UK PubMed Central (United Kingdom)

Growth differentiation factor-9 (GDF-9), an oocyte-secreted member of the transforming growth factor β superfamily, progesterone receptor, cyclooxygenase 2 (Cox2; Ptgs2), and the EP2 prostaglandin...Full Text Available

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Nerve growth factor (NGF), a survival factor for neurons enforces pain by sensitizing nociceptors. Also in the pancreas, NGF was associated with pain and it can stimulate the proliferation of pancreatic cancer cells. Hepatic stellate cells (HSC) respond to NGF with apoptosis. Transforming growth factor (TGF)-b, one of the strongest pro-fibrogenic activators of pancreatic stellate cells (PSC) induced NGF and its two receptors in an immortalized human cell line (ihPSC) and primary rat PSC (prPSC) as determined by RT-PCR, western blot, and immunofluorescence. In contrast to HSC, PSC expressed both NGF receptors, although p75NTR expression was weak in prPSC. In contrast to ihPSC TGF-b activated both Smad signaling cascades in prPSC. NGF secretion was diminished by the activin-like kinase (ALK)...

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Hematopoiesis is the cumulative result of intricately regulated signaling pathways that are mediated by cytokines and their receptors. Studies conducted over the past 10 to 15 years have revealed that...Full Text Available

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Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and ...Full Text Available

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Intervertebral disc (IVD) cell apoptosis has been suggested to play an important role in promoting the degeneration process. It has been demonstrated that IVD cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic reticulum (ER) pathway. Our study aimed to explore the relationship among these three pathways and grade of IVD degeneration (IVDD). IVDs were collected from patients with lumbar fracture, vertebral tumor, disc herniation or spondylolisthesis. IVDs were distinguished by MRI and histomorphological examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore, the correlation between apoptosis pathways biomarkers and disc pathology were analyzed. Nucleus pulpo...

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BackgroundThe epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available

UK PubMed Central (United Kingdom)

Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available

UK PubMed Central (United Kingdom)

Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available

International Nuclear Information System (INIS)

The p75 neurotrophin receptor (p75"N"T"R) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75"N"T"R retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (#DELTA#DD) dominant-negative antagonist of p75"N"T"R showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75"N"T"R-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75"N"T"R expressing cells occurred via the ...

UK PubMed Central (United Kingdom)

Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent...Full Text Available

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No abstract prepared.

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Insulin receptors on the surface of isolated rat adipocytes were photoaffinity labeled at 12 degrees C with the iodinated photoreactive insulin analogue, 125I-B2 (2-nitro-4-azidophenylacetyl)-des-PheB1-insulin, and the pathways in the intracellular processing of the labeled receptors were studied at 37 degrees C. During 37 degrees C incubations, the labeled 440-kDa insulin receptors were continuously internalized (as assessed by trypsin inaccessibility) and degraded such that up to 50% of the initially labeled receptors were lost by 120 min. Metabolic poisons (0.125-0.75 mM 2,4-dinitrophenol (DNP) and 1-10 mM NaF), which led to dose-dependent depletion of adipocyte ATP pools, inhibited receptor loss, and caused up to 3-fold increase in intracellular receptor accumulation. This effect was due to inhibition of intracellular ...

Science.gov (United States)

Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf promoters to drive the luciferase reporter ...

UK PubMed Central (United Kingdom)

BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available

UK PubMed Central (United Kingdom)

Nuclear hormone receptors comprise a characteristic family of transcription factors found in vertebrates, insects and nematodes. Here we show by cDNA and gene cloning that a Cnidarian, Tripedalia...Full Text Available

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BackgroundApolipoprotein E (ApoE), a cholesterol carrier associated with atherosclerosis, is a major risk factor for Alzheimer's disease (AD). The low-density lipoprotein receptor...Full Text Available

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Osteoblasts are the primary cells responsible for bone formation. They also support osteoclast formation from bone marrow precursors in response to osteotropic factors by inducing receptor activator...Full Text Available

UK PubMed Central (United Kingdom)

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available

International Nuclear Information System (INIS)

Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly ...

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BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available

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Asialoorosomucoid (ASOR) is internalized and degraded by HepG2 cells after binding to the asialoglycoprotein (ASGP) receptor, internalization through the coated pit/coated vesicle pathway, and trafficking to lysosomes. Primaquine, an 8-aminoquinoline antimalarial compound, inhibits ASOR degradation at concentrations greater than 0.2 mM by neutralizing intracellular acid compartments. This leads to alterations in surface receptor number, receptor-ligand dissociation, and receptor recycling. We have investigated the effects of primaquine on 125I-ASOR uptake and degradation as a function of primaquine concentration and duration of exposure. Concentrations below those required for neutralization of acidic compartments block 125I-ASOR degradation in HepG2 cells and lead to intracellular ligand accumulation. This effect is maximal at 80 microM primaquine. The intracellular 125I-ASOR is ...

Science.gov (United States)

Influenza virus infection during pregnancy has been implicated as one of cause of premature delivery, abortion and stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular, biological and immunochemical characteristics of MDI factors were investigated using human monocytic leukemia THP-1 cells by nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the nitroblue tetrazolium reduction ability, which was inhibited by the addition of superoxide dismutase and diphenyleneiodonium chloride, an inhibitor for reduced nicotinamide adenine dinucleotide phosphate oxidase. The phenomenon was also observed in human peripheral blood monocytes and histiocytic leukemia ...

UK PubMed Central (United Kingdom)

The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)₂ or...Full Text Available

UK PubMed Central (United Kingdom)

c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available

UK PubMed Central (United Kingdom)

G protein-coupled receptors (GPCRs) are known to modulate intracellular effectors involved in cardiac function. We recently reported homocysteine (Hcy)-induced ERK-phosphorylation was suppressed...Full Text Available

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As part of studies into the siting of a deep repository for nuclear waste, Swedish Nuclear Fuel and Waste Management Company (SKB) has commissioned the Alternative Models Project (AMP). The AMP is a comparison of three alternative modeling approaches for geosphere performance assessment for a single hypothetical site. The hypothetical site, arbitrarily named Aberg is based on parameters from the Aespoe Hard Rock Laboratory in southern Sweden. The Aberg model domain, boundary conditions and canister locations are defined as a common reference case to facilitate comparisons between approaches. This report presents the results of a discrete fracture pathways analysis of the Aberg site, within the context of the SR 97 performance assessment exercise. The Aberg discrete fracture network (DFN) site model is based on consensus Aberg parameters related to the Aespoe HRL site. Discrete fracture pathways are identified from canister locations in a ...

