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Sample records for activityin base excision

  1. Metal inhibition of human alkylpurine-DNA-N-glycosylase activityin base excision repair

    Wang, Ping; Guliaev, Anton B.; Hang, Bo

    2006-02-28

    Cadmium (Cd{sup 2+}), nickel (Ni{sup 2+}) and cobalt (Co{sup 2+}) are human and/or animal carcinogens. Zinc (Zn{sup 2+}) is not categorized as a carcinogen, and rather an essential element to humans. Metals were recently shown to inhibit DNA repair proteins that use metals for their function and/or structure. Here we report that the divalent ions Cd{sup 2+}, Ni{sup 2+}, and Zn{sup 2+} can inhibit the activity of a recombinant human N-methylpurine-DNA glycosylase (MPG) toward a deoxyoligonucleotide with ethenoadenine (var epsilonA). MPG removes a variety of toxic/mutagenic alkylated bases and does not require metal for its catalytic activity or structural integrity. At concentrations starting from 50 to 1000 {micro}M, both Cd{sup 2+} and Zn{sup 2+} showed metal-dependent inhibition of the MPG catalytic activity. Ni{sup 2+} also inhibited MPG, but to a lesser extent. Such an effect can be reversed with EDTA addition. In contrast, Co{sup 2+} and Mg{sup 2+} did not inhibit the MPG activity in the same dose range. Experiments using HeLa cell-free extracts demonstrated similar patterns of inactivation of the var epsilonA excision activity by the same metals. Binding of MPG to the substrate was not significantly affected by Cd{sup 2+}, Zn{sup 2+}, and Ni{sup 2+} at concentrations that show strong inhibition of the catalytic function, suggesting that the reduced catalytic activity is not due to altered MPG binding affinity to the substrate. Molecular dynamics (MD) simulations with Zn{sup 2+} showed that the MPG active site has a potential binding site for Zn{sup 2+}, formed by several catalytically important and conserved residues. Metal binding to such a site is expected to interfere with the catalytic mechanism of this protein. These data suggest that inhibition of MPG activity may contribute to metal genotoxicity and depressed repair of alkylation damage by metals in vivo.

  2. Mitochondrial base excision repair assays

    Maynard, Scott; de Souza-Pinto, Nadja C; Scheibye-Knudsen, Morten;

    2010-01-01

    The main source of mitochondrial DNA (mtDNA) damage is reactive oxygen species (ROS) generated during normal cellular metabolism. The main mtDNA lesions generated by ROS are base modifications, such as the ubiquitous 8-oxoguanine (8-oxoG) lesion; however, base loss and strand breaks may also occur....... Many human diseases are associated with mtDNA mutations and thus maintaining mtDNA integrity is critical. All of these lesions are repaired primarily by the base excision repair (BER) pathway. It is now known that mammalian mitochondria have BER, which, similarly to nuclear BER, is catalyzed by DNA...

  3. Base excision repair in sugarcane

    Agnez-Lima Lucymara F.

    2001-01-01

    Full Text Available DNA damage can be induced by a large number of physical and chemical agents from the environment as well as compounds produced by cellular metabolism. This type of damage can interfere with cellular processes such as replication and transcription, resulting in cell death and/or mutations. The low frequency of mutagenesis in cells is due to the presence of enzymatic pathways which repair damaged DNA. Several DNA repair genes (mainly from bacteria, yeasts and mammals have been cloned and their products characterized. The high conservation, especially in eukaryotes, of the majority of genes related to DNA repair argues for their importance in the maintenance of life on earth. In plants, our understanding of DNA repair pathways is still very poor, the first plant repair genes having only been cloned in 1997 and the mechanisms of their products have not yet been characterized. The objective of our data mining work was to identify genes related to the base excision repair (BER pathway, which are present in the database of the Sugarcane Expressed Sequence Tag (SUCEST Project. This search was performed by tblastn program. We identified sugarcane clusters homologous to the majority of BER proteins used in the analysis and a high degree of conservation was observed. The best results were obtained with BER proteins from Arabidopsis thaliana. For some sugarcane BER genes, the presence of more than one form of mRNA is possible, as shown by the occurrence of more than one homologous EST cluster.

  4. Sequence Context Specific Mutagenesis and Base Excision Repair

    Donigan, Katherine; Sweasy, Joann B.

    2009-01-01

    Base excision repair is critical for the maintenance of genome stability because it repairs at least 20,000 endogenously generated DNA lesions per cell per day. Several enzymes within the base excision repair pathway exhibit sequence context dependency during the excision and DNA synthesis steps of repair. New evidence is emerging that germ line and tumor-associated variants of enzymes in this repair pathway exhibit sequence context dependence that is different from their ancestral counterpar...

  5. Alar base reduction: the boomerang-shaped excision.

    Foda, Hossam M T

    2011-04-01

    A boomerang-shaped alar base excision is described to narrow the nasal base and correct the excessive alar flare. The boomerang excision combined the external alar wedge resection with an internal vestibular floor excision. The internal excision was inclined 30 to 45 degrees laterally to form the inner limb of the boomerang. The study included 46 patients presenting with wide nasal base and excessive alar flaring. All cases were followed for a mean period of 18 months (range, 8 to 36 months). The laterally oriented vestibular floor excision allowed for maximum preservation of the natural curvature of the alar rim where it meets the nostril floor and upon its closure resulted in a considerable medialization of alar lobule, which significantly reduced the amount of alar flare and the amount of external alar excision needed. This external alar excision measured, on average, 3.8 mm (range, 2 to 8 mm), which is significantly less than that needed when a standard vertical internal excision was used ( P < 0.0001). Such conservative external excisions eliminated the risk of obliterating the natural alar-facial crease, which did not occur in any of our cases. No cases of postoperative bleeding, infection, or vestibular stenosis were encountered. Keloid or hypertrophic scar formation was not encountered; however, dermabrasion of the scars was needed in three (6.5%) cases to eliminate apparent suture track marks. The boomerang alar base excision proved to be a safe and effective technique for narrowing the nasal base and elimination of the excessive flaring and resulted in a natural, well-proportioned nasal base with no obvious scarring. PMID:21404164

  6. Variant Base Excision Repair Proteins: Contributors to Genomic Instability

    Nemec, Antonia A.; Wallace, Susan S.; Sweasy, Joann B.

    2012-01-01

    Cells sustain endogenous DNA damage at rates greater than 20,000 DNA lesions per cell per day. These damages occur largely as a result of the inherently unstable nature of DNA and the presence of reactive oxygen species within cells. The base excision repair system removes the majority of DNA lesions resulting from endogenous DNA damage. There are several enzymes that function during base excision repair. Importantly, there are over 100 germline single nucleotide polymorphisms in genes that function in base excision repair and that result in non-synonymous amino acid substitutions in the proteins they encode. Somatic variants of these enzymes are also found in human tumors. Variant repair enzymes catalyze aberrant base excision repair. Aberrant base excision repair combined with continuous endogenous DNA damage over time has the potential to lead to a mutator phenotype. Mutations that arise in key growth control genes, imbalances in chromosome number, chromosomal translocations, and loss of heterozygosity can result in the initiation of human cancer or its progression. PMID:20955798

  7. Slow base excision by human alkyladenine DNA glycosylase limits the rate of formation of AP sites and AP endonuclease 1 does not stimulate base excision.

    Maher, Robyn L; Vallur, Aarthy C; Feller, Joyce A; Bloom, Linda B

    2007-01-01

    The base excision repair pathway removes damaged DNA bases and resynthesizes DNA to replace the damage. Human alkyladenine DNA glycosylase (AAG) is one of several damage-specific DNA glycosylases that recognizes and excises damaged DNA bases. AAG removes primarily damaged adenine residues. Human AP endonuclease 1 (APE1) recognizes AP sites produced by DNA glycosylases and incises the phophodiester bond 5' to the damaged site. The repair process is completed by a DNA polymerase and DNA ligase. If not tightly coordinated, base excision repair could generate intermediates that are more deleterious to the cell than the initial DNA damage. The kinetics of AAG-catalyzed excision of two damaged bases, hypoxanthine and 1,N6-ethenoadenine, were measured in the presence and absence of APE1 to investigate the mechanism by which the base excision activity of AAG is coordinated with the AP incision activity of APE1. 1,N6-ethenoadenine is excised significantly slower than hypoxanthine and the rate of excision is not affected by APE1. The excision of hypoxanthine is inhibited to a small degree by accumulated product, and APE1 stimulates multiple turnovers by alleviating product inhibition. These results show that APE1 does not significantly affect the kinetics of base excision by AAG. It is likely that slow excision by AAG limits the rate of AP site formation in vivo such that AP sites are not created faster than can be processed by APE1. PMID:17018265

  8. Ku80-Deleted Cells are Defective at Base Excision Repair

    Li, Han; Marple, Teresa; Hasty, Paul

    2013-01-01

    Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repa...

  9. Base excision repair mechanisms and relevance to cancer susceptibility

    The base excision repair (BER) pathway is considered the predominant DNA repair system in mammalian cells for eliminating small DNA lesions generated at DNA bases either exogenously by environmental agents or endogenously by normal cellular metabolic processes (e.g. production of oxyradical species, alkylating agents, etc). The main goal of this project is the understanding of the involvement of BER in genome stability and in particular in sporadic cancer development associated with inflammation such as gastric cancer (GC). A major risk factor of GC is the infection by Helicobacter pylori, which causes oxidative stress. Oxidative DNA damage is mainly repaired by BER

  10. Base Excision Repair, a Pathway Regulated by Posttranslational Modifications.

    Carter, Rachel J; Parsons, Jason L

    2016-05-15

    Base excision repair (BER) is an essential DNA repair pathway involved in the maintenance of genome stability and thus in the prevention of human diseases, such as premature aging, neurodegenerative diseases, and cancer. Protein posttranslational modifications (PTMs), including acetylation, methylation, phosphorylation, SUMOylation, and ubiquitylation, have emerged as important contributors in controlling cellular BER protein levels, enzymatic activities, protein-protein interactions, and protein cellular localization. These PTMs therefore play key roles in regulating the BER pathway and are consequently crucial for coordinating an efficient cellular DNA damage response. In this review, we summarize the presently available data on characterized PTMs of key BER proteins, the functional consequences of these modifications at the protein level, and also the impact on BER in vitro and in vivo. PMID:26976642

  11. uv photobiology: excision repair

    The following topics are discussed: steps in nucleotide excision; damage to DNA by uv-endonuclease; use of complementation to study DNA repair in Escherichia coli and mammalian cells; role of BUDR photolysis in excision repair, relation between DNA repair defect and human disease; base excision repair; and excision repair by removal of damaged region of a base in DNA without excision

  12. Nucleosomes determine their own patch size in base excision repair.

    Meas, Rithy; Smerdon, Michael J

    2016-01-01

    Base excision repair (BER) processes non-helix distorting lesions (e.g., uracils and gaps) and is composed of two subpathways that differ in the number of nucleotides (nts) incorporated during the DNA synthesis step: short patch (SP) repair incorporates 1 nt and long patch (LP) repair incorporates 2-12 nts. This choice for either LP or SP repair has not been analyzed in the context of nucleosomes. Initial studies with uracil located in nucleosome core DNA showed a distinct DNA polymerase extension profile in cell-free extracts that specifically limits extension to 1 nt, suggesting a preference for SP BER. Therefore, we developed an assay to differentiate long and short repair patches in 'designed' nucleosomes containing a single-nucleotide gap at specific locations relative to the dyad center. Using cell-free extracts or purified enzymes, we found that DNA lesions in the nucleosome core are preferentially repaired by DNA polymerase β and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a striking bias for incorporation of short patches into nucleosomal DNA. These results show that nucleosomes control the patch size used by BER. PMID:27265863

  13. Base excision repair deficiency in acute myeloid leukemia

    Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system arising from a transformed myeloid progenitor cell. Genomic instability is the hallmark of AML and characterized by a variety of cytogenetic and molecular abnormalities. Whereas 10% to 20% of AML cases reflect long-term sequelae of cytotoxic therapies for a primary disorder, the etiology for the majority of AMLs remains unknown. The integrity of DNA is under continuous attack from a variety of exogenous and endogenous DNA damaging agents. The majority of DNA damage is caused by constantly generated reactive oxygen species (ROS) resulting from metabolic by-products. Base excision repair (BER) is the major DNA repair mechanism dealing with DNA base lesions that are induced by oxidative stress or alkylation. In this study we investigated the BER in AML. Primary AML patients samples as well as AML cell lines were treated with hydrogen peroxide (H2O2). DNA damage induction and repair was monitored by the alkaline comet assay. In 15/30 leukemic samples from patients with therapy-related AML, in 13/35 with de novo AML and 14/26 with AML following a myelodysplastic syndrome, significantly reduced single strand breaks (SSBs) representing BER intermediates were found. In contrast, normal SSB formation was seen in mononuclear cells of 30 healthy individuals and 30/31 purified hematopoietic stem- and progenitor cell preparations obtained from umbilical cord blood. Additionally, in 5/10 analyzed AML cell lines, no SSBs were formed upon H2O2 treatment, either. Differences in intracellular ROS concentrations or apoptosis could be excluded as reason for this phenomenon. A significantly diminished cleavage capacity for 7,8-dihydro-8-oxoguanine as well as for Furan was observed in cell lines that exhibited no SSB formation. These data demonstrate for the first time that initial steps of BER are impaired in a proportion of AML cell lines and leukemic cells from patients with different forms of AML

  14. Ku80-deleted cells are defective at base excision repair

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  15. EXCISED DAMAGED BASE DETERMINES THE TURNOVER OF HUMAN N-METHYLPURINE-DNA GLYCOSYLASE

    Adhikari, Sanjay; Üren, Aykut; Roy, Rabindra

    2009-01-01

    N-Methylpurine-DNA glycosylase (MPG) initiates base excision repair in DNA by removing a wide variety of alkylated, deaminated, and lipid peroxidation-induced purine adducts. In this study, we tested the role of excised base on MPG’s enzymatic activity. After the reaction, MPG produced two products: free damaged base and AP-site containing DNA. Our results showed that MPG excises 1, N6-ethenoadenine (εA) from εA-containing oligonucleotide (εA-DNA) at a similar or slightly increased efficiency...

