KoreaScience (Korea)

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We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and ...

UK PubMed Central (United Kingdom)

Endothelial cells and mural cells (smooth muscle cells, pericytes, or fibroblasts) are known to communicate with one another. Their interactions not only serve to support fully functional blood...Full Text Available

UK PubMed Central (United Kingdom)

Petal senescence, one type of programmed cell death (PCD) in plants, is a genetically controlled sequence of events comprising its final developmental stage. We characterized the pollination-induced...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundSome breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell...Full Text Available

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Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage was independent on NO formation and involved the IFN-gamma signalling pathway as well as induction of apoptosis. If cytokines have similar effects in vivo, these may lead to energy deficiency and thus ...

UK PubMed Central (United Kingdom)

Adhesion of Spirogyra (tentatively, Spirogyra fluviatilis) cells to glass is described. The cells of an algal filament can adhere to a substrate only when they are...Full Text Available

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BackgroundClara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and...Full Text Available

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Abstract Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage o...

Science.gov (United States)

By applying lock-in thermography imaging, light-beam-induced current imaging, electron-beam-induced current imaging at different stages of sample preparation, and infrared light microscopy in transmission mode, the physical nature of the dominant material-induced shunts in multicrystalline solar cells made from p-type silicon material has been investigated. It turns out that these shunts are due to silicon carbide (SiC) filaments, which grow preferentially in grain boundaries and cross the whole cell. These filaments are highly n-type doped, like the emitter layer on the surface of the cells. They are electrically connected both with the emitter and with the back contact, thereby producing internal shunts in the solar cell.

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By applying lock-in thermography imaging, light-beam-induced current imaging, electron-beam-induced current imaging at different stages of sample preparation, and infrared light microscopy in transmission mode, the physical nature of the dominant material-induced shunts in multicrystalline solar cells made from p-type silicon material has been investigated. It turns out that these shunts are due to silicon carbide (SiC) filaments, which grow preferentially in grain boundaries and cross the whole cell. These filaments are highly n-type doped, like the emitter layer on the surface of the cells. They are electrically connected both with the emitter and with the back contact, thereby producing internal shunts in the solar cell.

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The analgesic, dipyrone (1,phenyl-2,3-dimethyl-5-pyrazolone-4-methylamino methane sulphonate sodium), at 20 mM concentration, inhibited the rejoining of single-strand scissions in DNA of Escherichia coli B/r cells induced by 20 krad gamma-radiation. The chemical altered the cell membrane structure as evidenced from the uptake of acriflavin, the efflux of potassium ions from the bacterial cells and the inhibition of alkaline phosphatase-a cell membrane associated enzyme. (author). 18 refs., 6 figures.

UK PubMed Central (United Kingdom)

The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available

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A brief overview if provided of selected reports presented at the International Symposium on Molecular Mechanisms of Radiation- and Chemical Carcinogen-Induced Cell Transformation held at Mackinac Island, Michigan on September 19-23, 1993.

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Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization....Full Text Available

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

Neonatal administration of the synthetic glucocorticoid, dexamethasone (DEX) retards brain growth, alters adult behaviors and induces cell death in the rat brain, thereby implicating glucocorticoids...Full Text Available

UK PubMed Central (United Kingdom)

PurposeTo investigate the effects of laser photocoagulation (LP)-induced ocular hypertension (OHT) on the survival and retrograde axonal transport of retinal ganglion cells (RGC),...Full Text Available

KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

 Telomere maintenance is essential for cellular immortality, and most cancer cells maintain their telomeres through the enzyme telomerase. Telomeres and telomerase represent promising anticancer...Full Text Available

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

The fusogenic orthoreoviruses express nonstructural fusion-associated small transmembrane (FAST) proteins that induce cell-cell fusion and syncytium formation. It has been speculated that the FAST proteins...Full Text Available

UK PubMed Central (United Kingdom)

The objective of this study was to determine if inflammatory tolerance and enhancement of innate immune function could be induced by the gram-positive cell wall component peptidoglycan (PGN)....Full Text Available

UK PubMed Central (United Kingdom)

Cancer cells constantly adapt to oxidative phosphorylation (OXPHOS) suppression resulting from hypoxia or mitochondria defects. Under the OXPHOS suppression, AMP-activated protein kinase (AMPK) regulates...Full Text Available

UK PubMed Central (United Kingdom)

DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients...Full Text Available

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Our studies have shown that endotoxin intratracheally instilled into the rat lung induces proliferation of alveolar type II cells. In that study, the alveolar type II cells. In that study, the alveolar type II cell hyperplasia occurred 2 d after instillation of endotoxin and persisted for a further 2 d. After hyperplasia, the lung remodeled and returned to a normal state within 24-48 h. Understanding the mechanisms involved in the remodeling process of this transient hyperplasia may be useful to identify molecular changes that are altered in neoplasia. The purpose of the present study was to corroborate induction of epithelial cell hyperplasia by endotoxin and to delineate mechanisms involved in tissue remodeling after endotoxin-induced alveolar type II cell hyperplasia. In conclusion, immonostaining with cyclin D1 and cytokeratin shows that ...

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

Chronic autoimmune or pathogen-induced immune reactions resulting in lymphoid neogenesis are associated with development of malignant lymphomas, mostly extranodal marginal zone B-cell lymphomas (MZBCLs)....Full Text Available

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A goal of our research is to identify biochemical factors that underlie the susceptibility of bone marrow cell populations to benzene metabolites so as to develop a mechanistically based chemoprotective...Full Text Available

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Maintenance of genomic integrity in embryonic cells is pivotal to proper embryogenesis, organogenesis and to the continuity of species. Cultured mouse embryonic stem cells (mESCs), a model for early embryonic cells, differ from cultured somatic cells in their capacity to remodel chromatin, in their repertoire of DNA repair enzymes, and in the regulation of cell cycle checkpoints. Using 129XC3HF1 mESCs heterozygous for Aprt, we characterized loss of Aprt heterozygosity after exposure to ionizing radiation. We report here that the frequency of loss of heterozygosity mutants in mESCs can be induced several hundred-fold by exposure to 5-10Gy of X-rays. This induction is 50-100-fold higher than the induction reported for mouse adult or embryonic fibroblasts. The primary mechanism underlying the...

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

Stromal cells from DBA/2 mouse bone marrow have been shown to be susceptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also...Full Text Available

UK PubMed Central (United Kingdom)

The initiation and progression of several forms of retinal degenerations involve excessive, repetitive, and/or sustained oxidative stress that, in turn, mediate photoreceptor cell damage and...Full Text Available

UK PubMed Central (United Kingdom)

PurposeCurcumin (Cur) has been reported to induce apoptosis in human renal carcinoma Caki cells. Dimethoxycurcumin (DMC), one of several synthetic Cur analogues, has been reported...Full Text Available

UK PubMed Central (United Kingdom)

Arsenic trioxide (As₂O₃), used to treat promyelocytic leukemia, triggers cell death via unknown mechanisms. To further our understanding of As₂O₃-induced...Full Text Available

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RNA interference has become a powerful biological tool over the last decade. In this study, a tetracycline-inducible shRNA vector system was designed for silencing CFP expression and delivered alongside the yfp marker gene into Chinese hamster ovary cells using impalefection on spatially indexed vertically aligned carbon nanofiber arrays (VACNFs). The VACNF architecture provided simultaneous delivery of multiple genes, subsequent adherence and proliferation of interfaced cells, and repeated monitoring of single cells over time. Following impalefection and tetracycline induction, 53.1% 10.4% of impalefected cells were fully silenced by the inducible CFP-silencing shRNA vector. Additionally, efficient CFP-silencing was observed in single cells among a population of cells that remained CFP-expressing. This effective ...

British Library Electronic Table of Contents (United Kingdom)

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...