Science.gov (United States)

Somatogenic hormones play an important role in regulation of receptors for prolactin (PRL) and estrogen. Plerocercoids of the tapeworm, S. mansonoides produce a factor which mimics some, but not all of the actions reported for GH. Intact female rats were subjected to a constant infusion of plerocercoid growth factor (PGF) via a subcutaneous infection for two weeks to determine if PGF influences receptors for PRL, GH or estradiol. The rate of weight gain in the PGF-treated rats was accelerated in spite of a marked reduction in serum GH. Partially-purified PGF specifically displaced [125I]hGH from rat liver receptors but microsomes prepared from rats treated with PGF specifically bound significantly less [125I]hGH than microsomes from control rats. The reduction in [125I]hGH binding was not due to occupancy or to a change in affinity but to a suppression in ...

British Library Electronic Table of Contents (United Kingdom)

Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot ...

UK PubMed Central (United Kingdom)

Syndrome X is a combination or co-occurrence of several known cardiovascular risk factors (including central obesity, dyslipidemias, fatty liver disease, hyperinsulinemia, insulin resistance,...Full Text Available

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The Epstein-Barr virus protein, LMP1, is a functional mimic of the cellular receptor CD40, but signals to B lymphocytes in an amplified and sustained manner compared to CD40. LMP1 contributes...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...

International Nuclear Information System (INIS)

Polish 2010 p. 101 Poland Gradzka, I. Sochanowicz, B. Wojewodzka,

UK PubMed Central (United Kingdom)

Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic...Full Text Available

UK PubMed Central (United Kingdom)

Neuropilin-1 (NRP1) acts as a co-receptor for class 3 semaphorins and vascular endothelial growth factor and is an attractive angiogenesis target for cancer therapy. In addition to the transmembrane...Full Text Available

UK PubMed Central (United Kingdom)

Mechanisms regulating sexual differentiation of the zebra finch song system appear to include both genetic and hormonal factors. Sorting Nexin 2 (SNX2), which is involved in trafficking proteins...Full Text Available

UK PubMed Central (United Kingdom)

Bacterial pathogens use virulence strategies to invade epithelial barriers, but active processes of epithelial cells may also contribute to the endocytosis of microbial particles. To focus on the latter,...Full Text Available

Science.gov (United States)

Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin ...

Science.gov (United States)

The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant ...

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The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, the authors report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. They have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. They localized (i) RXR[alpha] (RXRA) to chromosome 9 band q34.3; (ii) RXR[beta] (RXRB) to chromosome 6 band 21.3; and (iii) RXR[gamma] (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three ...

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Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available

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To investigate mechanisms responsible for positive and negative transcriptional control, the authors have utilized two types of promoters that are diffferentially regulated by thyroid hormone (T{sub 3}) receptors. Promoters containing the palindromic T{sub 3} response element TCAGGTCA TGACCTGA are positively regulated by the T{sub 3} receptor after the administration of T{sub 3}, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. They describe evidence that the transcriptional inhibitory effects of the T{sub 3} or estrogen receptors on the estrogen or T{sub 3} response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone-binding domains and that these sequences can transfer ...

British Library Electronic Table of Contents (United Kingdom)

Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios.

British Library Electronic Table of Contents (United Kingdom)

Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...

International Nuclear Information System (INIS)

Targeted studies completed include the evaluation of tritiated N-0437, evaluation of "3"5S-cysteamine, evaluation of "1"8F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic ...

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The scope of this RA is limited to the evaluation of potential human health risks associated with a failure event of a tank containing Basin F liquid. Section 1.0 contains an introduction to the health risk assessment. Section 2.0 describes the site history, location, and land use. Section 3.0 provides a brief description of exposure pathways and potention receptors. Section 4.0 describes the sources of data used and identifies chemicals of concern. Section 5.0 discusses the toxicity of concern. Section 6.0 explains the methods used for calculation of carcinogenic risks and the noncarcinogenic hazard indexes. Section 7.0 describes uncertainties inherent in the current methodology used to determine potential human health risks. Section 8.0 presents a summary of results and conclusions. Section 9.0 includes the references cited.

UK PubMed Central (United Kingdom)

The aim of this study is to determine the effects of silver nanoparticles (Ag-NP) on vascular endothelial growth factor (VEGF)-and interleukin-1 beta (IL-1β)-induced vascular permeability, and...Full Text Available

UK PubMed Central (United Kingdom)

Cyclin-Dependent Kinase 1 (CDK1) is the major M-phase kinase known also as the M-phase Promoting Factor or MPF. Studies performed during the last decade have shown many details of how CDK1 is regulated...Full Text Available

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Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater struct...

Science.gov (United States)

High salinity is one of the main factors limiting cotton growth and productivity. The genes that regulate salt stress in TM-1 upland cotton were monitored using microarray and real-time PCR (RT-PCR) with samples taken from roots. Microarray analysis showed that 1503 probe sets were up-regulated and 1490 probe sets were down-regulated in plants exposed for 3h to 100mM NaCl, and RT-PCR analysis validated 42 relevant/related genes. The distribution of enriched gene ontology terms showed such important processes as the response to water stress and pathways of hormone metabolism and signal transduction were induced by the NaCl treatment. Some key regulatory gene families involved in abiotic and biotic sources of stress such as WRKY, ERF, and JAZ were differentially expressed. Our transcriptome analysis might provide some useful insights into salt-mediated signal transduction pathways in cotton and offer a number of candidate ...

