calls attention to the proposition that CB1R neutral antagonists offer attractive opportunities for pharmacotherapeutic exploitation in the substance abuse/drug addiction space, whereas the restricted CNS accessibility of peripherally biased CB1R inverse agonists circumscribes their therapeutic utility for this indication. The unique preclinical pharmacology, efficacy profiles, and reduced adverse-event risk of CB1R neutral antagonists make them worthy of translational study for their potential therapeutic application beyond obesity/cardiometabolic disease to include substance-abuse/drug-addiction disorders.

Assessment of DNA synthesis in Islet-1+ cells in the adult murine heart

International Nuclear Information System (INIS)

Weinberger, Florian; Mehrkens, Dennis; Starbatty, Jutta; Nicol, Philipp; Eschenhagen, Thomas

2015-01-01

Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1 + ) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1 + cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ( 3 H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of 3 H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1 + cells. Whereas Islet − non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1 + cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes

Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development.

Science.gov (United States)

Wirrig, Elaine E; Snarr, Brian S; Chintalapudi, Mastan R; O'neal, Jessica L; Phelps, Aimee L; Barth, Jeremy L; Fresco, Victor M; Kern, Christine B; Mjaatvedt, Corey H; Toole, Bryan P; Hoffman, Stanley; Trusk, Thomas C; Argraves, W Scott; Wessels, Andy

2007-10-15

To expand our insight into cardiac development, a comparative DNA microarray analysis was performed using tissues from the atrioventricular junction (AVJ) and ventricular chambers of mouse hearts at embryonic day (ED) 10.5-11.0. This comparison revealed differential expression of approximately 200 genes, including cartilage link protein 1 (Crtl1). Crtl1 stabilizes the interaction between hyaluronan (HA) and versican, two extracellular matrix components essential for cardiac development. Immunohistochemical studies showed that, initially, Crtl1, versican, and HA are co-expressed in the endocardial lining of the heart, and in the endocardially derived mesenchyme of the AVJ and outflow tract (OFT). At later stages, this co-expression becomes restricted to discrete populations of endocardially derived mesenchyme. Histological analysis of the Crtl1-deficient mouse revealed a spectrum of cardiac malformations, including AV septal and myocardial defects, while expression studies showed a significant reduction in versican levels. Subsequent analysis of the hdf mouse, which carries an insertional mutation in the versican gene (CSPG2), demonstrated that haploinsufficient versican mice display septal defects resembling those seen in Crtl1(-/-) embryos, suggesting that reduced versican expression may contribute to a subset of the cardiac abnormalities observed in the Crtl1(-/-) mouse. Combined, these findings establish an important role for Crtl1 in heart development.

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

Energy Technology Data Exchange (ETDEWEB)

Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2013-03-15

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

Search for chargino-neutralino production in pp collisions at sq rt[s] = 1.96 TeV.

Science.gov (United States)

Aaltonen, T; Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Cilijak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Almenar, C Cuenca; Cuevas, J; Culbertson, R; Cully, J C; Daronco, S; Datta, M; D'Auria, S; Davies, T; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Dörr, C; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; da Costa, J Guimaraes; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraan, A C; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moon, C S; Moore, R; Morello, M; Fernandez, P Movilla; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; Denis, R St; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuno, S; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vazquez, F; Velev, G; Vellidis, C; Veramendi, G; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

2007-11-09

We present a search for associated production of the chargino and neutralino supersymmetric particles using up to 1.1 fb{-1} of integrated luminosity collected by the CDF II experiment at the Tevatron pp collider at sq rt[s]=1.96 TeV. We analyze events with a large transverse momentum imbalance and either three charged leptons or two charged leptons of the same electric charge. The numbers of observed events are consistent with standard model expectations. Upper limits on the production cross section are derived in different theoretical models.

(1R,2R,3R,4R,5S-2,3-Bis[(2S′-2-acetoxy-2-phenylacetoxy]-4-azido-1-[(2,4-dinitrophenylhydrazonomethyl]bicyclo[3.1.0]hexane

Directory of Open Access Journals (Sweden)

Robert McDonald

2008-02-01

Full Text Available In the title compound, C38H29N7O12, the five-membered ring adopts an envelope conformation in which the `flap' is cis to the cyclopropane group. This conformation is similar to those of other bicyclo[3.1.0]hexane analogues for which crystal structures have been reported. The absolute configuration of the stereogenic centers on the cyclopentane ring, as determined by comparison with the known configurations of the stereogenic centers in the (2S-2-acetoxy-2-phenylacetoxy groups, is 1(R, 2(R, 3(R, 4(R and 5(S. An intramolecular N—H...O hydrogen bond is present.

