Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factorreceptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available
Peroxisome proliferator-activatedreceptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
Binding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand-activated EGFR is also rapidly internalized...Full Text Available
BackgroundPolymorphisms in Epidermal Growth FactorReceptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available
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
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 receptoractivator...Full Text Available
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, the role of the AHR...Full Text Available
The capacity of bones to adjust their mass and architecture to withstand the loads of everyday activity derives from the ability of their resident cells to respond appropriately to the strains engendered....Full Text Available
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
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
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...
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 ...
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)...
The plerocercoid stage of the tapeworm Spirometra mansonoides produces a functional analog of human growth hormone (hGH). Among the similarities between plerocercoid growth factor (PGF) and hGH is competition for the same receptors on rabbit liver membranes. To take advantage of this characteristic in a purification scheme for PGF, rabbit liver microsomes were solubilized in Triton X-100 and the hGH receptors were purified over an hGH affinity column. The purified receptors from six rabbit livers were coupled to Affi-Gel-10 to create a receptor affinity column which was used to purify PGF. Chromatography of crude PGF over the receptor column resulted in a 1044 fold increase in specific activity. SDS-PAGE in the presence of 2-mercaptoethanol showed that the affinity-purified PGF contained three protein bands with apparent Mrs of 27.5 K, 22 K, ...
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 ...
The extracellular domain of human fibroblast growth factorreceptor (XC-FGF-R) was expressed in Escherichia coli. The protein was purified to homogeneity and the interaction with basic fibroblast growth...Full Text Available
BackgroundThe epidermal growth factorreceptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available
Background:Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers.Patients...Full Text Available
Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factorreceptor (EGFR) and human epidermal growth factorreceptor 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...
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
The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory neurons...Full Text Available
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
Epidermal growth factorreceptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available
Epidermal growth factorreceptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
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
The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factorreceptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available
We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: ...
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 ...
Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased ...
The glass gene is required for proper photo-receptor differentiation during development of the Drosophila eye glass codes for a DNA-binding protein containing five zinc fingers that we show is a transcriptional activator. A comparison of the sequences of the glass genes from two species of Drosophila and a detailed functional domain analysis of the Drosophila melanogaster glass gene reveal that both the DNA-binding domain and the transcriptional-activation domain are highly conserved between the two species. Analysis of the DNA-binding domain of glass indicates that the three carboxyl-terminal zinc fingers alone are necessary and sufficient for DNA binding. We also show that a deletion mutant of glass containing only the DNA-binding domain can behave in a dominant-negative manner both in vivo and in a cell culture assay that measures transcriptional activation. PMID:7604032
Aim: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factorreceptor (EGFR), the oestrogen receptor (ER), and the progesterone...Full Text Available
Epidermal growth factorreceptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available
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
Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on...Full Text Available
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
The receptors for IGF-I (IGF-IR) and insulin (IR) have been implicated in physiological cardiac growth, but it is unknown whether IGF-IR or IR signaling are critically required. We generated mice with...Full Text Available
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. ...
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 ...
The GABA-modulating and GABA-mimetic activities of the monoterpenoid thymol were explored on human GABAA and Drosophila melanogaster...Full Text Available
SUMMARYThe cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on target cells. Structural studies of...Full Text Available
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...Full Text Available
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
BACKGROUNDOff-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activatedreceptor-1...Full Text Available
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
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
Hepatic injury and regeneration of the liver are associated with activation of hepatic stellate cells (HSC). Fibroblast growth factors (FGFs) and their receptors are important regulators of repair in various tissues. HSC express FGFR3IIIc as well as FGFGR4 and different spliced FGFR1IIIc and FGFR2IIIc isoforms which differ in the presence or absence of the acid box and of the first Ig-like domain. Expression of FGF9, known to be capable to activate the HSC FGFR2/3-isoforms, was increased in HSC in liver slice cultures after exposition to carbon tetrachloride, as an acute liver injury model. FGF9 significantly stimulated 3-H thymidine incorporation of hepatocytes, but failed to induce DNA synthesis in HSC despite the fact that FGF9 induced a sustained activation of extracellular signal-related kinases (ERK) 1/2. FGF9 induced an increased phosphorylation of Tyr436 of the fibroblast ...
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...
BackgroundTo evaluate whether P2X receptors are involved in responses to noxious pulp stimulation, the P2X3 and P2X2/3 receptor agonist α,β-methyleneATP...Full Text Available
P2X1 receptors for ATP contribute to signalling in a variety of cell types and following stimulation undergo rapid desensitisation (within 1 s), and require ∼5 min to recover. In HEK293 cells...Full Text Available
Human epidermal growth factorreceptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2...Full Text Available
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
α1-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in liver and intestine, where it is implicated in the regulation...Full Text Available
The p75 neurotrophin receptor (p75"N"T"R) is a death receptor which belongs to the tumor necrosis factorreceptor 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 ...
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 ...
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 ["1"2"5I]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 ["1"2"5I]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 ...
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, ...
T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X7receptors play a key...Full Text Available
Objective:To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical.Methods:Experimentally:...Full Text Available
We sought to determine the effects of activation of peroxisome proliferator-activatedreceptor-γ (PPAR-γ) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male...Full Text Available
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-activatingreceptor-? (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 ...
Epidermal growth factorreceptor (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 ...
Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction ...
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 ...
Although peroxisome proliferator-activatedreceptor alpha (PPARα) is closely associated with myocardial fatty acid metabolism, the pathophysiological role of PPARα in myocardial infarction...Full Text Available
Peroxisome proliferator activatedreceptor-{gamma} (PPAR{gamma}) regulates metabolic homeostasis and adipocyte differentiation, and it is activated by oxidized and nitrated fatty acids. Here we report the crystal structure of the PPAR{gamma} ligand binding domain bound to nitrated linoleic acid, a potent endogenous ligand of PPAR{gamma}. Structural and functional studies of receptor-ligand interactions reveal the molecular basis of PPAR{gamma} discrimination of various naturally occurring fatty acid derivatives.
Incorporation of /sup 32/P from (gamma-32P)ATP into tyrosine residues of the insulin-like growth factor (IGF)-II receptor was observed in a Triton X-100-insoluble fraction of rat adipocyte plasma membranes. IGF-II receptor phosphorylation proceeded to a stoichiometry of approximately 0.5 mol of phosphate/IGF-II binding site after 10 min of incubation at 4 degrees C. A Km for ATP of 6 microM was calculated for this phosphorylation reaction. Addition of IGF-II caused an approximately 2-fold increase in tyrosine phosphorylation of the IGF-II receptor in this preparation. In contrast, phosphorylation of angiotensin II by the Triton X-100 washed membranes was not stimulated by IGF-II. Incubation of purified receptor immobilized on IGF-II agarose or of receptor-enriched low density microsomal membranes with (gamma-32P)ATP did not result in appreciable incorporation of ...
Keratinocyte growth factorreceptor (KGFR) and fibroblast growth factorreceptor (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 ...
In this study we compared the molecular signalling elicited by rexinoids, selective retinoid X receptor (RXR)-activators, in several organs (i.e. liver, kidney,...Full Text Available
The role of pheromone biosynthesis activating neuropeptide (PBAN) in the regulation of pheromone biosynthesis of several female moth species is well elucidated, but its role in the males has been a...Full Text Available
Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM...Full Text Available
BackgroundThiazolidinediones (TZDs) activate peroxisome proliferator-activatedreceptor gamma (PPARγ) and are used clinically to help restore peripheral insulin sensitivity...Full Text Available
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
Using an anti-receptor mAb that blocks the attachment of echovirus 7 and related viruses (echoviruses 13, 21, 29 and 33), we have isolated a complementary DNA clone that encodes the human decay-accelerating...Full Text Available
Methylxanthines and their derivatives are antagonists at cell surface adenosine receptors. They report here a systematic study of xanthine structure-activity relationships which compares potency at two adenosine receptor subtypes, R/sub a/ and R/sub i/. Adenylate cyclase stimulation (R/sub a/ in platelet membranes) and inhibition (R/sub i/ in adipocyte membranes) were used as models of receptoractivation. K/sub i/ values were obtained by Schild analysis. The orders of potency of the xanthines to attenuate the effects of adenosine analogues were similar to those previously reported. Earlier work utilizing radioligand binding (R/sub i/ and (/sup 3/H) cAMP formation (R/sub a/) claimed that IIX and PACPX are at least 10 and 400 fold, respectively, more potent at R/sub i/ than at R/sub a/. However, in their assays which utilize modulation of receptor-coupled ...
BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available
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
Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely...Full Text Available
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
Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull,...Full Text Available
Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factorreceptor (EGFR) mutations are frequent in glioblastoma,...Full Text Available
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
Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole...Full Text Available
Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane ...
Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) regulate cell growth and differentiation and have critical regulatory roles in the process of tissue repair and remodeling....Full Text Available
The effects of neuroactive steroids on the function of GABAAreceptors were studied using cell-attached records of single channel activity recorded from HEK293 cells transfected with α1...Full Text Available
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available
This report investigates acute changes in the sensitivity of 5-HT1Areceptors in dorsal raphe (dr) neurons in response to elevated serotonin. DR neurons were isolated from adult rats...Full Text Available
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 ...
A factor produced by plerocercoids of the tapeworm Spirometra mansonoides is similar to human growth hormone (hGH) in that it stimulates body growth, binds to hGH receptors, cross-reacts with anti-hGH antibodies, and has lactogenic and insulin-like activities. The purpose of this study was to determine whether plerocercoid growth factor (PGF) is similar to hGH in expressing diabetogenic activity in the genetically obese (ob/ob) mouse. To determine an effective dose for use in the obese mice, the ability of daily injections of PGF to stimulate growth of phenotypically normal mice of the same strain was assessed in a 10-day weight gain assay. Injections of PGF stimulated a dose-dependent weight gain (r = 0.83) and 25 ng eq/day of PGF stimulated a response not significantly different from that produced by 100 micrograms of bovine growth hormone/day. Diabetogenicity was assessed using ...
It is now known that various growth factors may also act in the central nervous system. Among them, it has recently been shown that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) may possess trophic effects in the mammalian brain. We report here on the respective autoradiographic distribution of ["1"2"5I]EGF and ["1"2"5I]IGF-I receptor binding sites in the rat brain, both during ontogeny and in adulthood. It appears that ["1"2"5I]EGF sites are mostly found in the rat forebrain during brain development. On the other hand, ["1"2"5I]IGF-I sites are more widely distributed both during ontogeny and in adulthood. These results reveal the plasticity of the expression of EGF and IGF-I receptor sites in the mammalian brain. This could be relevant for the respective role of these two growth factors in the development and maintenance of neuronal ...
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 ...
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 ...
Objective: To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1@a,25(OH)"2D"3 or soluble receptoractivator of nuclear factor-@kB ligand (s-RANKL). Materials and methods: Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10@mM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1@a,25(OH)"2D"3 (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1@a,25(OH)"2D"3 or s-R...
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 ...
Experience-dependent plastic changes in the central sensory systems are due to activation of both the sensory and neuromodulatory systems. Nonspecific changes of cortical auditory neurons elicited by...Full Text Available
Cervical spinal cord hemisection rostral to the phrenic nucleus leads to paralysis of the ipsilateral hemidiaphragm in adult rats. Respiratory function can be restored to the paralyzed hemidiaphragm...Full Text Available
SummaryTRPV1 is the founding and best-studied member of the family of temperature-activated transient receptor potential ion channels (thermoTRPs). Voltage, chemicals, and heat...Full Text Available
Receptoractivator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the...Full Text Available
Cleavage of membrane-associated proteins with the release of biologically active macromolecules is an emerging theme in biology. However, little is known about the nature and regulation of the involved...Full Text Available
Macrophage activation by the proinflammatory cytokine interferon-γ (IFN-γ) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature...Full Text Available
The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on neurological impairment and histologically measured infarction volume...Full Text Available
Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented...Full Text Available
We had previously identified a macrophage surface protein whose expression is highly induced, transient, and specific, as it is restricted to actively fusing macrophages in vitro and in vivo. This protein...Full Text Available
In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...Full Text Available
Recently, we demonstrated that the central ghrelin signalling system, involving the ghrelin receptor (GHS-R1A), is important for alcohol reinforcement. Ghrelin targets a key mesolimbic circuit involved...Full Text Available
Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions...Full Text Available
BackgroundMost rapidly evolving gene families are involved in immune responses and reproduction, two biological functions which have been assigned to the carcinoembryonic antigen...Full Text Available
Numerous xenobiotics, including therapeutics agents, are substrates for bioactivation to electrophilic reactive intermediates that may covalently modify biomolecules. Selective estrogen receptor...Full Text Available
Endogenous immune complexes present in sera from 10 different patients with systemic lupus erythematosus (SLE) in an active phase were allowed to bind to Raji cells; the ability of intact complement...Full Text Available
The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian...Full Text Available
Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a ...
ABSTRACT: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activatedreceptor ?/? (PPAR?/?) and PPAR?. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.See related research article: http://genomebiology.com/2011/12/8/R75. PMID:21861850
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 ...
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 ...
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-"1"4C]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"5 cells/ml) were incubated with either ["1"2"5I]insulin or ["1"2"5I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and "1"4C-incorporation into lipids. ...
Increased levels of epidermal growth factorreceptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to "2"3"9PuO_2- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)
Because of the instability of Factor VIII (antihaemophilic factor) in plasma in vitro, and since evidence has accumulated that the level of activity varies significantly between samples...Full Text Available
The synthesis and structure-activity relationship analysis of a novel class of amide-based biaryl NR2B-selective NMDA receptor antagonists are presented. Some of the studied compounds are potent, selective, non-competitive, and voltage-independent antagonists of NR2B-containing NMDA receptors. Like the founding member of this class of antagonists (ifenprodil), several interesting compounds of the series bind to the amino terminal domain of the NR2B subunit to inhibit function. Analogue potency is modulated by linker length, flexibility, and hydrogen bonding opportunities. However, unlike previously described classes of NR2B-selective NMDA antagonists that exhibit off-target activity at a variety of monoamine receptors, the compounds described herein show much diminished effects against the...
Somatostatin receptor expression has been demonstrated on a number of plasma cell lines. Therefore, we questioned whether somatostatin receptor scintigraphy (SRS) can be used to demonstrate in vivo multiple myeloma (MM) activity. SRS was performed in newly diagnosed (n = 9) or relapsing (n = 18) MM patients or in patients with localized plasmacytoma (n = 2). The results were compared with radiographic findings. A positive SRS was demonstrated in 44% of the newly diagnosed patients, in 83% of the relapsed patients and in both patients with plasmacytoma. The SRS findings corresponded with radiographic abnormalities in 40% of the patients. However, in relapsed patients 60% demonstrated increased SRS uptake in areas without new radiographic abnormalities. The positive SRS corresponded with histologically proven disease activity and responded upon treatment. Moreover, immunohistochemical staining of MM ...
Trastuzumab increases survival amongst women with human epidermal growth factorreceptor (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.
Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide ...
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. ...
A factor produced by the plerocercoid stage of S. mansonoides mimics some, but not all, of the actions reported for hGH. The biological actions of plerocercoid growth factor (PGF) suggest structural similarity to human GH (hGH). Plerocercoid membranes were solubilized, and PGF was purified more than 1000-fold by hGH receptor affinity chromatography. The ability of purified PGF to displace [125I]hGH from monoclonal antibodies specific for four distinct nonoverlapping antigenic determinants of hGH and from an anti-hGH polyclonal antibody was tested in liquid phase RIA. All of the hGH antibodies cross-reacted with PGF, with potencies ranging from more than 60% to less than 1% that of the hGH standard. Of the four major epitopes of hGH defined by the monoclonal antibodies used in this study, only one is not represented to a significant extent in PGF. The epitope of hGH that is only marginally present in PGF is highly ...
Dysregulation of the alternative pathway of complement activation, caused by mutations or polymorphisms in the genes encoding factor H, membrane co-factor protein, factor I or factor B, is associated...Full Text Available
In many species social behaviors are dependent on integration of chemosensory and hormonal cues. Many chemosensory stimuli are detected by the vomeronasal organ, which projects to many regions that contain steroid receptors, including the medial amygdala. In male hamsters, testosterone is known to acutely increase in response to chemosensory stimulation, and can facilitate sexual behavior by direct action within the medial amygdala. Conspecific stimuli activate the anterior (MeA) and posterior (MeP) medial amygdala, while heterospecific stimuli activate only MeA. Chemosensory stimuli with different social significance differentially activate the dorsal and ventral subdivisions of MeA and MeP. Therefore, it is likely that steroids differentially facilitate stimulation of the medial amygdala...