  16. Base excision repair activities differ in human lung cancer cells and corresponding normal controls

    Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C

    2010-01-01

    Oxidative damage to DNA is thought to play a role in carcinogenesis by causing mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway for the...

  17. Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase.

    B.P. Engelward (Bevin); G. Weeda (Geert); M.D. Wyatt; J.L.M. Broekhof (Jose'); J. de Wit (Jan); I. Donker (Ingrid); J.M. Allan (James); B. Gold (Bert); J.H.J. Hoeijmakers (Jan); L.D. Samson (Leona)

    1997-01-01

    textabstract3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA glyc

  18. The mitochondrial transcription factor A functions in mitochondrial base excision repair

    Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V;

    2010-01-01

    mitochondria, whereas base excision repair (BER) has been comprehensively characterized in these organelles. The BER proteins are associated with the inner membrane in mitochondria and thus with the mitochondrial nucleoid, where TFAM is also situated. However, a function for TFAM in BER has not yet been...

  19. Vertebrate POLQ and POLβ Cooperate in Base Excision Repair of Oxidative DNA Damage

    Yoshimura, Michio; Kohzaki, Masaoki; Nakamura, Jun; Asagoshi, Kenjiro; Sonoda, Eiichiro; Hou, Esther; Prasad, Rajendra; Wilson, Samuel H.; TANO, KEIZO; Yasui, Akira; Lan, Li; Seki, Mineaki; Wood, Richard D.; Arakawa, Hiroshi; Buerstedde, Jean-Marie

    2006-01-01

    Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage ind...

  20. Unplanned Excision of Extremity Soft Tissue Sarcoma in Korea: A Nationwide Study Based on a Claims Registry.

    Seungcheol Kang

    Full Text Available Unplanned excision of extremity soft tissue sarcoma (STS is common and has detrimental effects not only on patients' oncologic outcomes but also on functional and economic issues. However, no study has analyzed a nationwide population-based database. To estimate the incidence and treatment pattern of unplanned excision in extremity STS in the Korean population, a nationwide epidemiologic study was performed using the Korean Health Insurance Review and Assessment Service database, a centralized nationwide healthcare claims registry of Korea that covers the entire Korean population. Among 1,517 patients with extremity STS in the 4-year study period, 553 (36.5% underwent unplanned excision (unplanned group. About 80% of unplanned excisions were performed in tertiary or general hospitals. Of the unplanned group, 240 (43.4% underwent re-excision with or without radiation therapy and/or chemotherapy, and 51 (9.2% did not undergo re-excision but were treated with radiation therapy and/or chemotherapy; whereas, 262 (47.4% did not undergo any further treatment following unplanned excision. This study is the first nationwide population-based study on the unplanned excision of extremity STS. The results may have implications in establishing preventive or therapeutic measures to reduce the burden of unplanned excision of extremity STS.

  1. The role of DNA base excision repair in brain homeostasis and disease

    Akbari, Mansour; Morevati, Marya; Croteau, Deborah;

    2015-01-01

    Chemical modification and spontaneous loss of nucleotide bases from DNA are estimated to occur at the rate of thousands per human cell per day. DNA base excision repair (BER) is a critical mechanism for repairing such lesions in nuclear and mitochondrial DNA. Defective expression or function of p...... energy homeostasis, mitochondrial function and cellular bioenergetics, with especially strong influence on neurological function. Further studies in this area could lead to novel approaches to prevent and treat human neurodegenerative disease....

  2. XRCC1 and Base Excision Repair Balance in Response to Nitric Oxide

    Mutamba, James T; Svilar, David; Prasongtanakij, Somsak; Wang, Xiao-hong; Lin, Ying-Chih; Dedon, Peter C; Sobol, Robert W.; Engelward, Bevin P.

    2011-01-01

    Inflammation associated reactive oxygen and nitrogen species (RONs), including peroxynitrite (ONOO−) and nitric oxide (NO· ), create base lesions that potentially play a role in the toxicity and large-scale genomic rearrangements associated with many malignancies. Nevertheless, little is known about the functional role of base excision repair (BER) deficiencies following exposure to RONs. Here, we explore the role of XRCC1 in modulating the levels of RONs-induced genotoxicity. XRCC1 is a scaf...

  3. Gut Microbiota Imbalance and Base Excision Repair Dynamics in Colon Cancer

    Ray, Debolina; Kidane, Dawit

    2016-01-01

    Gut microbiota are required for host nutrition, energy balance, and regulating immune homeostasis, however, in some cases, this mutually beneficial relationship becomes twisted (dysbiosis), and the gut flora can incite pathological disorders including colon cancer. Microbial dysbiosis promotes the release of bacterial genotoxins, metabolites, and causes chronic inflammation, which promote oxidative DNA damage. Oxidized DNA base lesions are removed by base excision repair (BER), however, the role of this altered function of BER, as well as microbiota-mediated genomic instability and colon cancer development, is still poorly understood. In this review article, we will discuss how dysbiotic microbiota induce DNA damage, its impact on base excision repair capacity, the potential link of host BER gene polymorphism, and the risk of dysbiotic microbiota mediated genomic instability and colon cancer.

  4. Chk2-dependent phosphorylation of XRCC1 in the DNA damage response promotes base excision repair

    Chou, Wen-Cheng; Wang, Hui-Chun; Wong, Fen-Hwa; Ding, Shian-ling; Wu, Pei-Ei; Shieh, Sheau-Yann; Shen, Chen-Yang

    2008-01-01

    The DNA damage response (DDR) has an essential function in maintaining genomic stability. Ataxia telangiectasia-mutated (ATM)-checkpoint kinase 2 (Chk2) and ATM- and Rad3-related (ATR)-Chk1, triggered, respectively, by DNA double-strand breaks and blocked replication forks, are two major DDRs processing structurally complicated DNA damage. In contrast, damage repaired by base excision repair (BER) is structurally simple, but whether, and how, the DDR is involved in repairing this damage is un...

  5. Initial steps of the base excision repair pathway within the nuclear architecture

    Oxidative stress induced lesions threaten aerobic organisms by representing a major cause of genomic instability. A common product of guanine oxidation, 8-oxo-guanine (8- oxoG) is particularly mutagenic by provoking G to T transversions. Removal of oxidised bases from DNA is initiated by the recognition and excision of the damaged base by a DNA glycosylase, initiating the base excision repair (BER) pathway. In mammals, 8-oxoG is processed by the 8-oxoG-DNA-glycosylase I (OGG1), which biochemical mechanisms has been well characterised in vitro. However how and where this enzyme finds the modified base within the complex chromatin architecture is not yet understood. We show that upon induction of 8-oxoG, OGG1, together with at least two other proteins involved in BER, is recruited from a soluble fraction to chromatin. Formation kinetics of this patches correlates with 8-oxoG excision, suggesting a direct link between presence of this chromatin-associated complexes and 8-oxoG repair. More precisely, these repair patches are specifically directed to euchromatin regions, and completely excluded from heterochromatin regions. Inducing of artificial chromatin compaction results in a complete inhibition of the in vivo repair of 8-oxoG, probably by impeding the access of OGG1 to the lesion. Using OGG1 mutants, we show that OGG1 direct recognition of 8-oxoG did not trigger its re-localisation to the chromatin. We conclude that in response to the induction of oxidative DNA damage, the DNA glycosylase is actively recruited to regions of open chromatin allowing the access of the BER machinery to the lesions. (author)

  6. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  7. ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination.

    Müller, Tina A; Yu, Kefei; Hausinger, Robert P; Meek, Katheryn

    2013-01-01

    Potential roles of the abasic site lyase activity associated with AlkB homolog 1 (ALKBH1) were assessed by studies focusing on the two cellular processes that create abasic sites as intermediates: base excision repair and class switch recombination. Alkbh1(-/-) pups (lacking exon 3) were born at a lower than expected frequency from heterozygous parents, suggesting a reduced survival rate and non-Mendelian inheritance, and they exhibited a gender bias in favor of males (70% males and 30% females). To study ALKBH1's potential involvement in DNA repair, fibroblasts were isolated from Alkbh1(-/-) mice, spontaneously immortalized and tested for resistance to DNA damaging agents. Alkbh1(-/-) and isogenic cells expressing hALKBH1 showed no difference in survival to the DNA damaging agents methyl-methionine sulfate or H2O2. This result indicates that ALKBH1 does not play a major role in the base excision repair pathway. To assess ALKBH1's role in class switch recombination, splenic B cells were isolated from Alkbh1(-/-) and Alkbh1(+/+) mice and subjected to switching from IgM to IgG1. No differences were found in IgG1 switching, suggesting that Alkbh1 is not involved in class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation. PMID:23825659

  8. ALKBH1 is dispensable for abasic site cleavage during base excision repair and class switch recombination.

    Tina A Müller

    Full Text Available Potential roles of the abasic site lyase activity associated with AlkB homolog 1 (ALKBH1 were assessed by studies focusing on the two cellular processes that create abasic sites as intermediates: base excision repair and class switch recombination. Alkbh1(-/- pups (lacking exon 3 were born at a lower than expected frequency from heterozygous parents, suggesting a reduced survival rate and non-Mendelian inheritance, and they exhibited a gender bias in favor of males (70% males and 30% females. To study ALKBH1's potential involvement in DNA repair, fibroblasts were isolated from Alkbh1(-/- mice, spontaneously immortalized and tested for resistance to DNA damaging agents. Alkbh1(-/- and isogenic cells expressing hALKBH1 showed no difference in survival to the DNA damaging agents methyl-methionine sulfate or H2O2. This result indicates that ALKBH1 does not play a major role in the base excision repair pathway. To assess ALKBH1's role in class switch recombination, splenic B cells were isolated from Alkbh1(-/- and Alkbh1(+/+ mice and subjected to switching from IgM to IgG1. No differences were found in IgG1 switching, suggesting that Alkbh1 is not involved in class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation.

  9. Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil.

    Christophe Kunz

    2009-04-01

    Full Text Available 5-Fluorouracil (5-FU, a chemotherapeutic drug commonly used in cancer treatment, imbalances nucleotide pools, thereby favoring misincorporation of uracil and 5-FU into genomic DNA. The processing of these bases by DNA repair activities was proposed to cause DNA-directed cytotoxicity, but the underlying mechanisms have not been resolved. In this study, we investigated a possible role of thymine DNA glycosylase (TDG, one of four mammalian uracil DNA glycosylases (UDGs, in the cellular response to 5-FU. Using genetic and biochemical tools, we found that inactivation of TDG significantly increases resistance of both mouse and human cancer cells towards 5-FU. We show that excision of DNA-incorporated 5-FU by TDG generates persistent DNA strand breaks, delays S-phase progression, and activates DNA damage signaling, and that the repair of 5-FU-induced DNA strand breaks is more efficient in the absence of TDG. Hence, excision of 5-FU by TDG, but not by other UDGs (UNG2 and SMUG1, prevents efficient downstream processing of the repair intermediate, thereby mediating DNA-directed cytotoxicity. The status of TDG expression in a cancer is therefore likely to determine its response to 5-FU-based chemotherapy.

  10. Polymorphisms within base and nucleotide excision repair pathways and risk of differentiated thyroid carcinoma.

    Cipollini, Monica; Figlioli, Gisella; Maccari, Giuseppe; Garritano, Sonia; De Santi, Chiara; Melaiu, Ombretta; Barone, Elisa; Bambi, Franco; Ermini, Stefano; Pellegrini, Giovanni; Cristaudo, Alfonso; Foddis, Rudy; Bonotti, Alessandra; Romei, Cristina; Vivaldi, Agnese; Agate, Laura; Molinari, Eleonora; Barale, Roberto; Forsti, Asta; Hemminki, Kari; Elisei, Rossella; Gemignani, Federica; Landi, Stefano

    2016-05-01

    The thyrocytes are exposed to high levels of oxidative stress which could induce DNA damages. Base excision repair (BER) is one of the principal mechanisms of defense against oxidative DNA damage, however recent evidences suggest that also nucleotide excision repair (NER) could be involved. The aim of present work was to identify novel differentiated thyroid cancer (DTC) risk variants in BER and NER genes. For this purpose, the most strongly associated SNPs within NER and BER genes found in our previous GWAS on DTC were selected and replicated in an independent series of samples for a new case-control study. Although a positive signal was detected at the nominal level of 0.05 for rs7689099 (encoding for an aminoacid change proline to arginine at codon 117 within NEIL3), none of the considered SNPs (i.e. rs7990340 and rs690860 within RFC3, rs3744767 and rs1131636 within RPA1, rs16962916 and rs3136166 in ERCC4, and rs17739370 and rs7689099 in NEIL3) was associated with the risk of DTC when the correction of multiple testing was applied. In conclusion, a role of NER and BER pathways was evoked in the susceptibility to DTC. However, this seemed to be limited to few polymorphic genes and the overall effect size appeared weak. PMID:27062014

  11. A Novel Variable Index and Excision CFAR Based Ship Detection Method on SAR Imagery

    Kefeng Ji

    2015-01-01

    Full Text Available When applying the constant false alarm rate (CFAR detector to ship detection on synthetic aperture radar (SAR imagery, multiple interferers such as upwelling, breaking waves, ambiguities, and neighboring ships in a dense traffic area will degrade the probability of detection. In this paper, we propose a novel variable index and excision CFAR (VIE-CFAR based ship detection method to alleviate the masking effect of multiple interferers. Firstly, we improve the variable index (VI CFAR with an excision procedure, which censors the multiple interferers from the reference cells. And then, the paper integrates the novel CFAR concept into a ship detection scheme on SAR imagery, which adopts the VIE-CFAR to screen reference cells and the distribution to derive detection threshold. Finally, we analyze the performances of the VIE-CFAR under different environments and validate the proposed method on both ENVISAT and TerraSAR-X SAR data. The results demonstrate that the proposed method outperforms other existing detectors, especially in the presence of multiple interferers.