Home-based nursing interventions improve knowledge of disease and management in patients with heart failure 1

Science.gov (United States)

Azzolin, Karina de Oliveira; Lemos, Dayanna Machado; Lucena, Amália de Fátima; Rabelo-Silva, Eneida Rejane

2015-01-01

OBJECTIVE: to assess patient knowledge of heart failure by home-based measurement of two NOC Nursing Outcomes over a six-month period and correlate mean outcome indicator scores with mean scores of a heart failure Knowledge Questionnaire. METHODS: in this before-and-after study, patients with heart failure received four home visits over a six-month period after hospital discharge. At each home visit, nursing interventions were implemented, NOC outcomes were assessed, and the Knowledge Questionnaire was administered. RESULTS: overall, 23 patients received home visits. Mean indicator scores for the outcome Knowledge: Medication were 2.27±0.14 at home visit 1 and 3.55±0.16 at home visit 4 (P<0.001); and, for the outcome Knowledge: Treatment Regimen, 2.33±0.13 at home visit 1 and 3.59±0.14 at home visit 4 (P<0.001). The correlation between the Knowledge Questionnaire and the Nursing Outcomes Classification scores was strong at home visit 1 (r=0.7, P<0.01), but weak and non significant at visit 4. CONCLUSION: the results show improved patient knowledge of heart failure and a strong correlation between Nursing Outcomes Classification indicator scores and Knowledge Questionnaire scores. The NOC Nursing Outcomes proved effective as knowledge assessment measures when compared with the validated instrument. PMID:25806630

Functionalization of LDPE and mLLDPE via grafting trans-ethylene-1,2-dicarboxylic acid by reactive extrusion

Directory of Open Access Journals (Sweden)

2010-03-01

Full Text Available An investigation was made of grafting trans-ethylene-1,2-dicarboxylic acid (TEDA onto metallocene-linear low-density polyethylene (mLLDPE and low-density polyethylene (LDPE in the course of reactive extrusion. The initiator was 1,3-bis-(tert-butyl-peroxyisopropylbenzene. The graft efficiency of TEDA has been shown to increase with increasing initiator concentration, irrespective of polyethylene type. The graft values for LDPE were higher than for mLLDPE over the initiator concentration range (0.05 to 0.4 wt%. The rheological properties of mLLDPE were found to undergo more tangible changes during functionalization than those of LDPE. These changes were caused by side reactions, mainly macromolecular crosslinking. It has been established that some carboxyl groups get transformed to anhydride groups in the grafted product. The concentration of end double bonds reduces, but intramolecular unsaturation in both polyethylenes increases. Data are presented on thermal and stress-strain (mechanical properties of virgin and functionalized polymers, as well as rheological and viscoelastic properties of their melts.

Selection of reference genes for quantitative real-time RT-PCR studies in tomato fruit of the genotype MT-Rg1

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Karla L. González-Aguilera

2016-09-01

Full Text Available Quantitative real-time RT-PCR (qRT-PCR has become one of the most widely used methods for accurate quantification of gene expression. Since there are no universal reference genes for normalization, the optimal strategy to normalize raw qRT-PCR data is to perform an initial comparison of a set of independent reference genes to assess the most stable ones in each biological model. Normalization of a qRT-PCR experiment helps to ensure that the results are both statistically significant and biologically meaningful. Tomato is the model of choice to study fleshy fruit development. The miniature tomato (Solanum lycopersicum L. cultivar Micro-Tom (MT is considered a model system for tomato genetics and functional genomics. A new genotype, containing the Rg1 allele, improves tomato in vitro regeneration. In this work, we evaluated the expression stability of four tomato reference genes, namely CAC, SAND, Expressed and ACTIN2. We showed that the genes CAC and Exp are the best reference genes of the four we tested during fruit development in the MT-Rg1 genotype. Furthermore, we validated the reference genes by showing that the expression profiles of the transcription factors FRUITFULL1 (FUL1 and APETALA2c (AP2c during fruit development are comparable to previous reports using other tomato cultivars.

Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation.