To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in ...
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 ...
Targeted studies completed include the evaluation of tritiated N-0437, evaluation of /sup 35/S-cysteamine, evaluation of /sup 18/F-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 ...
BackgroundWe investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection...Full Text Available
Background: EGFR (epidermal growth factorreceptor) 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 ...
Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. ["1"1C]CUMI-101, proposed as the first 5-HT_1_A receptor agonist PET ligand, has been reported to behave as a potent 5-HT_1_A agonist in a cellular system stably expressing human recombinant 5-HT_1_A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: ["3"5S]-GTP#gamma#S binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT_1_A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT_1_A ...
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, ...
The possibilities for therapy in the field of severe cardiac insufficiency have been extended in recent years by the introduction of novel agents endowed with a positive inotropic action. These substances may be arranged in two large classes: sympathomimetic agents and "non sympathomimetic--non digitalis-like" inotropic agents. The stimulant action of noradrenaline, adrenaline and isoproterenol on beta-adrenergic myocardial receptors has been clearly demonstrated but the usefulness of these medicines is limited by their positive chronotropic and arrhythmogenic actions. Dopamine and dobutamine have proved to be very useful in the treatment of patients in intensive care units. However, the exclusively intravenous route of administration limits their importance to the medium or long term. Several compounds, which are active by the oral route, have been the subject of therapeutic trials for the short or medium term. The problems posed by their use ...
The ability of a number of mycobacteria and some of their components to activate complement was examined. Mycobacterium bovis BCG (Glaxo strain), Mycobacterium leprae, Mycobacterium lepraemurium, and...Full Text Available
Looking at all the indeterminate factors as a whole and regarding activity durations as independent random variables, the traditional stochastic network planning models ignore the inevitable relationship and dependence among activity durations when more than one activity is possibly affected by the same indeterminate factors. On this basis of analysis of indeterminate effect factors of durations, the effect factors-based stochastic network planning (EFBSNP) model is proposed, which emphasizes on the effects of not only logistic and organizational relationships, but also the dependent relationships, due to indeterminate factors among activity durations on the project period. By virtue of indeterminate factor analysis the model extracts and describes the quantitatively ...
Endogenous opioid peptides (EOP) are molecules affecting many biological functions influencing productive and reproductive performance. They increase in stress conditions and interact with specific opioidergic receptors (OR): delta, kappa and mu. Several studies in other animal species suggest that they can also affect sperm cell motility. In fish the ionic external environment modulates the increase of intracellular calcium ion that is required to activate sperm motility after spawning. In mammals OR are functionally associated to calcium channels and in fishes calcium is highly required for fish sperm activation. In this study the presence of OR on spermatozoa of two Perciform fish, the sharpsnout seabream (Diplodus puntazzo, family Sparidae) and the European sea bass (Dicentrarchus labr...
Previous studies from this laboratory have shown that certain N-substituted phthalimides (NSPs) exhibit GA-like activity in a range of specific bioassays and that bioactive NSPs compete with ({sup 3}H)-GA{sub 4} for soluble binding sites in cucumber homogenates. As such, these compounds may prove useful in the purification and characterization of GA receptor proteins. To this end, five azido-NSPs have been synthesized and are currently being screened for biological activity and photochemical stability. Three azido-NSPs elicit {alpha}-amylase production in barley half-seeds and stimulate tissue elongation in d{sub 5} maize, lettuce, sunflower, and soybean. Further evaluations are in progress and these data as well as the utility of these compounds as photo-affinity ligands will be discussed.
The gene encoding the human type I pituitary adenylate cyclase activating polypeptide receptor (ADCYAP1R1) was mapped to chromosome 7 by PCR analysis of genomic DNA from a human/rodent somatic cell hybrid mapping panel. This assignment was confirmed and the gene localized to chromosome band 7p14 by fluorescence in situ hybridization. A yeast artificial chromosome containing ADCYAP1R1 was identified in the CEPH {open_quotes}B{close_quotes} Mega-YAC library. This YAC includes two highly polymorphic dinucleotide repeat sequences that will facilitate genetic studies of the contribution of ADCYAP1R1 in disease states of the central nervous and neuroendocrine systems. 13 refs., 1 fig.
Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing...Full Text Available
Radioiodinated ..cap alpha..-bungarotoxin, the venom of Bungarus multicinctus, is commonly used for the detection and quantification of nicotinic acetylcholine receptors (nAChR) and anti-nAChR antibodies. A radioiodination method is described which is simple and yields a fully active product which, after fractionation, has a specific activity tenfold higher (900 Ci/mmol) than those routinely used, resulting in enhanced sensitivity of assays and conservation of material, especially muscle extracts.
The present paper further characterizes the cholinergic properties of acetylselenonium choline (ASeCh, (CH3)2Se+CH2CH2OCOCH3). The data demonstrate that ASeCh possesses muscarinic receptor agonist properties as evidenced by vasodepressor and smooth muscle contractile activities which are enhanced by physostigmine and antagonized by atropine. ASeCh also possessed nicotinic agonist activity on frog rectus abdominis tissue which was potentiated by physostigmine, and blocked by d-tubocurarine. The relative potencies of ASeCh ranged from approximately 1% to approximately 6% of the potency of acetylcholine in the three types of preparations examined. PMID:1435078
PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles and ...
The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in ...
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 ...
Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated....Full Text Available
Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X...Full Text Available
α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca2+-permeable homopentameric channels modulating cortical network activity and cognitive processing....Full Text Available
Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural...Full Text Available
Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic steatohepatitis (NASH) and associated with hypercholesterolemia, i.e. increased levels of plasma low-density...Full Text Available
In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 ± 9.2 pmol nitric...Full Text Available
Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available
The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown....Full Text Available
Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...
A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...
Fgf receptor 2c (Fgfr2c) was expressed in mature adipocytes of mouse white adipose tissue (WAT). To examine the role of Fgfr2c in mature adipocytes, we generated adipocyte-specific Fgfr2 knockout (Fgfr2 CKO) mice. The hypertrophy impairment of adipocytes in the mesenteric WAT but not in the subcutaneous WAT and decreased plasma free fatty acid (FFA) levels were observed in Fgfr2 CKO mice. Although the expression of genes involved in adipocyte differentiation and lipid metabolism in the mesenteric WAT was essentially unchanged, the expression of uncoupling protein 2 potentially involved in energy dissipation was significantly increased. Among potential Fgf ligands for Fgfr2c, Fgf9 was preferentially expressed in the mesenteric WAT. The present findings indicate that Fgfr2c potentially activ...
beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B chain was able to induce cytotoxic effects on SK-N-SH cells as beta-Bgt did. Abolishment of PLA(2) ...
A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. All three peptides are cleared by the natriuretic peptide-C receptor and degraded by ...
Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal structure of this truncated D-alaninamide derivative 13. Compound 11 displays properties compatible with development as an intranasal solution formulation, whereas oral ...
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not ...
The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery...Full Text Available
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
Orphan G protein-coupled receptors (GPCRs) are receptors lacking endogenous ligands. Found by molecular biological analyses, they became the roots of reverse pharmacology, in which receptors are attempted...Full Text Available
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
AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the...Full Text Available
The growth regulating factor CTGF/CCN-2 is an integral factor in growth and development, connective tissue maintenance, wound repair and cell cycle regulation. It has recently been reported that CTGF/CCN-2...Full Text Available
BackgroundHealthcare professionals can play a crucial role in optimizing the health status of patients with cardiovascular risk factors (abdominal obesity, high blood pressure, low...Full Text Available
Platelet Factor VIII-related antigen (VIIIR:Ag) represents a significant proportion of the total circulating VIIIR:Ag pool. However, its participation in the events of primary hemostasis has not been...Full Text Available
We investigated the effect of irradiation on the kinetic characteristics of amino acid and glucose transport, and the effect on the activity of the cell membrane-bound enzyme 5'-nucleotidase and on the receptor-mediated stimulation of cyclic adenosine monophosphate synthesis by prostaglandin E1. Irradiation inhibited the sodium-dependent amino acid transport by a reduced binding of the amino acid to the transport unit. The transport of glucose, which appeared to be a sodium-independent process, was temporarily stimulated by increased maximal velocity of the transport. No effect was found on the binding to the transport unit. Irradiation increased the 5'-nucleotidase activity and decreased the prostaglandin E1-stimulated cyclic adenosine monophosphate synthesis 48 h after exposure to 20 Gy. It is concluded that irradiation decreases sodium-dependent transport by impairment of the transport unit, does not ...
Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagoni...
The authors have shown previously that the domain recognizing receptors on activated human platelets is located on the human fibrinogen {gamma} chain between residues 400 and 411. To study the correlation between the structure of this segment of the {gamma} chain and its reactivity toward receptors on ADP-activated human platelets, they designed a series of analogues containing replacements at 9 out of 12 positions. A double substitution of the normal His{sup 400}-His{sup 401} sequence by Ala-Ala reduced the inhibitory potency of the dodecapeptide 3-fold. When Lys{sup 406} was replaced by Arg, the inhibitory potency of the dodecapeptide decreased 15 times. On the other hand, substitution of Ala{sup 408} with Arg increased the inhibitory potency of the dodecapeptide 6-fold. A drastic decrease in the reactivity of the dodecapeptide toward platelet receptors was observed when Val{sup ...
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
Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat...Full Text Available
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
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
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
Synthetic atrial natriuretic peptide (carperitide) and B-type natriuretic peptide (BNP; nesiritide) are used to treat congestive heart failure. However, despite beneficial cardiac unloading properties, reductions in renal perfusion pressures limit their clinical effectiveness. Recently, CD-NP, a chimeric peptide composed of C-type natriuretic peptide (CNP) fused to the C-terminal tail of Dendroaspis natriuretic peptide (DNP), was shown to be more glomerular filtration rate-enhancing than BNP in dogs. However, the molecular basis for the increased responsiveness was not determined. Here, we show that the DNP tail has a striking effect on CNP, converting it from a non-agonist to a partial agonist of natriuretic peptide receptor (NPR)-A while maintaining the ability to activate NPR-B. This effect is specific for human receptors because CD-NP was only a slightly better activator of rat NPR-A due to the ...
The purpose of this study was to examine relationships between weather and outdoor physical activity (PA). An online weather source was used to obtain daily max temperature [DMT], precipitation, and...Full Text Available
Astrocytes have important immune functions in CNS, and astrocytes stimulated by interferon-g were showed to have direct antimicrobial function. However whether astrocytes without the stimulation of cytokines have antibacterial function, and how this function is regulated are still largely unknown. In this study, we found that primary cultured astrocytes inhibited the growth of both gram-negative and gram-positive bacteria. Further more, we showed that interleukin-1b (IL-1b) enhanced the antibacterial effect in a dose-dependent manner, and the antibacterial effect of astrocytes from IL-1b receptor-deficient mice failed to be enhanced by IL-1b. IL-1b stimulated IkBa degradation, NF-kB nuclear translocation, and transactivation in astrocytes. NF-kB inhibitors blocked NF-kB activation and the ...
Studies of various established human bladder and renal carcinoma cell lines cultured in vitro demonstrated the presence of specific, saturable, high affinity binding sites for /sup 125/I-labeled human interferon Beta ser IFN-beta ser). This recombinant produced interferon labeled with approximately one atom of /sup 125/I/molecule of IFN expressed minimal or no loss of antiviral activity. A single class of binding sites (1000-2000/cell) with an affinity constant of 10(10)-10(11) L/M was measured at 4 degrees C for cells exhibiting widely different sensitivity to the antiproliferative effect of IFN-beta ser. Major fluctuations in the binding of /sup 125/I-labeled IFN-beta ser to cellular receptors were observed during in vitro proliferation of four of five cell lines examined. A significant decrease (P less than 0.001) in specific binding was observed 48 h after cultures were established. Cell cycle analysis suggested that within the first 24 h ...
Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected ...
In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 ...
Within 20 min after intraperitoneal injection of Salmonella enteritidis endotoxin in rats, blood platelet-activatingfactor (PAF) increased from 4.3 +/- 1.3 to 13.7 +/- 2.0 ng/ml (P less than 0.01)...Full Text Available
sigma-Aminolevulinate dehydratase has been found to be activated in vitro by dithiotreitol and factors isolated from radish cotyledons grown under continuous far-red light. Cross experiments, between fructose 1-6 bisphosphatase system, and sigma-aminolevulinate dehydratase, show that these factors are functionally identical to thioredoxin f.
Myostatin is a member of the transforming growth factor-{beta} (TGF-{beta}) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-{beta} class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. Overall, we have identified ...
Anthraquinones are widely present in plant kingdom, and clinically used as laxatives. Environmental contaminants, dioxins, develop various adverse effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We investigated the effects of 18 anthraquinones and 7 of their structurally related compounds on transformation of the AhR estimated by its DNA-binding activity in the cell-free system. 1,4-Dihydroxyanthraquinone (quinizarin), 1,5-dihydroxyanthraquinone (anthrarufin), 1,8-dihydroxyanthraquinone (danthron), and 5-hydroxy-1,4-naphthoquinone (juglone) strongly suppressed DNA-binding activity of the AhR induced by 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with their IC(50) values around 1 muM. On the other hand, anthraquinone, 2,6-dihydroxyanthraquinone (anthraflavic acid), and 2-hydroxy-1,4-naphthalendione (lawsone) showed moderate effects. Quantitative structure-activity ...
This paper is aimed to present a fuzzy decision making approach to deal with the performance measurement in supply chain systems. In the manufacturing environment, performance measurement is based on different quantitative and qualitative factors. Some of these factors may have a larger effect on the performance measure than others. Units of measure of the quantitative factors are different such as time, money, percentage, ratio, and counts. Thus, this paper presents a performance measurement approach based on fuzzy set theory and the pair-wise comparison of Analytical Hierarchy Process (AHP), which ensures the consistency of the designer's assignments of importance of one factor over another to find the weight of each of the manufacturing activity in the departmental organization. In the ...
The activity assay of a radiopharmaceutical administration to a patient is normally achieved via the use of a radionuclide calibrator. Because of the different geometries and elemental compositions between plastic syringes and glass vials, the calibration factors for syringes may well be significantly different from those for the glass containers. The magnitude of these differences depends on the energies of the emitted photons. For some radionuclides variations have been observed of 70 %, it is therefore important to recalibrate for syringes or use syringe calibration factors. Calibration factors and volume correction factors have been derived for the NPL secondary standard radionuclide calibrator, for a variety of commonly used syringes and needles, for the most commonly used medical radionuclide.
The effect of in vitro and in vivo administration of ethanol on the binding of "3"5S-t-butyl-bicyclophosphorothionate ("3"5S-TBPS) to cortical brain membranes of C57B1 mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal "3"5S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on "3"5S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of "3"5S-TBPS binding produced by diazepam. "3"5S-TBPS binding to cortical brain membranes was inhibited by the putative Cl"- channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol (#<=# 100 mM ethanol). Chronic ethanol ingestion in vivo, which produced tolerance to and physical ...
The functional interaction between the peroxisome proliferator-activatedreceptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and ...
The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam ...
We studied the effect of extracellular Ca"2"+ concentration ([Ca"2"+]_e) on adipocyte differentiation. Preadipocytes exposed to continuous [Ca"2"+]_e higher than 2.5 mmol/l accumulated little or no cytoplasmic lipid compared to controls in 1.8 mmol/l [Ca"2"+]_e. Differentiation was monitored by Oil Red O staining of cytoplasmic lipid and triglyceride assay of accumulated lipid, by RT-PCR analysis of adipogenic markers, and by the activity of glycerol-3-phosphate dehydrogenase (GPDH). Elevated [Ca"2"+]_e inhibited expression of peroxisome proliferator-activatedreceptor #gamma#, CCAAT/enhancer binding protein #alpha#, and steroid regulatory binding element protein. High [Ca"2"+]_e significantly inhibited differentiation marker expression including adipocyte fatty acid binding protein, and GPDH. The decrease in Pref-1 expression that accompanied differentiation also was prevented by high [Ca"2"+]_e. Treatment of 3T3-L1 cells ...
Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified binding protein yielded a lower limit molecular weight of ...
It is hypothesized that systemic ??-noradrenergic antagonists may interfere with the transmission of sensory stimulation, particularly vaginal--cervical stimulation (VCS), which is crucial for reproductive functioning. To determine if ??-noradrenergic transmission receptoractivity is necessary for transmission of sensory information important for VCS-dependent events, we conducted an experiment using prazosin, a ??-noradrenergic receptor antagonist. First, three doses of prazosin (1.0, 0.5 or 0.1 mg/kg) or the 10% ETOH in sesame oil vehicle were administered i.p. and sexual receptivity was assessed 30 min later in ovariectomized, hormone-treated female rats. The 1 mg/kg dose of prazosin significantly inhibited lordosis quotients and lordosis ratings. This dose of prazosin (1.0 mg/kg) was then administered 30 min prior to VCS or control scapular stimulation (CSS) and Fos-IR was examined in the posterodorsal medial amygdala ...
The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.
Peroxisome proliferator-activatedreceptor gamma coactivator-1 (PGC-1), a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells. In the present study, we first cloned a rat PGC-1 gene from a brown adipose tissue cDNA library which encodes a predicted 796-amino-acid protein and exhibits respectively 98% and 95% identity with the mouse and human homologues. Next, we examined the effect of swimming exercise training on the level of expression of the PGC-1 gene in rat epitrochlearis (Epi) muscle. PGC-1 mRNA level in Epi muscle in rats that swam 2 h a day for 3 and 7 days increased dramatically by 154% and 163%, respectively, compared to the non-exercised control group. PGC-1 mRNA up-regulation was not observed in an immersion group treated at 35 degrees C during the training program but without swimming exercise. These results demonstrate that expression of the ...
[alpha]-Melanocyte stimulating hormone ([alpha]-MSH), a hormone originally named for its ability to regulate pigmentation of melanocytes, is a 13-amino-acid post-translational product of the pro-opiomelanocortin (POMC) gene. [alpha]-MSH and the other products of POMC processing, which share the core heptapeptide amino acid sequence Met-Glu (Gly)-His-Phe-Arg-Trp-Gly (Asp), the adrenocorticotropic hormone (ACTH), [beta]-MSH, and [gamma]-MSH, are collectively referred to as melanocortins. While best known for their effects on the melanocyte (pigmentation) and adrenal cortical cells (steroidogenesis), melanocortins have been postulated to function in diverse activities, including enhancement of learning and memory, control of the cardiovascular system, analgesia, thermoregulation, immunomodulation, parturition, and neurotrophism. To identify the chromosomal band encoding the human melanocortin-1 receptor gene, 1 [mu]g of an EMBL clone coding region ...
Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding a3, a5 and b4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronchial cells and in lung cancer cell lines. In both cell types, silencing CHRNA5 or inhibiting receptors containing nAChR a5 with a-conotoxin MII exerted a nicotine-like effect, with increased motility and invasiveness in vitro and increasing calcium influx. The effects on motility were enhanced by addit...
The purpose of organization and management development activities in the commercial nuclear power industry is to foster high levels of power plant performance and safety through improved human performance. The NRC has been working to develop assessment tools to assay the effects of organizational factors on plant safety. The utility industry has been working on initiatives targeting individual accountability, the improvement of plant performance and the elimination of the items identified through the NRC assessment process. Organization and management activities do not focus on industry organizational charts, but on the personnel processes and dimensions (factors) that affect safety and economic performance. As individual terms these activities are often combined and referred to as organizational factors. As an area of study, organizational ...
Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the nucl2048 These connections are made via membrane-bound ...
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 ...
In order to study the intragenic profiles of active transcription, we determined the relative levels of active RNA polymerase II present at the 3′- and 5′-ends of 261 yeast genes by...Full Text Available
Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factorreceptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-l...
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.
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 ...
The activity of tyrosine aminotransferase (TAT) in the liver of mice subjected simultaneously to ionizing radiation and to local inflammatory process showed in the first 24 hours of the experiment statistically significant changes resulting from summation of the harmful effects of both factors. In the second 24-hour period an evident tendency was observed for return of a normal circadian rhythm of the enzyme. This points to presence of an endogenous mechanism of suppression of the manifestations of significant desynchronization of the circadian rhythm. The paper contains also a trial of mathematical analysis of changes in TAT activity in the circadian rhythm, a description and analysis or the suppression process, qualitative and quantitative determination of the phenomenon of cumulation of the effects of powerful stress factors acting on the animal organism. The obtained results were compared with the ...
BackgroundThe pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved...Full Text Available
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
Selective estrogen receptor modulators (SERMs) represent a class with a growing number of compounds that act as either estrogen receptor agonists or antagonists in a tissue-specific manner. This article...Full Text Available
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
Chemokine receptors control leukocyte chemotaxis and cell-cell communication but have also been associated with pathogen entry. GPR33, an orphan member of the chemokine-like receptor family,...Full Text Available
The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available
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
BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously...Full Text Available
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
We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) ...
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
Histamine and the histamine receptors are important regulators of a plethora of biological processes, including immediate hypersensitivity reactions and acid secretion in the stomach. In these...Full Text Available
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
In rat adipocyte membranes, both beta-adrenergic agonists and beta-adrenergic antagonists competed with (--)(/sup 3/H)dihydroalprenolol for high affinity (KD 2-4 nM) and low capacity binding sites. The antagonists but not the agonists competed with (--)(/sup 3/H)dihydroalprenolol for lower affinity and higher capacity sites. The present studies were performed in order to characterize the adipocyte beta-adrenergic receptor and distinguish it from low affinity, higher capacity sites which were heat-labile and not stereoselective. When isoproterenol was used to define the nonspecific binding, saturation studies showed a single binding site with a capacity of approximately 100 fmol/mg membrane protein (corresponding to approximately 50,000 sites/adipocyte). Binding was saturated by 10 nM (--)(/sup 3/H)dihydroalprenolol. Approximate KD's of 204 nM were observed. Kinetic analysis of (--)(/sup 3/H)dihydroalprenolol binding provided an independent measurement of ...
The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ({sup 14}C)AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ({sup 14}C)AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2{alpha}. Trace amounts of PGD2 and 6-keto-PGF1{alpha} but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10{sup {minus}7}, 10{sup {minus}7}M respectively). In contrast, dobutamine, norepinephrine, ...
The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ["1"4C]AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ["1"4C]AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2#alpha#. Trace amounts of PGD2 and 6-keto-PGF1#alpha# but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10"-"7, 10"-"7M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10"-"6M) did not ...
The radioiodination and in vivo evaluation of p-iodocaramiphen a muscarinic antagonist which binds with high affinity to the M[sub 1] receptor subtype in vitro are described. Biodistribution studies in female Fischer rats demonstrated that [[sup 125]I]-piodocaraminphen had significant cerebral localization, but the uptake did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors, and radioactivity washed out rapidly from the brain. In addition there was no significant blockage of activity when the rats were preinjected with quinuclidinyl benzilate. These results suggest that p-iodocaramiphen is not a good candidate for the in vivo study of M[sub 1] muscarinic receptor populations by SPECT. Because of the widespread interest and expected importance of the availability of large amounts of tungsten-188 required for the tungsten-188/rhenium-188 generator systems, we have ...
Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine 5'-(beta, ...
The power?time curves of mice splenic lymphocytes growth at 37??C affected by ginsenoside Rh2 were determined by microcalorimetry using a 3114/3236 TAM air bioactivity monitor with ampoule mode. Then, the minimal inhibitory concentration (MIC) of Rh2 on splenic lymphocytes growth was determined by serial dilution method. From factor analysis (FA) on six quantitative thermokinetic parameters from the power?time curves, the activity of Rh2 on splenic lymphocytes could be quickly evaluated by analyzing the changes in the two main parameters: growth rate constant k, and maximum heat-output power, P m. The results showed that Rh2 had strong inhibitory activity on splenic lymphocytes growth, and this inhibitory activity was strengthened with increasing concentration of Rh2 in the concentration r...
Global acetylation of histone H4 is a mark of gene transcriptional activation. The c-Myc transcription factor binds to specific DNA sites in cellular chromatin and induces the acetylation of...Full Text Available
Pituitary Fshb concentrations increase markedly and selectively beginning on Postnatal Day 20 in the male rat. To evaluate the factors potentially responsible for this rise...Full Text Available
... time, sucrase activity, a marker of intestinal epithelium (Matsushita, 1983) was observed in epithelial cells with CdxA ... PubMed, CSAIshii, Y., K. Fukuda, H. Saiga, S. Matsushita, and S. Yasugi. 1997. E...
A continuous stream of activating and repressing signals is processed by the transcription complex paused at the promoter of the c-myc proto-oncogene. The general transcription factor...Full Text Available
There is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in...Full Text Available
It has become increasing clear that alterations in cellular metabolism have a key role in the generation and maintenance of cancer. Some of the metabolic changes can be attributed to the activation...Full Text Available
Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study...Full Text Available
The processes regulating telomere function have major impacts on fundamental issues in human cancer biology. First, active telomere maintenance is almost always required for full oncogenic transformation...Full Text Available
Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and...Full Text Available
The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activatingfactor (DBPMAF) was examined using a mouse SCCVII...Full Text Available
Mammals possess multiple insulin-like growth factor (IGF) binding proteins (IGFBPs), and related proteins, that modulate the activity of insulin/IGF signalling (IIS), a conserved neuroendocrine signalling...Full Text Available
1. One hundred and thirty-two antidromically identified paraventricular (PV) and supraoptic (SO) neurones were studied during milk ejection evoked by the suckling of the young, in thirty-four lactating...Full Text Available
Genome endoreduplication during mammalian development is a rare event for which the mechanism is unknown. It first appears when fibroblast growth factor 4 (FGF4) deprivation induces differentiation...Full Text Available
The common factor that underlies several types of functional brain imaging is the electric current of masses of dendrites. The prodigious demands for the energy that is required to drive the...Full Text Available
Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several...Full Text Available
Activatable or “smart” magnetic resonance contrast agents have relaxivities that depend on environmental factors such as pH or enzymatic activity, but the MR signal depends on...Full Text Available
Among the several rotenoids, amorphigenin is isolated from the leaves of Amopha Fruticosa and it is known that has anti-proliferative effects and anti-cnacer effects in many cell types....Full Text Available
SummaryActivating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines...Full Text Available
BackgroundObesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates...Full Text Available
Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including...Full Text Available
CD44, a transmembrane receptor for hyaluronic acid, is implicated in various adhesion-dependent cellular processes, including cell migration, tumor cell metastasis and invasion. Recent studies demonstrated that CD44 expressed in cancer cells can be proteolytically cleaved at the ectodomain by membrane type 1-matrix metalloproteinase (MT1-MMP) to form soluble CD44 and that CD44 cleavage plays a critical role in cancer cell migration. Here, we show that transforming growth factor-b (TGF-b), a multifunctional cytokine involved in cell proliferation, differentiation, migration and pathological processes, induces MT1-MMP expression in MDA-MB-435s cells. TGF-b-induced MT1-MMP expression was blocked by the specific extracellular regulated kinase-1/2 (ERK1/2) inhibitor PD98059 and the specific pho...
One of the refinements of modern Nuclear Medicine is the capacity of providing dynamic and kinetics images of the administered radiopharmaceutical, reproducing its transport mechanism, action sites, receptor binding and excretion route. With the continues technological advances new radiopharmaceuticals have been developed in order to express higher specificity and with higher characters of affinity between receptor/complex. One radiopharmaceutical is formed by a reagent or bio molecule that has in its structure a radioisotope, that has the objectives of carrying it to the organs of affinity or to benign or malign tumoral process. Somatostatin inhibits the growing and proliferation of several tumoral cells. Somatostatin analogs bind to somatostatic receptors that are expressed in different kind of neoplasia DOTA-LANREOTIDE (DOTALAN) is an octapeptide analog to somatostatin. The interest of labeling the bio conjugate with ...
Microorganisms are ubiquitous in subsurface environments although their populations sizes and metabolic activities can vary considerably depending on energy and nutrient inputs. As a result of their metabolic activities and the chemical properties of their cell surfaces and the exopolymers they produce, microorganisms can directly or indirectly facilitate the biotransformation of radionuclides, thus altering their solubility and overall fate and transport in the environment. Although biosorption to cell surfaces and exopolymers can be an important factor modifying the solubility of some radionuclides under specific conditions, oxidation state is often considered the single most important factor controlling their speciation and, therefore, environmental behavior.
Organization factors have been known as an important contributor to plant safety. Previous studies associated with assessing organisation factors mainly deals with the aspect of safety of an organization. For an organization, however, efficiency or an aspect of economy related with work activities is also important. This paper introduces a conceptual model, SPOOM-EDM (Self Poly-Oriented Organizational Model - Evaluation Diamond Model), for evaluating an organization with respect to both safety and economy. It also shows how the proposed model can be applied for the evaluation of an organization through the analysis of real events. (author)
A process has been developed that exploits the characteristics of microwave heating for the vitrification of high-level radioactive liquid waste. This process, microwave vitrification, has been successfully operated at pilot plant scale in an active cell using simulated liquid waste containing several curies of radioactivity. Excellent decontamination factors have been achieved for both volatiles and nonvolatiles with an average ruthenium decontamination factor of 490 and a gross alpha emitter decontamination factor of 100,000. Almost all the radioactivity is incorporated in a glass block.
A process has been developed that exploits the characteristics of microwave heating for the vitrification of high-level radioactive liquid waste. This process, microwave vitrification, has been successfully operated at pilot plant scale in an active cell using simulated liquid waste containing several curies of radioactivity. Excellent decontamination factors have been achieved for both volatiles and nonvolatiles with an average ruthenium decontamination factor of 490 and a gross alpha emitter decontamination factor of 100,000. Almost all the radioactivity is incorporated in a glass block.
Abstract. The potential effects of synthetic unmethylated oligodeoxynucleotides (ODN) containing CpG motifs, mimicking bacterial DNA, has never been evaluated on the immune response in the teleost fish gilthead seabream (Sparus aurata), the most important fish species in Mediterranean aquaculture. First, binding and competition studies have demonstrated that binding is saturated and promiscuous, suggesting the participation of several receptors. Moreover, leucocyte cytotoxic (NCC) activity, production of ROIs (reactive oxygen intermediates), and expression of immune-relevant genes was greatly primed by ODNs. Focusing on the mechanism, the TLR9 gene is widely distributed in seabream tissues and differently regulated in vitro by several stimuli. Moreover, and for the first time in fish, TLR9...
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...
Inhibition of adipogenesis and lipid accumulation has a very crucial role to prevent obesity. Low molecular weight (LMW) chitosan is known to inhibit fat accumulation and adipogenesis. (N,O)-sulfated chitosan is a sulfation derivative of chitosan oligomers, and its anti-obesity effect is not yet reported. In this study, it has been reported that (N,O)-sulfated chitosan significantly decreased lipid accumulation, an indicator for adipogenesis, in differentiating 3T3-L1 preadipocyte cells. Furthermore, mRNA expressions and protein levels of key adipogenic markers such as peroxisome prolifetor-activatedreceptor (PPAR)-@c and CCAAT-enhancer binding protein (C/EBP)-@a were considerably decreased by (N,O)-sulfated chitosan treatment. As a consequence, sulfation of LMWC remarkably increased its ...
The class of Spirochetes comprises a wide array of clinically important pathogens, including Treponema pallidum causing syphilis as well as Borrelia burgdorferi, the agent of Lyme disease (LD). Diseases caused by spirochetes are characterized by specific sequelae of host reactions, and also by characteristic antibody response patterns. Over the last decades, research on the interaction of spirochetes with the hosts immune system had a strong emphasis on outer membrane lipoproteins. In fact, these structures have been convincingly shown to activate immune cells via CD14 and Toll-like receptor (TLR)-2, and recent data also indicate an interaction with lipopolysaccharide (LPS)-binding protein (LBP). In particular, the interaction of B. burgdorferi with TLR-2 could not only be demonstrated in ...
Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adhere...
Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not...