International Nuclear Information System (INIS)

The U.S. Department of Energy's (DOE) Savannah River Site (SRS) is decommissioning many of its excess facilities through removal of the facility structures leaving only the concrete-slab foundations in place. Site-specific, risk-based derived concentration guideline levels (DCGLs) for radionuclides have been determined for a future industrial worker potentially exposed to residual contamination on these concrete slabs as described in Jannik. These risk-based DCGLs were estimated for an exposure area of 100 m2. During deactivation and decommissioning (D and D) operations at SRS, the need for area factors for larger and smaller contaminated areas arose. This paper compares the area factors determined for an industrial worker exposed to a concrete slab end-state for several radionuclides of concern at SRS with 1) the illustrative area factors provided in MARSSIM, 2) the area correction factors provided in ...

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Tissue factor pathway inhibitor (TFPI), a protease inhibitor that circulates in association with plasma lipoproteins (VLDL, LDL and HDL), helps to regulate the extrinsic blood coagulation cascade. The authors have cloned a 125-kb genomic region containing the entire human TFPI gene on six overlapping cosmids and prepared a restriction map of this contig to clarify gene structure. More than half (45 kb) of the 85-kb gene is occupied with 5[prime] noncoding elements: coding begins at exon 3. A HindIII RFLP identified with one cosmid was genotyped in the CEPH panel of 559 reference families. Linkage analysis using markers on human chromosome 2 located the TFPI gene on 2q, 36 cM proximal to D2S43(pYNZ15) and 13 cM distal to the crystalline [gamma]-polypeptide locus CRYGP1(p5G1). 31 refs., 3 figs., 3 tabs.

International Nuclear Information System (INIS)

An analogue of hGH isolated from plerocercoids of the tapeworm Spirometra mansonoides displaces ["1"2"5I]hGH from its receptors in rabbit, rat, and hamster liver membranes. Biologically, plerocercoid growth factor (PGF) is more similar to hGH than to other mammalian GH's but has not been shown to bond human cells. Receptors specific for hGH have been described on cultured human lymphocytes (IM-9). In this study, the authors compared the binding of PGF and hGH in IM-9 cells and in rabbit hepatic membranes. IM-9 lymphocytes (12 x 10"6 cells/tube) were incubated with ["1"2"5I]hGH and increasing concentrations of hGH (ng/ml) or PGF (serial dilutions) for 90 min at 30"0 C. Specific binding (B_0 - NSB) was determined for each dose of hGH or PGF and the binding curves were analyzed by logit-log regression. The results show that PGF displaced ["1"2"5I]hGH from human cells in a dose dependent manner (r = 0.98). Based on the IM-9 ...

UK PubMed Central (United Kingdom)

Structural analysis of an acetylcholine receptor from Torpedo californica leads to a three-dimensional model in which a "monomeric" receptor is shown to contain subunits arranged around a central ionophoretic...Full Text Available

UK PubMed Central (United Kingdom)

Many microbial pathogens recognize oligosaccharides displayed on the surface of host cells as receptors for toxins and adhesins. These ligand-receptor interactions are critical for disease pathogenesis,...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...

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Managing sites contaminated with munitions constituents is an international challenge. Although the choice of approach and the use of Ecological Risk Assessment (ERA) tools may vary from country to country, the assurance of quality and the direction of ecotoxicological research are universally recognized as shared concerns. Drawing on a multidisciplinary team of contributors, 'Ecotoxicology of Explosives' provides comprehensive and critical reviews available to date on fate, transport, and effects of explosives. The book delineates the state of the science of the ecotoxicology of explosives, past, present, and recently developed. It reviews the accessible fate and ecotoxicological data for energetic materials (EMs) and the methods for their development. The chapters characterize the fate of explosives in the environment, then provide information on their ecological effects in key environmental media, including aquatic, sedimentary, and terrestrial habitats. The book ...

UK PubMed Central (United Kingdom)

The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both...Full Text Available

UK PubMed Central (United Kingdom)

Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend...Full Text Available

UK PubMed Central (United Kingdom)

To study the effect of agonist on the TRH (thyrotrophin-releasing hormone) receptor protein, an epitope-tagged receptor was stably expressed in HEK-293 cells (human embryonic kidney 293 cells) and receptor...Full Text Available

Science.gov (United States)

Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to that by E(2), whereas glycyrrhizin had no ...

British Library Electronic Table of Contents (United Kingdom)

Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...

Science.gov (United States)

The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as ...

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Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of (/sup 125/I)EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM (/sup 125/I)EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium ...

International Nuclear Information System (INIS)

Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with ...

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With regard to polybrominated diphenyl ether (PBDE), there is few scientific knowledge on the emission patterns into the environment and exposure pathways to humans, and basic information is insufficient to consider what measures effective are. For the purpose of promoting risk reduction of target substances more effectively and efficiently, it is desirable to comprehend accurately the causal chain from the target substances utilization to the risk intake, and to evaluate the measures covering the whole applications of target substances. As the existing researches on the PBDE emission inventory, there are EU risk assessment report (European Chemical Bureau 2000, 2002, 2003), Danish EPA (1999), Palm et al.(2002) and Alcock et al. (2003). In addition, emissions of DecaBDE are published in TRI (Toxic Release Inventory) of US EPA. However, the primary information of the previous inventories is often the same and estimations based on the measured values are few. In ...

UK PubMed Central (United Kingdom)

SummaryThe Hippo tumor-suppressor pathway controls tissue growth in Drosophila and mammals by regulating cell proliferation and apoptosis. The Hippo pathway includes...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Abstract Background: G proteins are ubiquitously expressed signal transduction proteins playing a key role in multiple signal transduction pathways. The Gas subunit has been considered as an apoptosis factor. In this study the role of GNAS T393C genotypes of the GNAS gene encoding Gas was analyzed for its influence on the development and progression of prostate cancer. Methods: Genotyping of the GNAS T393C polymorphism in 196 prostate cancer patients and 200 healthy controls was performed by DNA extraction followed by PCR and restriction analysis. Results: We observed no evidence of effects related to GNAS T393C genotype as demonstrated by a comparison of the genotype distribution in prostate cancer patients and healthy controls, the genotype distribution dependent on grade of the primary ...

British Library Electronic Table of Contents (United Kingdom)

Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1?year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study, we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray-based approach. Expression of 190 genes was impaired in murine ...

UK PubMed Central (United Kingdom)

The retinoic acid receptor-related orphan receptors α and γ (RORα (NR1F1) and RORγ (NR1F3)) are orphan nuclear receptors and perform critical roles in regulation of development,...Full Text Available

UK PubMed Central (United Kingdom)

While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates...Full Text Available

Science.gov (United States)

HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration ...