Science.gov (United States)

Yuan, Y; Zhang, G Q; Chai, W; Ni, M; Xu, C; Chen, J Y

2016-10-01

Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1. MiR-138-5p was significantly increased in OA cartilage and in chondrocytes in response to IL-1β-stimulation. Overexpression of miR-138-5p significantly increased the IL-1β-induced downregulation of COL2A1, ACAN, and GAGs, and increased the IL-1β-induced over expression of MMP-13.We found that FOXC1 is directly regulated by miR-138-5p. Additionally, co-transfection with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 resulted in higher levels of COL2A1, ACAN, and GAGs, but lower levels of MMP-13. miR-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes, possibly by targeting FOXC1.Cite this article: Y. Yuan, G. Q. Zhang, W. Chai,M. Ni, C. Xu, J

Increased transient receptor potential vanilloid type 1 (TRPV1) channel expression in hypertrophic heart

DEFF Research Database (Denmark)

Thilo, Florian; Liu, Ying; Schulz, Nico

2010-01-01

The aim of this study was to compare the expression of transient receptor potential vanilloid type 1 (TRPV1) channels in hypertrophic hearts from transgenic mice showing overexpression of the catalytic subunit alpha of protein phosphatase 2A alpha (PP2Ac alpha) with wild-type mice and with TRPV1-...... alpha transgenic mice compared to wild-type mice and TRPV1-/- mice (8.6±1.3mg/g; 5.4±0.3mg/g; and 5.4±0.4mg/g; respectively; p...

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1.

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Izuno, Hisanori; Kobayashi, Yasuna; Sanada, Yutaka; Nihei, Daisuke; Suzuki, Masako; Kohyama, Noriko; Ohbayashi, Masayuki; Yamamoto, Toshinori

2007-09-22

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.

Cytokines affecting CD4+T regulatory cells in transplant tolerance. III. Interleukin-5 (IL-5) promotes survival of alloantigen-specific CD4+ T regulatory cells.

Science.gov (United States)

Hall, Bruce M; Plain, Karren M; Tran, Giang T; Verma, Nirupama D; Robinson, Catherine M; Nomura, Masaru; Boyd, Rochelle; Hodgkinson, Suzanne J

2017-08-01

CD4 + T cells mediate antigen-specific allograft tolerance, but die in culture without activated lymphocyte derived cytokines. Supplementation of the media with cytokine rich supernatant, from ConA activated spleen cells, preserves the capacity of tolerant cells to transfer tolerance and suppress rejection. rIL-2 or rIL-4 alone are insufficient to maintain these cells, however. We observed that activation of naïve CD4 + CD25 + FOXP3 + Treg with alloantigen and the Th2 cytokine rIL-4 induces them to express interleukin-5 specific receptor alpha (IL-5Rα) suggesting that IL-5, a Th2 cytokine that is produced later in the immune response may promote tolerance mediating Treg. This study examined if recombinant IL-5(rIL-5) promoted survival of tolerant CD4 + , especially CD4 + CD25 + T cells. CD4 + T cells, from DA rats tolerant to fully allogeneic PVG heart allografts surviving over 100days without on-going immunosuppression, were cultured with PVG alloantigen and rIL-5. The ability of these cells to adoptively transfer tolerance to specific-donor allograft and suppress normal CD4 + T cell mediated rejection in adoptive DA hosts was examined. Tolerant CD4 + CD25 + T cells' response to rIL-5 and expression of IL-5Rα was also assessed. rIL-5 was sufficient to promote transplant tolerance mediating CD4 + T cells' survival in culture with specific-donor alloantigen. Tolerant CD4 + T cells cultured with rIL-5 retained the capacity to transfer alloantigen-specific tolerance and inhibited naïve CD4 + T cells' capacity to effect specific-donor graft rejection. rIL-5 promoted tolerant CD4 + CD25 + T cells' proliferation in vitro when stimulated with specific-donor but not third-party stimulator cells. Tolerant CD4 + CD25 + T cells expressed IL-5Rα. This study demonstrated that IL-5 promoted the survival of alloantigen-specific CD4 + CD25 + T cells that mediate transplant tolerance. Copyright © 2017 Elsevier B.V. All rights reserved.

Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

International Nuclear Information System (INIS)

Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

1985-01-01

The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators

Synthesis of carbasugars from aldonolactones, part III - A study on the allylic substitution of (1R,5R,8R)- and (1R,5R,8S)-8-hydroxy-2-oxabicyclo[3.3.0]oct-6-en-3-one derivatives - Preparation of (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H-adenine

DEFF Research Database (Denmark)

Johansen, Steen Karsk; Lundt, Inge

2001-01-01

The palladium-catalyzed substitution of acylated (1R,5R,8R)- and (1R,SR,8S)-8-hydroxy-2-oxabicyclo[3.3.0] ones has been studied using a number of C- and N-nucleophiles, In all cases, the exo derivatives (8R) were found to be more reactive than the corresponding endo derivatives (8S). The reaction...... with these nucleophiles. Additionally, Mitsunobu substitution of (1R,5R,8R)-8-hydroxy-2-oxabicyclo[3.3.0]oct-B-en-3-one (3) with 6-chloropurine, followed by reduction of the lactone moiety and treatment with Liquid ammonia, gave the carbocyclic nucleoside (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H...

Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice

International Nuclear Information System (INIS)

Lund, Amie K.; Goens, M. Beth; Nunez, Bethany A.; Walker, Mary K.

2006-01-01

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of AhR results in hypertension, and cardiac hypertrophy and fibrosis, associated with elevated plasma angiotensin II (Ang II) and endothelin-1 (ET-1), thus AhR appears to contribute to cardiovascular homeostasis. In these studies, we tested the hypothesis that ET-1 mediates cardiovascular pathology in AhR null mice via ET A receptor activation. First, we determine the time courses of cardiac hypertrophy, and of plasma and tissue ET-1 expression in AhR wildtype and null mice. AhR null mice exhibited increases in heart-to-body weight ratio and age-related expression of cardiac hypertrophy markers, β-myosin heavy chain (β-MHC), and atrial natriuretic factor (ANF), which were significant at 2 months. Similarly, plasma and tissue ET-1 expression was significantly elevated at 2 months and increased further with age. Second, AhR null mice were treated with ET A receptor antagonist, BQ-123 (100 nmol/kg/day), for 7, 28, or 58 days and blood pressure, cardiac fibrosis, and cardiac hypertrophy assessed, respectively. BQ-123 for 7 days significantly reduced mean arterial pressure in conscious, catheterized mice. BQ-123 for 28 days significantly reduced the histological appearance of cardiac fibrosis. Treatment for 58 days significantly reduced cardiac mass, assessed by heart weight, echocardiography, and β-MHC and ANF expression; and reduced cardiac fibrosis as determined by osteopontin and collagen I mRNA expression. These findings establish ET-1 and the ET A receptor as primary determinants of hypertension and cardiac pathology in AhR null mice

Common variation in ISL1 confers genetic susceptibility for human congenital heart disease.

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Kristen N Stevens

Full Text Available Congenital heart disease (CHD is the most common birth abnormality and the etiology is unknown in the overwhelming majority of cases. ISLET1 (ISL1 is a transcription factor that marks cardiac progenitor cells and generates diverse multipotent cardiovascular cell lineages. The fundamental role of ISL1 in cardiac morphogenesis makes this an exceptional candidate gene to consider as a cause of complex congenital heart disease. We evaluated whether genetic variation in ISL1 fits the common variant-common disease hypothesis. A 2-stage case-control study examined 27 polymorphisms mapping to the ISL1 locus in 300 patients with complex congenital heart disease and 2,201 healthy pediatric controls. Eight genic and flanking ISL1 SNPs were significantly associated with complex congenital heart disease. A replication study analyzed these candidate SNPs in 1,044 new cases and 3,934 independent controls and confirmed that genetic variation in ISL1 is associated with risk of non-syndromic congenital heart disease. Our results demonstrate that two different ISL1 haplotypes contribute to risk of CHD in white and black/African American populations.

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient.

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Nishihara, V; Sumimoto, R; Fukuda, Y; Southard, J H; Asahara, T; Dohi, K

1997-01-01

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-alpha) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-alpha secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-alpha secretion and white cell accumulation), thus resulting in an improved survival.

A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation.