Molybdopterin (MPT) is not produced by the Escherichia coli mutants chlA1, chlM, or chlN or by the Neurospora crassa mutant nit-1. Extracts of E. coli chlA1 contain an activity, the converting factor,...Full Text Available
A variety of stress situations may affect the activity and survival of plant-beneficial pseudomonads added to soil to control root diseases. This study focused on the roles of the sigma factor AlgU...Full Text Available
Effect of single and chronic irradiation on factors of hamsters natural immunity such as complement, lysozyme and antibodies in norm and in the cestode invasion has been investigated. Significant phase changes in the complement activity level, lysozyme content and specific antibodies tite have been shown to occur in hamster blood under the influence of ionizing radiation. Cestode invasion in irradiated host organism increases the negative effect of ionizing radiation on the hamster immyne system.
In monocytes, sulfatide, a lipid from Mycobacterium tuberculosis, blocked priming for enhanced release of superoxide (O2-) by the macrophage activatingfactors lipopolysaccharide, gamma interferon,...Full Text Available
Tumor necrosis factor alpha (TNF-alpha) plays a central role in activation of first-line defenses of a host against foreign organisms. To determine whether Brucella infection modulated TNF-alpha production,...Full Text Available
The carbon content of silicon single crystals and polycrystals has been measured by charged particle activation analysis (CPAA) and infrared absorption. The authors obtained a linear relationship between the absorption coefficient at 605 cm/sup -1/ and the carbon content obtained by CPAA. They obtained a conversion factor of (1.00 +- 0.03) 10/sup 17//cm/sup 2/ for a 100% substitutional carbon.
The serpin ZPI is a protein Z (PZ)-dependent specific inhibitor of membrane-associated factor Xa (fXa) despite having an unfavorable P1 Tyr. PZ accelerates the inhibition reaction ∼2000-fold...Full Text Available
Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the ?(2)?(1) integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS-BBB penetration. Our results suggest that the ...
Background: Protein disulfide isomerase (PDI) controls platelet integrin function, tissue-factor (TF) activation, and concentrates at fibrin and thrombus formation sites of vascular injury. Objective: We investigated involvement of surface thiol isomerases and especially PDI, in thrombin-mediated thrombin amplification on human platelets. Methods/Results: Using a new developed thrombin-dependent platelet thrombin generation assay we observed that the feedback activation of thrombin generation on the platelet surface does not depend on TF, as anti-TF antibodies inhibiting TF-induced thrombin formation in platelet-depleted plasma had no effect compared to vehicle-treated controls. Feedback activation of thrombin generation in the presence of platelets was significantly diminished by membrane impermeant thiol blockers or by the thiol isomerase-inhibitors bacitracin and anti-PDI antibody RL90, respectively. ...
BackgroundThe effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate (AMP) challenge...Full Text Available
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
Although the radioreceptor method is widely used for estrogen receptor assay in human tissue, it has several limitations and a number of alternative methods are being explored. An immunohistochemical method of estrogen receptor assay using a specific antibody to estradiol has been proposed as a suitable alternative. The present study was designed to evaluate the validity of this method in detecting true estrogen receptors in human tumor tissue. Using radioiodinated antibody to estrogen, we have demonstrated that the estrogen antibody can detect the estrogen when it is bound to 4S type receptor but is unable to bind to estrogen when the hormone is bound to 8S type receptor. Our observations suggest that the immunohistochemical method of detection of intracellular cytosolic receptor for estrogen is not a suitable alternative to the currently used radioreceptor ...
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 ...
Altogether 99 029 men aged 40-59, employed on the Italian railroad system, were classified in three levels of physical activity at work and three levels of job responsibility and then followed up for...Full Text Available
... Possibilities for summer activities become better, but socioeconomic factors such as age-structure may weaken the positive impact. Several research needs related to recreation and tourism were identified. The Finnish tourism industry seems to need more detailed and spatially informed scenarios concerning climate change and more information on its impacts on the different activities in the tourism sector. Also communication channels seem to need more attention. More information is ...
Available in abstract form only. Full text of publication follows: The uncertainties of decommissioning costs increase high due to several conditions. Decommissioning cost estimation depends on the complexity of nuclear installations, its site-specific physical and radiological inventories. Therefore, the decommissioning costs of nuclear research facilities must be estimated in accordance with the detailed sub-tasks and resources by the tasks of decommissioning activities. By selecting the classified activities and resources, costs are calculated by the items and then the total costs of all decommissioning activities are reshuffled to match with its usage and objectives. And the decommissioning cost of nuclear research facilities is calculated by applying a unit cost factor method on which classification of decommissioning works fitted with the features and specifications of decommissioning objects and ...
A factor which agglutinated the spores of Ceratocystis fimbriata in the presence of Ca2+ was purified from sweet potato (Ipomea batatas Lam cv. Norin[1]) root. Element composition of the purified factor was as follows; analysis found: C (29.8%), H (3.97%), O (65.34%), N (0.81%): calculated for C43H69O70N1: C (30.02%), H (4.01%), O (65.15%), N (0.81%). The factor was mainly composed of galacturonic acid (53% of dry weight) and contained arabinose, fucose, and unidentified component as minor components. The factor also agglutinated A-, B-, AB-, and O types of human erythrocytes to almost the same degree in the presence of Ca2+. The differential spore-agglutinating activity of the factor depended on the pH of the assay medium; it agglutinated similarly the germinated spores of sweet potato and coffee strains at pH 7.5 and 5.5, whereas it displayed a distinct ...
Abstract Background The increase in the incidence of atopic dermatitis (AD) in developed countries has been related to familiar and environmental factors. This survey was undertaken to investigate the family background, birthweight and the home environment of children suffering from AD in order to point out the possible factors that provoke the development of the disease. Methods The study uses data collected by means of self-administered questionnaires and discusses 461 cases of children (age 0-12) with active skin signs of AD. The control group comprised of 343 children (age 0-12) with no skin signs or positive lifetime history of AD. Associations between familiar and various home environmental factors and the risk of AD were calculated by means of odds ratios. Results There were statist...
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 receptor ...
The central benzodiazepine receptor tracer [N-methyl-"1"1C]iomazenil (Ro 16-0154) was synthesized by alkylation of the desmethyl precursor noriomazenil with ["1"1C]methyl iodide. The ["1"1C]CH_3I (prepared by reduction of ["1"1C]CO_2 with LiAlH_4 followed by reaction with HI) was reacted with noriomazenil inN,N -dimethylformamide and Bu_4N"+OH"- for 1 min at 80 deg. C and purified by HPLC (C_1_8, 34% CH_3CN/H_2O, 7 mL/min). The product was obtained with synthesis time 35 #+-# 5 min (mean #+-# SD, n = 7), radiochemical yield (EOB) 36 #+-# 16%, radiochemical purity 99 #+-# 1%, and specific activity 5100 #+-# 2800 mCi/#mu#mol. Absorbed radiation doses were calculated from previously acquired human biodistribution data. The urinary bladder wall received the highest dose (0.099 mGy/MBq) for 4.8 h voiding interval and the effective dose equivalent was 0.015 mSv/MBq. After i.v. injection of ["1"1C]iomazenil in an adult baboon or healthy human ...
1. Choline, and the choline analogues monoethylcholine (MEC) and N-aminodeanol (NAD) were examined for prophylactic activity in acute acetylcholinesterase inhibitor toxicity in mice. The rank order of potency of the compounds was MEC greater than NAD greater than choline. 2. Simultaneous administration of MEC (60 mg kg-1) or NAD (200 mg kg-1) with physostigmine reduced lethality to 17 and 13% respectively. MEC (60 mg kg-1) completely protected against disopropylfluorophosphate (DFP) and diazinon toxicity, and NAD reduced lethality to 17% for both agents. Choline (200 mg kg-1) exhibited only negligible antidotal activity against the inhibitors. 3. In vitro concentrations of choline, MEC, and NAD, similar to the estimated concentration obtained in vivo in the acute toxicity study, produced mixed inhibition of mouse brain acetylcholinesterase. The inhibition was dose-related and was additive to the inhibition produced by the cholinesterase ...
Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activatedreceptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 ...
Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with "9"9"mTc/"1"8"8Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at ...
The expression of motor activity levels in response to novel situations is under complex genetic and environmental control. Several genetic loci have been implicated in the regulation of this behavioral phenotype, but their relationship to epigenetic and epistatic interactions is relatively unknown. Here, we report on a quantitative trait locus (QTL) on mouse chromosome 1 for novelty-induced motor activity in the open field, using chromosome substitution strains derived from a high active host strain (C57BL/6J) and a low active donor strain (A/J). The QTL for open field (horizontal distance moved) peaked at the location of Kcnj9, however, QTL detection was initially masked by an interplay of both grandparent genetic origin and genetic co-factors influencing behavior on chromosome 1. Our fi...
Standard radiation monitoring has been conducted at Sendai nuclear power station for the purpose of estimation of 'source activity' during refueling outage and evaluation of countermeasures to reduce dose rate. Selected objects of the monitoring are radiation dose rate at maintenance area, radiation field at each equipment and piping, coolant chemistry and plant operation condition. Monitored data indicates that 'source activity' variation can be estimated to some extent using influential factors, and that evaluation of change of loose crud activity, which is presumed to be represented by the dose rate at letdown heat exchanger, is necessary to further explain change in radiation field at main work area. (author).
The Balandin type volcano plots have been considered for the main criterion both in catalysis and electrocatalysis to estimate their fundamental properties and optimal activity: ({alpha}) The ones, when some physical feature or catalytic activity itself is plotted usually along transition series, and ({beta}) The others, when catalytic activity arises as a function of some energetic property, the most usually of the adsorption enthalpy of intermediates bonding upon the substrate in the rate determining step (rds). 29 refs.
Removal of radioactive ions was studied from low and medium level radioactive waste solutions by electrodialysis using ion exchange membranes. The test solutions contained "1"3"7Cs"+, "1"0"6Ru"3"+ or fission products (F.P.) as active ions and NaCl, Na_2SO_4 or Ca(NO_3)_2 as inactive coexisting salts. The decontamination factor of the active ions was in the order: "1"3"7Cs"+ (greater than 99%) > "9"0Sr"2"+ > F.P. > "1"0"6Ru"3"+. The dialysis time required to attain the saturation was the shortest for monovalent cations K"+, Cs"+ and Na"+, intermediate for divalent cation Sr"2"+, and the longest for trivalent cation Ru"3"+. The ratio of the decontamination factor of an active ion eta sub( a) to the desalination factor of an inactive ion eta sub( b) was nearly equal to unity for "2"4Na, "4"2K, "1"3"7Cs and "9"0Sr. On the other hand, the apparent selective ...
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 ...
The thiazolidinedione (TZD) or glitazone class of peroxisome proliferator-activated-#gamma# (PPAR-#gamma#) ligands not only induce adipocyte differentiation and increase insulin sensitivity, but also exert growth inhibitory effects on several carcinoma cell lines in vitro as well as in vivo. In the current study the in vitro effect of four PPAR-#gamma# agonists (ciglitazone, pioglitazone, troglitazone, rosiglitazone) on the cell growth of seven human neuroblastoma cell lines (Kelly, LAN-1, LAN-5, LS, IMR-32, SK-N-SH, SH-SY5Y) was investigated. Growth rates were assessed by a colorimetric XTT-based assay kit. Expression of PPAR-#gamma# protein was examined by immunohistochemistry and Western blot analysis. All glitazones inhibited in vitro growth and viability of the human neuroblastoma cell lines in a dose-dependent manner showing considerable effects only at high concentrations (10 #mu#M and 100 #mu#M). Effectiveness of the glitazones on neuroblastoma cell growth ...
The production of molecularly imprinted polymers (MIPs) for the recognition of C-terminal cholecystokinin pentapeptide (CCK-5) in the presence of metal ion is reported. The MIPs were produced under the same molar ratio of template to monomers (acrylamide, N,N'-methylene bisacrylamide) in the presence or absence of nitrilotriacetic acid-nickel (Ni-NTA) complex. Scanning electron microscopy images of MIPs were obtained in an attempt to correlate the adsorption characteristics with polymer's morphology. Subsequently Ni2+ was removed and substituted by other divalent ions such as Mg2+, Fe2+, Zn2+, Co2+ and Cu2+. It was found that polymers containing the metal ion complex with the order Fe-NTA, Ni-NTA and Cu-NTA presented lower dissociation constant values than the rest thus exhibiting stronger guest binding activity. The percentage of theoretical maximum binding sites Bmax was almost the same for these ions, indicating that the ion-template coordination is responsible ...
This report documents the activities by Rogers and Associates Engineering Corporation personnel in the second year of a grant from the Office of Health and Environmental Research at the US Department of Energy. The project objective is to integrate theories of all significant radon generation and transport mechanisms into a unified, self-consistent theory. During the second year of the project, the following activities were performed. Several field permeabilities were measured to develop a soils data base for a simple permeability correlation. Simple soil gas permeability and radon diffusion coefficient correlations were developed from the RAE data base. A methodology was developed to characterize the air permeabilities and radon diffusion coefficients of soils in general, and the Soil Conservation Service soil classifications in particular. The RAETRAN code was benchmarked against two different sets of measurements. Using RAETRAD, a ...
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 ...
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 ...
The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the ...
A clone encoding a human D{sub 2} dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D{sub 2} receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.
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...
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.
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 ...
We previously reported that the peroxisome proliferator-activatedreceptor gamma coactivator-1 (PGC-1) mRNA in rat epitrochlearis muscle was increased after swimming exercise training. In the present study, we demonstrated further that PGC-1 mRNA expression in the epitrochlearis muscle of 4-5-week-old male Sprague-Dawley rats was increased after a 6-h acute bout of low-intensity swimming exercise. With this increase, the expression level was approximately 8-fold of control and immersion group rats that stayed for 6-h in warm water, maintained at the identical temperature of the swimming barrel (35 degrees C) (p<0.01). Second, PGC-1 mRNA expression in the muscle was found to have increased 6-h after 30 10-s tetani contractions were induced by in vitro electrical stimulation. Finally, PGC-1 mRNA expression in the muscle incubated for 18-h with 0.5mM 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR: a 5' AMP-activated ...
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 ...
Recently we have found that carbon nano-materials have ability to recognize softer actinides(III). In this presentation, separation of americium(III) from lanthanides(III) by chromatography with carbon nano-materials, such as carbon nano-tubes and graphite, has been investigated by batch adsorption experiments and chromatography. The separation factor (SF) between americium(III) and lanthanide(III) was about 2 in the range of pH from 1 to 4 by using carbon nano-tube, graphite and activated charcoal. The separation factor depended on the diameter of carbon nano-tubes. Smaller one, 3-20 nm diameter, showed the best selectivity for americium(III), which separation factor was about 2.0, although larger one, 40-70 nm, showed almost no selectivity. The same behavior has been observed by using graphite powder and activated charcoal although acid- or alkali pretreated ...
Quantitative bone scans were evaluated in 16 patients with osteoporosis and in a control group of 7 healthy subjects. Along with a detailed biochemical analysis of calcium-phosphorus metabolism and standartized reongenographs, a quantitative dynamic bone scintigraphy was performed according to the method proposed by the authors. The bone-accumulating factor K_b was determined on the base of mathematical analysis of the graph reflecting activity changes in bone tissue unit during the investigation, the blood-elimination factor K_h and kidney-elimination factor K_k. In addition the accumulation index AI (in %) was calculated as a relation between the activity in bone tissue unit, registered in 20 min interval, and the activity in soft tissues for the same time. Whereas the static gamma camera scintigraphy, made 3-4 hrs after injecting of the osteotrope ...
The size of the market for pulverized activated charcoal and particulate activated charcoal prepared by the Association of Inorganic Chemicals of Japan is 55,000t/y (1987) in total. Individually, some fields showed the expansion such as water purification, water treatment and gas treatment on the one hand, but on the other hand, several fields showed the decline such as sugar refining, dextrin sugar and soda glutamate. As a whole, the market showed no marked fluctuations or a very slight increase. Many of the above usages are traditional in the chemical industry and the food industry, etc., and the new usages developed in the past several years have not grown to influence the statistics as yet. Selection of raw material is the key for determining the character of activated charcoal. And the factors of determining the characteristic features are fine pore, surface area and surface ...