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Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen ...

International Nuclear Information System (INIS)

Bisaminoethanethiol (BAT) ligands with various gem-dimethyl and amide groups were prepared, and the corresponding neutral Tc-99m complexes were prepared and evaluated for their relative stabilities by ligand-exchange reactions. It was demonstrated that technetium complexes containing gem-dimethyl substituents have higher lipophilicities, whereas those with an amide group possess greater stability, which enhances ligand-exchange reaction. The most interesting observation was that the brain uptake in rats is not determined only by lipophilicity. Apparently, Tc-99m complexes with an amide functional group display lower brain uptakes in rats compared to those without an amide group. The brain uptake was strongly influenced by substituents on the BAT ligand. These factors are critically important and should be taken into consideration when designing Tc-99m-labeled agents for CNS receptor imaging.

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This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the ...

UK PubMed Central (United Kingdom)

The aspartate receptor involved in chemotaxis is modified by methyl esterification at four distinct glutamate residues during the adaptive response of this receptor. To explain the high degree of specificity...Full Text Available

UK PubMed Central (United Kingdom)

The adenovirus fiber knob causes the first step in the interaction of adenovirus with cell membrane receptors. To obtain information on the receptor binding site(s), the interaction of labeled cell...Full Text Available

UK PubMed Central (United Kingdom)

1. The effects of stimulation of atrial receptors on hypothalamic neurosecretory cells were investigated in anaesthetized dogs and cats. Atrial receptors were activated by stretching the left and the...Full Text Available

UK PubMed Central (United Kingdom)

A specific immunoglobulin, the receptor antibody, can be found in most patients with myasthenia gravis. In order to study the kinetic properties of this antibody, serial determinations of receptor antibody,...Full Text Available

UK PubMed Central (United Kingdom)

Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen...Full Text Available

Science.gov (United States)

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization ...

UK PubMed Central (United Kingdom)

Unlike in normal rabbits, pulmonary rapidly adapting receptors (RARs) in rabbits with chronic mitral regurgitation (MR) do not respond to small changes in extravascular...Full Text Available

UK PubMed Central (United Kingdom)

Halothane, chloroform, and carbon tetrachloride, in the vapor and liquid phases, stimulate the water receptor of the blowfly Phormia regina. There are three successive phases of response to long-lasting...Full Text Available

Norwegian Open Research Archives (NORA)

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Science.gov (United States)

Four-enzyme section of the shikimate pathway (Aro B, D, E, and K) of Streptococcus pneumoniae has been studied. Kinetic properties of the individual enzymes and three- and four-enzyme linked reactions have been characterized in vitro. On the basis of the data measured in spectrophotometric and LC-MS experiments, kinetic mechanisms of the enzymes have been suggested and all kinetic parameters have been identified. Kinetic models for these three- and four-enzyme sections of the shikimate pathway have been constructed and validated. The model of the four-enzyme section of shikimate pathway has been employed to design an inhibition-sensitive reconstituted pathway for a high-throughput screening effort on the shikimate pathway. It was demonstrated that using the model it was possible to optimize this reconstituted pathway in such a way to provide equal sensitivity of ...

Science.gov (United States)

Poncirin, flavanone glycoside, isolated from the fruit of Poncirus trifoliata, has anti-bacterial and anti-inflammatory activities. In this study, the effects of poncirin on the differentiation of mesenchymal stem cells were investigated. The C3H10T1/2 mesenchymal stem cells and primary bone marrow mesenchymal stem cells were studied. In the C3H10T1/2 cells, poncirin prevented adipocyte differentiation, as demonstrated by inhibition of cytoplasm lipid droplet accumulation and peroxisome proliferator-activating receptor-? (PPAR-?) and CCAAT-enhancer-binding protein-? (C/EBP-?) mRNA expression. By contrast, poncirin enhanced the expression of the key osteogenic transcription factors, runt-related transcription factor 2 (Runx2) and transcriptional coactivator with PDZ-binding motif (TAZ). Poncirin also enhanced expression of the osteogenic marker genes including alkaline phosphatase (ALP) and osteocalcin (OC). Poncirin ...

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Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC(50) approximately 1muM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves ...

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The hypothesis that intracellular Ca/sup 2 +/ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca/sup 2 +/ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl/sub 2/ and the Ca/sup 2 +/ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl/sub 2/ from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of cells with 100 ..mu..M quin-2 or quin-2 AM had ...

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PMID:21331648

KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

BackgroundThe orphan nuclear receptor estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily. It was identified through a search for genes...Full Text Available

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An /alpha//sub 2/-adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet /alpha//sub 2/-adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet /alpha//sub 2/-adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the /alpha//sub 2/-adrenergic ligand (/sup 3/H)rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the /alpha//sub 2/B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet /alpha//sub 2/-adrenergic receptor (/alpha//sub 2/A) lies on chromosome 10. This ...

Science.gov (United States)

The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2?, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in which the ER stress induced by CVB3 was not relieved due to the lack of Irgm3 expression. In addition, the tunicamycin-triggered ER stress promoted the subsequent CVB3 ...

International Nuclear Information System (INIS)

The purpose of this paper is to evaluate a complete set of environmental pathways for disposal options and conditions that the Nuclear Regulatory Commission (NRC) may analyze for a low-level radioactive waste (LLW) license application. The regulations pertaining In the past, shallow-land burial has been used for the disposal of low-level radioactive waste. However, with the advent of the State Compact system of LLW disposal, many alternative technologies may be used. The alternative LLW disposal facilities include below- ground vault, tumulus, above-ground vault, shaft, and mine disposal This paper will form the foundation of an update of the previously developed Sandia National Laboratories (SNL)/NRC LLW performance assessment methodology. Based on the pathway assessment for alternative disposal methods, a determination will be made about whether the current methodology can satisfactorily analyze the pathways and phenomena ...