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Andreas Schaefer

Full Text Available Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC and heterotopic heart transplantation (hHTx in rats.To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations.50 TAC procedures were performed with a survival of 92% (46/50. When compared to healthy rats left ventricular surface decreased to 5.8±1.0 mm² (vs. 9.6± 2.4 mm² (p = 0.001 after three weeks with a fractional shortening (FS of 23.7± 4.3% vs. 28.2± 1.5% (p = 0.01. Six weeks later, systolic function decreased to 17.1± 3.2% vs. 28.2± 1.5% (p = 0.0001 and left ventricular inner surface increased to 19.9±1.1 mm² (p = 0.0001. Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46. All transplanted organs survived two weeks of mechanical unloading.Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure.

Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI-treated patients.

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André F A Santos

Full Text Available BACKGROUND: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H is poorly understood. METHODS AND FINDINGS: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naïve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher's exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. CONCLUSIONS: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.

Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer.

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Buck, Elizabeth; Gokhale, Prafulla C; Koujak, Susan; Brown, Eric; Eyzaguirre, Alexandra; Tao, Nianjun; Rosenfeld-Franklin, Maryland; Lerner, Lorena; Chiu, M Isabel; Wild, Robert; Epstein, David; Pachter, Jonathan A; Miglarese, Mark R

2010-10-01

Insulin-like growth factor-1 receptor (IGF-1R) is a receptor tyrosine kinase (RTK) and critical activator of the phosphatidylinositol 3-kinase-AKT pathway. IGF-1R is required for oncogenic transformation and tumorigenesis. These observations have spurred anticancer drug discovery and development efforts for both biological and small-molecule IGF-1R inhibitors. The ability for one RTK to compensate for another to maintain tumor cell viability is emerging as a common resistance mechanism to antitumor agents targeting individual RTKs. As IGF-1R is structurally and functionally related to the insulin receptor (IR), we asked whether IR is tumorigenic and whether IR-AKT signaling contributes to resistance to IGF-1R inhibition. Both IGF-1R and IR(A) are tumorigenic in a mouse mammary tumor model. In human tumor cells coexpressing IGF-1R and IR, bidirectional cross talk was observed following either knockdown of IR expression or treatment with a selective anti-IGF-1R antibody, MAB391. MAB391 treatment resulted in a compensatory increase in phospho-IR, which was associated with resistance to inhibition of IRS1 and AKT. In contrast, treatment with OSI-906, a small-molecule dual inhibitor of IGF-1R/IR, resulted in enhanced reduction in phospho-IRS1/phospho-AKT relative to MAB391. Insulin or IGF-2 activated the IR-AKT pathway and decreased sensitivity to MAB391 but not to OSI-906. In tumor cells with an autocrine IGF-2 loop, both OSI-906 and an anti-IGF-2 antibody reduced phospho-IR/phospho-AKT, whereas MAB391 was ineffective. Finally, OSI-906 showed superior efficacy compared with MAB391 in human tumor xenograft models in which both IGF-1R and IR were phosphorylated. Collectively, these data indicate that cotargeting IGF-1R and IR may provide superior antitumor efficacy compared with targeting IGF-1R alone.

Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design.

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Bartunek, Jozef; Davison, Beth; Sherman, Warren; Povsic, Thomas; Henry, Timothy D; Gersh, Bernard; Metra, Marco; Filippatos, Gerasimos; Hajjar, Roger; Behfar, Atta; Homsy, Christian; Cotter, Gad; Wijns, William; Tendera, Michal; Terzic, Andre

2016-02-01

Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy. Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months. The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF. NCT01768702. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Predicting renal graft failure by sCD30 levels and de novo HLA antibodies at 1year post-transplantation.

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Wang, Dong; Wu, Guojun; Chen, Jinhua; Yu, Ziqiang; Wu, Weizhen; Yang, Shunliang; Tan, Jianming

2012-06-01

HLA antibodies and sCD30 levels were detected in the serum sampled from 620 renal graft recipients at 1 year post-transplantation, which were followed up for 5 years. Six-year graft and patient survivals were 81.6% and 91.0%. HLA antibodies were detected in 45 recipients (7.3%), of whom there were 14 cases with class I antibodies, 26 cases with class II, and 5 cases with both class I and II. Much more graft loss was record in recipients with HLA antibodies than those without antibodies (60% vs. 15.1%, psCD30 levels were recorded in recipients suffering graft loss than the others (73.9±48.8 U/mL vs. 37.3±14.6 U/mL, psCD30 levels, recipients with low sCD30 levels (sCD30 on graft survival was not only independent but also additive. Therefore, post-transplantation monitoring of HLA antibodies and sCD30 levels is necessary and recipients with elevated sCD30 level and/or de novo HLA antibody should be paid more attention in order to achieve better graft survival. Copyright © 2012 Elsevier B.V. All rights reserved.