International Nuclear Information System (INIS)

Swelling hemoglobin CC erythrocytes stimulates a ouabain-insensitive K flux that restores original cell volume. Studies were performed with the K analog, "8"6Rb. This volume regulatory pathway was characterized for its anion dependence, sensitivity to loop diuretics, and requirement for Na. The swelling-induced K flux was eliminated if intracellular chloride was replaced by nitrate and both swelling-activated K influx and efflux were partially inhibited by 1 mM furosemide or bumetanide. K influx in swollen hemoglobin CC cells was not diminished when Na in the incubation medium was replaced with choline, indicating Na independence of the swelling-induced flux. Identical experiments with hemoglobin AA cells also demonstrated a swelling-induced increase in K flux, but the magnitude and duration of this increase were considerably less than that seen with hemoglobin ...

International Nuclear Information System (INIS)

The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H_2O_2(toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H_2O_2)-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H_2O_2(or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or ...

British Library Electronic Table of Contents (United Kingdom)

Abstract: The ability of melatonin as a potent antioxidant was used as a rationale for testing its antiapoptotic ability in normal cells. Recently, melatonin was shown to possess proapoptotic action by increasing reactive oxygen species in certain cancer cells. The modification of radiation-induced apoptosis by melatonin and the expression of apoptosis-associated upstream regulators were studied in normal mice splenocytes and Jurkat T leukemia cells. C57BL/6 mice were exposed to a single whole body X-ray radiation dose of 2 Gy with or without 250 mg/kg melatonin pretreatment. The Jurkat cells were divided into four groups of control, 1 mm melatonin alone, 4 Gy irradiation-only and melatonin pretreatment before irradiation. The highest level of apoptosis in the normal splenic white pulp was...

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BackgroundThe Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged....Full Text Available

UK PubMed Central (United Kingdom)

Unequal segregation of cell fate determinants at mitosis is a conserved mechanism whereby cell fate diversity can be generated during development. In Drosophila, each sensory organ...Full Text Available

UK PubMed Central (United Kingdom)

Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from...Full Text Available

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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, ...

Science.gov (United States)

Multicellular tumor spheroids (MCTS) are three dimensional cell culture systems induced by suspension culture. MCTS are widely used in cancer research because of their similarity to solid tumors. CaSki cells are derived from a metastatic cervical cancer containing human papillomavirus 16 (HPV16). Cell death of CaSki cells in MCTS has been previously reported, and our model is used to better characterize the mechanisms of cell death of HPV16-positive keratinocytes. In this study, we found that apoptosis of CaSki cells was induced by suspension culture along with the formation of MCTS after 24 h of incubation. In suspended CaSki cells, monoclonal antibodies blocking E-cadherin function inhibited MCTS formation and suppressed suspension-induced apoptosis in a dose-dependent manner. ...

British Library Electronic Table of Contents (United Kingdom)

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, na...

British Library Electronic Table of Contents (United Kingdom)

Colorectal cancer is the second most common cause of cancer death in the world and about half of the patients with colorectal cancer require adjuvant therapy after surgical resection. Therefore, the eradication of cancer cells via chemotherapy constitutes a viable approach to treating patients with colorectal cancer. In this study, the effects of bufalin isolated from a traditional Chinese medicine were evaluated and characterized in HT-29 and Caco-2 human colon cancer cells. Contrary to its well-documented apoptosis-promoting activity in other cancer cells, bufalin did not cause caspase-dependent cell death in colon cancer cells, as indicated by the absence of significant early apoptosis as well as poly(ADP-ribose) polymerase and caspase-3 cleavage. Instead, bufalin activated an autophagy...

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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...

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The expression of three c-onc genes (c-erb, c-myc, c-myb) was investigated in five cell lines established from fibrosarcomas induced with 20-methylcholanthrene (MCA) of Japanese quails. These cell lines showed low levels of the three c-onc genes, with the exception of two cell lines that accumulated moderate (MCAQ 1-4) and large amounts (MCAQ 3-5) of c-myc RNA. Molecular cloning and restriction endonuclease analyses indicated that expression of c-myc in these two cell lines were not associated with detectable rearrangements in the c-myc locus, that the size of the c-myc transcript (2.7 kb) in MCAQ 3-5 was similar to that of the normal c-myc messenger RNAs (mRNA) and that the transcriptional activatin observed in MCAQ 3-5 was not mediated by the LTR (long terminal repeat) of a proximate ALV (avian leukosis virus) provirus. Finally, when analyzed with the restriction enzymes Msp I and ...

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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 ...

International Nuclear Information System (INIS)

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

UK PubMed Central (United Kingdom)

Exercise training is known to induce an increase in free radical production potentially leading to enhanced muscle injury. Vitamins C and E are well known antioxidants that may prevent muscle cell damage....Full Text Available

UK PubMed Central (United Kingdom)

DNA double-strand breaks (DSBs) and other lesions occur frequently during cell growth and in meiosis. These are often repaired by homologous recombination (HR). HR may result in the formation of DNA...Full Text Available

UK PubMed Central (United Kingdom)

Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer...Full Text Available

UK PubMed Central (United Kingdom)

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary...Full Text Available

UK PubMed Central (United Kingdom)

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

UK PubMed Central (United Kingdom)

Copy number variants (CNVs) are an important component of genomic variation in humans and other mammals. Similar de novo deletions and duplications, or copy number changes (CNCs), are now known to be...Full Text Available

UK PubMed Central (United Kingdom)

ObjectiveTo evaluate the prognostic significance of adjuvant concurrent chemoradiotherapy-induced neutropenia with survival in patients with squamous cell carcinoma of the uterine...Full Text Available

UK PubMed Central (United Kingdom)

The ability to achieve tumor selective expression of therapeutic genes is an area that needs improvement for cancer gene therapy to be successful. One approach to address this is through the...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundWe have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial...Full Text Available

UK PubMed Central (United Kingdom)

Tubular membrane structures are widespread in eukaryotic cells, but the mechanisms underlying their formation and stability are not well understood. Previous work has focused on tube extrusion from...Full Text Available

UK PubMed Central (United Kingdom)

Host cells use metabolic signaling through the LXRα nuclear receptor to defend against Listeria monocytogenes infection. 25-Hydroxycholesterol is a natural ligand of LXRs that...Full Text Available

UK PubMed Central (United Kingdom)

As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a target gene of c-Myc...Full Text Available

UK PubMed Central (United Kingdom)

Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally-induced expression of neuronal plasticity utilizes an NMDA_R-dependent,...Full Text Available

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UK PubMed Central (United Kingdom)

Retinoic acid inducible gene I (RIG-I) is a pattern recognition receptor (PRR) responsible for detection of nucleic acids from pathogens in the cytoplasm of infected cells and induction of type I interferon...Full Text Available

UK PubMed Central (United Kingdom)

PurposeTo address the roles of the stromal derived factor-1 (SDF-1) α in the course of experimental corneal neovascularization (CNV).MethodsCNV...Full Text Available

UK PubMed Central (United Kingdom)

Cytokines produced by Th2 cells are responsible for the pathogenesis of asthma. Th1-biased immune responses caused by attenuated salmonella have the potential to relieve asthmatic symptoms. We evaluated...Full Text Available

UK PubMed Central (United Kingdom)

Tetherin (BST2/CD317) has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By...Full Text Available

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... Regine, Nader Hanna, Michael C. Garofalo, Austin Doyle, Susanne Arnold, Ritesh Kataria, Jacqueline Sims, Ming Tan, Mohammed Mohiuddin. ( ... ...

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BackgroundFor the detection of allergen-specific IgE in sera, solid-phase IgE-binding assays like the CAP test are commonly used. Although such immunochemical methods are very sensitive,...Full Text Available

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ObjectivesTo assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. MethodsProstate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potenti...