  12. The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions

    Mullins, Elwood A.; Shi, Rongxin; Parsons, Zachary D.; Yuen, Philip K.; David, Sheila S.; Igarashi, Yasuhiro; Eichman, Brandt F.

    2015-11-01

    Threats to genomic integrity arising from DNA damage are mitigated by DNA glycosylases, which initiate the base excision repair pathway by locating and excising aberrant nucleobases. How these enzymes find small modifications within the genome is a current area of intensive research. A hallmark of these and other DNA repair enzymes is their use of base flipping to sequester modified nucleotides from the DNA helix and into an active site pocket. Consequently, base flipping is generally regarded as an essential aspect of lesion recognition and a necessary precursor to base excision. Here we present the first, to our knowledge, DNA glycosylase mechanism that does not require base flipping for either binding or catalysis. Using the DNA glycosylase AlkD from Bacillus cereus, we crystallographically monitored excision of an alkylpurine substrate as a function of time, and reconstructed the steps along the reaction coordinate through structures representing substrate, intermediate and product complexes. Instead of directly interacting with the damaged nucleobase, AlkD recognizes aberrant base pairs through interactions with the phosphoribose backbone, while the lesion remains stacked in the DNA duplex. Quantum mechanical calculations revealed that these contacts include catalytic charge-dipole and CH-π interactions that preferentially stabilize the transition state. We show in vitro and in vivo how this unique means of recognition and catalysis enables AlkD to repair large adducts formed by yatakemycin, a member of the duocarmycin family of antimicrobial natural products exploited in bacterial warfare and chemotherapeutic trials. Bulky adducts of this or any type are not excised by DNA glycosylases that use a traditional base-flipping mechanism. Hence, these findings represent a new model for DNA repair and provide insights into catalysis of base excision.

  13. X-ray repair cross complementing protein 1 in base excision repair

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour;

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...... multiprotein DNA repair complexes as well as facilitate the recruitment of DNA repair proteins to sites of DNA damage. Moreover, XRCC1 is present in constitutive DNA repair complexes, some of which associate with the replication machinery. Because of the critical role of XRCC1 in DNA repair, its common...... variants Arg194Trp, Arg280His and Arg399Gln have been extensively studied. However, the prevalence of these variants varies strongly in different populations, and their functional influence on DNA repair and disease remains elusive. Here we present the current knowledge about the role of XRCC1 and its...

  14. XRCC1 and base excision repair balance in response to nitric oxide.

    Mutamba, James T; Svilar, David; Prasongtanakij, Somsak; Wang, Xiao-Hong; Lin, Ying-Chih; Dedon, Peter C; Sobol, Robert W; Engelward, Bevin P

    2011-12-10

    Inflammation associated reactive oxygen and nitrogen species (RONs), including peroxynitrite (ONOO(-)) and nitric oxide (NO), create base lesions that potentially play a role in the toxicity and large genomic rearrangements associated with many malignancies. Little is known about the role of base excision repair (BER) in removing these endogenous DNA lesions. Here, we explore the role of X-ray repair cross-complementing group 1 (XRCC1) in attenuating RONs-induced genotoxicity. XRCC1 is a scaffold protein critical for BER for which polymorphisms modulate the risk of cancer. We exploited CHO and human glioblastoma cell lines engineered to express varied levels of BER proteins to study XRCC1. Cytotoxicity and the levels of DNA repair intermediates (single-strand breaks; SSB) were evaluated following exposure of the cells to the ONOO(-) donor, SIN-1, and to gaseous NO. XRCC1 null cells were slightly more sensitive to SIN-1 than wild-type cells. We used small-scale bioreactors to expose cells to NO and found that XRCC1-deficient CHO cells were not sensitive. However, using a molecular beacon assay to test lesion removal in vitro, we found that XRCC1 facilitates AAG-initiated excision of two key NO-induced DNA lesions: 1,N(6)-ethenoadenine and hypoxanthine. Furthermore, overexpression of AAG rendered XRCC1-deficient cells sensitive to NO-induced DNA damage. These results show that AAG is a key glycosylase for BER of NO-induced DNA damage and that XRCC1's role in modulating sensitivity to RONs is dependent upon the cellular level of AAG. This demonstrates the importance of considering the expression of other components of the BER pathway when evaluating the impact of XRCC1 polymorphisms on cancer risk. PMID:22041025

  15. Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair

    A. Campalans (Anna); R. Amouroux (Rachel); H. Menoni (Hervé); W. Vermeulen (Wim); J.P. Radicella (Pablo)

    2013-01-01

    textabstractSingle-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1,

  16. Repair of 3-methyladenine and abasic sites by base excision repair mediates glioblastoma resistance to temozolomide

    John R Silber

    2012-11-01

    Full Text Available Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma multiforme (GBM. More recently, inclusion of temozolomide (TMZ, an orally administered methylating agent with low systemic toxicity, during radiotherapy and afterward has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O6-methylguanine (O6-meG mediates GBM cell killing. Moreover, low or absent expression of O6-methylguanine-DNA methyltransferase (MGMT, the sole human repair protein that removes O6-meG from DNA, is frequently associated with longer survival in GBMs treated with TMZ, promoting interest in developing inhibitors of MGMT to counter resistance. However, the clinical efficacy of TMZ is unlikely to be due solely to O6-meG, as the agent produces approximately a dozen additional DNA adducts, including cytotoxic N3-methyladenine (3-meA and abasic sites. Repair of 3-meA and abasic sites, both of which are produced in greater abundance than O6-meG, is mediated by the base excision repair (BER pathway, and occurs independently of removal of O6-meG. These observations indicate that BER activities are also potential targets for strategies to potentiate TMZ cytotoxicity. Here we review the evidence that 3-meA and abasic sites mediate killing of GBM cells. We also present in vitro and in vivo evidence that alkyladenine-DNA–glycosylase, the sole repair activity that excises 3-meA from DNA, and Ape1, the major human abasic site endonuclease, mediate TMZ resistance in GBMs and represent potential anti-resistance targets.

  17. Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

    Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin

  18. Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

    Soltys, Daniela Tathiana; Pereira, Carolina Parga Martins; Ishibe, Gabriela Naomi; Souza-Pinto, Nadja Cristhina de, E-mail: nadja@iq.usp.br

    2015-06-15

    Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin.

  19. Polysulfide compounds as inhibitors of the key base excision repair enzymes

    Salakhutdinov N. F.

    2012-06-01

    Full Text Available Aim. To increase the capacity of antitumor therapy based on DNA damage it is important to minimize the repair of DNA lesions that can be achieved by inhibiting the activity of key DNA repair enzymes. To this end several benzopentathiepine and benzo[1,3]dithiol derivatives were synthesized and tested as inhibitors of the key base excision repair (BER enzymes, PARP1, DNA polymerase β, and APE1. Methods. The procedure of synthesis of several new compounds was developed. The inhibitory capacity of the compounds was estimated by comparison of the enzyme activities in specific tests in the presence of compounds versus their absence. Results. Benzopentathiepine derivative bearing trifluoromethyl group at the 1st position was shown to be a weak inhibitor of PARP1. Cyclic substituents at the 1st position attached through amide bond bring about moderate enhancement of pol β inhibition. Each studied substituent at the 1st position considerably increases the inhibition of APE1-catalyzed hydrolysis of AP sites as compared to parent compound. Conclusions. Several new inhibitors of BER enzymes were revealed. The directions for further modification of compounds to improve their inhibitory activity were found out.

  20. Oxidative DNA damage background estimated by a system model of base excision repair

    Sokhansanj, B A; Wilson, III, D M

    2004-05-13

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  1. Pol β associated complex and base excision repair factors in mouse fibroblasts.

    Prasad, Rajendra; Williams, Jason G; Hou, Esther W; Wilson, Samuel H

    2012-12-01

    During mammalian base excision repair (BER) of lesion-containing DNA, it is proposed that toxic strand-break intermediates generated throughout the pathway are sequestered and passed from one step to the next until repair is complete. This stepwise process is termed substrate channeling. A working model evaluated here is that a complex of BER factors may facilitate the BER process. FLAG-tagged DNA polymerase (pol) β was expressed in mouse fibroblasts carrying a deletion in the endogenous pol β gene, and the cell extract was subjected to an 'affinity-capture' procedure using anti-FLAG antibody. The pol β affinity-capture fraction (ACF) was found to contain several BER factors including polymerase-1, X-ray cross-complementing factor1-DNA ligase III and enzymes involved in processing 3'-blocked ends of BER intermediates, e.g. polynucleotide kinase and tyrosyl-DNA phosphodiesterase 1. In contrast, DNA glycosylases, apurinic/aprymidinic endonuclease 1 and flap endonuclease 1 and several other factors involved in BER were not present. Some of the BER factors in the pol β ACF were in a multi-protein complex as observed by sucrose gradient centrifugation. The pol β ACF was capable of substrate channeling for steps in vitro BER and was proficient in in vitro repair of substrates mimicking a 3'-blocked topoisomerase I covalent intermediate or an oxidative stress-induced 3'-blocked intermediate. PMID:23042675

  2. On-bead fluorescent DNA nanoprobes to analyze base excision repair activities

    Graphical abstract: -- Highlights: •On magnetic beads fluorescent enzymatic assays. •Simple, easy, non-radioactive and electrophoresis-free functional assay. •Lesion-containing hairpin DNA probes are selective for repair enzymes. •The biosensing platform allows the measurement of DNA repair activities from purified enzymes or within cell free extracts. -- Abstract: DNA integrity is constantly threatened by endogenous and exogenous agents that can modify its physical and chemical structure. Changes in DNA sequence can cause mutations sparked by some genetic diseases or cancers. Organisms have developed efficient defense mechanisms able to specifically repair each kind of lesion (alkylation, oxidation, single or double strand break, mismatch, etc). Here we report the adjustment of an original assay to detect enzymes’ activity of base excision repair (BER), that supports a set of lesions including abasic sites, alkylation, oxidation or deamination products of bases. The biosensor is characterized by a set of fluorescent hairpin-shaped nucleic acid probes supported on magnetic beads, each containing a selective lesion targeting a specific BER enzyme. We have studied the DNA glycosylase alkyl-adenine glycosylase (AAG) and the human AP-endonuclease (APE1) by incorporating within the DNA probe a hypoxanthine lesion or an abasic site analog (tetrahydrofuran), respectively. Enzymatic repair activity induces the formation of a nick in the damaged strand, leading to probe's break, that is detected in the supernatant by fluorescence. The functional assay allows the measurement of DNA repair activities from purified enzymes or in cell-free extracts in a fast, specific, quantitative and sensitive way, using only 1 pmol of probe for a test. We recorded a detection limit of 1 μg mL−1 and 50 μg mL−1 of HeLa nuclear extracts for APE1 and AAG enzymes, respectively. Finally, the on-bead assay should be useful to screen inhibitors of DNA repair activities

  3. Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay - A methodological overview

    Azqueta, A.; Langie, S. A. S.; Slyšková, Jana; Collins, A. R.

    2013-01-01

    Roč. 12, č. 11 (2013), s. 1007-1010. ISSN 1568-7864 Grant ostatní: EU FP6(XE) LSHB-CT-2006-037575 Institutional support: RVO:68378041 Keywords : comet assay * base excision repair * nucleotide excision repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.362, year: 2013

  4. Nonhomologous end joining of complex DNA double-strand breaks with proximal thymine glycol and interplay with base excision repair.

    Almohaini, Mohammed; Chalasani, Sri Lakshmi; Bafail, Duaa; Akopiants, Konstantin; Zhou, Tong; Yannone, Steven M; Ramsden, Dale A; Hartman, Matthew C T; Povirk, Lawrence F

    2016-05-01

    DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol at the first (Tg1), second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3' terminus, was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate base was a major barrier to end joining (>10-fold reduction in ligated products) and an absolute barrier when present at both ends. Dideoxy trapping of base excision repair intermediates indicated that Tg was excised from Tg1, Tg2 and Tg3 largely if not exclusively after DSB ligation. However, Tg was rapidly excised from the Tg5 substrate, resulting in a reduced level of DSB ligation, as well as slow concomitant resection of the opposite strand. Ligase reactions containing only purified Ku, XRCC4, ligase IV and XLF showed that ligation of Tg3 and Tg5 was efficient and only partially XLF-dependent, whereas ligation of Tg1 and Tg2 was inefficient and only detectable in the presence of XLF. Overall, the results suggest that promoting ligation of DSBs with proximal base damage may be an important function of XLF, but that Tg can still be a major impediment to repair, being relatively resistant to both trimming and ligation. Moreover, it appears that base excision repair of Tg can sometimes interfere with repair of DSBs that would otherwise be readily rejoined. PMID:27049455

  5. Trypanosoma cruzi contains a single detectable uracil-DNA glycosylase and repairs uracil exclusively via short patch base excision repair

    Pena Diaz, Javier; Akbari, Mansour; Sundheim, Ottar; Farez-Vidal, M Esther; Andersen, Sonja; Sneve, Ragnhild; Gonzalez-Pacanowska, Dolores; Krokan, Hans E; Slupphaug, Geir

    2004-01-01

    Enzymes involved in genomic maintenance of human parasites are attractive targets for parasite-specific drugs. The parasitic protozoan Trypanosoma cruzi contains at least two enzymes involved in the protection against potentially mutagenic uracil, a deoxyuridine triphosphate nucleotidohydrolase (d......UTPase) and a uracil-DNA glycosylase belonging to the highly conserved UNG-family. Uracil-DNA glycosylase activities excise uracil from DNA and initiate a multistep base-excision repair (BER) pathway to restore the correct nucleotide sequence. Here we report the biochemical characterisation of T.cruzi UNG (Tc......UNG) and its contribution to the total uracil repair activity in T.cruzi. TcUNG is shown to be the major uracil-DNA glycosylase in T.cruzi. The purified recombinant TcUNG exhibits substrate preference for removal of uracil in the order ssU>U:G>U:A, and has no associated thymine-DNA glycosylase activity. T.cruzi...