The decontamination of the dissolution tank from spent fuel reprocessing out-ling device is studied, by using FL-AP decontamination agent. The decontamination factor per step is 2.2, 2.4, respectively for #alpha#, #beta# activities. After dissecting the tank, residual contamination in inner surface of the tank was found to be non-uniform. The exact original contamination value of the tank surface could be approximated by calculating the total amounts of radionuclide distributed on the hanging specimens, the dissecting specimen, and radioactive level in waste decontamination agent. Therefore, it can be concluded that the hanging specimens method is feasible for measuring the decontamination factor of spent fuel dissolution tank. (authors)
A series of radioactive catastrophes (from 1948 to 1967) in the Southern Urals in the USSR led to intensive environmental contamination. Radioactive wastes were dispersed over the 20000 km(2) territory of four provinces-Chelyabinsk, Sverdlovsk, Tyumen' and Kurgan-due to the activity of the military facility that was built in 1948 for the production of nuclear bomb plutonium. The results of 50 years of investigations into the consequences of these disasters allow a general picture of the events that occurred to be reconstructed and allow the medical consequences of the irradiation of about half a million residents to be depicted. However, due to the atmosphere of secrecy and inadequate medical procedures, the results of medical studies of radiation victims are scant. The current protocols present a unique opportunity to study the DNA damage at the nucleotide resolution level in the genome of inhabitants of the given region, who presumably received chronic doses of ...
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...
A solvent extraction method was developed to obtain methanolic extracts rich in antioxidants from banana peel. Central composite design ''2^3+star'' and response surface methodology were used in order to optimise the number of extraction steps, extraction temperature and extraction time. The number of extractions was statistically the most significant factor in scavenging activity against both DPPH? and ABTS?^+ radicals and in the inhibition of TBARS formation, while the extraction temperature had an important impact on the capacity to prevent b-carotene bleaching. However, the effect of the extraction time on antioxidant activity was less important. The optimum values of the factors that influence the capacity to scavenge DPPH? and ABTS?^+ radicals or to inhibit b-carotene bleaching were ...
We previously reported that puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) is required for vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis and for endothelial differentiation from embryonic stem (ES) cells via the aminopeptidase activity of PILSAP. In this study, we searched for molecules that function during angiogenesis with PILSAP. We performed proteome analysis of nuclear extracts from embryoid bodies (EBs) made from ES cells transfected with mutant PILSAP lacking aminopeptidase activity and mock EBs. We identified pigpen, a 67-kDa nuclear coiled body component protein. Immunoprecipitation and western blotting demonstrated the binding of PILSAP and pigpen in endothelial cells (ECs), and this interaction was enhanc...
The paper presents some aspects relating to the importance of a good communication and cooperation between all factors involved in procurement process at Societatea Nationala 'Nuclearelectrica', SNN. In order to comply with the internal and international rules related to safety in nuclear field and public procurement requirements and for maintaining a high standard of operational performance of Cernavoda NPP, adequate procurement systems were developed by SNN SA. The importance of human factor and the training activities for all personnel from this chain of procurement process is the main key issue to maintain high quality of their activities considering that procurement documents are reviewed and approved before to be issued by all departments involved in procurement process. The specialized department for public acquisition is supervising that the procurement processes initiated at the level of ...
Adsorption by activated red mud (ARM) is investigated as a possible alternative to the conventional methods of Cr(VI) removal from aqueous synthetic solutions and industrial effluents. Adsorption characteristics suggest the heterogenous nature of the adsorbent surface sites with respect to the energy of adsorption. Various factors such as pH, contact time, Cr(VI) concentration, amount of adsorbent, and temperature are taken into account, and promising results are obtained. The applicability of the Langmuir as well as Freundlich adsorption isotherms for the present system is tested. The loading factor (i.e., milligrams Cr(VI) adsorbed per gram of ARM) increased with initial Cr(VI) concentration, whereas a negative trend was observed with increasing temperature. The influence of the addition of anions on the adsorption of Cr(VI) depends on the relative affinity of the anions for the surface and the relative concentrations of ...
The purpose of this study was to determine whether resistance exercise training-induced reductions in inflammation are mediated via melanocortin 3 receptor expression in obese (BMI 32.7 ± 3.7)...Full Text Available
The plant hormone cytokinin is perceived by membrane-located sensor histidine kinases. Arabidopsis (Arabidopsis thaliana) possesses three cytokinin receptors: ARABIDOPSIS HISTIDINE...Full Text Available
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
G-protein-coupled receptor signalling has been suggested to be voltage dependent in a number of cell types; however, the limits of sensitivity of this potentially important phenomenon are unknown. Using...Full Text Available
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
1. The structural requirements of an allosteric barbiturate binding site on acetylcholine receptor-rich membranes isolated from Torpedo electroplaques have been characterized by the ability of fourteen...Full Text Available
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
There is increasing evidence that receptor-mediated events impact one or more stages responsible for tumor development in experimental animals and humans. Although many chemicals and endogenous hormones...Full Text Available
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
BackgroundBaculovirus, which has a width of 40 nm and a length of 250-300 nm, can display functional peptides, receptors and antigens on its surface by their fusion with a baculovirus...Full Text Available
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
Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system and participate in the synaptic process particularly associated with acetylcholine, GABA, and glutamate...Full Text Available
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
The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available
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
Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor...Full Text Available
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
The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous...Full Text Available
TSH receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs in Graves’ disease (GD-IgG). Whether TSHR is involved in the pathogenesis of thyroid associated...Full Text Available
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
OBJECTIVEPrevious studies showed that genetic deletion or pharmacological blockade of the receptor for advanced glycation end products (RAGE) prevents the early structural changes...Full Text Available
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
Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS). However, the discovery that these glial cells may potentially express receptors capable...Full Text Available
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
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
Polyclonal antibodies were raised in rabbits by immunization with free peptides corresponding to positions 197-222 of the human beta 1-adrenergic receptor (beta 1 peptide) and the corresponding sequence...Full Text Available
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
The acetylcholine receptor from the electric tissue of Torpedo californica is a large, integral membrane protein containing four different types of polypeptide chains. The structure of the purified...Full Text Available
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
IntroductionVarious multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing...Full Text Available
Gamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain...Full Text Available
The treatment of chronic pain conditions continue to present a challenge to the medical field. Physical therapy treatment needs to approach the management of chronic pain differently than the approach used to resolve acute pain. Patients with chronic pain often have many factors that have perpetuated the pain condition. These factors, as well as pain itself, influence their ability to reactivate and perform functional daily activities. Physical therapists can begin to address some of the factors, including fear and deconditioning, by building confidence and body awareness in a self-care model including a slow graduated reactivation program. There is evidence that patients with chronic pain conditions have altered motor control that may be influencing reoccurrences and possible flares of pa...
Transfer factors of "2"1"0Po from soil to parsley and mint have been determined. Artificial polonium isotope ("2"0"8Po) was used as a tracer to determine transfer factor of Po from soil to plant in pot experiments. Two plant growing systems were used for this study namely, an outdoor system and a sheltered system by a polyethylene tent. "2"0"8Po and "2"1"0Po were determined in soil and different parts of the studied plants (stem and leaf), using alpha spectroscopy. The results have shown that there was a clear uptake of "2"0"8Po by roots to leaves and stems of both plants. Higher values of transfer factors using the "2"1"0Po activity concentrations than the "2"0"8Po activity concentration were observed. Transfer factors of "2"1"0Po from soil to parsley varied between 20 x 10"-"2 and 50 x 10"-"2 and 22 x 10"-"3 and 67 x 10"-"3 in mint, while "2"0"8Po transfer ...
The results from a hot test, using authentic HLLW solution, of the CTH actinide separation process are reported. The process consists of three solvent extraction cycles for separation of actinides and technetium from reprocessing high level liquid waste, utilizing HDEHP, TBP, and HDEHP in sequence, and an optional step for sorption on inorganic ion exchangers of the fission product content in the process raffinate. In general the process worked according to predictions but a malfunctioning feed pump gave a 10% loss of Pu to one stream. The hot test indicating that U and Pu can be recovered with losses below 0.1% and Am, Cm with a loss below 0.2%. Np and Tc were difficult to follow because of the low activity of /sup 237/Np and because /sup 99/Tc is a pure beta emitter, but the results indicate that also these elements behaved according to predictions, i.e., that recoveries >= 99.8% for Np and >= 97% for Tc can be achieved. For the HLLW stream the solvent ...
The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of #gamma# -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in #gamma# -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic Bcl-2 family was increased in irradiated mice ovaries. PARP as DNA ...
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 ...
The hypothesis that intracellular Ca"2"+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca"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_2 and the Ca"2"+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl_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 ...
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
The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly....Full Text Available
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
We have cloned and characterized a 77-kDa oestrogen receptor (ER) from an oestrogen-independent subclone of the MCF-7 human breast cancer cell line. This receptor contains an in-frame, tandem duplication...Full Text Available
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms ...
The Eph tyrosine kinase receptors and their ephrin ligands play a central role in several human cancers and their deregulated expression or function promotes tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE) have been recently found to inhibit Eph-kinase phosphorylation. In order to evaluate the potential contribution of edible and medicinal plants on EphA2-ephrinA1 modulation, 133 commercially available plant extracts used as food supplements, essential and fixed oils were screened with an ELISA-based binding assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in a dose-dependent manner (IC"5"0 0.83-24@mg/ml). Functional studies on PC3 prostate adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc-induced EphA2-pho...
Angiotensin II has adverse actions in heart failure including vasoconstriction, aldosterone secretion, and activation of the sympathetic nervous system. Valsartan, a potent specific angiotensin II type 1 receptor blocker, may produce beneficial effects in heart failure. The purpose of this study was to evaluate the steady-state pharmacokinetics of valsartan 40, 80, and 160 mg each given every 12 h for 7 days in heart failure patients. Eighteen patients with chronic stable heart failure and left ventricular ejection fractions power model, showed that doubling the dose increased the AUC and Cmax 1.8 times. The pharmacokinetics of valsartan are predictable in heart failure patients within the dose range of 40-160 mg BID. Age did not appear to have influenced the valsartan clearance in heart failure patients. The pharmacokinetic values were higher in heart failure patients than in healthy volunteers. All doses were generally safe and well ...
CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino-acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B, but without inducing excessive hypotension. Here we report the first-in-human studies for CD-NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic guanosine monophosphate-activating, natriuretic, and aldosterone-suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first-in-class new cardiovascular therapeutic in human heart failure, which are now underway worldwide. PMID:19395584
The Rocky Flats Environmental Technology Site (RFETS) has historically released radionuclide chemicals of potential concern into the surrounding environment. The off-site environment was evaluated for Pu"2"3"9"/"2"4"0 and Am"2"4"1 occurrence. An evaluation of exposure and effects to the aquatic ecology within off-site areas including: Standley Lake, Great Western Reservoir, Mower Reservoir and portions of Big Dry Creek, Walnut Creek, and Woman Creek was performed for the completion of an Ecological Risk Assessment. Collocated sampling activities were performed for surface water, sediment, benthic macroinvertebrates and fish. Results of the analytical data were used to assess ongoing exposure and effects. Data collected to determine effects (chemical content of fish tissue, diversity and density of macroinvertebrate populations) provided some of the necessary information needed to evaluate risk. However, due to conditions of interfering stressor effects, a ...
Calcium (Ca) plays an important role in regulating various cellular processes. In a variety of cell types, Ca signaling occurs within microdomains where channels deliver localized pulses of Ca which activate a nearby collection of Ca-sensitive receptors. The small number of channels involved ensures that the signaling process is stochastic. The aggregate response of several thousand of these microdomains yields a whole-cell response which dictates the cell behavior. Here, we study analytically the statistical properties of a population of these microdomains in response to a trigger signal. We apply these results to understand the relationship between Ca influx and Ca release in cardiac cells. In this context, we use a first passage time approach to show analytically how Ca release in the whole cell depends on the single channel kinetics of Ca channels and the properties of microdomains. Using these results, we explain the underlying mechanism ...
1. The benzyl carbamyl analogue of lignocaine [2-(diethylaminoacetamido)-3-carbamyl-4-methyl-5-benzylpyrrole] at an intravenous dose of 4 mg/kg caused a blood pressure decrease of 54 mmHg. 2. A greater hypotensive effect was observed in hypertensive compared to normotensive animals. Anaesthesia magnified the vasodepressor effect in both groups. 3. The analogue did not possess centrally-mediated effects on blood pressure but exerted its hypotensive effect via a peripheral mechanism. 4. The analogue produced a relaxant effect on intestinal and vascular smooth muscle while exerting minimal effects on muscarinic, sympathetic, or ganglionic nicotinic receptors. 5. The analogue exhibited less cardiac depressant action on left ventricular rate (dp/dt) and force of contraction than lignocaine. 6. Lethal effects for the analogue were first observed at 16 mg/kg following intravenous administration and at 500 mg/kg following intraperitoneal administration. 7. In conclusion, ...
Unfamiliar male meadow voles induce pregnancy disruptions when they are in physical contact with females, but the presence of the female's original mate partially protects her from the blocking effects of an unfamiliar male. This research examines how behavioral interactions affect pregnancy disruptions by testing two hypotheses: a) original males protect females by reducing the aggressive interactions between females and strange males; and b) administration of clonidine, an alpha 2-adrenergic receptor agonist that decreases activity, aggression, and sexual motivation, will decrease the pregnancy-blocking ability of strange males. Strange males were more aggressive when the original sire was absent, indicating that this change in behavior may be related to their greater success in disrupting pregnancy. When injected with clonidine, males were less likely to block pregnancy, and they showed less contact and mating behavior than when they ...
Sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) has worse outcome because of multiresistance to a large group of antibiotics, which may lead to death from septic shock. In the present study, we firstly found that artesunate in combination with oxacillin was capable of protecting mice challenged with live MRSA WHO-2 (WHO-2) and the protection was related to the reduced TNF-a and IL-6 levels and decreased bacterial load. Based on above results, artesunate was further investigated from two aspects in vitro, anti-inflammation effect and antibacterial enhancement effect on antibiotics. Artesunate not only inhibited TNF-a and IL-6 release but also inhibited mRNA and protein expressions of TLR2 and Nod2, two important receptors, in murine peritoneal macrophages stimulated wit...
The activation of nuclear factor-kappa B1 (NFκB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for...Full Text Available
Information is presented concerning new trends in licensing; seismic considerations and system structural behavior; TMI-2 risk assessment and thermal hydraulics; statistical assessment of potential accidents and verification of computational methods; issues with respect to improved safety; human factors in nuclear power plant operation; diagnostics and activities in support of recovery; LOCA transient analysis; unresolved safety issues and other safety considerations; and fission product transport.
Information is presented concerning new trends in licensing; seismic considerations and system structural behavior; TMI-2 risk assessment and thermal hydraulics; statistical assessment of potential accidents and verification of computational methods; issues with respect to improved safety; human factors in nuclear power plant operation; diagnostics and activities in support of recovery; LOCA transient analysis; unresolved safety issues and other safety considerations; and fission product transport.
Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent ‘spatial’ navigation,...Full Text Available
Autophagy is a regulated catabolic process triggered in cells deprived of nutrients or growth factors that govern nutrient uptake. Here we report that autophagy is induced by cetuximab, a therapeutic...Full Text Available
Hyperthermia (HT) is a strong adjuvant treatment with radiotherapy and chemotherapy because it causes tumor reoxygenation. However, the detailed molecular mechanisms of how HT enhances tumor oxygenation...Full Text Available
The Monthly Energy Review (MER) presents an overview of the Energy Information Administration`s recent monthly energy statistics. The statistics cover the major activities of US production, consumption, trade, stocks, and prices for petroleum, natural gas, coal, electricity, and nuclear energy. Also included are international energy and thermal and metric conversion factors. 37 figs., 61 tabs.
This publication presents an overview of the Energy information Administration`s recent monthly energy statistics. The statistics cover the major activities of US production, consumption, trade, stocks, and prices for petroleum, natural gas, coal, electricity, and nuclear energy. Also included are international energy and thermal and metric conversion factors. Two brief ``energy plugs`` (reviews of EIA publications) are included, as well.
Proper estimation of shipping emissions is essential for an impact assessment of shipping on air quality and health in port cities and coastal regions. In the Netherlands shipping is an important source of particulate matter. This report provides an internationally accessible and transparent summary and description of the methodologies used in the Netherlands Pollutant Release and Transfer Register (PRTR) to estimate PM emissions from shipping, including recently implemented updates.