British Library Electronic Table of Contents (United Kingdom)

Abstract Purpose: To describe the pattern of expression of the cyclin-dependent kinase inhibitors (CDKIs) p16, p21 and p27, and the cell cycle in SRA 01/04 cells relative to contact inhibition. Methods: SRA 01/04 cells were grown to overconfluence under normal conditions. At various phases of the cell growth, cells were assayed by flow cytometry and Western blotting for the expression of CDKIs. Results: Expression of p16 was detected from early logarithmic growth to stationary phases, during which the number of cells in G0/G1 increased from 46 to 69%. Expression of p21 was detected only during the overgrowth phase, when 60% of the cells were in G0/G1. Expression of p27 was not observed in SRA 01/04 cells. Conclusions: p16 expression was likely mediated by G0/G1 arrest to induce contact inh...

Science.gov (United States)

Summary.? It is widely believed that hepatocellular cancer (HCC), especially HBV associated HCC, is highly resistant to chemotherapy. To investigate the molecular influence of HBx protein on multidrug resistance (MDR) in HCC and the potential role of the NF-?B pathway in this process. We established HBx-expressing cells by liposome-mediated transfection of the HBx into the HepG2 cell line. We found that HBx expression in HCC cells induces drug resistance against multiple drugs, a significantly lower apoptosis ratio in HepG2-HBx and HepG2.2.15 cells, compared with HepG2 and HepG2-3.1 cells (P?HCC cells were downregulated by IMD-0354 treatment, which is the NF-?B pathway inhibitor. Taken together, these results suggest that HBx protein might be one of the causes for the occurrence of MDR in HCC, and the NF-?B pathway might be involved in this ...

International Nuclear Information System (INIS)

The process of mouse skin tumor formation is subdivided into three operational stages. These stages include initiation, promotion and progression. Ionizing radiation has been found to be a weak initiating agent in the production of malignant squamous cell carcinomas, a complete carcinogen and an agent effective in causing tumor progression. Four skin tumor histologies have been seen with ionizing radiation: benign papillomas, squamous (SCC) and basal (BCC) cell carcinomas and fibrosarcomas. Distinct non-ras transforming genes have been detected in radiation initiated SCCs. A benign papilloma cell line (308) was used as a model system to study ionizing radiation induced progression. A variant 308 cell line (308 10 Gy 5) derived by irradiation of the parental 308 cell has been characterized. The 308 10 Gy 5 cells unlike the parental 308 ...

British Library Electronic Table of Contents (United Kingdom)

Wnt signaling negatively regulates adipocyte differentiation, and ectopic expression of Wnt-1 in 3T3-L1 cells induces several downstream molecules of Wnt signaling, including Wnt-1 inducible signaling pathway protein (WISP)-2. In this study, we examined the role of WISP-2 in the process of adipocyte differentiation using an in vitro cell culture system. In the differentiation of 3T3-L1 cells, WISP-2 expression was observed in growing cells and declined thereafter. In the mitotic clonal expansion phase of adipocyte differentiation, WISP-2 expression was transiently down-regulated concurrently with up-regulation of CCAAT/enhancer-binding protein d expression. Treatment of 3T3-L1 cells in the differentiation medium with lithium, an activator of Wnt signaling, inhibited the differentiation pro...

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

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Glycosaminoglycan synthesis was studied in cell populations of ultraviolet light-induced murine cutaneous fibrosarcoma cells under conditions of varying growth rates in vitro. After labeling with the precursors, /sup 3/H-glucosamine and /sup 35/SO/sub 4/, sulfated glycosaminoglycans recoverable by direct proteolysis of the culture monolayers increased approximately 5-fold on a per cell basis from sparsely populated, exponential cell cultures (greater than 85% of cells in S, G2, or M phases) to stationary cultures inhibited by high cell density (greater than 50% of cells in G1). Within this cell surface-associated material, the relative ratio of heparan sulfate to the chondroitin sulfates was approximately 60/40% under conditions of exponential growth; in the growth-arrested cultures, the reverse ...

Science.gov (United States)

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

UK PubMed Central (United Kingdom)

PurposeTo identify those metallothionein and α-crystallin/small heat-shock genes induced by toxic metals in human lens cells and to evaluate...Full Text Available

Science.gov (United States)

Ionizing radiation is a standard treatment for various human solid tumors. However, several clinical studies showed that a significant proportion of patients undergoing radiotherapy for hepatocellular carcinoma (HCC) develop intrahepatic and extrahepatic metastasis. Understanding of radiation-induced cancer cell invasiveness and behavior is essential and of great important for developing suitable treatment strategies to contain cancer spread. Therefore, in this study we evaluated the effectiveness of using swept source optical coherence tomography (SS-OCT) to monitor the enhancement of HCC cell invasiveness by radiation. SS-OCT images were acquired and recorded to obtain three-dimensional data sets per four hours in 48 hours after irradiating HepG2 cells with 7.5 Gy. The cell migration behavior in three-dimensional tissue models was quantified from images of ...

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Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg/sup 2 +/ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.

International Nuclear Information System (INIS)

Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 domain that is known to interfere with the ...

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With an ageing population the demand for cheap, efficient implants is ever increasing. Laser surface treatment offers a unique means of varying biomimetic properties to determine generic parameters to predict cell responses. This paper details how a KrF excimer laser can be employed for both laser-induced patterning and whole area irradiative processing to modulate the wettability characteristics and osteoblast cell response following 24h and 4 day incubation. Through white light interferometry (WLI) it was found that the surface roughness had considerably increased by up to 1.5mm for the laser-induced patterned samples and remained somewhat constant at around 0.1mm for the whole area irradiative processed samples. A sessile drop device determined that the wettability characteristics diffe...

International Nuclear Information System (INIS)

Studies have shown that CCl_4 administration to rats inhibits endoplasmic reticulum calcium pump activity and reduces the amount of calcium associated with subsequently isolated microsomal subcellular fractions. This report confirms that exposure of isolated hepatocytes to CCl_4 rapidly produces these effects in isolated parenchymal cells and demonstrates that when isolated hepacytes are exposed to CCl_4 calcium is rapidly released from cells. This release can be detected with a calcium ion-selective electrode when cells are incubated in a medium with low extracellular calcium. Calcium released from an intracellular pool(s) may initiate hepatotoxic changes in liver. (author).

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We have been investigating radiation-induced neoplastic transformants of C3H 10T1/2 mouse fibroblasts for evidence of heritable changes. C3H 10T1/2 cells were treated with 8 Gy X rays. After approximately 8 weeks of culture, type II/III foci were isolated from the monolayer using cloning rings. Cell lines developed from these foci, and clones established from these cell lines, were examined for DNA content. The isolated focus-derived populations and derived clones often display aneuploidy and/or polyploidization. In one instance a clone (derived from a single cell) displayed multiple polyploidies. During passage the ploidy of many of the anomalous populations gradually reverted to the ploidy of the non-neoplastically transformed state. The morphological features associated with the neoplastic transformation event were nevertheless retained. The results demonstrate that exposure to ...

International Nuclear Information System (INIS)

The role of the HCR system in the repair of prelethal lesions induced by UV light, #gamma# radiation and alkylating agents was studied in the Bacillus subtilis SPP1 phage, its heat sensitive mutants (N3, N73 nad ts_1) and corresponding infectious DNA. The survival of phages and their transfecting DNA after treatment with UV light is substantially higher in hcr"+ cells than in hcr cells, the differences being more striking in intact phages than in their transfecting DNA's. Repair inhibitors reduce survival in hcr"+ cells: caffeine lowers the survival of UV-irradiated phage SPP1 in exponentially growing hcr"+ cells but has no effect on its survival in competent hcr"+ cells; acriflavin and ethidium bromide decrease the survival of the UV-irradiated SPP1 phage in both exponentially growing and competent hcr"+ cells to the level of survival ...