Hemodynamic analysis of sequential graft from right coronary system to left coronary system.

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Wang, Wenxin; Mao, Boyan; Wang, Haoran; Geng, Xueying; Zhao, Xi; Zhang, Huixia; Xie, Jinsheng; Zhao, Zhou; Lian, Bo; Liu, Youjun

2016-12-28

Sequential and single grafting are two surgical procedures of coronary artery bypass grafting. However, it remains unclear if the sequential graft can be used between the right and left coronary artery system. The purpose of this paper is to clarify the possibility of right coronary artery system anastomosis to left coronary system. A patient-specific 3D model was first reconstructed based on coronary computed tomography angiography (CCTA) images. Two different grafts, the normal multi-graft (Model 1) and the novel multi-graft (Model 2), were then implemented on this patient-specific model using virtual surgery techniques. In Model 1, the single graft was anastomosed to right coronary artery (RCA) and the sequential graft was adopted to anastomose left anterior descending (LAD) and left circumflex artery (LCX). While in Model 2, the single graft was anastomosed to LAD and the sequential graft was adopted to anastomose RCA and LCX. A zero-dimensional/three-dimensional (0D/3D) coupling method was used to realize the multi-scale simulation of both the pre-operative and two post-operative models. Flow rates in the coronary artery and grafts were obtained. The hemodynamic parameters were also showed, including wall shear stress (WSS) and oscillatory shear index (OSI). The area of low WSS and OSI in Model 1 was much less than that in Model 2. Model 1 shows optimistic hemodynamic modifications which may enhance the long-term patency of grafts. The anterior segments of sequential graft have better long-term patency than the posterior segments. With rational spatial position of the heart vessels, the last anastomosis of sequential graft should be connected to the main branch.

Interleucina 1β correlaciona-se com MIBG e parâmetros do exercício, na insuficiência cardíaca? Do interleukin-1β levels correlate with MIBG and exercise parameters in heart failure?

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Leandro Rocha Messias

2013-05-01

Full Text Available FUNDAMENTO: Na insuficiência cardíaca, níveis de interleucina 1β (IL 1β se associam a prognóstico. A atividade adrenérgica cardíaca avaliada através da cintilografia com metiodobenzilguanidina (I123 MIBG e parâmetros do exercício são importantes preditores de prognóstico. A relação entre essas variáveis não está bem definida. OBJETIVO: Avaliar associação entre níveis de IL 1β com parâmetros do exercício e do I123 MIBG. MÉTODOS: Estudo observacional transversal, com avaliação de 25 pacientes consecutivos com insuficiência cardíaca e fração de ejeção menor que 45%, através de: dosagem de IL 1β; parâmetros do I123 MIBG [relação coração/mediastino precoce e tardia, taxa de washout (WO]; e teste ergométrico em esteira pelo protocolo de Rampa. RESULTADOS: Separados em dois grupos pelos níveis de IL 1β (normal vs. elevado, o grupo com níveis aumentados apresentava menor reserva de duplo produto (RDP, menor capacidade funcional (CF e recuperação mais lenta da frequência cardíaca no 1º (RFC 1º e 2º minuto (RFC 2º, e maior WO. Na análise univariada, todas as variáveis se correlacionaram com a IL 1β; RDP: r = 0,203, p = 0,024; CF: r = 0,181, p = 0,034; RFC 1º: r = 0,182, p = 0,034; RFC 2º: r = 0,204, p = 0,023; WO: r = 0,263, p = 0,009. Na multivariada, apenas a WO permaneceu com correlação significativa (r2 = 0,263, p = 0,009. CONCLUSÃO: A hipertonia adrenérgica foi o principal determinante dos níveis de IL 1β, demonstrando que a atividade simpática excessiva influencia a atividade inflamatória sistêmica. As variáveis do teste ergométrico não foram capazes de identificar pacientes com níveis elevados de IL 1β.BACKGROUND: Interleukin 1β (IL 1β levels are associated with prognosis in heart failure. The cardiac adrenergic activity as assessed by metaiodobenzylguanidine (I123 MIBG scintigraphy along with exercise parameters are important predictors of prognosis. The relationship between

Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes.