Science.gov (United States)

Chlorinated organics are frequently found as harmful soil contaminants and persisted for extended periods of time. A novel approach, named pulsed corona discharge plasma (PCDP), was employed for the degradation of pentachlorophenol (PCP) in soil. Experimental results showed that 87% of PCP could be smoothly removed in 60 min. Increasing pulse voltage, enhancing soil pH, lowering humic acid (HA) in soil and reducing granular size of the soil were found to be favorable for PCP degradation efficiency. Oxidation and physical processes simultaneously contributed to PCP removal in soil and ozone was the main factor in PCDP treatment. C-Cl bonds in PCP were cleaved during PCDP treatment by Fourier transform infrared spectroscopy (FTIR) analysis. The mineralization of PCP was confirmed by total organic carbon (TOC) and dechlorination analyses. The main intermediate products such as tetrachlorocatechol, tetrachlorohydroquinone, acetic acid, formic acid, and oxalic acid were ...

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Attention deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children. Symptoms of ADHD include hyperactivity, low frustration tolerance, impulsivity, and inattention. While the biological pathways leading to ADHD are not clearly delineated, a number of genetic and environmental risk factors for the disorder are recognized. In the early 1970s, research conducted by Dr. Benjamin Feingold found that when hyperactive children were given a diet free of artificial food additives and dyes, symptoms of hyperactivity were reduced. While some clinical studies supported these findings, more rigorous empirical studies conducted over the next 20 years were less positive. As a result, research on the role of food additives in contributing to ADHD waned. In recent years, however, interest in this area has revived. In response to more recent research and public petitions, in December 2009 the British government requested ...

British Library Electronic Table of Contents (United Kingdom)

Huntington?s disease (HD) is caused by an expansion of a polyglutamine repeat of more than 35?units in the huntingtin protein. The expanded repeat length is inversely correlated with the age at onset (AAO); however, additional genetic factors apart from the expanded CAG repeat length can modify the course and the AAO in HD. Aberrations in macroautophagy have been observed in Huntington, Alzheimer, Parkinson, motor neuron and prion diseases. Therefore, we hypothesized that polymorphisms in autophagy-related (Atg) genes might contribute to the variation in the AAO. We initially tested eight single nucleotide polymorphisms in five Atg genes (Atg3, Atg5, Atg7, Atg16L1 and Beclin-1) for their frequency of ?1%. Subsequently, we investigated the polymorphisms Atg7 V471A and Atg16L1 T281A for a di...

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The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate (U-/sup 14/C)glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10/sup 5/ cells/ml) were incubated with either (/sup 125/I)insulin or (/sup 125/I)hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and /sup 14/C-incorporation into lipids. Insulin, ...

Energy Technology Data Exchange (ETDEWEB)

Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of six contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl`s ...

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This analysis report is one of a series of technical reports that document the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the geologic repository at Yucca Mountain. This report is one of the five biosphere reports that develop input parameter values for the biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes the conceptual model, as well as the mathematical model and its input parameters. Figure 1-1 is a graphical representation of the documentation hierarchy for the ERMYN. This figure shows relationships among the products (i.e., scientific analyses and model reports) developed for biosphere modeling and biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan: for Biosphere Modeling and Expert Support'' (BSC 2004 [DIRS 169573]). The purpose of this ...

UK PubMed Central (United Kingdom)

Inhibiting insulin/IGF-1 signalling extends lifespan and delays age-related disease in species throughout the animal kingdom. This life-extension pathway, the first to be defined, was discovered through...Full Text Available

UK PubMed Central (United Kingdom)

Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like), EXTL1 (exostoses (multiple)-like 1), HS6ST1...Full Text Available

UK PubMed Central (United Kingdom)

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold...Full Text Available

UK PubMed Central (United Kingdom)

The insulin/IGF-1 signaling (IIS) pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1...Full Text Available

International Nuclear Information System (INIS)

... air pollution coprecipitation isotope production lead 203 proton beams

British Library Electronic Table of Contents (United Kingdom)

Summary Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB r...

British Library Electronic Table of Contents (United Kingdom)

The relationship between single nucleotide polymorphism (SNP) of interleukin-17 (IL-17A), transforming growth factor @b (TGF-@b), as well as its receptor (TGFR-@b2) and susceptibility to intracerebral hemorrhage in patients with brain arteriovenous malformation (BAVM) was investigated in the present study. A total of 53 patients with BAVM and 120 healthy controls were recruited, all of whom were Han Chinese from South China. There were no statistically significant differences in the IL-17A-197 guanine/adenine (G/A) or TGF-@b1-509 cytosine/thymine (C/T) genotypes or gene frequencies between BAVM patients and controls (p>0.05), but the gene frequency of the TGFR-@b2-875 A/G genotype in patients with BAVM was significantly higher (p<0.05). Furthermore, the frequencies of the G allele of IL-17...

International Nuclear Information System (INIS)

The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue ...

Science.gov (United States)

The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be ...

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Eukaryotic genomes encode a zinc finger protein (ZPR1) with tandem ZPR1 domains. In response to growth stimuli, ZPR1 assembles into complexes with eukaryotic translation elongation factor 1A (eEF1A) and the survival motor neurons protein. To gain insight into the structural mechanisms underlying the essential function of ZPR1 in diverse organisms, we determined the crystal structure of a ZPR1 domain tandem and characterized the interaction with eEF1A. The ZPR1 domain consists of an elongation initiation factor 2-like zinc finger and a double-stranded {beta} helix with a helical hairpin insertion. ZPR1 binds preferentially to GDP-bound eEF1A but does not directly influence the kinetics of nucleotide exchange or GTP hydrolysis. However, ZPR1 efficiently displaces the exchange factor eEF1B from preformed nucleotide-free complexes, suggesting that it may function as a negative regulator of eEF1A activation. Structure-based ...