International Nuclear Information System (INIS)

Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-[2-3H] inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total [3H]inositol phosphates [[3H]inositol mono-, di-, and triphosphates (IP, IP2, and IP3)] in FSH-treated cultures was 75-120% the levels in control cultures over the various time intervals studied. ...

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

Science.gov (United States)

A novel single-chain immunotoxin was constructed by combining a CD33-specific single chain Fv (scFv) antibody fragment with an engineered variant of Pseudomonas exotoxin A (ETA). The variant toxin carries the KDEL peptide at its C-terminus, a cellular peptide mediating improved retrograde transport to the endoplasmic reticulum. The purified recombinant fusion protein induced potent apoptosis of the human myeloid cell lines U937, HL-60 and THP-1. Up to 98% of U937 cells were eliminated after treatment for 72 h with a single dose of 500 ng/ml (c. 7 nmol/l). Killing was antigen-specific and occurred by apoptosis. A control protein, consisting of a CD19-specific scFv antibody fragment fused to the ETA-KDEL toxin, failed to induce death of the CD19-negative cell lines U937, HL-60 and THP-1. The CD33-ETA toxin also mediated apoptosis of fresh patient-derived acute myeloid leukaemia ...

International Nuclear Information System (INIS)

One rationale proposals to increase the efficiency of PDT is to combine photo-sensitization with other treatment modalities, including modulation of arachidonic acid metabolism. In combine treatment we examined the effects of 48 h and 24 h pre-treatment of cells with 5- lipoxygenase inhibitor MK-886 prior to photoactivation of hypericin on cell cycle distribution and DNA synthesis. All parameters were examined 24 hours after hypericin activation. Pre-treatment of HT-29 with 5-lipoxygenase inhibitor MK-886 followed by PDT resulted in most significant effects on cell cycle perturbations. Administration of MK-886 alone as well as combination of low doses MK-886 with hypericin induced S phase accumulation. Increasing of MK-886 concentration induced massive changes in the cell cycle progression. Pre-treatment of HT-29 cells with MK-886 alone (15 ...

British Library Electronic Table of Contents (United Kingdom)

The mammalian placenta consists of different trophoblast cell types that assist in the variety of functions required for the maintenance of pregnancy. In rodents, labyrinthine trophoblasts of the placenta are especially important, because they are capable of differentiating into fused labyrinthine cells, which form the feto-maternal exchange surface. Even though the molecular signals triggering labyrinthine trophoblast differentiation are poorly understood, transforming growth factor-b (TGF-b) has been shown to be present in the placental environment and alter trophoblast development. In this study, we investigated the effects of TGF-b on the differentiation of the labyrinthine trophoblast stem cell lines SM10 and HRP-1. RT-PCR analyses demonstrated that while the molecular expression of l...

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Photoluminescence spectroscopy measurements were carried out for silicon 50{mu}m BSFR space solar cells irradiated with 1MeV electrons with a fluence exceeding 1 x 10{sup 16} e/cm{sup 2} and 10MeV protons with a fluence exceeding 1 x 10{sup 13} p/cm{sup 2}. The results were compared with the previous result performed in a relative low fluence region, and the radiation-induced defects which cause anomalous degradation of the cell performance in such large fluence regions were discussed. As far as we know, this is the first report which presents the PL measurement results at 4.2K of the large fluence radiation irradiated silicon solar cells. (author)

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Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

International Nuclear Information System (INIS)

Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.

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The autoradiographic appearance of the gastric mucosa, 5 hours after administration of indomethacin, was investigated in 29 adult rats. Indomethacin induced superficial gastric erosions. Autoradiography demonstrated the presence of viable gastric cells (as deduced by their ability to incorporate 3H-cytidin, an RNA precursor) not only in the mucosa without erosions, but also in the mucosa underneath the superficial erosions. The results indicate that indomethacin induced gastric erosions are not the superficial expression of a necrotic process taking place in the full thickness of the gastric mucosa at a particular site. A lumen-borne mechanism appears to be responsible for the formation of erosive areas in the mucosa.

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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 ...

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Low temperature Nonphotochemical Hole Burning (NPHB) Spectroscopy of the dye rhodamine 800 (MF680) was applied for the purpose of discerning differences between cultured normal and carcinoma ovarian surface epithelial (OSE) cells. Both the cell lines were developed and characterized at the Mayo Clinic (Rochester, MN), with the normal cell line having been transfected with a strain of temperature sensitive Simian Virus 40 Large T Antigen (SV40) for the purpose of extending the life of the cell culture without inducing permanent changes in the characteristics of the cell line. The cationic lipophilic fluorophore rhodamine 800 preferentially locates in in situ mitochondria due to the high lipid composition of mitochondria and the generation of a large negative membrane potential (relative to the cellular cytoplasm) for oxidative phosphorylation. Results presented ...

British Library Electronic Table of Contents (United Kingdom)

Dissolved microcystins (MCs) are regularly present in water dominated by microcystin-producing, bloom-forming cyanobacteria. In vitro experiments with environmentally feasible concentrations (5 ? 10?7 M) of the three most common microcystins, MC-LR, MC-RR, and MC-YR, revealed that they influence the metabolism of different representative phytoplanktons. At light intensities that are close to the cyanobacterial bloom environment (50??mol m?2 s?1), they produce morphological and physiological changes in both microcystin-producing and -nonproducing Microcystis aeruginosa strains and also have similar effects on the green alga Scenedesmus quadricauda that is frequently present in cyanobacterial blooms. All three microcystin variants tested induce cell aggregation, increase in cell volume, and ...

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Experiments were performed to investigate the involvement of the cell membrane in the excision DNA repair process in Escherichia coli. Two membrane-binding drugs, procaine and phenethyl alcohol (PEA), inhibited liquid-holding recovery (LBR) in u.v.-irradiated E. coli wild-type and recA strains. In uvrB and polA strains where, after u.v.-irradiation, LHR was absent the two drugs had no effect. Both drugs markedly reduced the removal of u.v.-induced thymine dimers in the DNA of wild-type cells (H/r30). Analysis by alkaline sucrose gradients revealed that PEA inhibited the incision step in excision repair. In contrast, procaine had no effect on incision but apparently inhibited the late steps in excision repair. PEA dissociated DNA from the cell membrane, whereas procaine did not. The results suggest that the two drugs PEA and procaine inhibit LHR and the excision repair process operating on ...

British Library Electronic Table of Contents (United Kingdom)

Radiofrequency electromagnetic fields (EMF) are harmful to public health, but the certain anti-irradiation mechanism is not clear yet. The present study was performed to investigate the possible protective effects of green tea polyphenols against electromagnetic radiation-induced injury in the cultured rat cortical neurons. In this study, green tea polyphenols were used in the cultured cortical neurons exposed to 1800?MHz EMFs by the mobile phone. We found that the mobile phone irradiation for 24?h induced marked neuronal cell death in the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and protective effects of green tea polyphenols on the injured cortical neurons were demonstrated by testing the content ...

Science.gov (United States)

Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and ?-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the ...

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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.

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Since microwaves are used in human cancer therapy, information on specific biological effects of microwaves at elevated temperatures is important. To help supply this information, we exposed mammalian cells (CHO) and bacteria (Serratia marcescens) to hyperthermal temperatures (43, 44, and 45/sup o/C for CHO and 48, 49, and 50/sup o/C for the bacteria) with and without microwave irradiation. Temperature control was maintained by a refrigeration-reheat system and high-velocity water recirculation. The 2450-MHz microwave source was operated in a pulsed mode with power density up to 500 mW/cm/sup 2/. As expected, the survival curve slopes for both cell types increased rapidly with temperature, doubling for each degree Celsius. Microwave irradiation produced no significant change in extrapolation number for either cell type. However, survival curves of CHO cells which received microwaves were steeper by a ...