BackgroundTristetraprolin (TTP/ZFP36) family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential...Full Text Available
Thirty years ago, in 1967, the new definition of the second based on a quantum phenomenon, the hyperfine splitting of the groundstate of the "1"3"3Cs atom, was passed by the 13th General Conference on Weight and Measure. What followed was a fascinating improvement of the performance of caesium clocks which is still pursued. Their total uncertainty could be reduced, until 1995, by 4 orders of magnitude. With the development of the so-called fountain clocks, another factor of ten is within reach. (orig.)
In Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative σ factor σ54 (RpoN) directly activates transcription of another alternative σ...Full Text Available
Three simulated low-level reactor wastes were dried using a spray dryer-baghouse system. The three aqueous feedstocks were sodium sulfate waste characteristic of a BWR, boric acid waste characteristic of a PWR, and a waste mixture of ion exchange resins and filter aid. These slurries were spiked with nonradioactive iron, cobalt, and manganese (representing corrosion products) and nonradioactive cesium and iodine (representing fission products). The throughput for the 2.1-m-diameter spray dryer and baghouse system was 160-180 kg/h, which is comparable to the requirements for a full-scale commercial installation. A free-flowing, dry product was produced in all of the tests. The volume reduction factor ranged from 2.5 to 5.8; the baghouse decontamination factor was typically in the range of 10"3 to 10"4. Using an overall system decontamination factor of 10"6, the activity of the off-gas was calculated to ...
Magnetically driven non-stationary acceleration of jets in active galactic nuclei results in the leading parts of the flow being accelerated to much higher Lorentz factors than in the case of steady-state acceleration with the same parameters. The higher Doppler-boosted parts of the flow may dominate the high-energy emission of blazar jets. We suggest that highly variable GeV and TeV emission in blazars is produced by the faster moving leading edges of highly magnetized non-stationary ejection blobs, while the radio data trace the slower-moving bulk flow. Thus, the radio and gamma-ray emission regions have different, but correlated, Doppler factors. High-energy emission is generated, typically within the optically thick core, in the outer parts of the broad-line emission region, avoiding the radiative drag on the faster parts of the flow. The radio emission should correlate with the gamma-ray emission, delayed with ...
Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that ...
Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that ...
The deactivation rate of a resid hydrotreating catalyst is determined by a complex set of factors involving both chemical and physical changes in the catalyst structure. The various chemical changes that are associated with resid conversion involve thermal and catalytic steps of relatively large molecular weight species with the overall rates significantly affected by mass transfer limitations. The deposition of coke and the variation in the effective promoter level by the accumulation of metals deposited from the resid are the principal factors governing deactivation. The relative importance of mass transfer restrictions on activity and catalyst deactivation can be observed in studies where the average pore diameter of the catalyst has been varied. Several models have been proposed to characterize the deactivation of resid hydroprocessing catalysts. In this paper, the authors discuss some accelerated aging tests with a ...
Twenty autopsy cases with 2009 pandemic influenza A (2009 H1N1) virus infection, performed between August 2009 and February 2010, were histopathologically analyzed. Hematoxylin-eosin staining, immunohistochemistry for type A influenza nucleoprotein antigen, and real-time reverse transcription-PCR assay for viral RNA were performed on formalin-fixed and paraffin-embedded specimens. In addition, the D222G amino acid substitution in influenza virus hemagglutinin, which binds to specific cell receptors, was analyzed in formalin-fixed and paraffin-embedded trachea and lung sections by direct sequencing of PCR-amplified products. There were several histopathological patterns in the lung according to the most remarkable findings in each case: acute diffuse alveolar damage (DAD) with a hyaline membrane (four cases), organized DAD (one case), acute massive intra-alveolar edema with variable degrees of hemorrhage (three cases), neutrophilic bronchopneumonia (five cases) and ...
Abstract Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical...
We have investigated the effect of excimer laser annealing (ELA) on transient enhanced diffusion (TED) and activation of boron implanted in Si during subsequent rapid thermal annealing (RTA). It is observed that ELA with partial melting of the implanted region causes reduction of TED in the region that remains solid during ELA, where the diffusion length of boron is reduced by a factor of #approx#4 as compared to the as-implanted sample. This is attributed to several mechanisms such as liquid-state annealing of a fraction of the implantation induced defects, introduction of excess vacancies during ELA, and solid-state annealing of the defects beyond the maximum melting depth by the heat wave propagating into the Si wafer. The ELA pretreatment provides a substantially improved electrical activation of boron during subsequent RTA.
The HEU and LEU fuel elements used in the ORR whole-core demonstration were gamma-scanned to determine the axial distribution of the {sup 140}La and {sup 137}Cs activities. Analysis of this data is now complete. From the {sup 140}La activity distributions cycle-averaged powers were determined while the {sup 137}Cs data provided a measure of the final {sup 235}U burnup in the fuel elements. A method for calculating correction factors for activity gradients transverse to the fuel element axis is presented and is applied to the first mixed core used in the demonstration during the gradual transition to an all LEU core. Results based on the gamma-scanning of the LEU fuel followers are also presented. Improved burnup calculations against which the experimental results are to be compared are now in progress. 7 refs., 21 figs., 3 tabs.
High temperature deformation behaviour of an experimental Beta-titanium alloy Ti-10V has been studied in the temperature range 800 to 945 degree C by using the method of crosshead speed cycling. Although subgrain formation was observed but the alloy did not exhibit superplastic behaviour in the entire temperature range studied. A very large initial grain size and elongation of grains during the deformation are considered the main factors responsible for absence of superplastic behaviour. The activation energy values for regions II and III of the ln sigma vs. ln small epsilon plots are close to the lower of the two activation energy values proposed together to describe self diffusion in beta-phase suggesting that the rate controlling mechanism is that for lattice diffusion rather then grain boundary diffusion. (author)
The study of chemoattractant receptors on human monocytes had been limited by the lack of a radioligand suitable for use with the small numbers of cells routinely available from human donors. A new synthetic oligopeptide radioligand f(/sup 35/S)Met-leu-phe, with a higher specific radioactivity than was available with the tritiated compound, was used to characterize a chemoattractant receptor on freshly isolated human blood monocytes. These cells bind f(/sup 35/)met-leu-phe with a dissociation constant (KD) of 30.2 +/- 5.6 nM and contain 84,000 +/- 11,300 receptors per cell. f(/sup 35/)met-leu-phe does not bind specifically to blood lymphocytes. The specificity of the oligopeptide receptor on monocytes is indistinguishable from the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes. Using f(/sup 35/)met-leu-phe, it will now be feasible to study the ...
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 ...
The adipocytokine adiponectin is released by adipocytes upon activation of the peroxisome proliferator-activatedreceptor gamma (PPAR gamma). PPAR gamma has binding sites for thiazolidinediones and free fatty acids (FFAs). To evaluate if adiponectin serum concentrations are synergistically regulated by FFAs and thiazolidinediones IN VIVO plasma FFAs were acutely elevated in healthy subjects pre-treated with rosiglitazone or placebo. Sixteen healthy male subjects (23-37 years) were included in this double-blind, randomized, placebo-controlled parallel-group study. Rosiglitazone 8 mg or placebo was administered daily for 21 days. On the last day plasma FFA concentrations were increased by an intravenous triglyceride/heparin infusion. Blood for determination of adiponectin, C-reactive protein (CRP), leptin, resistin, FFAs, glucose, and insulin was drawn at baseline and on day 21 before and after 5 hours of triglyceride/heparin ...
The optimal concentrations of nutrient medium components, aeration conditions, and pH providing for maximum biomass yields, as well as fumarase and L-aspartase activities, during submerged cultivation of Erwinia sp. were determined. The data showed that different concentrations of carbon source (molasses) and pH of the nutrient medium were required to reach the maximum fumarase and L-aspartase activities. Calculations performed by application of the additive lattice model suggested that the combination of these optimized factors would result in 3.2-, 3.4-, and 3.8-fold increases as compared to the experimental means in Erwinia sp. biomass, and L-aspartase and fumarase activities, respectively. The conditions of the fumaric acid biotransformations into L-malic and L-aspartic acids were optimized on the basis of intact Erwinia sp. cells, a fumarase and L-aspartase producer. In the cases of fumarate ...
A program is currently in progress at Argonne National Laboratory to evaluate and develop evaporator technology for concentrating radioactive waste streams. By concentrating radioactive waste streams, disposal costs can be significantly reduced. To effectively reduce the volume of waste, the evaporator must achieve high decontamination factors so that the distillate is sufficiently free of radioactive material. One technology that shows a great deal of potential for this application is being developed by LICON, Inc. In this program, Argonne plans to apply LICON`s evaporator designs to the processing of radioactive solutions. Concepts that need to be incorporated into the design of the evaporator include, criticality safety, remote operation and maintenance, and materials of construction. To design an effective process for concentrating waste streams, both solubility and vapor-liquid equilibrium data are needed. The key issue, however, is the high decontamination ...
Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TF^f^l^o^x^/^f^l^o^x mice treated with ANIT, but not in TF^f^l^o^x^/^f^l^o^x/LysMCre mice (TFD^M^y^e^l^o^i^d mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but redu...
Plerocercoids of the tapeworm Spirometra mansonoides produce a substance that stimulates growth of experimental hosts. We report purification of plerocercoid growth factor (PGF) to homogeneity by a process involving isolation and solubilization of plerocercoid membranes, isoelectric point selection by chromatofocusing chromatography or preparative isoelectric focusing, and anion-exchange chromatography. A radioreceptor assay (RRA) for human growth hormone (hGH) was used to detect PGF and purity of the 27.5-kDa protein was judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Proteolytic activity was detected in the 27.5-kDa protein by gelatin substrate PAGE. Characterization of PGF as a neutral cysteine proteinase was based on substrate and inhibitor specificities and dependence on pH and thiol-containing reagents. The association of hGH agonist and proteinase activities was shown by comparing RRA ...
Flue gas desulfurizing capacities of active carbon fibers (ACF) made from polyacrylonitrile (PAN-ACF) were studied, the features were clarified and at the same time the factors governing the capacities were studied to get guides for better products. Desulfurization capacities of 17 kinds of ACFs were studied. Two kinds of PAN-ACF, FE-200 and FE-300, especially the latter exhibited the higher desulfurization capacity. The capacity of FE-300 was about 20 times higher than those of fibers other than PAN systems and about 4 times higher than that of active coke for desulfurization. From the influence of reacting conditions on the desulfurizating capacity and the desorption profiles of adsorbed SO {sub 2}, it was concluded that the capacity was determined by the effective adsorption capacity of ACF and SO {sub 2} was retained on ACF as sulfuric acid. It was suggested that main factors governing the ...
We describe a new concept for a MEMS-based active spatial filter for astronomical spectroscopy. The goal of this device is to allow the use of a diffraction-limited spectrometer on a seeing limited observation at improved throughput over a comparable seeing-limited spectrometer, thus reducing the size and cost of the spectrometer by a factor proportional to r0/D (For the case of a 10 meter telescope this size reduction will be approximately a factor of 25 to 50). We use a fiber-based integral field unit (IFU) that incorporates an active MEMS mirror array to feed an astronomical spectrograph. A fast camera is used in parallel to sense speckle images at a spatial resolution of lambda/D and at a temporal frequency greater than that of atmospheric fluctuations. The MEMS mirror-array is used as an active shutter to feed speckle images above a preset intensity threshold to the ...
When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipo-protein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements ...
With the increase of cross-Strait economic activity, the interaction between Taiwanese business people and the Chinese government has gradually changed. As Taiwanese investment grew in volume, so did the number and frequency of contacts between the parties; a more institutionalised form regulating these contacts was established as a result. Nowadays Taiwanese businessmen have become an identifiable factor in Chinese governmental policy implementation; the process also has far-reaching implications. This paper argues that Taiwanese capital has become a Chinese governmental security asset and examines the importance of this factor when discussing conventional government/business interaction. This paper concludes that a superior national interest guides the warm welcome given by the Chinese g...
The treatment of peat with the solutions of phosphoric, citric, and oxalic acids in concentrations of 10???4 and 10???2 mol/l at solid phase to liquid ratios of 1: 2.5 and 1: 5 increased the absorption of ammonia by 6.4???39.7%. The absorption of ammonia was higher than the concentration of doping ion-exchange groups by a factor of 5???2000. With the use of EPR and IR spectroscopy, it was found that this phenomenon was caused by the transformation of polyconjugation systems as a result of the interaction of acids with the organic matrix of peat by a macrocoordination mechanism, which also improved the technological characteristics of the resulting sorbents. The absence of the destruction of organic matter with the use of low concentrations of weak acids makes it possible to use these sorbe...
Abstract Acid-treated cobia (Rachycentron canadum) skin was extracted in a retort (121C) to obtain retorted skin gelatin hydrolysates (RSGHs) containing antioxidant peptides with noticeable antioxidant properties. To improve the antioxidant activity of cobia RSGHs, five processing factors including alkali concentration, alkali pretreatment time, phosphoric acid concentration (PC), water/skin ratio (WS) and retorting time (RT) in RSGH production were screened using a fractional factorial design to identify critical factors. It indicated that PC, WS and RT had significant effects on ,-diphenyl--picrylhydrazyl (DPPH) scavenging by RSGHs. Subsequently, the optimization of PC, WS and RT on the DPPH scavenging of RSGHs was studied using a central composite design to collect data that resulted in...
Biopharmaceutical R&D complexes are major emission sources of volatile organic compounds (VOCs), which may pose potential health risks for staff on site and residents nearby. In this paper health risk assessments were performed for the VOCs in the ambient air of a typical biopharmaceutical R&D complex in China. Results showed halogenated and alkyl compounds were dominant components among 24 major VOCs from 9 selected sampling sites, inside or around the complex. The principal component analysis (PCA) indicated VOCs were generated predominantly from the biopharmaceutical research activities (factor 1 (F1), 71.6%) and traffic vehicles (factor 2 (F2), 15.4%), which were confirmed by contour maps of five selected VOCs (benzene, toluene, chlorobenzene, methylene chloride and n-hexane) simulated...
Lichens were collected in France in the surroundings of a military nuclear facility in Burgundy, near the la Hague reprocessing plant and in an area away from any direct source of contamination. Organically bound tritium (OBT) has been analysed on 18 samples and radiocarbon on 11. It appeared that on the most contaminated spots, the OBT activity in lichens was higher than the background by a factor of 1000 and was still a factor 10-100 at a distance of 20 km from the source. Radiocarbon from la Hague could be traced by lichens. The slow metabolism of lichens makes them suitable for the follow-up of {sup 3}H and {sup 14}C, which have been incorporated by photosynthesis.
An easy and simple method for gamma assay of large multi-gamma lines samples was introduced in this work. This method performs the assay using point source calibration. The correction factors for volume and self-attenuation are experimentally deduced from the spectra of different thicknesses samples utilizing the following two simple well known facts: large and small samples of the same homogenous material have identical specific activities; the self-attenuation of gamma line decreases as its energy increases. The method was successfully applied to naturally occurring radioactive material (NORM) large samples. This method does not require complicated mathematical procedures. Neither sample matrix data nor detector unit composition is needed.
An easy and simple method for gamma assay of large multi-gamma lines samples was introduced in this work. This method performs the assay using point source calibration. The correction factors for volume and self-attenuation are experimentally deduced from the spectra of different thicknesses samples utilizing the following two simple well known facts: large and small samples of the same homogenous material have identical specific activities; the self-attenuation of gamma line decreases as its energy increases. The method was successfully applied to naturally occurring radioactive material (NORM) large samples. This method does not require complicated mathematical procedures. Neither sample matrix data nor detector unit composition is needed.
An easy and simple method for gamma assay of large multi gamma lines samples was introduced in this work. This method performs the assay using point source calibration. The correction factors for volume and self-attenuation are experimentally deduced from the spectra of different thicknesses samples utilizing the following tow simple well known facts: Large and small samples of the same homogenous material have identical activities; the self attenuation of gamma line decreases as its energy increases. The method was successfully applied to NORM (Naturally Occurring Radioactive Material) large samples. This method doesn't require complicated mathematical procedures. Neither sample matrix data nor detector unit composition is needed. (author)
ALLEYNE G., HANCOCK C. & HUGHES P. (2011) Chronic and non-communicable diseases: a critical challenge for nurses globally. International Nursing Review58, 328-331 Background:- Chronic and non-communicable diseases (NCDs) are a growing and enormous challenge that faces countries across the world. Low- and middle-income countries are disproportionately affected. Contributory factors:- Three risk factors - tobacco use, poor diet (including excessive alcohol intake) and lack of physical activity - contribute to four major chronic diseases - cardiovascular, chronic obstructive pulmonary disease, diabetes and some cancers, which are responsible for over 50% of deaths worldwide. Potential solutions:- International governmental and non-governmental agencies are becoming increasingly concerned and ...