  6. Comparative assessment of plasmid and oligonucleotide DNA substrates in measurement of in vitro base excision repair activity

    Hou, Esther W.; Prasad, Rajendra; Asagoshi, Kenjiro; Masaoka, Aya; Wilson, Samuel H.

    2007-01-01

    Mammalian base excision repair (BER) is mediated through at least two subpathways designated ‘single-nucleotide’ (SN) and ‘long-patch’ (LP) BER (2-nucleotides long/more repair patch). Two forms of DNA substrate are generally used for in vitro BER assays: oligonucleotide- and plasmid-based. For plasmid-based BER assays, the availability of large quantities of substrate DNA with a specific lesion remains the limiting factor. Using sequence-specific endonucleases that cleave only one strand of D...

  7. Repair of DNA damage in mammalian cells after treatment with UV and dimethyl sulphate: discrimination between nucleotide and base excision repair by their temperature dependence.

    Hjertvik, M; Erixon, K; Ahnström, G

    1998-03-01

    Alkylating agents have been reported to give rise to both short and long patches of repair. The reason for the different patch sizes is not known. One possibility is that alkylating agents can trigger both base and nucleotide excision repair. Another possibility is that base excision repair itself can result in different patch sizes. Recognition and incision at lesions is the rate limiting step in excision repair. In order to discriminate between base and nucleotide excision repair it would be desirable to be able to distinguish between different incision activities. In order to accurately measure incision rates, the rejoining of the strand-breaks formed must be inhibited. We have used two inhibitors, aphidicolin and 3-aminobenzamide. Aphidicolin, an inhibitor of DNA polymerases alpha/delta/epsilon. caused accumulation of single-strand breaks both after UV and dimethylsulphate. 3-Aminobenzamide, an inhibitor of poly(ADP-ribose)-polymerase caused accumulation of single-strand breaks only after alkylating agents and is thus specific for base excision repair. Enzymatic activities can be characterised by their activation energy. In order to discriminate between base and nucleotide excision repair the temperature dependence of incision activities was determined. When the temperature is decreased, the incision rate is reduced to a larger extent for UV than for DMS-induced repair. Incisions in UV-irradiated cells are practically cut off at temperatures of 15 degrees C and below, whereas DMS-exposed cells still are actively repairing at this temperature. In DMS treated cells the temperature dependence was the same whether aphidicolin or 3-aminobenzamide was used, speaking against an involvement of nucleotide excision repair. In addition, cell lines deficient in nucleotide excision repair responded in the same way to aphidicolin after DMS treatment as normal cells and were able to make incisions at 15 degrees C. This indicates that nucleotide excision repair is not to any

  8. Differential modes of DNA binding by mismatch uracil DNA glycosylase from Escherichia coli: implications for abasic lesion processing and enzyme communication in the base excision repair pathway

    Grippon, Seden; Zhao, Qiyuan; Robinson, Tom; Marshall, Jacqueline J. T.; O’Neill, Rory J.; Manning, Hugh; Kennedy, Gordon; Dunsby, Christopher; Neil, Mark; Halford, Stephen E.; French, Paul M. W.; Baldwin, Geoff S.

    2010-01-01

    Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway. As with other DNA glycosylases, the abasic product is potentially more harmful than the initial lesion. Since Mug is known to bind its product tightly, inhibiting enzyme turnover, understanding how Mug binds DNA is of significance when considering how Mug interacts with downstream enzymes in the base-excision repair pathway. We have demonstrated differential binding modes o...

  9. Mutants of the Base Excision Repair Glycosylase, Endonuclease III: DNA Charge Transport as a First Step in Lesion Detection

    Romano, Christine A.; Sontz, Pamela A.; Barton, Jacqueline K.

    2011-01-01

    Endonuclease III (EndoIII) is a base excision repair glycosylase that targets damaged pyrimidines and contains a [4Fe-4S] cluster. We have proposed a model where BER proteins that contain redox-active [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in the detection of DNA lesions. Here, several mutants of EndoIII were prepared to probe their efficiency of DNA/protein charge transport. Cyclic voltammetry experiments on DNA-modified electrodes show that aromatic residues F30...

  10. Mammalian Base Excision Repair: Functional Partnership between PARP-1 and APE1 in AP-Site Repair.

    Rajendra Prasad

    Full Text Available The apurinic/apyrimidinic- (AP- site in genomic DNA arises through spontaneous base loss and base removal by DNA glycosylases and is considered an abundant DNA lesion in mammalian cells. The base excision repair (BER pathway repairs the AP-site lesion by excising and replacing the site with a normal nucleotide via template directed gap-filling DNA synthesis. The BER pathway is mediated by a specialized group of proteins, some of which can be found in multiprotein complexes in cultured mouse fibroblasts. Using a DNA polymerase (pol β immunoaffinity-capture technique to isolate such a complex, we identified five tightly associated and abundant BER factors in the complex: PARP-1, XRCC1, DNA ligase III, PNKP, and Tdp1. AP endonuclease 1 (APE1, however, was not present. Nevertheless, the complex was capable of BER activity, since repair was initiated by PARP-1's AP lyase strand incision activity. Addition of purified APE1 increased the BER activity of the pol β complex. Surprisingly, the pol β complex stimulated the strand incision activity of APE1. Our results suggested that PARP-1 was responsible for this effect, whereas other proteins in the complex had no effect on APE1 strand incision activity. Studies of purified PARP-1 and APE1 revealed that PARP-1 was able to stimulate APE1 strand incision activity. These results illustrate roles of PARP-1 in BER including a functional partnership with APE1.

  11. Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair

    Akbari, Mansour; Keijzers, Guido; Maynard, Scott;

    2014-01-01

    Base excision repair (BER) is the most prominent DNA repair pathway in human mitochondria. BER also results in a temporary generation of AP-sites, single-strand breaks and nucleotide gaps. Thus, incomplete BER can result in the generation of DNA repair intermediates that can disrupt mitochondrial...... rotenone. Our results suggest that the amount of DNA ligase III in mitochondria may be critical for cell survival following prolonged oxidative stress, and demonstrate a functional link between mitochondrial DNA damage and repair, cell survival upon oxidative stress, and removal of dysfunctional...... DNA replication and transcription and generate mutations. We carried out BER analysis in highly purified mitochondrial extracts from human cell lines U2OS and HeLa, and mouse brain using a circular DNA substrate containing a lesion at a specific position. We found that DNA ligation is significantly...

  12. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons

  13. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Kim, Hyun-Suk [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Guo, Chunlu; Thompson, Eric L. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Jiang, Yanlin [Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Lee, Suk-Hee, E-mail: slee@iu.edu [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States)

    2015-09-15

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons.

  14. Distinct spatio temporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair

    Single-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1, responsible for the initial recognition of the break. The recruitment of XRCC1 to BER is still poorly understood. Here we show by using both local and global induction of oxidative DNA base damage that XRCC1 participation in BER complexes can be distinguished from that in SSBR by several criteria. We show first that XRCC1 recruitment to BER is independent of PARP. Second, unlike SSBR complexes that are assembled within minutes after global damage induction, XRCC1 is detected later in BER patches, with kinetics consistent with the repair of oxidized bases. Third, while XRCC1-containing foci associated with SSBR are formed both in eu- and heterochromatin domains, BER complexes are assembled in patches that are essentially excluded from heterochromatin and where the oxidized bases are detected. (authors)

  15. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

    Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline;

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of th...

  16. Variation within 3' UTRs of base excision repair genes and response to therapy in colorectal cancer patients: a potential modulation of microRNAs binding.

    Pardini, B.; Rosa, F.; Barone, E.; Di Gaetano, C.; Slyšková, Jana; Novotný, J.; Levý, M.; Garritano, S.; Vodičková, Ludmila; Buchler, T.; Gemignani, F.; Landi, S.; Vodička, Pavel; Naccarati, Alessio

    2013-01-01

    Roč. 19, č. 21 (2013), s. 6044-6056. ISSN 1078-0432 R&D Projects: GA ČR GAP304/10/1286; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : colorectal cancer * base excision repair * survival Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.193, year: 2013

  17. The Base Excision Repair system of Salmonella enterica serovar typhimurium counteracts DNA damage by host nitric oxide.

    Anthony R Richardson

    2009-05-01

    Full Text Available Intracellular pathogens must withstand nitric oxide (NO. generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO. sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO. fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO.-dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO.. These observations demonstrate that host-derived NO. damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity.

  18. Reprint of "Oxidant and environmental toxicant-induced effects compromise DNA ligation during base excision DNA repair".

    Çağlayan, Melike; Wilson, Samuel H

    2015-12-01

    DNA lesions arise from many endogenous and environmental agents, and such lesions can promote deleterious events leading to genomic instability and cell death. Base excision repair (BER) is the main DNA repair pathway responsible for repairing single strand breaks, base lesions and abasic sites in mammalian cells. During BER, DNA substrates and repair intermediates are channeled from one step to the next in a sequential fashion so that release of toxic repair intermediates is minimized. This includes handoff of the product of gap-filling DNA synthesis to the DNA ligation step. The conformational differences in DNA polymerase β (pol β) associated with incorrect or oxidized nucleotide (8-oxodGMP) insertion could impact channeling of the repair intermediate to the final step of BER, i.e., DNA ligation by DNA ligase I or the DNA Ligase III/XRCC1 complex. Thus, modified DNA ligase substrates produced by faulty pol β gap-filling could impair coordination between pol β and DNA ligase. Ligation failure is associated with 5'-AMP addition to the repair intermediate and accumulation of strand breaks that could be more toxic than the initial DNA lesions. Here, we provide an overview of the consequences of ligation failure in the last step of BER. We also discuss DNA-end processing mechanisms that could play roles in reversal of impaired BER. PMID:26596511

  19. 3CAPS – a structural AP–site analogue as a tool to investigate DNA base excision repair

    Schuermann, David; Scheidegger, Simon P.; Weber, Alain R.; Bjørås, Magnar; Leumann, Christian J.; Schär, Primo

    2016-01-01

    Abasic sites (AP-sites) are frequent DNA lesions, arising by spontaneous base hydrolysis or as intermediates of base excision repair (BER). The hemiacetal at the anomeric centre renders them chemically reactive, which presents a challenge to biochemical and structural investigation. Chemically more stable AP-site analogues have been used to avoid spontaneous decay, but these do not fully recapitulate the features of natural AP–sites. With its 3′–phosphate replaced by methylene, the abasic site analogue 3CAPS was suggested to circumvent some of these limitations. Here, we evaluated the properties of 3CAPS in biochemical BER assays with mammalian proteins. 3CAPS-containing DNA substrates were processed by APE1, albeit with comparably poor efficiency. APE1-cleaved 3CAPS can be extended by DNA polymerase β but repaired only by strand displacement as the 5′–deoxyribophosphate (dRP) cannot be removed. DNA glycosylases physically and functionally interact with 3CAPS substrates, underlining its structural integrity and biochemical reactivity. The AP lyase activity of bifunctional DNA glycosylases (NTH1, NEIL1, FPG), however, was fully inhibited. Notably, 3CAPS-containing DNA also effectively inhibited the activity of bifunctional glycosylases on authentic substrates. Hence, the chemically stable 3CAPS with its preserved hemiacetal functionality is a potent tool for BER research and a potential inhibitor of bifunctional DNA glycosylases. PMID:26733580

  20. C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins.

    Anderson, Edward N; Corkins, Mark E; Li, Jia-Cheng; Singh, Komudi; Parsons, Sadé; Tucey, Tim M; Sorkaç, Altar; Huang, Huiyan; Dimitriadi, Maria; Sinclair, David A; Hart, Anne C

    2016-03-01

    Moderate stress can increase lifespan by hormesis, a beneficial low-level induction of stress response pathways. 5'-fluorodeoxyuridine (FUdR) is commonly used to sterilize Caenorhabditis elegans in aging experiments. However, FUdR alters lifespan in some genotypes and induces resistance to thermal and proteotoxic stress. We report that hypertonic stress in combination with FUdR treatment or inhibition of the FUdR target thymidylate synthase, TYMS-1, extends C. elegans lifespan by up to 30%. By contrast, in the absence of FUdR, hypertonic stress decreases lifespan. Adaptation to hypertonic stress requires diminished Notch signaling and loss of Notch co-ligands leads to lifespan extension only in combination with FUdR. Either FUdR treatment or TYMS-1 loss induced resistance to acute hypertonic stress, anoxia, and thermal stress. FUdR treatment increased expression of DAF-16 FOXO and the osmolyte biosynthesis enzyme GPDH-1. FUdR-induced hypertonic stress resistance was partially dependent on sirtuins and base excision repair (BER) pathways, while FUdR-induced lifespan extension under hypertonic stress conditions requires DAF-16, BER, and sirtuin function. Combined, these results demonstrate that FUdR, through inhibition of TYMS-1, activates stress response pathways in somatic tissues to confer hormetic resistance to acute and chronic stress. C. elegans lifespan studies using FUdR may need re-interpretation in light of this work. PMID:26854551

  1. An inverse switch in DNA base excision and strand break repair contributes to melphalan resistance in multiple myeloma cells.

    Mirta M L Sousa

    Full Text Available Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating DNA damage signaling and -repair in RPMI8226 multiple myeloma cells and its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state levels of DNA glycosylases UNG2, NEIL1 and MPG in the resistant cells and cross-resistance to agents inducing their respective DNA base lesions. Conversely, repair of alkali-labile sites was apparently enhanced in the resistant cells, as substantiated by alkaline comet assay, autoribosylation of PARP-1, and increased sensitivity to PARP-1 inhibition by 4-AN or KU58684. Reduced base-excision and enhanced single-strand break repair would both contribute to the observed reduction in genomic alkali-labile sites, which could jeopardize productive processing of the more cytotoxic Melphalan-induced interstrand DNA crosslinks (ICLs. Furthermore, we found a marked upregulation of proteins in the non-homologous end-joining (NHEJ pathway of double-strand break (DSB repair, likely contributing to the observed increase in DSB repair kinetics in the resistant cells. Finally, we observed apparent upregulation of ATR-signaling and downregulation of ATM-signaling in the resistant cells. This was accompanied by markedly increased sensitivity towards Melphalan in the presence of ATR-, DNA-PK, or CHK1/2 inhibitors whereas no sensitizing effect was observed subsequent to ATM inhibition, suggesting that replication blocking lesions are primary triggers of the DNA damage response in the Melphalan resistant cells. In conclusion, Melphalan resistance is apparently contributed by modulation of the DNA damage response at multiple levels, including downregulation of specific repair pathways to avoid repair intermediates that could impair efficient processing of cytotoxic ICLs and ICL-induced DSBs. This study has revealed several novel

  2. DNA polymerase X from Deinococcus radiodurans implicated in bacterial tolerance to DNA damage is characterized as a short patch base excision repair polymerase.