International Nuclear Information System (INIS)

Nitroaromatic radiosensitizers become metabolically bound preferentially to hypoxic cells and at least 10/sup 9/ adducts/cell can be tolerated as non-toxic. EMT-6 tumor cells have been incubated in hypoxia in the presence of /sup 3/H-Misonidazole and /sup 125/I-Azomycin Riboside for various times and the amount of /sup 3/H or /sup 125/I bound/cell was determined. Cells were stored as monolayers at 25"0C for up to 96 hr to accumulate radioactive decays and transferred at various times to 37"0C for colony-forming assays. No radiation inactivation was measured in cells which had incorporated at least 10/sup 6/ /sup 3/H or 10/sup 5/ /sup 125/I atoms. Previous studies had shown that -- 1% of MISO adducts to EMT-6 cells was associated with cellular DNA. These data indicate that the radiation-induced damage produced by these ...

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Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not ...

International Nuclear Information System (INIS)

The evolution of metallic substance atomic structure is studied on temperature variation including crystal heating up to melting points, a crystal- liquid phase transition and initiation of a high-density liquid specific structure. It is marked that heat induced changes of simple metal structure can be described as changes around a natural elementary cell which is common for both a crystal and a liquid and consists of a central atom and Z_1 atoms of the first coordination sphere. On this basis the vacancy model of melting is verified. Concentrations of melting vacancies are determined by coordination numbers in the form of Z_1/(1+Z_1)"2 which are the same for both a crystal and a natural elementary cell. The size of natural elementary cells is in an agreement with that of the coordination sphere featured in the liquid and phase transition statistical theory. Calculated data are given for a number of ...

British Library Electronic Table of Contents (United Kingdom)

This study correlates the post start cell performance and impedance with the cold start process in the subzero environment. The sequential failed cold starts are deliberately conducted as well as the start at small current density. Here the failed cold start means the cell voltage drops to or below zero within very short time during the start process. It is found that there are reversible performance losses for the sequential failed cold starts, while not obvious degradation and no recovery happen for the start at small current density. Using the thin film and agglomerate model, it is confirmed that this is due to the water blocking effect. Comparing the results from different start processes, a model with respect to the shifting of reactive region within the catalyst layer is applied to e...

British Library Electronic Table of Contents (United Kingdom)

Objective: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. Methods: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage,...

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Abstract Objective. Anti-TNF-a antibodies has been suggested to modulate regulatory T cell (Treg) percentages in rheumatoid arthritis, but results from studies of Crohn's disease (CD) are conflicting. We investigated dynamic changes of circulating Tregs in CD during treatment with the anti-TNF-a-antibody adalimumab (Humira, Abbott Laboratories A/S, Emdrupvej 28C, DK-2100 Copenhagen). Material and methods. Blood samples from 26 CD patients were analysed using flow cytometry before and 1 and 26 weeks after initiation of adalimumab treatment to determine the percentage of Tregs among CD4++ T cells. Results. In spite of a significant decline in disease activity scores and biochemical markers of inflammation, during the first week of treatment, we did not observe early modulating effects of ada...

UK PubMed Central (United Kingdom)

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis,...Full Text Available

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Abstract Overall Numbers Small, But Study Finds SSRI Exposure, Autism Link Additional Drug Safety, Efficacy Data Needed for Pediatric Bipolar Disorder SGA Safety and Efficacy in Children and Adolescents Aripiprazole Safety and Tolerability for Irritability in Autism No Lisdexamfetamine Effect on Sleep Disturbances in Children With ADHD Sickle Cell Disease With Comorbid Depression Homeopathy in Psychiatry Manic Symptoms Induced by Marijuana in a Healthy Adolescent New Warnings Safety Labeling Changes

UK PubMed Central (United Kingdom)

While a great deal of evidence has directly implicated the importance of O6-alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this lesion...Full Text Available

UK PubMed Central (United Kingdom)

We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone...Full Text Available

UK PubMed Central (United Kingdom)

Despite intensive efforts, the intracellular signaling pathways that mediate apoptosis remain unclear. The human B lymphoma cell line, B104, possesses characteristics that make it an attractive model...Full Text Available

Science.gov (United States)

Adolescent exposure to anabolic androgenic steroids (AAS) alters the development and activity of the glutamate neural system in the latero-anterior hypothalamus (LAH) in hamsters (Mesocricetus auratus); that is, an important neural component of the adolescent AAS-induced aggressive response. In this article, we used retrograde tracing to investigate glutamate-specific alterations in the connections between the LAH and several other nuclei implicated in adolescent AAS-induced aggression. Briefly, hamsters were treated with AAS or sesame-oil control during adolescence and then microinjected with retrograde tracer into the medial amygdala (MeA), lateral septum (LS), or bed nucleus of the stria terminalis (BNST). Brains were then processed for vesicular glutamate transporter 2 (VGLUT2) and examined for AAS-induced changes in the number VGLUT2 cells containing retrograde tracer (VGLUT2/tracer) within the ...

UK PubMed Central (United Kingdom)

X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare inherited disorder characterized by mild anemia and ataxia. XLSA/A is caused by mutations in the ABCB7 gene, which encodes...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

This thesis deals with the evaluation of Solar Grade Silicon (SoG-Si) purified by different techniques, and also the fabrication and characterization of high efficiency and advanced bifacial solar cells. In the beginning of Chapter 1, various SoG-Si production methods relevant for this work are qualitatively described. The three feedstock materials used in this work are from the Fluidized Bed Reactor (FBR) process, metallurgical feedstock-I and feedstock-II process. In metallurgical feedstock-I, the lifetime of the minority charge carriers in multicrystalline silicon (mc-Si) samples at the grain boundaries are found to be higher than the grains themselves possibly due to lower resistivities in the grain boundaries. The efficiency of the best solar cell obtained using the mc-Si metallurgical feedstock-I is 16.1%. It has been identified that the fast light induced degradation, whose magnitude is lower than that of a reference ...

International Nuclear Information System (INIS)

Radioactive particles as well as x irradiation from an external source has been used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In order to clarify effects of ionizing irradiation on synovial cells, radioactive gold ("1"9"8Au) and yttrium ("9"0Y) were added to fibroblast cultures derived from human synovial membranes. Other cultures were irradiated by a Picker x-ray machine. Fibroblast growth and hyaluronic acid production were measured. Radioactive gold and yttrium particles induced a significant increase of hyaluronic acid synthesis rate (pg/cell/day) and inhibited fibroblast growth. Fibroblasts continued to overproduce hyaluronic acid and to show growth inhibition 3 weeks after irradiation with radioactive gold. Hydrocortisone inhibited hyaluronic acid overproduction induced by radioactive gold. Overproduction of hyaluronic acid induced ...

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We describe the isolation and genetic characterization of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutations in the phage P22 mnt repressor gene cloned in plasmid pBR322. Mutations in the mnt repressor gene or its operator on this plasmid, pPY98, confer a tetracycline resistance phenotype, whereas the wild-type plasmid confers tetracycline sensitivity. Cells carrying pPY98 were briefly exposed to MNNG to give 20 to 40% survival and a 50- to 100-fold increase in tetracycline-resistant cells. DNA sequence analysis showed that 29 to 30 MNNG-induced mutations were GC-to-AT transitions and one was an AT-to-GC transition. About 80% of the mutations are in three hotspots. This mutation spectrum is consistent with the proposed mechanism of mutagenic action of MNNG, which involves mispairing of an alkylated base, O/sup 6/-methylguanine. The mnt gene may be a useful target for determining ...