UK PubMed Central (United Kingdom)

The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABA_A and Drosophila melanogaster...Full Text Available

UK PubMed Central (United Kingdom)

The plant hormone cytokinin is perceived by membrane-located sensor histidine kinases. Arabidopsis (Arabidopsis thaliana) possesses three cytokinin receptors: ARABIDOPSIS HISTIDINE...Full Text Available

UK PubMed Central (United Kingdom)

Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation...Full Text Available

UK PubMed Central (United Kingdom)

The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M₃ subtype, with the M₂...Full Text Available

UK PubMed Central (United Kingdom)

We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice....Full Text Available

UK PubMed Central (United Kingdom)

The neonatal Fc receptor FcRn provides IgG molecules with their characteristically long half-lives in vivo by protecting them from intracellular catabolism and then returning them to...Full Text Available

UK PubMed Central (United Kingdom)

The presence of albumin structures with the capacity to bind to a surface receptor in group C and G streptococci was studied in serum samples from 45 mammalian species representing 15 different orders,...Full Text Available

UK PubMed Central (United Kingdom)

Antagonists for kainate receptors (KARs), a family of glutamate-gated ion channels, are efficacious in a number of animal models of neuropathologies, including epilepsy, migraine pain, and anxiety....Full Text Available

UK PubMed Central (United Kingdom)

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present...Full Text Available

UK PubMed Central (United Kingdom)

We have characterized the kinetic response of gene targets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available

UK PubMed Central (United Kingdom)

TCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic...Full Text Available

UK PubMed Central (United Kingdom)

To study the expression of Fc receptors in human alveolar macrophages (AM), the cells were collected from 12 healthy controls and 22 patients with sarcoidosis and the activity involved in binding to...Full Text Available

UK PubMed Central (United Kingdom)

Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available

UK PubMed Central (United Kingdom)

The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available

UK PubMed Central (United Kingdom)

Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha...Full Text Available

UK PubMed Central (United Kingdom)

The Wistar Kyoto (WKY) rat strain is a putative genetic model of comorbid depression and anxiety. Previous research showing increased κ-opioid receptor (KOR)...Full Text Available

UK PubMed Central (United Kingdom)

Single-channel currents from acetylcholine receptor channels of garter snake neuromuscular junctions were recorded using the patch-clamp technique. Low concentrations of acetylcholine or carbamylcholine...Full Text Available

UK PubMed Central (United Kingdom)

BACKGROUNDOff-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Abstract The Hippo pathway is an evolutionally conserved protein kinase cascade involved in regulating organ size in vivo and cell contact inhibition in vitro by governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is linked to cancer development. Its first core kinase Warts was identified in Drosophila more than 15 years ago, but it gained much attention when other core components of the pathway were identified 8 years later. Major discoveries of the pathway were made during past several years. The core kinase components Hippo, Salvador, Warts, and Mats in the fly and Mst1/2, WW45, Lats1/2, and Mob1 in mammals phosphorylate and inactivate downstream transcriptional co-activators Yorkie in the fly, Yes-associated protein (YAP) and transcriptional co-activator with ...

UK PubMed Central (United Kingdom)

BackgroundTo evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X₃ and P2X_2/3 receptor agonist α,β-methyleneATP...Full Text Available

UK PubMed Central (United Kingdom)

SummaryThe transcriptional co-repressor SMRT utilizes two major receptor interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification....Full Text Available

UK PubMed Central (United Kingdom)

Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized....Full Text Available

International Nuclear Information System (INIS)

This paper describes an approach to solve air quality problems which frequently occur during iterations of the baseline change process. From a schedule standpoint, it is desirable to perform this evaluation in as short a time as possible while budgetary pressures limit the size of the staff available to do the work. Without a method in place to deal with baseline change proposal requests the environment analysts may not be able to produce the analysis results in the time frame expected. Using a concept called the Rapid Response Air Quality Analysis System (RAAS), the problems of timing and cost become tractable. The system could be adapted to assess other atmospheric pathway impacts, e.g., acoustics or visibility. The air quality analysis system used to perform the EA analysis (EA) for the Salt Repository Project (part of the Civilian Radioactive Waste Management Program), and later to evaluate the consequences of proposed baseline changes, consists of three ...

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Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. ...

International Nuclear Information System (INIS)

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone ...

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This analysis report is one of a series of technical reports that document the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), a biosphere model supporting the total system performance assessment (TSPA) for the geologic repository at Yucca Mountain. This report is one of the five biosphere reports that develop input parameter values for the biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes the conceptual model, as well as the mathematical model and its input parameters. Figure 1-1 is a graphical representation of the documentation hierarchy for the ERMYN. This figure shows relationships among the products (i.e., scientific analyses and model reports) developed for biosphere modeling and biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan for Biosphere Modeling and Expert Support'' (BSC 2005 [DIRS 172782]). The purpose of this ...

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The authors have investigated insulin receptor phosphorylation in differentiated cultured BC3H-1 myocytes. As for other insulin-responsive cell systems in partially purified wheat germ agglutinin receptor preparations, insulin stimulates the phosphorylation of its own receptor (95K ..beta..-subunits) in a dose dependent manner (0-400 nM), as identified by immunoprecipitation with antiinsulin receptor antibodies and SDS-PAGE. In the same preparations they show that 12-0-tetradecanyl phorbol acetate (TPA), which in many respect ..beta..-subunits in the same dose dependent manner (0-5 ..mu..M). In addition, antiinsulin receptor antibodies (B-10) also induced phosphorylation of mimics insulin action, also induced phosphorylation of the insulin receptor and HPLC tryptic maps of the /sup 32/P-labeled ..beta..-subunit were identical to those for insulin-induced ...

UK PubMed Central (United Kingdom)

Myriad genetic and epigenetic alterations are required to drive normal cells toward malignant transformation. These somatic events commandeer many signaling pathways that cooperate to endow aspiring...Full Text Available

UK PubMed Central (United Kingdom)

This manuscript discusses the physiology of the autonomic nervous system (ANS). The following topics are presented: regulation of activity; efferent pathways; sympathetic and parasympathetic divisions;...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Pathway analyses are regarded by National Plant Protection Organizations as a very efficient way to address the risks posed by invasive alien species. Data on import of aquatic plants was obtained from 10 EPPO countries (Austria, Czech Republic, Estonia, France, Germany, Hungary, the Netherlands, Latvia, Switzerland and Turkey) and aggregated in order to consider whether invasive or potentially invasive alien plants could be introduced in the EPPO region through this pathway. This study highlights that this pathway mainly consists of the import of tropical plants for use in aquaria, and which do not represent a risk due to their climatic requirements. However, a few species require thorough attention owing to the threats they cause. Of the 247 species recorded as imported, only 10 are curr...