    Khairnar, Nivedita P; Misra, Hari S

    2009-09-01

    The Deinococcus radiodurans R1 genome encodes an X-family DNA repair polymerase homologous to eukaryotic DNA polymerase beta. The recombinant deinococcal polymerase X (PolX) purified from transgenic Escherichia coli showed deoxynucleotidyltransferase activity. Unlike the Klenow fragment of E. coli, this enzyme showed short patch DNA synthesis activity on heteropolymeric DNA substrate. The recombinant enzyme showed 5'-deoxyribose phosphate (5'-dRP) lyase activity and base excision repair function in vitro, with the help of externally supplied glycosylase and AP endonuclease functions. A polX disruption mutant of D. radiodurans expressing 5'-dRP lyase and a truncated polymerase domain was comparatively less sensitive to gamma-radiation than a polX deletion mutant. Both mutants showed higher sensitivity to hydrogen peroxide. Excision repair mutants of E. coli expressing this polymerase showed functional complementation of UV sensitivity. These results suggest the involvement of deinococcal polymerase X in DNA-damage tolerance of D. radiodurans, possibly by contributing to DNA double-strand break repair and base excision repair. PMID:19542005

  3. Excised radicle tips as a source of genomic DNA for PCR-based genotyping and melting curve analysis in cotton

    P Srinivasa Rao; P Sateesh Kumar; Ramesh V Sonti

    2013-03-01

    Genomic DNA isolation in cotton is complicated because of the presence of secondary metabolites that are inhibitory to PCR amplification. We report here that radicle tips, but not other parts of cotton seedlings, yield high-quality DNA that is readily amenable for PCR. The radicle-tip-excised seedlings retain viability because of the formation of adventitious roots. We demonstrate the utility of this method in distinguishing homozygotes from heterozygotes in a cotton breeding population and in hybrid seed purity testing.

  4. The role of base excision repair in the development of primary open angle glaucoma in the Polish population

    Cuchra, Magda; Markiewicz, Lukasz; Mucha, Bartosz [Department of Clinical Chemistry and Biochemistry, Medical University of Lodz (Poland); Pytel, Dariusz [The Abramson Family Cancer Research Institute, Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425 (United States); Szymanek, Katarzyna [Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw (Poland); Szemraj, Janusz [Department of Medical Biochemistry, Medical University of Lodz, Lodz (Poland); Szaflik, Jerzy; Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw (Poland); Majsterek, Ireneusz, E-mail: ireneusz.majsterek@umed.lodz.pl [Department of Clinical Chemistry and Biochemistry, Medical University of Lodz (Poland)

    2015-08-15

    Highlights: • We suggested the association of XRCC1 gene with the increase risk of POAG development. • We indicated the association of clinical factor and XRCC1, MUTYH, ADPRT and APE1 genes with POAG progression. • We postulated the increase level of oxidative DNA damage in group of patients with POAG in relation to healthy controls. • We suggested the slightly decrease ability to repair of oxidative DNA damage. • This is the first data that showed the role of BER mechanism in POAG pathogenesis. - Abstract: Glaucoma is a leading cause of irreversible blindness in developing countries. Previous data have shown that progressive loss of human TM cells may be connected with chronic exposure to oxidative stress. This hypothesis may suggest a role of the base excision repair (BER) pathway of oxidative DNA damage in primary open angle glaucoma (POAG) patients. The aim of our study was to evaluate an association of BER gene polymorphism with a risk of POAG. Moreover, an association of clinical parameters was examined including cup disk ratio (c/d), rim area (RA) and retinal nerve fiber layer (RNFL) with glaucoma progression according to BER gene polymorphisms. Our research included 412 patients with POAG and 454 healthy controls. Gene polymorphisms were analyzed by PCR-RFLP. Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. The 399Arg/Gln genotype of the XRCC1 gene (OR 1.38; 95% CI 1.02–1.89 p = 0.03) was associated with an increased risk of POAG occurrence. It was indicated that the 399Gln/Gln XRCC1 genotype might increase the risk of POAG progression according to the c/d ratio (OR 1.67; 95% CI 1.07–2.61 P = 0.02) clinical parameter. Moreover, the association of VF factor with 148Asp/Glu of APE1 genotype distribution and POAG progression (OR 2.25; 95% CI 1.30–3.89) was also found. Additionally, the analysis of the 324Gln/His MUTYH polymorphism gene distribution in the patient group according to RNFL factor showed that it might

  5. The role of base excision repair in the development of primary open angle glaucoma in the Polish population

    Highlights: • We suggested the association of XRCC1 gene with the increase risk of POAG development. • We indicated the association of clinical factor and XRCC1, MUTYH, ADPRT and APE1 genes with POAG progression. • We postulated the increase level of oxidative DNA damage in group of patients with POAG in relation to healthy controls. • We suggested the slightly decrease ability to repair of oxidative DNA damage. • This is the first data that showed the role of BER mechanism in POAG pathogenesis. - Abstract: Glaucoma is a leading cause of irreversible blindness in developing countries. Previous data have shown that progressive loss of human TM cells may be connected with chronic exposure to oxidative stress. This hypothesis may suggest a role of the base excision repair (BER) pathway of oxidative DNA damage in primary open angle glaucoma (POAG) patients. The aim of our study was to evaluate an association of BER gene polymorphism with a risk of POAG. Moreover, an association of clinical parameters was examined including cup disk ratio (c/d), rim area (RA) and retinal nerve fiber layer (RNFL) with glaucoma progression according to BER gene polymorphisms. Our research included 412 patients with POAG and 454 healthy controls. Gene polymorphisms were analyzed by PCR-RFLP. Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. The 399Arg/Gln genotype of the XRCC1 gene (OR 1.38; 95% CI 1.02–1.89 p = 0.03) was associated with an increased risk of POAG occurrence. It was indicated that the 399Gln/Gln XRCC1 genotype might increase the risk of POAG progression according to the c/d ratio (OR 1.67; 95% CI 1.07–2.61 P = 0.02) clinical parameter. Moreover, the association of VF factor with 148Asp/Glu of APE1 genotype distribution and POAG progression (OR 2.25; 95% CI 1.30–3.89) was also found. Additionally, the analysis of the 324Gln/His MUTYH polymorphism gene distribution in the patient group according to RNFL factor showed that it might

  6. Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase {beta} in long patch base excision repair

    Sukhanova, Maria; Khodyreva, Svetlana [Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk (Russian Federation); Lavrik, Olga, E-mail: lavrik@niboch.nsc.ru [Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk (Russian Federation)

    2010-03-01

    Poly(ADP-ribose)polymerase 1 (PARP1), functioning as DNA nick-sensor, interacts with base excision repair (BER) DNA intermediates containing single-strand breaks. When bound to DNA breaks, PARP1 catalyzes synthesis of poly(ADP-ribose) covalently attached to itself and some nuclear proteins. Autopoly(ADP-ribosyl)ation of PARP1 facilitates its dissociation from DNA breaks and is considered as a factor regulating DNA repair. In the study, using system reconstituted from purified BER proteins, bovine testis nuclear extract and model BER DNA intermediates, we examined the influence of PARP1 and its autopoly(ADP-ribosyl)ation on DNA polymerase {beta} (Pol {beta})-mediated long patch (LP) BER DNA synthesis that is accomplished through a cooperation between Pol {beta} and apurinic/apyrimidinic endonuclease1 (APE1) or flap endonuclease 1 (FEN1) and gap-filling activity of Pol {beta}. PARP1 upon interaction with nicked LP BER DNA intermediated, formed after gap-filling, was shown to suppress the subsequent steps in LP pathway. PARP1 interferes with APE1-dependent stimulation of DNA synthesis by Pol {beta} via strand-displacement mechanism. PARP1 also represses Pol {beta}/FEN1-mediated LP BER DNA synthesis via a 'gap translation' mechanism inhibiting FEN1 activity on the nicked DNA intermediate. Poly(ADP-ribosyl)ation of PARP1 abolishes its inhibitory influence on LP BER DNA synthesis catalyzed by Pol {beta} both via APE1-mediated strand-displacement and FEN1-mediated 'gap translation' mechanism. Thus PARP1 may act as a negative regulator of Pol {beta} activity in LP BER pathway and poly(ADP-ribosyl)ation of PARP1 seems to play a critical role in enablement of Pol {beta}-mediated DNA synthesis in this process. In contrast, interaction of PARP1 with one nucleotide gapped DNA mimicking the intermediate of short patch (SP) BER slightly inhibits the gap-filling activity of Pol {beta} and the overall efficiency of SP BER is practically unaffected by PARP1. Thus

  7. Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase β in long patch base excision repair

    Poly(ADP-ribose)polymerase 1 (PARP1), functioning as DNA nick-sensor, interacts with base excision repair (BER) DNA intermediates containing single-strand breaks. When bound to DNA breaks, PARP1 catalyzes synthesis of poly(ADP-ribose) covalently attached to itself and some nuclear proteins. Autopoly(ADP-ribosyl)ation of PARP1 facilitates its dissociation from DNA breaks and is considered as a factor regulating DNA repair. In the study, using system reconstituted from purified BER proteins, bovine testis nuclear extract and model BER DNA intermediates, we examined the influence of PARP1 and its autopoly(ADP-ribosyl)ation on DNA polymerase β (Pol β)-mediated long patch (LP) BER DNA synthesis that is accomplished through a cooperation between Pol β and apurinic/apyrimidinic endonuclease1 (APE1) or flap endonuclease 1 (FEN1) and gap-filling activity of Pol β. PARP1 upon interaction with nicked LP BER DNA intermediated, formed after gap-filling, was shown to suppress the subsequent steps in LP pathway. PARP1 interferes with APE1-dependent stimulation of DNA synthesis by Pol β via strand-displacement mechanism. PARP1 also represses Pol β/FEN1-mediated LP BER DNA synthesis via a 'gap translation' mechanism inhibiting FEN1 activity on the nicked DNA intermediate. Poly(ADP-ribosyl)ation of PARP1 abolishes its inhibitory influence on LP BER DNA synthesis catalyzed by Pol β both via APE1-mediated strand-displacement and FEN1-mediated 'gap translation' mechanism. Thus PARP1 may act as a negative regulator of Pol β activity in LP BER pathway and poly(ADP-ribosyl)ation of PARP1 seems to play a critical role in enablement of Pol β-mediated DNA synthesis in this process. In contrast, interaction of PARP1 with one nucleotide gapped DNA mimicking the intermediate of short patch (SP) BER slightly inhibits the gap-filling activity of Pol β and the overall efficiency of SP BER is practically unaffected by PARP1. Thus, PARP1 differentially influences DNA synthesis in SP- and

  8. Oxidative stress alters base excision repair pathway and increases apoptotic response in Apurinic/apyrimidinic endonuclease 1/Redox factor-1 haploinsufficient mice

    Unnikrishnan, Archana; Raffoul, Julian J.; Patel, Hiral V.; Prychitko, Thomas M.; Anyangwe, Njwen; Meira, Lisiane B.; Friedberg, Errol C.; Cabelof, Diane C.; Heydari, Ahmad R.

    2009-01-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-κB, and the major 5’-endonuclease in base excision repair (BER). We utilized mice containing heterozygous gene-targeted deletion of APE1/Ref-1 (Apex+/-) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency re...

  9. 碱基切除修复与抗肿瘤药物耐药%Base excision repair and antineoplastic drug resistance

    况里杉; 王宇亮; 周向东

    2013-01-01

    Chemotherapy is one of the main methods to treat malignant tumors in clinical practice. Resistance to antineoplastic agents is one of the important reasons for treatment failure. The antineoplastic mechanism of various chemotherapeutic agents is to cause DNA damage, then result in apoptosis of tumor cells. It is suggested that the function of DNA repair is directly associated with the efficacy of antineoplastic agents. Current studies suggest that there are four major DNA repair pathways including BER (base excision repair), NER (nucleotide excision repair), MMR (mismatch repair) and DSBR (double strand break repair). Of these four pathways, BER is one of the main mechanisms of DNA repair and its malfunction is closely related to the resistance to antineoplastic agents. Recently, many kinds of agents and strategies targeting BER have been developed to reverse chemoresistance. This review summarizes the progress in research in this area and discusses the mechanism of resistance to antineoplastic agents and the potential preventive and therapeutic strategies.%化疗是目前临床上治疗肿瘤的主要方法之一,抗肿瘤药物耐药则是导致肿瘤治疗失败的重要原因之一.多种化疗药物抗肿瘤的主要机制是引起DNA损伤,进而导致肿瘤细胞凋亡;因此,DNA修复功能状态与抗肿瘤药物疗效有着直接的关系.目前,已知有4种主要的DNA修复途径:碱基切除修复(base excision repair,BER)、核苷酸切除修复(nucleotide excision repair,NER)、错配修复(mismatch repair,MMR)和双键断裂修复(double strand break repair,DSBR).其中,BER是主要的DNA修复机制之一,其修复功能异常与抗肿瘤药物耐药有着密切的联系.近年来,以BER为靶点开发了多种逆转耐药的药物或方法.本文将简要综述相关的研究进展,深入探讨抗肿瘤药物耐药的发生机制及防治措施.