British Library Electronic Table of Contents (United Kingdom)

The levels of General Transcription Factor (TF) IIA were examined during mammalian brain development and in rat embryo fibroblasts and transformed cell lines. The large TFIIA subunit paralogues ab and t are largely produced in unsynchronized cell lines, yet only TFIIA ab is observed in a number of differentiated tissue extracts. Steady-state protein levels of the TFIIA t, ab, and g subunits were significantly reduced when human embryonal (ec) and hepatic carcinoma cell lines were stimulated to differentiate with either all-trans-retinoic acid (ATRA) or sodium butyrate. ATRA-treated NT2-ec cells required replating to induce a neuronal phenotype and loss of detectable TFIIA t and g proteins. High levels of TFIIA t, ab, and g and Sp factors were identified in extracts from human fetal and rat...

DEFF Research Database (Denmark)

Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non-dividing cells. Here we overcome this problem by using two mutants that bypass the nutritional requirements and respond to the M-factor mating pheromone in rich medium. The first mutant lacks the cyr1 gene which encodes adenylate cyclase and these cells contain no measurable amounts of cAMP. When M-factor is added to a growing h+ cyr1- strain it causes a transient G1 arrest of cell division, transcription of mat1-Pm, and elongation of the cells to form shmoos. The second mutant contains the temperature-sensitive pat1-114 allele. At 30 degrees C this mutant was previously shown not only to bypass the nutritional signal but also to stop growing ...

British Library Electronic Table of Contents (United Kingdom)

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, a...

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Natural sunlight induces a genotoxic response in cultured CHO cells pre-treated with shale oil retort process water. Near ultraviolet light (NUV) component of the solar spectrum is the apparent radiation responsible for photoactivation. Cultured human skin fibroblasts are acutely sensitive to the genotoxic effects of photoactivated process water. The mutagenic potential of photoactivated process water in human cells is the same as that witnessed for an equivalent killing dose of the potent skin carcinogen FUV. DNA repair processes are involved in modulating genotoxic effects of this photo-induced process. The exact magnitude of the potential health-related and environmental risks resulting from photoactivation of retort process waters and other oil shale by-products is unassessed at this time. Our demonstration that a significant rate of mutation occurs in cultured human cells ...

British Library Electronic Table of Contents (United Kingdom)

Thymic epithelial cells (TECs) constitute a major component of the thymic stroma which provides a microenvironment critical for developing thymocytes. We have previously demonstrated that doxycycline (Dox), a tetracycline derivative, enhances the proliferation of the mouse thymic epithelial cell line 1 (MTEC1) via MAPK/ERK signal pathway. Herein we provide evidence that Dox also has profound impact on the cytokine production by MTEC1. Specifically, the expression of IL-6 and GM-CSF, both at mRNA and protein levels, was found to be increased in a time- and dose-dependent manner with the addition of Dox. Western blotting analysis revealed that treatment with Dox-induced phosphorylation of the p65 subunit of NF-kB and ERK. Notably, Dox-induced up-regulation of IL-6 and GM-CSF was largely abol...

International Nuclear Information System (INIS)

The addition of paraquat (methyl viologen) to a growing culture of Escherichia coli K-12 led within 1 hr to a 10- to 20-fold increase in the level of endonuclease IV, a DNase for apurinic/apyrimidinic sites. The induction was blocked by chloramphenicol. Increases of 3-fold or more were also seen with plumbagin, menadione, and phenazine methosulfate. H_2O_2 produced no more than a 2-fold increase in endonuclease IV activity. The following agents had no significant effect: streptonigrin, nitrofurantoin, tert-butyl hydroperoxide, #gamma# rays, 260-nm UV radiation, methyl methanesulfonate, mitomycin C, and ascorbate. Paraquat, plumbagin, menadione, and phenazine methosulfate are known to generate superoxide radical anions via redox cycling in vivo. A mutant lacking superoxide dismutase was unusually sensitive to induction by paraquat. In addition, endonuclease IV could be induced by merely growing the mutant in pure O_2. The levels of endonuclease IV in uninduced or ...

International Nuclear Information System (INIS)

IL-4-induced Stat6 signaling is active in a variety of cell types and plays a role in cell proliferation/growth and resistance to apoptosis. Using EMSA, we identified differential IL-4/Stat6 activities in colorectal cancer cell lines, HT-29 being active Stat6"h"i"g"h phenotype and Caco-2 being defective Stat6"n"u"l"l phenotype, respectively. Active Stat6"h"i"g"h HT-29 cells exhibited resistance to apoptosis by flowcytometry and aggressive metastasis by Transwell assay compared with defective Stat6"n"u"l"l Caco-2 cells. Comparing one another using RT-PCR, Stat6"h"i"g"h HT-29 cells expressed more mRNA of anti-apoptotic and pro-metastatic genes Survivin, MDM2, and TMPRSS4, while Stat6"n"u"l"l Caco-2 cells expressed more mRNA of pro-apoptotic and anti-metastatic genes BAX, CAV1, and P53, respectively. This is the first study ...

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The COOH-terminus of telomerase reverse transcriptase (hTERT) has been shown to participatein the nuclear translocation of TERT. Here, we constructed plasmids expressing the COOH-terminal M(r) 27,000 polypeptide of hTERT (hTERTC27) withthe telomerase RNA-binding domains and the reverse transcriptase domains deleted. We showed that ectopic overexpression of this polypeptide caused a defect in telomere maintenance in hTERT-positive HeLa cells, which led to senescence-like growth arrest and apoptosis. The hTERTC27 appears to work by inducing telomere dysfunction, exemplified by significantly increased anaphase chromosome end-to-end fusion events in transfected cells. Significantly, it had no effect on the cellular telomerase enzymatic activity or telomere length. The in vivo effect was further demonstrated as HeLa cells stably expressing hTERTC27 have significantly lower growth rate and reduced ...

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The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression ...

International Nuclear Information System (INIS)

In the use of doxorubicin and radiation for treatment of human malignant tumors in vivo, the relationship between treatment-induced apoptosis and Ki-67 labeling index was investigated. Four human tumor xenografts (ependymoblastoma, NNE; primitive neuroectodermal tumor, YKP; small cell lung carcinoma, GLS; glioblastoma, KYG) were transplanted under the skin of thigh of the nude mice (BALB/cA JcL-nu). The mice were given a single radiation dose of 1 Gy, or doxorubicin alone intraperitoneally at a dose of 8 mg/kg. After treatment, sections of tumor specimens were prepared from paraffin-embedded tissues. Hematoxylin and eosin staining, TUNEL staining, and immunohistochemical analysis of Ki-67 were performed. In NNE, apoptotic cells appeared most frequently after treatment compared with all other tumors, and the incidence of apoptosis in the radiation-treated group was much higher than in the doxorubicintreated group. As the ...

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Spice extracts under the form of essential oils were tested for their efficiency to increase the relative radiosensitivity of Listeria monocytogenes and Escherichia coli O157H7 in culture media. The two pathogens were treated by gamma-irradiation alone or in combination with oregano essential oil to evaluate their mechanism of action. The membrane murein composition, and the intracellular and extracellular concentration of ATP was determined. The bacterial strains were treated with two irradiation doses: 1.2 kGy to induce cell damage and 3.5 kGy to cause cell death for L. monocytogenes. A dose of 0.4 kGy to induce cell damages, 1.1 kGy to obtain viable but nonculturable (VBNC) state and 1.3 kGy to obtain a lethal dose was also applied on E. coli O157H7. Oregano essential oil was used at 0.020% and 0.025% (w/v), which is the minimum inhibitory concentration (MIC) for L. ...

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Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the ...

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The effect of X-irradiation on production of MUC1 was studied with human colon carcinoma HT-29 cells. As evaluated by immunocytochemical staining, the percentages or MUC1-positive cells in cells at 4 days after 6 Gy irradiation and in unirradiated control cells were 52#+-#3.5% (n=6) and 26#+-#2.8% (n=6), respectively. Flow-cytometric analysis of living cells showed that MUC1 began to rise from day 1, reaching a plateau by day 4 after 6 Gy irradiation. Western blot analysis with monoclonal antibody MY.1E12 against glycosylated MUC1 (mature form) showed dose-dependent increases of two bands (500 and 390 kDa) corresponding to two polymorphic MUC1 alleles. Premature forms of MUC1 (350 and 240 kDa) were detectable with monoclonal antibody HMFG-2 only in irradiated cells, suggesting that new core protein synthesis had been induced. The ...