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The Liver Carcinogenesis Section uses the modern technologies of molecular biology, cell biology, protein chemistry and genetics to investigate the biochemical and genetic pathways involved in human liver cancer.

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The ingestion pathway consequences following an accidental tritium release from the Savannah River Site Tritium Facilities are evaluated.

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Turbine Afterword The SHARP cannon. Hydrogen is compressed in the tube on top, the gun barrel is on bottom. When Jules Verne wrote in 1865 "From Earth to the Moon" he envisioned...

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Pathways of salicylic acid (SA) biosynthesis and metabolism in tobacco have been recently identified. SA, an endogenous regulator of disease resistance, is a product of phenylpropanoid metabolism formed...Full Text Available

International Nuclear Information System (INIS)

The authors have been involved for the last few years in developing high affinity sigma-receptor-specific radiopharmaceuticals for use in nuclear medicine. They recently demonstrated that sigma-1 receptors are expressed in human melanoma cells and that sigma receptors could be used as external markers for non-invasive imaging. In order to determine the presence of sigma receptors in other human tumors they have screened numerous non-small cell lung carcinoma, melanoma and breast cancer cell lines. All of these cell lines expressed high sigma receptor densities using commercially available ["3H]-(+)-pentazocine or ["3H]DTG tritiated sigma ligands. Therefore, a sigma ligand with high affinity in both sigma-1 and sigma-2 subtype pharmacological assays could be potentially useful for imaging a variety of primary and metastatic sites of various origins. The authors describe recent ...

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The results of a scoping study of onsite radiation exposures which could take place in each of three types of postulated reactor accidents are presented. The accident types are (1) a fuel handling accident at a Mark III BWR; an interfacing system LOCA or V sequence at a PWR; and and Anticipated Transient Without Scram (ATWS) at a Mark I BWR. Both external and internal dose pathways are considered. The results of the study indicate the prohibitively high radiation doses could be received in some plant areas if personnel were to remain there. However, times of the order of a few minutes to a few hours, depending on the type of accident, would be available before life-threatening doses would be accumulated assuming that the provided full face respiratory protection equipment were used promptly. Special attention was given radiation doses possibly received by control room personnel for several control room air in-leakage assumptions. For occupancy during severe ...

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Objectives: We have previously shown that chronic exposure to ambient fine particulate matter (less than 2.5 ?m in aerodynamic diameter, PM(2.5)) pollution in conjunction with high-fat diet induces insulin resistance through alterations in inflammatory pathways. In this study we evaluated the effects of PM(2.5) exposure over a substantive duration of a rodent's lifespan and focused on the impact of long-term exposure on adipose structure and function.Methods and Results: C57BL/6 mice were exposed to PM(2.5) or filtered air (FA) (6 hours/day, 5 days/week) for duration of 10 months in Columbus, OH. At the end of the exposure, PM(2.5)-exposed mice demonstrated insulin resistance (IR) and a decrease in glucose tolerance compared with the FA-exposed group. Although there were no significant differences in circulating cytokines between PM(2.5)- and FA-exposed groups, circulating adiponectin and leptin were significantly decreased in PM(2.5)-exposed group. PM(2.5) ...

International Nuclear Information System (INIS)

Based on results from recent studies of elemental dietary intake and organ or tissue content for adult Chinese men, quoted nationwide elemental concentrations in Chinese soil and newly published national average consumption of dietary foods, values of both transfer coefficients and discrimination factor (DF) for transfer from soil via the diet to both critical organs and the whole body have been calculated for important elements in radiation protection, including alkaline earths, alkali metals, rare earths and other related elements. These calculations have used both the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) model and the DF method. In the UNSCEAR model, the basic parameters used to describe the transport of radionuclides are the transfer coefficients P_i_j, which describe the relationship of concentrations or other amounts between compartment i and the following compartment j, whereas the DF is the ratio between the ...

International Nuclear Information System (INIS)

To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile derivative (HS-1200). Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-19 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. The dose required for the half maximal inhibition (IC_5_0) of the HT-29 cell growth was 100 #approx# 150 #mu# M of HS-1200. Several changes, associated with the apoptosis ...

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... 16, 2001 0006-2979 BIORAK v. 40(2) APPLIED LIFE SCIENCES azido

UK PubMed Central (United Kingdom)

SummaryMammalian iron homeostasis is regulated by the interaction of the liver-produced peptide hepcidin and its receptor, the iron transporter ferroportin. Hepcidin binds to...Full Text Available

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... and R. L. Momparler. DNA methylation of retinoic acid receptor beta in breast cancer and possible therapeutic role of ... ...

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... estrogen receptor status. Cancer Lett., 253, 291-300. 39. Xin,X ... and resistant mice. Brain Res.Bull., 52, 235-242. 40. Foster,BA ...

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Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the ...

UK PubMed Central (United Kingdom)

The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles...Full Text Available

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The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with (/sub 3/H)-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and true affinity constants (-log K/sub A/-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific (/sup 3/H)-1-Quinuclidinyl benzilate binding sites respectively to be compared ...

UK PubMed Central (United Kingdom)

This paper describes attempts to isolate and characterize glycosaminoglycan (GAG)-binding molecules on the surface of lymphocytes and lymphoma cell lines and relate their expression to splenic and lymph...Full Text Available

UK PubMed Central (United Kingdom)

Carbohydrate-directed endocytosis is mediated by a receptor, the hepatic binding protein; it is responsible for the clearance of galactose-terminated glycoproteins from the circulation. This process...Full Text Available

UK PubMed Central (United Kingdom)

Measurements of the taste thresholds of blowflies for a wide variety of carbohydrates, presented individually and in combination, showed that the stimulating effects of the compounds are not always...Full Text Available

UK PubMed Central (United Kingdom)

Glucose metabolism through glycolysis and hexosamine pathway has been shown to be altered in type 2 diabetes. However, its fate through the pentose phosphate pathway (PPP) is currently unclear....Full Text Available

UK PubMed Central (United Kingdom)

2,4-Dichlorophenoxyacetic acid (2,4-D) promotes the accumulation of tryptophan-derived indole-3-acetic acid (IAA) in carrot cell cultures during callus proliferation by a biosynthetic pathway that is...Full Text Available