  10. Nuclear translocation contributes to regulation of DNA excision repair activities

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne; Nielsen, Finn Cilius; Rasmussen, Lene Juel

    2009-01-01

    DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA, it is...... co-import appears to be a mechanism employed by the composite repair systems NER and MMR to enhance and regulate nuclear accumulation of repair proteins thereby ensuring faithful DNA repair....

  11. Value of histopathologic analysis of subcutis excisions by general practitioners

    Verweij Wim

    2007-01-01

    Full Text Available Abstract Background Only around 60% of skin lesions excised by GPs are referred to a pathologist. Clinical diagnoses of skin excisions by GPs may not be very accurate. Subcutis excisions are rarely done by GPs, and there is hence little information in the literature on the histopathological yield of subcutis excisions by GPs with regard to malignancies. The aim of this study was to evaluate the yield of histopathological investigation of a relatively large group of subcutis excisions by GPs, with special emphasis on discrepancies between clinical and histopathological diagnoses of malignancy. Methods We investigated a series of 90 subcutis excisions, which was derived from a database of consecutive GP submissions from the years 1999–2000 where in the same time period 4595 skin excisions were performed by the same group of GPs. This underlines the apparent reluctance of GPs to perform subcutis excisions. Results The final diagnosis was benign in 88 cases (97.8% and malignant in 2 cases (2.2%. Seven cases had no clinical diagnosis, all of which were benign. Of the 83 clinically benign cases, 81 (97.6% were indeed benign and 2 (2.4% were malignant: one Merkel cell carcinoma and one dermatofibrosarcoma protuberans. The former was clinically thought to be a lipoma, and the latter a trichilemmal cyst. The dermatofibrosarcoma protuberans presented at the age of 27, and the Merkel cell carcinoma at the age of 60. Both were incompletely removed and required re-excision by a surgical oncologist. Conclusion Histopathological investigation of subcutis excisions by GPs yields unexpected and rare malignancies in about 2% of cases that may initially be excised inadequately. Based on these data, and because of the relatively rareness of these type of excisions, it could be argued that it may be worthwhile to have all subcutis excisions by GPs routinely investigated by histopathology.

  12. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes

    Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFß1, IGFBP3) were evaluated. Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; 95% CI 1.3–3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFß1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P. Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role

  13. Base excision repair efficiency and mechanism in nuclear extracts are influenced by the ratio between volume of nuclear extraction buffer and nuclei—Implications for comparative studies

    Highlights: • We examine effect of volume of extraction buffer relative to volume of isolated nuclei on repair activity of nuclear extract. • Base excision repair activity of nuclear extracts prepared from the same batch and number of nuclei varies inversely with the volume of nuclear extraction buffer. • Effect of the volume of extraction buffer on BER activity of nuclear extracts can only be partially reversed after concentration of the more diluted extract by ultrafiltration. - Abstract: The base excision repair (BER) pathway corrects many different DNA base lesions and is important for genomic stability. The mechanism of BER cannot easily be investigated in intact cells and therefore in vitro methods that reflect the in vivo processes are in high demand. Reconstitution of BER using purified proteins essentially mirror properties of the proteins used, and does not necessarily reflect the mechanism as it occurs in the cell. Nuclear extracts from cultured cells have the capacity to carry out complete BER and can give important information on the mechanism. Furthermore, candidate proteins in extracts can be inhibited or depleted in a controlled way, making defined extracts an important source for mechanistic studies. The major drawback is that there is no standardized method of preparing nuclear extract for BER studies, and it does not appear to be a topic given much attention. Here we have examined BER activity of nuclear cell extracts from HeLa cells, using as substrate a circular DNA molecule with either uracil or an AP-site in a defined position. We show that BER activity of nuclear extracts from the same batch of cells varies inversely with the volume of nuclear extraction buffer relative to nuclei volume, in spite of identical protein concentrations in the BER assay mixture. Surprisingly, the uracil–DNA glycosylase activity (mainly UNG2), but not amount of UNG2, also correlated negatively with the volume of extraction buffer. These studies demonstrate

  14. Polymorphisms in base excision DNA repair genes and association with melanoma risk in a pilot study on Central-South Italian population.

    Santonocito, Concetta; Scapaticci, Margherita; Penitente, Romina; Paradisi, Andrea; Capizzi, Rodolfo; Lanza-Silveri, Sara; Ficarra, Silvana; Landi, Francesco; Zuppi, Cecilia; Capoluongo, Ettore

    2012-10-01

    Base excision repair plays a key role in the removing of DNA damage from exposure to endogenous and exogenous carcinogens. The BER pathway removes alterations of a single oxidized, reduced or methylated base. Recently some studies have explored the association between risk for cutaneous melanoma and non-synonymous single-nucleotide polymorphisms (nsSNPs) in DNA-repair genes, although with contradictory results. We hypothesized that common nsSNPs of BER genes, specifically ADPRT rs1136410, XRCC1 rs25487, rs25489, rs1799782, APEX1 rs1130409, OGG1 rs1052133, LIG3 rs3136025 and MUTYH rs3219466, may contribute to risk of melanoma. The aim of this study is to investigate whether or not a correlation between these nsSNPs and melanoma risk and/or aggressiveness is present. 167 melanoma patients and 186 healthy control subjects were analysed. By multivariate statistical analysis no association was found between nsSNP and melanoma aggressiveness, while only the two XRCC1 (rs25487 and rs25489) nsSNPs showed a strong correlation (p<0.001) with melanoma risk. To our knowledge this is the first study reporting an association between BER nsSNPs and melanoma risk in Central-South Italian individuals. Our findings, if confirmed in larger population studies, will allow the inclusion of these XRCC1 nsSNPs in a screening panel for those individuals at higher risk for melanoma. PMID:22687647

  15. Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice.

    Unnikrishnan, Archana; Raffoul, Julian J; Patel, Hiral V; Prychitko, Thomas M; Anyangwe, Njwen; Meira, Lisiane B; Friedberg, Errol C; Cabelof, Diane C; Heydari, Ahmad R

    2009-06-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is the redox regulator of multiple stress-inducible transcription factors, such as NF-kappaB, and the major 5'-endonuclease in base excision repair (BER). We utilized mice containing a heterozygous gene-targeted deletion of APE1/Ref-1 (Apex(+/-)) to determine the impact of APE1/Ref-1 haploinsufficiency on the processing of oxidative DNA damage induced by 2-nitropropane (2-NP) in the liver tissue of mice. APE1/Ref-1 haploinsufficiency results in a significant decline in NF-kappaB DNA-binding activity in response to oxidative stress in liver. In addition, loss of APE1/Ref-1 increases the apoptotic response to oxidative stress, in which significant increases in GADD45g expression, p53 protein stability, and caspase activity are observed. Oxidative stress displays a differential impact on monofunctional (UNG) and bifunctional (OGG1) DNA glycosylase-initiated BER in the liver of Apex(+/-) mice. APE1/Ref-1 haploinsufficiency results in a significant decline in the repair of oxidized bases (e.g., 8-OHdG), whereas removal of uracil is increased in liver nuclear extracts of mice using an in vitro BER assay. Apex(+/-) mice exposed to 2-NP displayed a significant decline in 3'-OH-containing single-strand breaks and an increase in aldehydic lesions in their liver DNA, suggesting an accumulation of repair intermediates of failed bifunctional DNA glycosylase-initiated BER. PMID:19268524

  16. Is the Oxidative DNA Damage Level of Human Lymphocyte Correlated with the Antioxidant Capacity of Serum or the Base Excision Repair Activity of Lymphocyte?

    Yi-Chih Tsai

    2013-01-01

    Full Text Available A random screening of human blood samples from 24 individuals of nonsmoker was conducted to examine the correlation between the oxidative DNA damage level of lymphocytes and the antioxidant capacity of serum or the base excision repair (BER activity of lymphocytes. The oxidative DNA damage level was measured with comet assay containing Fpg/Endo III cleavage, and the BER activity was estimated with a modified comet assay including nuclear extract of lymphocytes for enzymatic cleavage. Antioxidant capacity was determined with trolox equivalent antioxidant capacity assay. We found that though the endogenous DNA oxidation levels varied among the individuals, each individual level appeared to be steady for at least 1 month. Our results indicate that the oxidative DNA damage level is insignificantly or weakly correlated with antioxidant capacity or BER activity, respectively. However, lymphocytes from carriers of Helicobacter pylori (HP or Hepatitis B virus (HBV tend to give higher levels of oxidative DNA damage (P<0.05. Though sera of this group of individuals show no particular tendency with reduced antioxidant capacity, the respective BER activities of lymphocytes are lower in average (P<0.05. Thus, reduction of repair activity may be associated with the genotoxic effect of HP or HBV infection.

  17. The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis.

    Ida Casorelli

    Full Text Available BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/- mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS. The Mutyh(-/- phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/- mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/- mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+ regulatory T cells were observed only in Mutyh(-/- mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

  18. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

    Ana Osorio

    2014-04-01

    Full Text Available Single Nucleotide Polymorphisms (SNPs in genes involved in the DNA Base Excision Repair (BER pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase, and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2 gene (HR: 1.09, 95% CI (1.03-1.16, p = 2.7 × 10(-3 for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3. DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

  19. POLYMORPHISMS IN THE DNA BASE EXCISION REPAIR GENES APEX1 AND XRCC1 AND LUNG CANCER RISK IN XUAN WEI, CHINA

    The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in revers...

  20. Multidirectional Vector Excision Leads to Better Outcomes than Traditional Elliptical Excision of Facial Congenital Melanocytic Nevus

    Seung Il Oh

    2013-09-01

    Full Text Available Background The elliptical excision is the standard method of removing benign skin lesions,such as congenital melanocytic nevi. This technique allows for primary closure, with little to nodog-ear deformity, but may sacrifice normal tissue adjacent to the lesion, resulting in scarswhich are unnecessarily long. This study was designed to compare the predicted results ofelliptical excision with those resulting from our excision technique.Methods Eighty-two patients with congenital melanocytic nevus on the face were prospectivelystudied. Each lesion was examined and an optimal ellipse was designed and marked onthe skin. After an incision on one side of the nevus margin, subcutaneous undermining wasperformed in the appropriate direction. The skin flap was pulled up and approximated alongseveral vectors to minimize the occurrence of dog-ear deformity.Results Overall, the final wound length was 21.1% shorter than that achieved by ellipticalexcision. Only 8.5% of the patients required dog-ear repair. There was no significant distortionof critical facial structures. All of the scars were deemed aesthetically acceptable based ontheir Patient and Observer Scar Assessment Scale scores.Conclusions When compared to elliptical excision, our technique appears to minimize dogeardeformity and decrease the final wound length. This technique should be considered analternative method for excision of facial nevi.

  1. Correlation between base-excision repair gene polymorphisms and levels of in-vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes.

    Hongping Yu

    Full Text Available In vitro benzo[a]pyrene diol epoxide (BPDE-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual's DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P(trend = 0.030. Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36-0.98 and adjusted OR = 0.47, 95% CI: 0.26-0.86, respectively; P(trend = 0.012 among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512. Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression.

  2. Application of a Pattern-based Classification System for Invasive Endocervical Adenocarcinoma in Cervical Biopsy, Cone and Loop Electrosurgical Excision (LEEP) Material: Pattern on Cone and LEEP is Predictive of Pattern in the Overall Tumor.

    Djordjevic, Bojana; Parra-Herran, Carlos

    2016-09-01

    A pattern-based classification system has been recently proposed for invasive endocervical adenocarcinoma, which is predictive of the risk of nodal metastases. Identifying cases at risk of nodal involvement is most relevant at the time of biopsy and loop electrosurgical excision procedure (LEEP) to allow for optimal surgical planning, and, most importantly, consideration of lymphadenectomy. This study aims to determine the topography of patterns of stromal invasion in invasive endocervical adenocarcinoma with emphasis on patterns in biopsy, cone, and LEEP. Invasive pattern was assessed following the pattern-based classification (Patterns A, B, and C) in 47 invasive endocervical adenocarcinomas treated with hysterectomy or trachelectomy and correlated with pattern of invasion at the tumor surface (2 mm of tumor depth) and on preoperative biopsy and cone/LEEP. Patterns A, B, and C were present in 21.3%, 36.2%, and 42.5% of cases, respectively. Most pattern A cases were Stage IA (90%), whereas most Pattern B and C cases were Stage IB (76.5% and 80%, respectively). Horizontal spread was on average larger in Pattern C (24.1 mm) than in Patterns A and B (7.7 and 12.3 mm, respectively). Pattern at the tumor surface correlated with the overall pattern in 95.7% of cases. Concordance between patterns at cone/LEEP and hysterectomy was 92.8%; the only discrepant case was upgraded from Pattern A on LEEP to C on final excision. Agreement between patterns in biopsy and the overall tumor, however, was only 37.5%. In all discrepant cases, biopsy failed to reveal destructive invasion, which was evident on excision. All discrepant biopsies with pattern A showed glandular complexity resembling exophytic papillary growth but did not meet criteria for destructive invasion. On excision, marked gland confluence with papillary architecture was evident. We conclude that the pattern of invasion on cone/LEEP is a good predictor of pattern of invasion on hysterectomy, particularly if there is

  3. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature

    Vilmar, A.; Sorensen, J.B.

    2009-01-01

    BACKGROUND: Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementat......BACKGROUND: Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross......-complementation group 1 (ERCC1) has shown potential as a predictive marker in patients with NSCLC treated with cisplatin-based chemotherapy. Carboplatin has gained widespread use in the treatment of advanced NSCLC and its mechanisms of action are likely similar to that of cisplatin. MATERIALS AND METHODS: A literature...... articles and 1 clinical abstract were identified. Laboratory methods were mainly RT-PCR (reverse transcriptase polymerase chain reaction) or immunohistochemistry (IHC) for expression of ERCC1. Preclinical studies pointed towards similar mechanisms of chemotherapy-resistance among platinum compounds. A...