Two inactive tracer techniques for determination of the decontamination factor (DF) of evaporation plants for radioactive waste water are described. One method was used for determination of the DF of an one stage pilot plant. The elements Mg, Cd and Co were employed as tracers. The analyses were performed by atomic absorption spectroscopy. The measurements being fast and simple are especially advantageous with test series in pilot plants. In the second method activation analysis was used for measurement of the tracer to determine the DF of a two stage evaporation plant. Europium is added to the stock solution in a concentration of 70 ppm only. With this method a DF of up to 3 . 10"8 can still be determined. (Auth.).
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 ...
Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, ...
Since living things began their activities on the earth, the extermination of living things in large number on global scale occurred twice 230 million years ago (P-Tr boundary) and 65 million years ago (K-T boundary). As to the cause of exterminating living things in short period, there are volcano eruption theory, meteorite collision theory and so on, but still it is not decided. Therefore, as to the strata of P-Tr boundary in south-western part of China where it has been known the preservation of P-Tr strata is especially good, the existence of elements was measured by instrument neutron activation analysis and ICP-MS, and the state of change was examined. According to the results, the change occurred at the P-Tr boundary on the earth, and further, the possibility of meteorite collision by paying attention to Ir were examined. The samples, the neutron activation analysis, the ICP-MS and the results are reported. The ...
In the radiochemical reprocessing of spent fuel from nuclear reactors, a considerable amount of liquid, solid, and gaseous waste is formed; this waste is potentially dangerous to humans and requires the development of special and complex technological techniques for its localization and reliable long-term storage. The most hazardous are liquid wastes of high specific activity - water-tailings solutions obtained in the first cycle of extraction after the removal of uranium and plutonium. These solutions contain more than 99.9% of all the other transuranic elements - isotopes of neptunium, americium, and curium. Where necessary, some fission products and actinides may be removed from wastes of high specific activity for subsequent use. The quantity, composition, and activity of these wastes varies within broad limits, depending on the type and power of the reactor, the initial nuclide composition of the fuel, and its specific ...
The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate...Full Text Available
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
SUMMARYTestosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior...Full Text Available
The rejection thresholds of Phormia regina Meigen for twenty-four glycols have been determined. A definite relationship between the concentration of the test material and the distribution...Full Text Available
There is considerable evidence that purines are vasoactive molecules involved in the regulation of blood flow. Adenosine is a well known vasodilator that also acts as a modulator of the response to...Full Text Available
Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological...Full Text Available
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 ...
A study was made of the kinetics of L-(/sup 3/H)quinuclidinyl benzilate binding with membrane-bound muscarine cholinoreceptors from the rat brain. Determination was made of the rate constants of this process, and constants as a function of ligand concentration was investigated, indicating that there is a complex mechanism of interaction of antagonists with muscarine receptor. With up to 3.5 nM concentrations of L-(/sup 3/H)quinuclidinyl benzilate, the binding reaction occurs in two stages: rapid equilibrated binding is followed by a slow process of conformational isomerization of the receptor-ligand complex. At higher ligand concentrations, there is additional drastic increase in constant of rate of ligand binding a new plateau is reached. Such dependence of rate constant on ligand concentration is indicative of the cooperative nature of interaction between antagonists and muscarine receptors. This is possible if there are ...
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
BackgroundWhereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development,...Full Text Available
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 ...
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
OBJECTIVES:To investigate the effect of opioid receptor blockade on the myocardial protection conferred by chronic exercise and to compare exercise training with different strategies...Full Text Available
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
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
A carrier coprecipitation procedures has been developed for the removal of radioactive strontium from caustic liquid low-level waste (LLLW) generated at Oak Ridge National Laboratory. The two-step treatment process involves the addition of normal Sr (as SrCl{sub 2}) to the waste matrix, which is composed primarily of 0.3 M NaOH and 0.6 M Na{sub 2}CO{sub 3}. The active Sr equilibrates with the normal Sr carrier and coprecipitates as SrCO{sub 3} at pH 13. A liquid/solid separation is made before the pH of the supernate is reduced to pH 8 with sulfuric acid. During the neutralization step, the aluminum is the waste precipitates as Al(OH){sub 3}. Further Sr decontamination is achieved as traces of active Sr sorb to the Al(OH){sub 3} that precipitates during the neutralization step. A final liquid/solid separation is made at pH 8 to remove the sorbed active Sr. Maximum Sr decontamination of the LLLW is obtained when at least 50 ...
The patients studied were referred for routine abscess localization with indium-111 labelled autologous leukocytes. One series (n=15) was studied at 1 day after reinjection of labelled cells and a second series (n=9) was studied between 4 hours and 4 days after reinjection of labelled cells. The leukocytes were isolated by a gravity sedimentation method and labelled with In-111 oxinate according to Roevekamp and co-workers. The labelled cell suspension administered to the patient contained between 11 and 15 MegaBq (300-400 microCi). The indium-111 concentration in the liver and spleen was quantitated using a scintillation camera and an on-line computer system. Phantom studies were carried out to obtain conversion factors from geometric mean counts to MegaBq of activity for both liver and spleen. Once determined, the amount of activity in liver and spleen was corrected for physical decay of In-111 and expressed as a ...
Compounds isolated from Magnolia officinalis such as magnolol, honokiol and obovatol exhibit several pharmacological effects on CNS including depressant, anxiolytic and anticonvulsant effects, as well as neuroprotective effects against chemical and heat damages. Recently, honokiol was found to have a neurotrophic effect in fetal rat cortical neurons. In the present study, we show that 4-O-methylhonokiol, a novel compound from Magnolia officinalis, promotes neurite outgrowth in a concentration- dependent manner in rat embryonic neuronal cells. In parallel with the neurite outgrowth activity, the expression of neurite outgrowth marker proteins is also increased by treatment with 4-O-methylhonokiol. We also found that 4-O-methylhonokiol promotes the release of NGF and BDNF into cell culture medium. In addition, lower concentration of 4-O-methylhonokiol (1 and 2 lM) further enhanced neurite outgrowth and expression of neurite outgrowth marker proteins in the presence ...
The uncertainty of the elemental analysis is one of the major factors governing the utility of on-line Prompt Gamma Neutron Activation Analysis (PGNAA) in the blending and sorting of bulk materials. In this paper, a general method applicable to Gamma spectra processing is presented and applied to PGNAA in mineral industry. Based on the Fourier transform of spectra and their de-correlation in the Fourier space (the improvement of the conditioning of the correlation matrix), processing of overlapping of characteristic peaks minimizes the propagation of random errors, which optimizes the accuracy and decreases the detection limits of elemental analyses. In comparison with classical methods based on the linear combinations of relevant regions of spectra the improvement may be considerable, especially when several elements are interfering. The method is applied to four case stories covering both borehole logging and on-line analysis on conveyor belt ...
In this work, the antibacterial effect of fluoroquinolones (FQs) upon Escherichia coli (E.coli) was measured with and without application of 40kHz ultrasound (US) stimulation. The research results demonstrated that simultaneous application of 40kHz US apparently enhanced the antibacterial effectiveness of FQs. That is, the synergistic effect was observed and the bacterial viability was reduced when FQs and US were combined. In addition, various influencing factors, such as FQs drug concentration, US irradiation time and solution temperature, on the inhibition of E.coli were also investigated. The antibacterial activity was enhanced apparently with increasing of FQs drug concentration, US irradiation time and solution temperature. Furthermore, we discussed preliminarily the mechanism of US ...
Unlike the well-characterized nuclear function of the Notch intracellular domain, it has been difficult to identify a nuclear role for the ligands of Notch. Here we provide evidence for the nuclear function of the Notch ligand Delta-like 1 in colon cancer (CC) cells exposed to butyrate. We demonstrate that the intracellular domain of Delta-like 1 (Dll1icd) augments the activity of Wnt signaling-dependent reporters and that of the promoter of the connective tissue growth factor (CTGF) gene. Data suggest that Dll1icd upregulates CTGF promoter activity through both direct and indirect mechanisms. The direct mechanism is supported by co-immunoprecipitation of endogenous Smad2/3 proteins and Dll1 and by chromatin immunoprecipitation analyses that revealed the occupancy of Dll1icd on CTGF promot...
The nitrogen content of 10 medicinal plant species has been determined by fast-neutron activation analysis (FNAA). Correction factors for the effects of the /sup 16/O(p,..cap alpha..)/sup 13/N knock-on proton-induced reaction and the (n,2n) reactions, which produce interfering positron-emitting radionuclides, have also been determined. The total relative interference from the /sup 16/O(p,..cap alpha..)/sup 13/N and (n,2n) reactions of K, Cl, Fe and Br was found to be 5.1 to 32.1% for the plant samples.
Environmental assessment in an arid coal mining area requires an understanding of the influences of coal mining, the arid climate and ecological remediation. To that end, we selected vegetation as the key environmental factor to observe. Remote sensing approaches to monitoring the spatio-temporal variation of vegetation caused by mining activities, the arid climate and ecological remediation in the Shengdong coal mining area are described. Over a large regional scale it was found that the vegetation was improved as a result of ecological remediation activities. At the local scale, however, the vegetation coverage and soil moisture in the mined areas were slightly lower than those in un-mined areas due to mining subsidence. These differences are partly attributed to ground fissures that inj...
Summary The aim of this cross-sectional study was to find possible relationships between insulin-like growth factor-1 (IGF-1), adipocytokines (leptin and adiponectin) and twitch contraction (TC) characteristics of the knee extensor (KE) muscles in healthy physically active postmenopausal women (n = 28, 64-78 years old). We hypothesized that IGF-1 is related at least to isometric TC peak torque (Pt) as the highest value of isometric torque production and maximal voluntary contraction (MVC) torque, and there will not be any relationships between TC characteristics and leptin and adiponectin. During the measurement of MVC torque and twitch contractile properties of KE muscles, the subjects sat in a custom-made dynamometric chair with the knee and hip angles equal to 90degree and 100degree, re...
We analyze the driven resonantly coupled Jaynes-Cummings model in terms of a quasienergy approach by switching to a frame rotating with the external modulation frequency and by using the dressed atom picture. A quasienergy surface in phase space emerges whose level spacing is governed by a rescaled effective Planck constant. Moreover, the well-known multiphoton transitions can be reinterpreted as resonant tunneling transitions from the local maximum of the quasienergy surface. Most importantly, the driving defines a quasienergy well which is nonperturbative in nature. The quantum mechanical quasienergy state localized at its bottom is squeezed. In the Purcell limited regime, the potential well is metastable and the effective local temperature close to its minimum is uniquely determined by the squeezing factor. The activation occurs in this case via dressed spin flip transitions rather than via quantum activation as in other ...
Abstract Tumor necrosis factor (TNF)- is a pro-inflammatory cytokine associated with psoriasis pathogenesis. Anti-TNF- therapies are effective in psoriasis. A significant weight gain has been reported in patients treated with anti-TNF- agents. The aim of the present study was to evaluate the body composition changes in psoriatic patients receiving anti-TNF- therapies according with disease phenotype. Forty patients affected with psoriasis were followed up for 24 weeks and divided into two groups: psoriasis vulgaris (PsO) and psoriatic arthritis (PsA). Anthropometric, blood biochemical, body composition parameters, resting metabolic rate, and disease activity indexes were measured at baseline and at week 24. After 24 weeks of anti-TNF- administration, the disease activity indexes and concen...
The hybrid squeeze-film damper bearing with active control is proposed in this paper and the lubricating with couple stress fluid is also taken into consideration. The pressure distribution and the dynamics of a rigid rotor supported by such bearing are studied. A PD (proportional-plus-derivative) controller is used to stabilize the rotor-bearing system. Numerical results show that, due to the nonlinear factors of oil film force, the trajectory of the rotor demonstrates a complex dynamics with rotational speed ratio s. Poincare maps, bifurcation diagrams, and power spectra are used to analyze the behavior of the rotor trajectory in the horizontal and vertical directions under different operating conditions. The maximum Lyapunov exponent and fractal dimension concepts are used to determine ...
MINER?A is a high resolution, fully active detector designed to study neutrino interactions on nuclei in the NuMI beam at Fermi National Accelerator Laboratory. The active volume of the detector consists of 3 tons of plastic scintillator and includes embedded targets of 4He, C, H2O, Fe and Pb. The MINER?A collaboration expects to perform precision, A-dependent neutrino cross section measurements in the 1?10 GeV region, measure the axial form factor, and study nuclear shadowing of F2, quark-hadron duality and coherent pion production, among other topics. MINER?A began data taking in the fall of 2009. This paper describes the MINER?A experiment and provides an overview of the physics objectives along with estimated uncertainties of the measurements and the tentative projected schedule of dat...
In looking to the future and the development of new approaches or strategies for managing hazardous waste, it is important to understand and appreciate the factors that have contributed to current successful approaches. In the United States, several events in the last two decades have had a significant impact in advancing remediation of hazardous waste, including environmental legislation, legislative reforms on licensing federally funded research, and electronic transfer of information. Similar activities also have occurred on a global level. While each of these areas is significant, the electronic exchange of information has no national boundaries and has become an active part of major hazardous waste research and management programs. It is important to realize that any group or society that is developing a comprehensive program in hazardous waste management should be able to take advantage of this advanced approach in ...
Perceptions of sensation and pain in healthy people are believed to be the net result of sensory input and descending modulation from brainstem and cortical regions depending on emotional and cognitive factors. Here, the influence of attention on neural activity in the spinal cord during thermal sensory stimulation of the hand was investigated with functional magnetic resonance imaging by systematically varying the participants' attention focus across and within repeated studies. Attention states included (1) attention to the stimulus by rating the sensation and (2) attention away from the stimulus by performing various mental tasks of watching a movie and identifying characters, detecting the direction of coherently moving dots within a randomly moving visual field and answering mentally-...
In several vertebrate classes, the M?ller glia are capable of de-differentiating, proliferating, and acquiring a progenitor-like state in response to acute retinal injury or in response to exogenous growth factors. Our previous study has shown that M?ller cells can be activated and de-differentiated into retinal progenitors during Royal College of Surgeons (RCS) rats' degeneration, although the limited proliferation cannot maintain retinal function. We now report that rat retinal stem cells (rSCs) transplanted into RCS rats slowed the progression of retinal morphological degeneration and prevented the functional disruption. Further, we found that retinal progenitor cells labeled with Chx10 were increased significantly after rSCs transplantation, and most of them are mainly from activated M...
Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identify gene targets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...
The nature of the `inner engine' that accelerate and collimate the relativistic flow at the cores of GRBs is the most interesting current puzzle concerning GRBs. Numerical simulations have shown that the internal shocks' light curve reflects the activity of this inner engine. Using a simple analytic toy model we clarify the relations between the observed $ \\gamma $-rays light curve and the inner engine's activity and the dependence of the light curves on the inner engine's parameters. This simple model also explains the observed similarity between the observed distributions of pulses widths and the intervals between pulses and the correlation between the width of a pulse and the length of the preceding interval. Our analysis suggests that the variability in the wind's Lorentz factors arises due to a modulation of the mass injected into a constant energy flow.
Experiments have been performed to study the usefulness of several types of plastic foils as filter to separate radon and thoron. Time-integrated alpha-activity measurements have been carried out by using the so-called ''can-technique'' equipped with both LR-115 and CR-39 track detectors. The track density observed on the detectors, taken as a measure of radon activity concentration, has been determined as a function of the thickness of filter foils. The radon permeability and the thoron separation factors have been determined. It is shown that various plastic foils exhibit considerable differences in radon diffusion coefficient owing to their different chemical structures. Among the plastic foils investigated the polyethylene proved to have the highest gas diffusion coefficient.
Active contrast material extravasation can be recognized with conventional CT scanners, though it has been considered a rare finding. Helical CT seems to increase the detection rate and especially to boost the radiologist's confidence in this diagnosis. Though active bleeding is defined in severely-injured subjects requiring urgent intervention and may be associated with findings of hypovolaemic shock, it should not be considered itself as a negative prognostic factor. Contrast extravasation is due to ongoing hemorrhage and its detection is critical for urged treatment. Accurate anatomical location permits to choose surgical management or transcatheter embolization and thus decreases time consumption for precis e bleeding site identification.