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Morrison, R Ray; Teng, Bunyen; Oldenburg, Peter J; Katwa, Laxmansa C; Schnermann, Jurgen B; Mustafa, S Jamal

2006-10-01

To examine ischemic tolerance in the absence of A(1) adenosine receptors (A(1)ARs), isolated wild-type (WT) and A(1)AR knockout (A(1)KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A(1)AR deletion and/or ischemia-reperfusion. A(1)KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A(1)AR deletion. After 20 min of ischemia, CF was attenuated in A(1)KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A(1)KO hearts (54.4 +/- 5.1 vs. WT 81.1 +/- 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A(1)KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A(1)AR transcript in A(1)KO hearts, and the message for A(2A), A(2B), and A(3) adenosine receptors was similar in uninstrumented A(1)KO and WT hearts. Ischemia-reperfusion increased A(2B) mRNA expression 2.5-fold in both WT and A(1)KO hearts without changing A(1) or A(3) expression. In WT hearts, ischemia transiently doubled A(2A) mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A(1)KO hearts. Together, these data affirm the cardioprotective role of A(1)ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts.

Downregulation of miR-221-3p contributes to IL-1β-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway.

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Zheng, Xin; Zhao, Feng-Chao; Pang, Yong; Li, Dong-Ya; Yao, Sheng-Cheng; Sun, Shao-Song; Guo, Kai-Jin

2017-06-01

Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4

In vivo evaluation of expression of TGFβ1 in the irradiated heart

International Nuclear Information System (INIS)

Affonso Junior, Renato Jose; Oshima, Celina Tizuko Fujiyama; Silva, Maria Regina Regis; Kimura, Edna Teruko; Egami, Mizue Imoto; Segreto, Roberto Araujo; Segreto, Helena Regina Comodo

2004-01-01

The objectives of this study were to assess the latent and active TGFβ1 localization in the heart, to evaluate whether or not radiation induces latent TGFβ1 activation, and to study the distribution of collagen fibers in the irradiated heart. Thirty-two C 57 BL mice were randomly assigned in two groups: GI (non irradiated animals) and GII (irradiated animals). The mice from G II received a single whole-body radiation dose of 7 Gy, using a 60 Co source at a dose rate of 0.97 Gy/min. The animals were sacrificed by cervical dislocation at 1, 14, 30 and 90 days after irradiation. The irradiated hearts showed: nuclear changes and muscle cells with decreased striations; significant increase in the collagen deposition 90 days after irradiation; latent TGFβ1 activation in the cardio myocytes and connective tissue cells after irradiation. Our results show the importance of TGFβ1 protein in the process of radiation-induced heart fibrosis and suggest that cardio myocytes and connective cells may play a role in this mechanism acting as cellular sources of active TGFβ1. (author)

(1R,2R-N,N′-Bis(ferrocenylmethyl-1,2-diphenylethane-1,2-diamine

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Yi Guo

2010-08-01

Full Text Available The title compound, [Fe2(C5H52(C26H26N2], was synthesized from a chiral diamine and ferrocenecarboxaldehyde and subsequent reduction with NaBH4. It has two chiral centers which both exhibit an R configuration. Two ferrocene groups are present in the molecular structure, with their cyclopentadienyl ring planes showing an almost perpendicular arrangement [dihedral angle 88.6 (1°].

Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism.

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Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K; Lehtonen, Jukka Y A

2016-04-20

As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.

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Abdul-Ghani, Mohammad; Suen, Colin; Jiang, Baohua; Deng, Yupu; Weldrick, Jonathan J; Putinski, Charis; Brunette, Steve; Fernando, Pasan; Lee, Tom T; Flynn, Peter; Leenen, Frans H H; Burgon, Patrick G; Stewart, Duncan J; Megeney, Lynn A

2017-10-01

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.

Expression and function of Kv1.1 potassium channels in human atria from patients with atrial fibrillation.