  4. Nucleotide excision repair in humans.

    Spivak, Graciela

    2015-12-01

    The demonstration of DNA damage excision and repair replication by Setlow, Howard-Flanders, Hanawalt and their colleagues in the early 1960s, constituted the discovery of the ubiquitous pathway of nucleotide excision repair (NER). The serial steps in NER are similar in organisms from unicellular bacteria to complex mammals and plants, and involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. The transcription-coupled repair (TCR) subpathway of NER, discovered nearly two decades later, is dedicated to the removal of lesions from the template DNA strands of actively transcribed genes. In this review I will outline the essential factors and complexes involved in NER in humans, and will comment on additional factors and metabolic processes that affect the efficiency of this important process. PMID:26388429

  5. Moving black holes via singularity excision

    We present a singularity excision algorithm appropriate for numerical simulations of black holes moving throughout the computational domain. The method is an extension of the excision procedure previously used to obtain stable simulations of single, non-moving black holes. The excision procedure also shares elements used in recent work to study the dynamics of a scalar field in the background of a single, boosted black hole. The excision method is tested with single black-hole evolutions using a coordinate system in which the coordinate location of the black hole, and thus the excision boundary, moves throughout the computational domain

  6. Effect of radiotherapy on survival of women with locally excised ductal carcinoma in situ of the breast: a Surveillance, Epidemiology, and End Results population-based analysis

    Qian GW

    2015-06-01

    Full Text Available Guo-Wei Qian,1,* Xiao-Jian Ni,1,* Zheng Wang,2 Yi-Zhou Jiang,1 Ke-Da Yu,1 Zhi-Ming Shao1 1Department of Breast Surgery, 2Department of Radiation Oncology, Shanghai Cancer Center and Cancer Institute, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Although it has been previously reported that radiotherapy (RT effectively reduced the incidence of local recurrence of ductal carcinoma in situ (DCIS following breast-conserving surgery (BCS, little is known about the effect of RT on survival of patients with locally excised DCIS. Patients and methods: Using Surveillance, Epidemiology, and End Results registry data, we selected 56,968 female DCIS patients treated with BCS between 1998 and 2007. Overall survival (OS and breast cancer-specific survival (BCSS were compared among patients who received RT or no RT using the Kaplan–Meier methods and Cox proportional hazards regression models. Results: Median follow-up was 91 months. In the multivariable model, patients receiving postoperative RT had better OS than those undergoing BCS alone (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.53–0.67, P<0.001. This pattern remained after stratification by estrogen receptor (ER status and age. In contrast, RT delivery was not significantly associated with improved BCSS (HR 0.71, 95% CI 0.48–1.03, P=0.073. However, after stratifying by the above two variables, RT contributed to better BCSS in ER-negative/borderline patients (HR 0.41, 95% CI 0.19–0.88, P=0.023 and younger patients (≤50 years old; HR 0.37, 95% CI 0.15–0.91, P=0.030. Conclusion: Our analysis confirms the beneficial effect of RT on OS in women with locally excised DCIS and reveals the specific protective effect of RT on BCSS in ER-negative/borderline and younger patients. Keywords: ductal carcinoma in situ, breast cancer, breast-conserving surgery, radiotherapy, survival

  7. Excision repair cross complementation group 1 is a chemotherapy-tolerating gene in cisplatin-based treatment for non-small cell lung cancer.

    Wang, Shoufeng; Pan, Hong; Liu, Desen; Mao, Naiquan; Zuo, Chuantian; Li, Li; Xie, Tong; Huang, Dingming; Huang, Yaoyuan; Pan, Qi; Yang, Li; Wu, Junwei

    2015-02-01

    This study aimed to evaluate the biological functions of excision repair cross complementation goup 1 (ERCC1) in cell proliferation, cell cycle, invasion and cisplatin response of non-small cell lung cancer (NSCLC) cells. Firstly, ERCC1 gene was successfully transfected into H1299 cells by gene cloning and transfection techniques. Then, cell proliferation was determined with the cell growth curve and colony-forming assays. Flow cytometry (FCM) was employed to investigate the cell cycle distribution. The ability of cell invasion was estimated by means of Matrigel invasion assays. Response of NSCLC cells to cisplatin was detected utilizing MTT assays, and the intracellular drug concentrations were determined by the high performance liquid chromatography (HPLC) analysis. Expression of the two cell membrane proteins, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP), was also evaluated utilizing FCM technique. By contrast, ERCC1 expression in the NSCLC A549 cells was silenced by small interfering RNA (siRNA) through RNAi technique. In addition, the cytotoxic effect of cisplatin on A549 cells was detected by MTT assays. In the present study, the results demonstrated that ERCC1 had no effect on cell proliferation, cell cycle and the ability of invasion, but showed significant impact on cisplatin response of the NSCLC H1299 cells. Furthermore, siRNA-induced suppression of ERCC1 evidently enhanced sensitivity to cisplatin of NSCLC A549 cells. Therefore, it is confirmed that ERCC1 is a chemotherapy-tolerating gene and a promising predictor in tailoring chemotherapy of NSCLC. PMID:25434755

  8. Local excision for selected colorectal carcinomas.

    Lawrence, M A; Goldberg, S M

    1989-07-01

    In summary, local excision is a useful tool in the management of selected colorectal carcinomas. The advent of the fibreoptic colonoscope has revised the concept of local excision when dealing with carcinoma-containing polyps of the colon. The clinician now has the means of locally excising certain carcinomas which would have required laparotomy in the not so distant past. In dealing with carcinoma of the rectum, local excision is not advocated for all rectal carcinomas. In fact, when the previously discussed tumour related factors are considered, local excision should be the ultimate procedure in less than 5% of operations performed for rectal carcinomas. However, when appropriately used, local excision provides a less morbid alternative to more radical procedures without compromising patient survival rates or local recurrence rates. PMID:2692739

  9. 27 CFR 26.30 - Excise taxes.

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Excise taxes. 26.30 Section 26.30 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Into the United States From Areas Other Than Puerto Rico and the Virgin Islands § 26.30 Excise...

  10. 27 CFR 70.412 - Excise taxes.

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Excise taxes. 70.412 Section 70.412 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Beer § 70.412 Excise taxes. (a) Collection. Taxes on distilled spirits, wines, and beer are paid...

  11. Nucleotide excision repair in the test tube.

    N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan)

    1995-01-01

    textabstractThe eukaryotic nucleotide excision-repair pathway has been reconstituted in vitro, an achievement that should hasten the full enzymological characterization of this highly complex DNA-repair pathway.

  12. Efficient Excise Taxation: The Evidence from Cigarettes.

    Benjamin, Daniel K; William R. Dougan

    1997-01-01

    The authors develop a model in which optimizing policy makers in adjacent government jurisdictions levy excise taxes on a commodity that has a unique point of production from which all shipments emanate. From this model the authors derive an unusually specific predicted geographical pattern of those excise taxes in which these taxes rise at specific decreasing rate as one moves outward from the point of production. The authors compare these predictions to the observed pattern of cigarette tax...

  13. Intraoral excision of large submental dermoid

    Ankur Bhatnagar; Vinay Kumar Verma; Pankaj Kumar Patel

    2013-01-01

    Sublingual dermoids are the rarest forms of craniofacial dermoids mostly seen in young individuals. Excision of large and deep submental dermoid is generally done via extraoral approach scarring the most prominent part of the face, which can lead to post operative scar hypertrophy and hyperpigmentation especially in non-Caucasian races. Presence of such scars leads to adverse psychological effects in young individuals. Excision via intraoral route, although technically demanding, can be simpl...

  14. Giant rhinophyma: Excision with coblation assisted surgery

    Caner Sahin; Mesut Turker; Bulent Celasun

    2014-01-01

    An 83-year-old man presented with an unusually severe case of rhinophyma. Giant rhinopyhma is very rare in literature. The giant lesion was widely excised using sharp surgical incision and coblation assisted surgery. Using direct coblation to the nasal dorsum may cause edema in the surrounding tissue. There was minimal edema in surrounding tissue using this technique. A full thickness-skin graft was applied after excision. Cosmetic and functional postoperative results were satisfactory.

  15. Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein.

    Kubota, Y; Nash, R. A.; Klungland, A; Schär, P; Barnes, D E.; Lindahl, T

    1996-01-01

    Repair of a uracil-guanine base pair in DNA has been reconstituted with the recombinant human proteins uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta and DNA ligase III. The XRCC1 protein, which is known to bind DNA ligase III, is not absolutely required for the reaction but suppresses strand displacement by DNA polymerase beta, allowing for more efficient ligation after filling of a single nucleotide patch. We show that XRCC1 interacts directly with DNA polym...

  16. Terahertz pulsed imaging of freshly excised human colonic tissues

    Reid, C. B.; Fitzgerald, A; Reese, G.; Goldin, R; Tekkis, P; O Kelly, P. S.; Pickwell-MacPherson, E.; Gibson, A. P.; Wallace, V.P.

    2011-01-01

    We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured...

  17. European Union Harmonized Excise Taxation : Occasional Importation Process

    Tanhua, Taina

    2013-01-01

    This thesis was written with the intent to compile the information related to occasional importation process and European Union harmonized taxation into a single package. The process is based on European Union legislation and the aim of it is to unify the taxation within the internal market area. The national excise duties are not part of the occasional importation process but are partly linked to it. The first part of the thesis discusses the occasional importation of goods subject to ha...

  18. 29 CFR 794.121 - Exclusion of excise taxes.

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Exclusion of excise taxes. 794.121 Section 794.121 Labor... Exclusion of excise taxes. The computation of the annual gross volume of sales of the enterprise for purposes of section 7(b)(3) is made “exclusive of excise taxes.” It will be noted that the excise...

  19. The incision-excision technique in minor auricular deformities.

    Heppt, Werner J

    2004-11-01

    In 1972, in the search for a method to cope with all deformities in protruding ears and other common minor auricular deformities, Claus Walter published a surgical technique based on various incisions and excisions of the cartilage. The procedure consists of a complete separation of the auricle into two parts, combined with remodeling of antihelical, helical, and lobular structures without use of adjusting sutures. Thus, even in patients with stiff and unyielding cartilage and in revisional surgery, pleasing aesthetic results may be achieved. The recurrence rate has found to be reduced markedly. Considering all pros and cons and optional surgical modifications, the incision-excision technique can be adopted for every protruding ear as well as for lop ears, moderate cup ear deformities, and secondary revisions. Because of the extent of cartilage dissection, this technique is not recommended for beginners but should be restricted to experienced surgeons with profound knowledge of basic remodeling procedures. PMID:15778916

  20. PARP-1 enhances the mismatch-dependence of 5′-directed excision in human mismatch repair in vitro

    Liu, Yiyong; Kadyrov, Farid A; Modrich, Paul

    2011-01-01

    End-directed mismatch-provoked excision has been reconstituted in several purified systems. While 3′-directed excision displays a mismatch dependence similar to that observed in nuclear extracts (≈ 20-fold), the mismatch dependence of 5′-directed excision is only 3 to 4-fold, significantly less than that in extracts (8 to 10-fold). Utilizing a fractionation-based approach, we have isolated a single polypeptide that enhances mismatch dependence of reconstituted 5′-directed excision and have sh...

  1. Intraoral excision of large submental dermoid

    Ankur Bhatnagar

    2013-01-01

    Full Text Available Sublingual dermoids are the rarest forms of craniofacial dermoids mostly seen in young individuals. Excision of large and deep submental dermoid is generally done via extraoral approach scarring the most prominent part of the face, which can lead to post operative scar hypertrophy and hyperpigmentation especially in non-Caucasian races. Presence of such scars leads to adverse psychological effects in young individuals. Excision via intraoral route, although technically demanding, can be simplified using basic principles of plastic surgery leading to optimal aesthetic outcome with least downtime. We excised a large sublingual dermoid extending deep to the mylohyoid muscle through intraoral approach with excellent cosmetic results. Clinicians dealing with such lesions should keep these principals in their armamentarium when dealing with this rare subset of cases.

  2. An arteriovenous fistula following chalazion excision

    Dias-Amborcar Yuri

    2007-01-01

    Full Text Available An arteriovenous fistula secondary to a chalazion is a rare occurrence. It may follow spontaneous necrosis or surgical trauma. Digital subtraction angiography and identification of the arterial feeders combined with direct puncture of the nidus and embolization is recommended, as surgical excision becomes much easier and results in a complete excision of the lesion. Conchal cartilage graft is a useful lining material for reconstruction of the tarsal plate due to its natural curvature. It restores lid integrity and ensures a stable and functional eyelid.

  3. Kinetic Mechanism for the Flipping and Excision of 1,N 6-Ethenoadenine by AlkA

    Taylor, Erin L.; O’Brien, Patrick J.

    2014-01-01

    Escherichia coli 3-methyladenine DNA glycosylase II (AlkA), an adaptive response glycosylase with a broad substrate range, initiates base excision repair by flipping a lesion out of the DNA duplex and hydrolyzing the N-glycosidic bond. We used transient and steady state kinetics to determine the minimal mechanism for recognition and excision of 1,N 6-ethenoadenine (εA) by AlkA. The natural fluorescence of this endogenously produced lesion allowed us to directly monitor the nucleotide flipping...

  4. Recombinant methods for screening human DNA excision repair proficiency

    A method for measuring DNA excision repair in response to ultraviolet radiation (UV)-induced DNA damage has been developed, validated, and field-tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiologic studies seeking to investigate associations between excision repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the belief that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum (XP) primarily is a result of the reduced capacity of patients cells to repair UV-induced DNA damage. For assay, UV-irradiated non-replicating recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (CAT) indicator gene is introduced into lymphocytes using DEAE-dextran short-term transfection conditions. Exposure to UV induces transcriptionally-inactivating DNA photoproducts in the plasmid DNA which inactivate CAT gene expression. Excision repair of the damaged CAT gene is monitored indirectly as a function of reactivated CAT enzyme activity following a 40 hour repair/expression incubation period

  5. 29 CFR 779.264 - Excise taxes separately stated.

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Excise taxes separately stated. 779.264 Section 779.264... Coverage Excise Taxes § 779.264 Excise taxes separately stated. A tax is separately stated where it clearly... was no invoice or sales slip. In the absence of a sales slip or invoice, the amount of the tax...