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Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian ...

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In defining criteria for good protection against ionizing radiation, it is important to assess quantitatively the likely risk of any radiation exposure. The 'somatic' risks to the individual result mainly from induction of cancer in the organs irradiated, and these risks can now be estimated on the basis of numerous detailed epidemiological surveys of exposed human populations. Estimates of the risk of hereditary effects, from genetic changes induced in germ cells, are based largely on the frequency with which such effects are induced in other species. In both cases the risk at very low dose can be inferred using knowledge of the way in which radiation damage is caused in tissues. Coherent systems of radiation protection are based on a restriction of doses to the whole body and to individual organs, such that the induction of cancer and genetic harm is infrequent, and the threshold dose for causing other, 'non-stochastic', ...

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We describe the analysis of forward mutations induced in the tetracycline resistance gene of the plasmid pBR322 by directing the reaction of the carcinogen N-acetoxy-N-2-acetylaminofluorene (N-AcO-AAF) to a small restriction fragment (BamHI, SalI) that is located in the proximal part of the antibiotic-resistance gene. Mutant plasmids obtained both in wild type and excision repair deficient (uvrA) bacterial cells are compared. Preliminary data showing the distribution of the -AAF adducts along this restriction fragments are discussed in relation to the observed spectrum of mutations. 20 references, 4 figures.

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Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...

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Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant apoptotic response in cells ...

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Abstract Sam68 (Src-associated protein in mitosis 68-kDa) is a multifunctional protein, known to govern cellular signal transduction, transcription, RNA metabolism, proliferation, apoptosis, and HIV-1 replication. Although intrinsic mechanisms that modulate Sam68 function are beginning to emerge, the regulatory events contributing to its expression remain elusive. We previously reported that heat shock protein-22 (Hsp22) antagonizes Sam68 function in rev-response element (RRE)-mediated gene expression. We now demonstrate that Sam68 levels correlate inversely with Hsp22 in a variety of cells, including U87, Jurkat, 293T, and U-937. In U87 glioblastoma cells, which contained high levels of Hsp22 than other cell lines tested, Hsp22 knockdown dramatically increased both Sam68 mRNA and protein,...

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The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose ...

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In this work, a three-dimensional multiphase non-isothermal model incorporated with a capillary-extended sub-model in gas channels is used to investigate the coupled phenomena of water and thermal transport in proton exchange membrane fuel cells. Distributions of water and temperature along the flow path in the channel are highlighted and the pros and cons of various operating temperatures are elaborated. In addition, this work also sheds light on the impacts of temperature variations of bipolar plates induced by non-uniform cooling conditions, which have been overlooked by most previous works. An important phenomenon of water distribution, dry-out at inlets and flooding at outlets (DIFO), is observed and this non-uniform distribution is revealed to be greatly influenced by the operating t...

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Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.

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Abstract Herpesvirus saimiri (HVS) causes acute lymphoma and leukemia upon experimental infection of various monkey species. HVS strain C488 is also capable of transforming human T-lymphocytes to stable growth in culture. The most susceptible species for oncogenesis are New World primates, in particular the cottontop tamarin (Saguinus oedipus). However, Old World monkeys such as macaques are the most used animal model for the close-to-human situation. The limited data on HVS infection in Old World monkeys prompted us to investigate susceptibility to infection and disease induction by HVS in macaques. After having established that rhesus macaques can be infected productively, and that rhesus T-cells can be transformed in vivo by HVS, we observed induction of lymphoma in all inoculated anima...

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Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animals exhibiting altered valu...

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A one-dimensional, steady-state, two-phase direct methanol fuel cell (DMFC) model is developed to precisely investigate complex physiochemical phenomena inside DMFCs. In this model, two-phase species transport through the porous components of a DMFC is formulated based on Maxwell-Stefan multi-component diffusion equations, while capillary-induced liquid flow in the porous media is described by Darcy's equation. In addition, the model fully accounts for water and methanol crossover through the membrane, which is driven by the effects of electro-osmotic drag, diffusion, and the hydraulic pressure gradient. The developed model is validated against readily available experimental data in the literature. Then, a parametric study is carried out to investigate the effects of the operating temperat...

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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 fluidity was supported by: ileal contraction that was induced by ...

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In isolated rat adipocytes, insulin inhibits lipolysis to a greater extent than would be predicted by the decrease in (-/+)cAMP activity ratio of cAMP-dependent protein kinase (A-kinase), from which it was speculated that insulin promotes the dephosphorylation of hormone-sensitive lipase. They have examined the phosphorylation state of cellular proteins under conditions of varying A-kinase activities in the presence and absence of insulin. Protein phosphorylation was determined by SDS-PAGE electrophoresis of extracts from /sup 32/P-loaded cells; glycerol and A-kinase activity ratios were measured in the cytosolic extracts from control, non-radioactive cells. Increased protein phosphorylation in general occurred over the same range of A-kinase activity ratios, 0.1-0.3, associated with increased glycerol release. The insulin-induced decrease in lipolysis was associated with a decrease in the /sup 32/P content of several ...

International Nuclear Information System (INIS)

The present study sought a biochemical explanation for retarded brain development in the heterozygous offspring of the phenylketonuric (PKU) mother. Two rat models of simulated maternal PKU, one induced by p-chloropheylalanine and phenylalanine and the other by phenylacetate, were employed in this investigation. Maternal PKU had no influence on cerebral concentrations of DNA, protein, and cholesterol, which were normal in the 2 d old pup. However, there was a noticeable disruption of the normal ganglioside pattern and a significant reduction of sialoglycoproteins. Concomitant with a delayed drop in the gangliosides Q/sub 1b/ and D_3, was a slower rise in M_1 and D/sub 1a/. At least 66% of sialoglycoproteins located on SDS-PAGE gel chromatograms, by radioactivity incorporated in vivo from radiolabeled N-acetylmannosamine and by ("3H) sialic acid released by neuraminidase from periodate-("3H) borohydride labeled glycoproteins, have mobilites of the ...

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For most cells there exists an optimum cooling rate. Both supraoptimal rates and suboptimal rates can be very damaging. The optimal rate varies enormously from less than or equal to 1/sup 0/C/min for mammalian preimplantation embryos to greater than or equal to 800/sup 0/C/min for the human red cell. Death at supraoptimal rates is the result of the formation of intracellular ice and its recrystallization during warming. Intracellular ice occurs when cells are cooled too rapidly to allow them to equilibrate by the osmotic withdrawal of intracellular water. The definition of too rapid depends chiefly on the size of the cell and its permeability to water. Death at suboptimal rates is a consequence of the major alterations in aqueous solutions produced by ice formation. The chief effects are a major reduction in the fraction of the solution remaining unfrozen at a given temperature and a major increase in ...

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Polymerizing effects of high energy radiation has been found suitable for preparation of wood-polymer composites. In the present work after evaluating polymer products that have been obtained by irradiation method, wood-polymer composites have been prepared by in situ polymerization of vinyl acetate, acrylic acid and acrylic acid/styrene mixture using two samples of Iranian hardwoods, Beech and Hornbeam. These woods and their composites have been tested for their physical and mechanical properties. The results have shown that chemical bonding between polymer and the cell wall component lead to better strength properties in the composites. (author).