Science.gov (United States)

Glasscock, Edward; Voigt, Niels; McCauley, Mark D; Sun, Qiang; Li, Na; Chiang, David Y; Zhou, Xiao-Bo; Molina, Cristina E; Thomas, Dierk; Schmidt, Constanze; Skapura, Darlene G; Noebels, Jeffrey L; Dobrev, Dobromir; Wehrens, Xander H T

2015-09-01

Voltage-gated Kv1.1 channels encoded by the Kcna1 gene are traditionally regarded as being neural-specific with no known expression or intrinsic functional role in the heart. However, recent studies in mice reveal low-level Kv1.1 expression in heart and cardiac abnormalities associated with Kv1.1-deficiency suggesting that the channel may have a previously unrecognized cardiac role. Therefore, this study tests the hypothesis that Kv1.1 channels are associated with arrhythmogenesis and contribute to intrinsic cardiac function. In intra-atrial burst pacing experiments, Kcna1-null mice exhibited increased susceptibility to atrial fibrillation (AF). The atria of Kcna1-null mice showed minimal Kv1 family ion channel remodeling and fibrosis as measured by qRT-PCR and Masson's trichrome histology, respectively. Using RT-PCR, immunocytochemistry, and immunoblotting, KCNA1 mRNA and protein were detected in isolated mouse cardiomyocytes and human atria for the first time. Patients with chronic AF (cAF) showed no changes in KCNA1 mRNA levels relative to controls; however, they exhibited increases in atrial Kv1.1 protein levels, not seen in paroxysmal AF patients. Patch-clamp recordings of isolated human atrial myocytes revealed significant dendrotoxin-K (DTX-K)-sensitive outward current components that were significantly increased in cAF patients, reflecting a contribution by Kv1.1 channels. The concomitant increases in Kv1.1 protein and DTX-K-sensitive currents in atria of cAF patients suggest that the channel contributes to the pathological mechanisms of persistent AF. These findings provide evidence of an intrinsic cardiac role of Kv1.1 channels and indicate that they may contribute to atrial repolarization and AF susceptibility.

Coronary heart disease after radiotherapy for peptic ulcer disease

International Nuclear Information System (INIS)

Carr, Zhanat A.; Land, Charles E.; Kleinerman, Ruth A.; Weinstock, Robert W.; Stovall, Marilyn; Griem, Melvin L.; Mabuchi, Kiyohiko

2005-01-01

Purpose: To evaluate the risk of coronary heart disease (CHD) and cerebrovascular disease after radiotherapy (RT) for peptic ulcer disease. Methods and materials: Peptic ulcer disease patients treated with RT (n = 1859) or by other means (n = 1860) at the University of Chicago Medical Center between 1936 and 1965, were followed through 1997. The observed numbers of cause-specific deaths were compared with the expected numbers from the general population rates. During RT, 5% of the heart was in the treatment field and the remainder of the heart mostly received scattered radiation. A volume-weighted cardiac dose was computed to describe the average tissue dose to the entire organ. We used Cox proportional hazards regression analysis to analyze the CHD and cerebrovascular disease risk associated with RT, adjusting for confounding factors. Results: Greater than expected CHD mortality was observed among the irradiated patients. The irradiated patients received volume-weighted cardiac doses ranging from 1.6 to 3.9 Gy and the portion of the heart directly in the field received doses of 7.6-18.4 Gy. The CHD risk increased with the cardiac dose (p trend = 0.01). The cerebrovascular disease risk was not associated with the surrogate carotid dose. Conclusion: The excess CHD risk in patients undergoing RT for peptic ulcer disease decades previously indicates the need for long-term follow-up for cardiovascular disease after chest RT

Computerization of nuclear material accounting and control at storage facilities of RT-1 plant, PA Mayak

International Nuclear Information System (INIS)

Krakhmal'nik, V.I.; Menshchikov, Yu.L.; Mozhaev, D.A.

1999-01-01

Computerized system for nuclear material (NM) accounting and control at RT-1 plant is being created on the basis of advanced engineering and programming tools, which give a possibility to ensure prompt access to the information required, to unify the accounting and report documentation, make statistical processing of the data, and trace the NM transfers in the chain of its storage at facilities of RT-1 plant. Currently, the accounting is performed in parallel, both by the old methods and with computerized system. The following functions are performed by the system at the current stage: input of data on the end product's (plutonium dioxide) quantitative and qualitative composition; data input on the localization of containers with finished products at storage facilities of the plant and the product's temporary characteristics; selective verification of the data on containers and batches, according to the criteria prespecified by the user; data protection against unauthorized access; data archiving; report documents formation and providing [ru

Establishment of a novel monoclonal antibody SMab-1 specific for IDH1-R132S mutation