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A multiple comparison approach using whole genome transcriptional arrays was used to identify genes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila....Full Text Available

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Six species having characteristics of plants with the C4 dicarboxylic photosynthetic pathway, Echinochloa utilis L. Ohwi et Yabuno (Japanese millet), Cynodon dactylon L. (Bermuda grass), Kyllinga brevifolia Rottb., Amaranthus tricolor L. cv. Early splendour, Kochia childsii Hort., and Portulaca grandiflora Hook (rose moss), responded decisively to 0.1 milliequivalent per liter NaCl supplied to their culture solutions initially containing less than 0.08 microequivalent per liter Na. Chlorosis and necrosis occurred in leaves of plants not receiving sodium. Portulaca failed to set flower in the sodium-deficient cultures. Under similar conditions Poa pratensis L. (Kentucky blue grass) having characteristics of the C3 photosynthetic pathway made normal growth and did not respond to the addition of sodium. It is concluded from these results and previously reported work that sodium is generally essential for species having the C4 ...

International Nuclear Information System (INIS)

Background: In an effort to standardise radiological practices in the Republic of Ireland, current legislation states that 'written protocols for every type of standard radiological practice shall be established'. In order to fulfil this requirement the Irish Medical Council recommends the protocols issued by the Commission of European Communitees (CEC) for adoption in the country. Whilst this document does provide good guidance with regard to various radiographic factors, patient shielding instructions are notably ambiguous. The aim of this study was to remove some of this ambiguity by defining the optimal method of positioning patient shielding in antero-posterior (AP) and lateral lumbar spine radiographic examinations. These projections were chosen on the basis of their area of coverage being in close to and in some cases including the reproductive organs. They also represent the highest source of collective population dose of any conventional radiographic ...

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Platelets from dogs with Basset Hound Hereditary Thrombopathy (BHT) display a thrombasthenia-like aggregation defect but have been shown to have normal amounts of platelet membrane glycoproteins IIb and IIIa (GP IIb-IIIa). In order to investigate the possibility of a functionally abnormal GPIIb-IIIa complex, which might be unable to bind fibrinogen after stimulation, fibrinogen binding in BHT was evaluated. Two canine fibrinogen preparations were used, one from BHT dogs and one from normal control dogs, as well as a human fibrinogen preparation. Platelets from BHT and normal dogs were activated with 1 x 10/sup -5/M ADP in the presence of /sup 125/I-labeled fibrinogen and the surface bound radioactivity quantitated. For all fibrinogen preparations, the amount of fibrinogen bound by BHT platelets was not significantly different than that bound by normal dog platelets. BHT platelets bound 23,972 +/- 3612 and normal dog platelets bound 23,033 +/- 3971 molecules of fibrinogen per platelet. ...

Science.gov (United States)

Streptococcus pneumoniae colonizes the mucosal surface of the human upper respiratory tract. A colonization event is gradually cleared through phagocytosis by monocytes/macrophages that are recruited to the airway lumen. Here, we sought to define the bacterial and host factors that promote monocyte/macrophage influx and S. pneumoniae clearance using intranasal bacterial challenge in mice. We found that the recruitment of monocytes/macrophages required their expression of the chemokine receptor CCR2 and correlated with expression of the CCR2 ligand CCL2. Production of CCL2 and monocyte/macrophage recruitment were deficient in mice lacking digestion of peptidoglycan by lysozyme (LysM) and cytosolic sensing of the products of digestion by Nod2. Ex vivo macrophages produced CCL2 following bacterial uptake, digestion by LysM, and sensing of peptidoglycan by Nod2. Sensing of digested peptidoglycan by Nod2 also required the pore-forming toxin ...

UK PubMed Central (United Kingdom)

SummaryThe receptors for the second messenger InsP₃ comprise a family of closely related ion channels that release Ca²⁺ from intracellular stores, most prominently...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe status of estrogen receptor-α (ERα) is critical to the clinical prognosis and therapeutic approach in breast cancer. ERα-negative breast cancer...Full Text Available

UK PubMed Central (United Kingdom)

1. The induction of long-term potentiation (LTP) was investigated in the rat dentate gyrus in the presence of ryanodine, an agent which is known to selectively bind to the ryanodine receptor (RyR) Ca2+...Full Text Available

UK PubMed Central (United Kingdom)

σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available

UK PubMed Central (United Kingdom)

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp...Full Text Available

UK PubMed Central (United Kingdom)

AimsTo characterize the pharmacokinetics of terbogrel, a new combined thromboxane A₂ (TxA₂) receptor and synthase inhibitor, in healthy human subjects after...Full Text Available

UK PubMed Central (United Kingdom)

Although peroxisome proliferator-activated receptor alpha (PPARα) is closely associated with myocardial fatty acid metabolism, the pathophysiological role of PPARα in myocardial infarction...Full Text Available

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(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied ...

UK PubMed Central (United Kingdom)

Backgroundβ₂-Adrenergic receptors (β₂AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available

UK PubMed Central (United Kingdom)

The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and...Full Text Available

UK PubMed Central (United Kingdom)

The substantia nigra pars reticulata (SNR) controls seizures in a sex-specific manner. At postnatal day 15 (P15), SNR infusion of GABA_A receptor agonist muscimol have proconvulsant...Full Text Available

UK PubMed Central (United Kingdom)

This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary...Full Text Available

UK PubMed Central (United Kingdom)

Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A₁R, A_2AR, A_2BR, and A₃R)....Full Text Available

UK PubMed Central (United Kingdom)

1-Naphthylphthalamic acid (NPA) is a specific inhibitor of polar auxin transport that blocks carrier-mediated auxin efflux from plant cells. To allow identification of the NPA receptor thought to be...Full Text Available

International Nuclear Information System (INIS)

The authors used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate (["3H]QNB). At 37 degree C, specific ["3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of ["3H]QNB for its receptor. The IC_5_0 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 #mu#M, respectively. Hill coefficients were 0.67 for both, suggesting more complex interaction involving receptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that (1) contraction is mediated by ...

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The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated ...

Science.gov (United States)

Hypercholesterolemia