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The authors have demonstrated that induction of mitogenesis in human T lymphocytes is associated with the tyrosine phosphorylation of a 66KD soluble substrate-TPP 66. Since DMSO has been shown to be a non-specific stimulator of tyrosine protein kinases they have examined the effect of DMSO on both activation and tyrosine phosphorylation in human T cells. Human peripheral blood T lymphocytes were isolated by dextran sedimentation, Ficol/Paque centrifugation and nylon wool filtration. Phosphorylation was performed in cells incubated with ["3"2P] orthophosphate followed by DMSO for 30 min. TPP 66 was identified by 2-D PAGE, autoradiography, and HV electrophoresis of the hydrolyzed protein. Concentrations of DMSO from 1% to 50% induced the tyrosine phosphorylation of TPP 66 with maximal stimulation seen at 20%. DMSO alone did not activate the T cells (measured by ["3H] thymidine incorporation) when tested ...

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Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells (SMCs) for constructing tissue-engineered vascular grafts. However, the details of how specific combinations of vascular microenvironmental factors regulate MSCs are not well understood. Previous studies have suggested that both mechanical stimulation with uniaxial cyclic strain and chemical stimulation with transforming growth factor {beta}1 (TGF-{beta}1) can induce smooth muscle markers in MSCs. In this study, we investigated the combined effects of uniaxial cyclic strain and TGF-{beta}1 stimulation on MSCs. By using a proteomic analysis, we found differential regulation of several proteins and genes, such as the up-regulation of TGF-{beta}1-induced protein ig-h3 (BGH3) protein levels by TGF-{beta}1 and up-regulation of calponin 3 protein level by cyclic strain. At the gene expression level, BGH3 was ...

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Although low-energy ion radiation has been proven to have a wide range of biological effects and led to fruitful achievements as a new mutagenic source for genetic modification, there still exist some disputes about its mutagenic mechanisms because of its short-penetrating property. In present research, Arabidopsis thaliana transgenic for GUS recombination substrate was used to evaluate the genomic instability induced by irradiations of alpha particle (3.3MeV) and Low-energy-Argon ion (30 KeV). A pronounced effects of alpha particle irradiation to Arabidopsis thaliana seedlings and Argon ion irradiation to seeds on the somatic homologous recombination frequency (sHRF) were reported. The sHRFs increased 1.88-fold and 2.42-fold, respectively, which indicated that the short-penetrating radiation could effectively induce the plant genomic instability in either dry seeds or seedlings with active metabolism. The local alpha particle irradiation of ...

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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 impair a sodium-independent process, and has ...

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Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...

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Fish retinal ganglion cells (RGCs) can survive and regrow their axons after optic nerve injury. Injured RGCs express anti-apoptotic proteins, such as Bcl-2, after nerve injury; however, upstream effectors of this anti-apoptotic protein are not yet fully understood. Heat shock proteins (HSPs) play a crucial role in cell survival against various stress conditions. In this study, we focused on HSP70 expression in the zebrafish retina after optic nerve injury. HSP70 mRNA and protein levels increased rapidly 2.3-fold in RGCs by 1-6 h after injury and returned to control levels by 1-3 days. HSP70 transcription is regulated by heat shock factor 1 (HSF1). HSF1 mRNA and phosphorylated-HSF1 protein rapidly increased by 2.2-fold in RGCs 0.5-6 h after injury. Intraocular injection of HSP inhibitor I s...

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Pregnant rats in 11d and 16d of their pregnancy were given one-off whole body exposure by "1"3"7Cs #gamma# rays to 0.2, 0.4, 0.9 and 2.0 Gy, respectively. Changes were observed in conditioned drinking response and cerebrum hippocampi cone cell number of the baby rats exposed to the #gamma# rays in different periods of their embryo development. As a result, that pregnant rats exposed to "1"3"7Cs #gamma# rays in different pregnant periods may induce significant decrease in cerebrum hippocampi cone cell number and achieving rate of conditioned drinking response of the babies. The dose-response relationship can be described by Y=a-b log_1_0D. The achieving rate of conditioned drinking response were significantly correlated to cerebrum hippocampi cone cell number in the babies, and the achieving rate of conditioned drinking response of the babies exposed at pregnant 11d was lower than others exposed at ...

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Described herein are the results of the FY1994 research program for structural defects of silicon-based amorphous materials for solar cells. The study on light generation defects of the a-Si:H system and rejuvenation process by annealing establishes the effects of light irradiation time on changed neutral dangling bond density as a result of light irradiation at varying temperature of 77K, room temperature and 393K. The study on annealing to rejuvenate light generation defects of various types of a-Si-H systems establishes the activation energy distribution with respect to annealing to remove light-induced defects, showing that hydrogen affects the distribution of light-induced defects. The study on decaying process of light-induced ESR for undoped and N-doped a-Si:H systems observes the decaying process of light-induced ESR, after light is cut off, extending for a period of several ...

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Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently ...

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BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing ...

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Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ...

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In order to demonstrate possible specific effects of microwaves at the cellular level V-79 Chinese hamster cells were exposed to 2.45-GHz radiation at power levels of 20-200 mW/cm2 and at specific absorption rates of 10-100 mW/g. Intracellular cytoplasmic changes were observed by fluorescence polarization using a method based on the intracellular enzymatic hydrolysis of nonfluorescent fluorescein diacetate (FDA). At levels of absorbed energy below 90 J/g, modifications of microviscosity and mitochondrial state were absent, but a slight stimulation of enzymatic hydrolysis of FDA was observed which may be explained by microwave-induced alterations of cellular membranes possibly due to differences in heating pattern of microwaves compared to water-bath heating. At levels of absorbed energy above 90 J/g, the decrease of enzymatic hydrolysis of FDA, increase in degree of polarization, and increase of permeation of the fluorescent marker correlated ...

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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 relationships analysis demonstrated that ...

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This study investigated whether estradiol influenced the survival of new granule neurons, independent of altering cell proliferation, in the adult rodent dentate gyrus and whether estradiol-induced changes in new neuron number relate to any observed changes in hippocampus-dependent behavior. To test whether estradiol specifically promotes the survival of new neurons we injected castrated adult male meadow voles with the cell synthesis marker bromodeoxyuridine (BrdU; 50 mg/kg) twice on day 0 and then injected either estradiol (10 microg) or vehicle for 5 consecutive days either over days 1-5, days 6-10 or days 11-15 and perfused them on day 16. Estradiol doubled the number of hippocampal BrdU-labeled neurons but only when administered during a discrete period (days 6-10; P< or =0.01) when most new neurons extend their axons [J Comp Neurol 413 (1999) 146]. To test whether the estradiol-induced increase ...

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Large-scale field tracer experiments have been conducted on Ulchin, Wolsung and Daeduk sites for the purpose of validating FADAS and of analyzing the environmental characteristics around the nuclear sites. The most influential factor in atmospheric dispersion is the meteorological condition. During the experiment, meteorological data were measured on the release point and the selected positions among sampling points. Once radioactive materials are released to the atmosphere, members of public may be exposed through the environmental media such as air, soil and foods. Therefore, to protect the public, adequate countermeasures should be taken at due time for those exposure pathways. both processes, of justification and optimization are applied to a countermeasure simultaneously for decision-making. The work scope of Biological research for the radiation protection had contained the search of biological microanalytic methods for assessing the health effect by {gamma}-radiation and toxic ...

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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 ...

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Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including innate immune responses in plants. However, the mechanism of the E3 ligase involvement in plant innate immunity is unclear. We report that a rice gene, OsBBI1, encoding a RING finger protein with E3 ligase activity, mediates broad-spectrum disease resistance. The expression of OsBBI1 was induced by rice blast fungus Magnaporthe oryzae, as well as chemical inducers, benzothiadiazole and salicylic acid. Biochemical analysis revealed that OsBBI1 protein possesses E3 ubiquitin ligase activity in vitro. Genetic analysis revealed that the loss of OsBBI1 function in a Tos17-insertion line increased susceptibility, while the overexpression of OsBBI1 in transgenic plants conferred enhanced resi...

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Treatment Induced Hypertension