The gliding modes of a duplex Ti-6Al-4V titanium alloy were investigated through in situ (scanning electron microscopy) tensile tests. A method based on electron back-scattering diffraction (EBSD) measurements was used to identify activated slip systems. The approach applied to a large number of grains allowed a statistical analysis of the nature (basal, prismatic, pyramidal) and distribution of the slip systems according to the crystallographic texture. A discussion concerning the pertinence of Schmid's law to explain the occurrence and succession of slip events is then proposed. The domain in favor of each type of slip system is finally presented by using inverse pole figures mapped with Schmid's factor iso-curves.
Abstract Recent work (Schawinski et al.) indicates that star-forming early-type galaxies residing in the blue cloud migrate rapidly to the red sequence within around a Gyr, passing through several phases of increasingly strong active galactic nucleus (AGN) activity in the process. We show that natural depletion of the cold gas reservoir through star formation (i.e. in the absence of any feedback from the AGN) induces a blue-to-red reddening rate that is several factors lower than that observed by Schawinski et al. This is because the gas depletion rate due to star formation alone is too slow, implying that another process needs to be invoked to remove cold gas from the system and accelerate the reddening rate. We develop a simple phenomenological model, in which a fraction of the AGN-s lum...
We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-? (TNF-?) and Interferon-gamma (IFN-?) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092
The main goal of this paper is to present a methodology for calculating the radioactivity in the moderator and heat transport systems of Cernavoda NPP Unit 1, with the intention to improve the knowledge on the radionuclides inventories in the operational waste streams, and to aid the licensing process of new near surface repository. In the present paper we describe our methodology for estimating H-3 and C-14 production rates in the heavy-water moderator and heat transport systems using the capacity factors from 1997 to 2007 years. The radioactivity of the difficult-to-measure nuclides is predicted by scaling method using measured concentration in reference CANDU 6 reactor Gentilly-2. The difficult-to-measure radionuclides of primary interest in this study were those with long half-lives which have a significant role for post-closure safety assessment. The equation used to scale fission products (parents and daughters) is based on the equilibrium solution of the ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse erythroleukemia cell can ...
Inhalation of radon and its daughter products makes the major contribution to the total exposure of the population to natural radiations. In implementing a complex ecological survey, concentrations of radon and its daughter products were measured in different regions of Russia, namely, in the St. Petersburg Region, the Central Territories and the Altay Territory. Two suitable low price versions of the dosemeters for measuring environmental radon concentrations based on track-etch and activated-charcoal detectors were used. The radon daughter product activity and the effective dose equivalents were calculated with an equilibrium factor of 0.5 and a recommended effective dose equivalent factor of 0.061 mSv (Bq m{sup -3}){sup -1}. Indoor measurements were taken in more than 1000 dwellings and public and industrial buildings of 21 towns and villages. The track chambers were exposed for about 2-3 months and ...
Inhalation of radon and its daughter products makes the major contribution to the total exposure of the population to natural radiations. In implementing a complex ecological survey, concentrations of radon and its daughter products were measured in different regions of Russia, namely, in the St. Petersburg Region, the Central Territories and the Altay Territory. Two suitable low price versions of the dosemeters for measuring environmental radon concentrations based on track-etch and activated-charcoal detectors were used. The radon daughter product activity and the effective dose equivalents were calculated with an equilibrium factor of 0.5 and a recommended effective dose equivalent factor of 0.061 mSv (Bq m"-"3)"-"1. Indoor measurements were taken in more than 1000 dwellings and public and industrial buildings of 21 towns and villages. The track chambers were exposed for about 2-3 months and the ...
To understand the molecular mechanisms of how 5^oC-incubation activates mRNA expression of Hsp70a and Samui genes in Bombyx mori diapause eggs, we first searched the 5'-upstream regions of the Hsp70a and Samui genes for heat shock elements (HSEs) and found two regions [Hsp70aHSE-1 (-95 to -58) and -2 (-145 to -121), and SamuiHSE-1 (-84 to -55) and -2 (-304 to -290)] corresponding to HSEs (repeats of nGAAn and/or nTTCn). We cloned four cDNAs encoding heat shock factor (HSF)-a2 (627 amino acids), -b (685 aa), -c (682 aa) and -d (705 aa), which were produced by alternative splicing. When we exposed diapause eggs to 5^oC beginning at 2 day post-oviposition to break diapause, HSFd mRNA only increased after chilling for 6-8 days, a pattern very similar to those of Hsp70a and Samui mRNAs. To exam...
Hoogenstraaten's heating rate method has generally been considered as a reliable method for determining thermoluminescence trapping parameters of first order glow peaks. However, experience has shown that in some cases the deviation between the heating rate method and glow curve fitting method can be quite significant (considering only the linear part of the heating rate plot, of course). In this study it is shown that one of the main reasons for this deviation can be a systematic increase of a temperature lag between the measured and real temperature of the sample with increasing heating rate. It appears that this systematic increase of the temperature lag affects the method in the range of low heating rates (linear part of the heating rates plots) more than has been previously realised. The effect of the temperature lag on Hoogenstraaten's heating rate method is a decrease in activation energy and frequency factor and is more important for ...
Hoogenstraaten's heating rate method has generally been considered as a reliable method for determining thermoluminescence trapping parameters of first order glow peaks. However, experience has shown that in some cases the deviation between the heating rate method and glow curve fitting method can be quite significant (considering only the linear part of the heating rate plot, of course). In this study it is shown that one of the main reasons for this deviation can be a systematic increase of a temperature lag between the measured and real temperature of the sample with increasing heating rate. It appears that this systematic increase of the temperature lag affects the method in the range of low heating rates (linear part of the heating rates plots) more than has been previously realised. The effect of the temperature lag on Hoogenstraaten's heating rate method is a decrease in activation energy and frequency factor and is ...
To reduce the volume of radioactive wastes after evaporation, activity carriers can be separated from the inactive salt load. Boric acid separation from PWR concentrates was considered a preliminary stage for nuclide precipitation. In connection with the precipitation process, the reaction conditions for boric acid separation were determined by bench-scale experiments. After evaluating the known purification processes, crystallization was suggested as a practicable method. After inactive bench-scale experiments, mixed crystal formation with iron hexacyanoferrate for Cs removal was chosen. The disturbing effect of the complexing agents was neutralized by a pre-dose of iron-III-salts. By specifying the precipitation conditions, for Cs-134 an activity separation from 3,0 E + 06 Bg/l to 1,9 E + 02 Bg/l, and for Cs-137 from 5,9 E + 06 Bg/l to 1,2 E + 02 Bg/l was achieved. Accordingly, the decontamination factor for Cs-134 was ...
We hypothesized that I kappa B kinase (IKK)-mediated nuclear factor kappa B and forkhead BoxO3a phosphorylation will be associated with age-related endothelial dysfunction. Endothelium-dependent dilation and aortic protein expression/phosphorylation were determined in young and old male B6D2F1 mice and old mice treated with the IKK inhibitor, salicylate. IKK activation was greater in old mice and was associated with greater nitrotyrosine and cytokines. Endothelium-dependent dilation, nitric oxide (NO), and endothelial NO synthase phosphorylation were lower in old mice. Endothelium-dependent dilation and NO bioavailability were restored by a superoxide dismutase mimetic. Nuclear factor kappa B and forkhead BoxO3a phosphorylation were greater in old and were associated with increased express...
Attacks by herbivorous insects reduce biomass production in willow plantations. The long-term goal of our research is to develop sustainable plant protection against these insect pests. Two lines of research are pursued. The first concentrates on identifying factors involved in the regulation of leaf-eating beetles. These insects vary in density among plantations, sometimes reaching outbreak levels resulting in complete defoliation. Mortality factors of eggs and larvae in plantations with low and high beetle densities have been investigated. The importance of plant resistance has also been investigated. The second line of research considers the mechanisms behind an earlier demonstrated resistance in certain willow clones against a gall midge. By using molecular techniques we have searched for markers of resistance. Promising results have been found concerning so called PR proteins; in particular chitinase seems to be present in high ...
Metabolic engineering of photosynthetic organisms is required for utilization of light energy and for reducing carbon emissions.Control of transcriptional regulators is a powerful approach for changing cellular dynamics, because a set of genes is concomitantly regulated. Here, we show that overexpression of a group 2 ? factor, SigE, enhances the expressions of sugar catabolic genes in the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Transcriptome analysis revealed that genes for the oxidative pentose phosphate pathway and glycogen catabolism are induced by overproduction of SigE. Immunoblotting showed that protein levels of sugar catabolic enzymes, such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glycogen phosphorylase, and isoamylase, are increased. Glycogen levels are reduced in the SigE-overexpressing strain grown under light. Metabolome analysis revealed that metabolite levels of the TCA cycle and acetyl-CoA are ...
Postresection villus hyperplasia is a major compensatory mechanism in the short-bowel patient. Substances capable of augmenting postresection mucosal hyperplasia could have therapeutic implications. Human growth hormone (hGH) and human growth hormone releasing factor (hGHRF) stimulate growth of the gastrointestinal tract; however, the diabetogenic actions of growth hormone limit its usefulness in clinical practice. Plerocercoid larvae of the tapeworm Spirometra mansonoides produce an analog of hGH void of diabetogenic side effects. We assessed effects of plerocercoid growth factor (PGF) on mucosal adaptation following 70% proximal jejunoileal resection in young rats. Mucosal weight, DNA, protein, and total sucrase activity per centimeter of bowel were increased in resected PGF-treated animals compared to resected controls. We conclude PGF augments intrinsic postresection mucosal hyperplasia following extensive intestinal ...
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 ...
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 ...
Humoral immune response to human epidermal growth factorreceptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated ...
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 ...
Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodies that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with ...
The thermal degradation and crystallisation behaviours of polyamide12/isotactic polypropylene (PA12/PP) blends were studied. Effects of blend ratio and compatibiliser concentration on the thermal degradation properties of the blends were analysed. The activation energy for degradation in compatibilised and uncompatibilised blends computed using Horowitz-Metzger equation was reported. The blend ratio as well as the presence of compatibiliser has significant effect on the thermal stability of the blends. Phase morphology was found to be one of the decisive factors that affected the thermal stability of both uncompatibilised and compatibilised blends. Melting and crystallisation behaviours of the blends in the presence and absence of compatibiliser were evaluated. It was observed that blendin...
The paper presents results of measurements of the natural radioactivity of tap water where samples were taken in front of, and behind the ceramic filter commonly used in houses for the purification of tap water. Altogether, 289 samples were taken, processed and measured during 1985-1986 in Kuwait. Results reveal the fact that ceramic filters reduce substantially the natural radioactivity in water (the 'gross' alpha activity reduced by the factor 2.18 #+-# 18%; the 'gross' beta by 1.53 #+-# 1.6%. (author).
The effects of variable hardness, pH, alkalinity, humics, and suspended clay on the chemical speciation of copper and its toxicity to fathead minnow larvae in Lake Superior water were investigated. Two proposed methods (toxicity factors and chemical speciation) for predicting LC50 values in specific natural waters from laboratory toxicity data and the average site specific values of general water quality parameters were evaluated. The accuracy of the cupric ion-selective electrode in determining CU/sup +2/ activities in ambient and chemically altered Lake Superior water was also determined.
The importance of ecosystem restoration to land reclamation is discussed. If a plant community is to be self sustaining, natural diversity processes provide a useful model for restoration. Biodiversity is important for utilitarian, ecological, and ethical/aesthetic reasons. Issues that must be considered include sampling and management scales, the separate richness of the diverse array of species playing a role in ecosystem productivity and stability, and natural trends in diversity. Ecological restoration comprises two fundamental activities: management for some pre-disturbance level of biodiversity and the combination of species in a manner that is essentially experimental. Endeavours to restore biological diversity are a useful method of experimenting with the factors that control ecosystem structure and function. 21 refs.
Corrosion is increasingly becoming an important factor reducing the reliability of many nuclear power plant components. The significance is evaluated of corrosion phenomena with respect to the reliability of primary circuit components of LWR's, viz., the reactor pressure vessel, primary piping, steam generator, and fuel elements. The mechanism of corrosion phenomena is explained and methods of minimizing their effects are presented. An analysis is made of the needs to solve the corrosion problems of nuclear power plants from the point of view of Czechoslovak producers and research and development activities. International cooperation is reviewed and main problems are formulated on which the solution of corrosion problems of structural materials used in WWER type nuclear power plants should be focussed. (author).
A new band gap profile (exponential profile) for the active layer of the a-SiGe:H single junction cell has been designed and experimentally demonstrated. By computer simulations we show how bending the grading of the band gap in the i-layer contributes to the enhancement of the carrier collection, improving the fill factor and efficiency. The differences observed between experiments and simulations are studied using Rutherford Backscattering Spectrometry (RBS). The results highlight weak points during the deposition process, whose control enables us to bring together experimental and computational results.
During the 1990s, a debate took place in Sweden concerning Conductive Education. Proponents of this method focused their critique on the role and methods of physiotherapists but this profession was not active in the debate. Instead, the medical profession came out as defenders of habilitation services and methods. Departing from sociology of the professions, our objective in this article is to analyze the physiotherapists' silence in relation to the profession's position and its relation to the medical profession. The analysis is based on data from interviews with members of habilitation teams and other key persons, and on documents. The relative silence of physiotherapists is found to be related to both interprofessional factors (the subordination under the medical profession paired with ...
A new simple multi-well plate-based assay to determine monocyte differentiation-inducing activity was developed. It is based on the increase of macrophage adherence after the induction of monocyte differentiation. The assay was conducted using a human monocytic leukemia cell line, THP-1, treated with either 12-O-tetradecanoylphorbol 13-acetate or cytokines, such as tumor necrosis factor-alpha and interferon-gamma. This method is sensitive and easy to perform, especially in case of analyzing a large number of samples. PMID:17920620
A new simple multi-well plate-based assay to determine monocyte differentiation-inducing activity was developed. It is based on the increase of macrophage adherence after the induction of monocyte differentiation. The assay was conducted using a human monocytic leukemia cell line, THP-1, treated with either 12-O-tetradecanoylphorbol 13-acetate or cytokines, such as tumor necrosis factor-? and interferon-?. This method is sensitive and easy to perform, especially in case of analyzing a large number of samples.
The Salt Decontamination Demonstration confirmed that the precipitation process could be used for large-scale decontamination of radioactive waste sale solution. Although a number of refinements are necessary to safely process the long-term requirement of 5 million gallons of waste salt solution per year, there were no observations to suggest that any fundamentals of the process require re-evaluation. Major accomplishments were: (1) 518,000 gallons of decontaminated filtrate were produced from 427,000 gallons of waste salt solution from tank 24H. The demonstration goal was to produce a minimum of 200,000 gallons of decontaminated salt solution; (2) cesium activity in the filtrate was reduced by a factor of 43,000 below the cesium activity in the tank 24 solution. This decontamination factor (DF) exceeded the demonstration goal of a DF greater than 10,000; (3) average strontium-90 ...
For the purpose of searching some effective absorbents of gaseous radioactive iodine, 16 substances considered as having an affinity for iodine were investigated with regular iodine and /sup 125/I. In a preliminary survey, only tetrathiafulvalene (TTF) was found to have satisfactory absorbing properties comparable to activated charcoal. A further detailed comparison of the properties between TTF and activated charcoal led us to the conclusion that the former has more preferable properties as absorbent of radioactive iodine than the latter in all points studied. The results are summarized as follows: (1) The absorption of iodine on TTF in atmosphere was about twice as much as that on activated charcoal. Desorption of iodine from saturatedly absorbed iodine on TTF was practically negligible except trace amount of initial desorption, while that on activated charcoal was considerable (3%/50h) even in the ...
The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases ...
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
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 undegraded, dissociated ...
Backgroundβ2-Adrenergic receptors (β2AR) play important regulatory roles in a variety of cells and organ systems and are important therapeutic...Full Text Available
An unusual S1-nuclease sensitive microsatellite (STMS) has been found in the single copy, rat polymeric immunoglobulin receptor gene (PIGR) terminal exon. In Fisher rats, elements within or beyond the...Full Text Available
The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available