  6. Local excision carcinoma in early stage

    Ji-Dong Gao; Yong-Fu Shao; Jian-Jun Bi; Su-Sheng Shi; Jun Liang; Yu-Hua Hu

    2003-01-01

    AIM: To assess the validity of local excision for the early stage low rectal cancer as an effective treatment alternative to radical resection.METHODS: A retrospective medical chart review was done in 47 patients with early stage low rectal carcinoma who underwent local excision from November 1980 through November 1999 at Cancer Hospital of Chinese Academy of Medical Sciences (CAMS). The patients were treated by either transanal (40 cases), trans-sacral (5 cases), or trans-vaginal (2 cases) excision of tumors and no death was related to surgery. Sixteen patients received postoperative radiotherapy.RESULTS: T1 and T2 lesion was found in 36 (76.6 %) and 11 patients (23.4 %) respectively. The overall local tumor recurrence rate was 14.9 % (7/47), with an average recurrence time of 21 months. Among these 7 recurrent patients, there were 4 T1 and 3 T2 lesions. Microscopically,the surgical incisal margin was negative in 45 (95.7 %) and positive in 2 patients (4.3 %); Both of the later had developed local recurrence. The overall 5-year survival rate was 91.7 %,in which there were 94.4 % for T1 and 83.3 % for T2 tumors.T stage, intravessel tumor thrombosis, lymphocytic infiltration and histological grade were not found to be significant by related to the local recurrence and survival (P>0.05).CONCLUSION: Local tumor excision was a safe procedure for the treatment of early stage low rectal carcinoma with minimal morbidity and mortality, which might serves as one of the primary surgical treatment methods for the disease of this kind.

  7. Fate of Kaluza-Klein black holes: Evaporation or excision?

    We study the evaporation process of black strings which are typical examples of Kaluza-Klein black holes. Taking into account the backreaction of the Hawking radiation, we deduce the evolution equation for the radion field. By solving the evolution equation, we find that the shape of the internal space is necked by the Hawking radiation and the amount of the deformation becomes large as the evaporation proceeds. Based on this analysis, we speculate that the Kaluza-Klein black holes would be excised from the Kaluza-Klein spacetime before the onset of the Gregory-Laflamme instability and therefore before the evaporation

  8. Phonatory characteristics of excised pig, sheep, and cow larynges

    Alipour, Fariborz; Jaiswal, Sanyukta

    2008-01-01

    The purpose of this study was to examine the phonatory characteristics of pig, sheep, and cow excised larynges and to find out which of these animal species is the best model for human phonation. Excised pig, sheep, and cow larynges were prepared and mounted over a tapered tube on the excised bench that supplied pressurized, heated, and humidified air in a manner similar to that for excised canine models. Each excised larynx was subjected to a series of pressure-flow experiments with adductio...

  9. Coding and reimbursement of primary care debridement and excision procedures.

    Zuber, T J; Purvis, J R

    1992-12-01

    Current medical practice requires physicians to accurately report services provided to patients. Patient billing for debridement and excision procedures involves the selection of specific 1992 Physicians' Current Procedural Terminology codes. Although a site-specific surgical procedure code often yields higher reimbursement than a general procedure code, physicians should select the code that most accurately reflects the procedure performed. This review identifies the codes used to report destruction and excision procedures performed by primary care physicians. Included in this review are skin debridement, burn debridement, excision of benign and malignant lesions of the skin and subcutaneous tissue, cyst and ganglion excision, nail excision, anorectal lesion excision, shave, paring, and skin tag excision procedures, and foreign body removal. The Health Care Financing Administration's relative value units and one state's published Medicaid payment rates are included for each procedure code. Instructions are provided for selecting between multiple coding options when more than one code describes the service provided. PMID:1453151

  10. Descriptive Study of Patients Receiving Excision and Radiotherapy for Keloids

    Purpose: To review and describe our institution's outcomes in patients treated with external beam radiotherapy after keloid excision. Methods and Materials: This was a retrospective study. Patients who received radiotherapy between July 1994 and January 2004 after keloid excision were identified. A questionnaire was mailed regarding sociodemographic factors, early and late radiation toxicities, the need for additional therapy, and satisfaction level. All patients had received a total of 15 Gy in three daily 5-Gy fractions. Treatment started within 24 h after surgery and was delivered on a Siemens orthovoltage machine. The data were analyzed using the STATA statistical package. Results: A total of 234 patients were approached. The response rate was 41%, and 75% were female. The mean age was 36.5 years (range, 16-69 years). The patients were mainly of European (53.1%) or African (19.8%) descent. For early toxicity outcomes, 54.2% reported skin redness and 24% reported skin peeling. For late toxicity outcomes, 27% reported telangiectasia and 62% reported permanent skin color changes. No association was found with gender, skin color, or age for the late toxicity outcomes. Of the patients responding, 14.6% required adjuvant treatment. On a visual scale of 1-10 for the satisfaction level, 60% reported a satisfaction level of ≥8. Telangiectasia was the most significant predictor of a low satisfaction level (≤3, p < 0.005). Conclusion: The results of our study have shown that orthovoltage-based radiotherapy after surgical excision for keloids is a good method for the prevention of relapse. It is well tolerated, causes little toxicity, and leads to a high patient satisfaction level

  11. Nucleotide Excision Repair in Caenorhabditis elegans

    Hannes Lans; Wim Vermeulen

    2011-01-01

    Nucleotide excision repair (NER) plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vi...

  12. Histone displacement during nucleotide excision repair

    Dinant, C.; Bartek, J.; Bekker-Jensen, S.

    2012-01-01

    Nucleotide excision repair (NER) is an important DNA repair mechanism required for cellular resistance against UV light and toxic chemicals such as those found in tobacco smoke. In living cells, NER efficiently detects and removes DNA lesions within the large nuclear macromolecular complex called......, thus allowing repair proteins to efficiently access DNA. On the other hand, after completion of the repair, the chromatin must be returned to its previous undamaged state. Chromatin remodeling can refer to three separate but interconnected processes, histone post-translational modifications, insertion...

  13. Photobiomodulatory effects of He-Ne laser on excision wounds

    Prabhu, Vijendra; Rao, Satish B. S.; Kumar, Pramod; Rao, Lakshmi; Mahato, Krishna K.

    2011-03-01

    Presently, great importance has been given to Low Level Laser Therapy (LLLT) with the intent of promoting wound healing process. The present study was aimed to investigate the promotive effect of LLLT on full thickness excision wounds in Swiss albino mice using optical fiber probe based light device. Circular wounds of diameter 15 mm were illuminated with single exposure of various laser doses 1, 2, 3, 4, 6, 8 and 10 J/cm2 along with appropriate controls. Further, an optimal dose of 2 J/cm2 was applied to excision wounds at different post-wounding treatment schedules (0, 24 h and 48 h) to explicate the relations between treatment schedule and its tissue regeneration potential. Wound area, mean wound healing time along with hydroxyproline and glucosamine levels from wound ground tissue was assessed to evaluate the resultant photobiostimulatory outcome. Histological analysis was performed on day 10 of post-wounding. A significant increase in hydroxyproline (P< 0.001) and glucosamine levels (P< 0.01) were observed in 2 J/cm2 irradiation group, which was also substantiated by histological findings. In conclusion, the present study demonstrated that the immediate irradiation of 2 J/cm2 dose following wounding hasten the healing process compared to the unilluminated control.

  14. Multispectral and Photoplethysmography Optical Imaging Techniques Identify Important Tissue Characteristics in an Animal Model of Tangential Burn Excision.

    Thatcher, Jeffrey E; Li, Weizhi; Rodriguez-Vaqueiro, Yolanda; Squiers, John J; Mo, Weirong; Lu, Yang; Plant, Kevin D; Sellke, Eric; King, Darlene R; Fan, Wensheng; Martinez-Lorenzo, Jose A; DiMaio, J Michael

    2016-01-01

    Burn excision, a difficult technique owing to the training required to identify the extent and depth of injury, will benefit from a tool that can cue the surgeon as to where and how much to resect. We explored two rapid and noninvasive optical imaging techniques in their ability to identify burn tissue from the viable wound bed using an animal model of tangential burn excision. Photoplethysmography (PPG) imaging and multispectral imaging (MSI) were used to image the initial, intermediate, and final stages of burn excision of a deep partial-thickness burn. PPG imaging maps blood flow in the skin's microcirculation, and MSI collects the tissue reflectance spectrum in visible and infrared wavelengths of light to classify tissue based on a reference library. A porcine deep partial-thickness burn model was generated and serial tangential excision accomplished with an electric dermatome set to 1.0 mm depth. Excised eschar was stained with hematoxylin and eosin to determine the extent of burn remaining at each excision depth. We confirmed that the PPG imaging device showed significantly less blood flow where burn tissue was present, and the MSI method could delineate burn tissue in the wound bed from the viable wound bed. These results were confirmed independently by a histological analysis. We found these devices can identify the proper depth of excision, and their images could cue a surgeon as to the preparedness of the wound bed for grafting. These image outputs are expected to facilitate clinical judgment in the operating room. PMID:26594863

  15. Excision repair of 5,6-dihydroxydihydrothymine from the DNA of Micrococcus radiodurans

    One of the major ionizing radiation products, 5,6-dihydroxydihydrothymine (thymine glycol), was measured in the DNA of Micrococcus radiodurans following exposure of cells to 6.8-MeV electrons or 254-nm ultraviolet light. Removal of 5,6-dihydroxydihydrothymine was measured in both an ionizing radiation-sensitive strain (262) and a highly radioresistant strain (the wild type W+) of Micrococcus radiodurans. Within 30 min of incubation (330C) following exposure to ultraviolet light (2400 J/m2) approximately 60% of the thymine glycols were excised, whereas in the case of ionizing radiation (250 krad) only 35% were removed from the cellular DNA of the wild-type strain. In contrast less than 50% of the thymine glycols were excised from the sensitive strain. The amount of DNA degradation induced by radiation was less than 10% in both strains. The results suggest a possible correlation between reduced excision repair of base damage and increased radiation sensitivity

  16. Lower Lip Reconstruction after Wide Excision of a Malignancy with Barrel-Shaped Excision or the Webster Modification of the Bernard Operation

    Yong Chan Bae

    2013-01-01

    Full Text Available Background Because there are numerous methods for reconstruction of the lower lip,it is not easy to choose the optimal method. In choosing the surgical method for lowerlip reconstruction, we obtained acceptable outcomes based on our treatment strategy,which included either a barrel-shaped excision or the Webster modification of the Bernardoperation. We report on the surgical outcomes based on our treatment strategy.Methods This study included 26 patients who underwent lower lip reconstructive surgeryfrom September 1996 to September 2010. The operation was done using either a barrelshapedexcision or the Webster modification, considering the location of the defect, the size ofthe defect, and the amount of residual tissue on the lateral side of the vermilion after excision.Results In our series, 3 patients underwent a single barrel-shaped excision, and nine patientsunderwent a double barrel-shaped excision. In addition, the unilateral Webster modificationwas performed on in 6 patients, and there were eight cases of bilateral Webster modification.All of the patients except one were satisfied with the postoperative shape of the lip. In onecase both recurrence and dehiscence occurred. One patient had a good postoperative lip shape,but had difficulty wearing a denture, and also underwent commissuroplasty. Furthermore,there were two patients who complained of drooling, and 4 with paresthesia.Conclusions A soft tissue defect resulting from wide excision of a lower lip malignancy canbe successfully reconstructed using only one of two surgical methods: the barrel-shapedexcision or the Webster modification of the Bernard operation.

  17. Kinetics of excision of purine lesions from DNA by Escherichia coli Fpg protein.

    Karakaya, A; Jaruga, P; Bohr, V A; Grollman, A P; Dizdaroglu, M

    1997-01-01

    The kinetics of excision of damaged purine bases from oxidatively damaged DNA by Escherichia coli Fpg protein were investigated. DNA substrates, prepared by treatment with H2O2/Fe(III)-EDTA or by gamma-irradiation under N2O or air, were incubated with Fpg protein, followed by precipitation of DNA. Precipitated DNA and supernatant fractions were analyzed by gas chromatography/isotope-dilution mass spectrometry. Kinetic studies revealed efficient excision of 8-hydroxyguanine (8-OH-Gua), 2,6-dia...

  18. Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision

    WANG Huixian; Hays, John B.

    2007-01-01

    Eukaryotic mismatch-repair (MMR) proteins MutSα and MutLα couple recognition of base mismatches to strand-specific excision, initiated in vivo at growing 3′ ends and 5′ Okazaki-fragment ends or, in human nuclear extracts, at nicks in exogenous circular substrates. We addressed five biochemical questions relevant to coupling models. Excision remained fully efficient at DNA:MutSα ratios of nearly 1 to 1 at various mismatch-nick distances, suggesting a requirement for only one MutSα molecule per...

  19. Retrorectal tumors: excision by transanal endoscopic microsurgery.

    Zoller, S; Joos, A; Dinter, D; Back, W; Horisberger, K; Post, S; Palma, P

    2007-09-01

    Tumours within the retrorectal space are uncommon. Due to their rarity and diverse symptoms they are often misdiagnosed or mistreated. We report three cases of women presenting a variety of symptoms including increased rectal pain, recurrent abscesses/fistulas and constipation. Upon clinical examination and further investigations using MR scan, endorectal ultrasound and endoscopy, a retrorectal mass was suspected in all three cases. In order to achieve a complete excision of the tumor while minimizing trauma, transanal endoscopic microsurgery (TEM) was performed. The histology of the multicystic tumor revealed in all three cases a tailgut cyst. As far as we know this is the first report describing the use of TEM for surgical treatment of tumors located in the retrorectal space. PMID:18052651

  20. Regulation of nucleotide excision repair through ubiquitination

    Jia Li; Audesh Bhat; Wei Xiao

    2011-01-01

    Nucleotide excision repair (NER) is the most versatile DNA-repair pathway in all organisms.While bacteria require only three proteins to complete the incision step of NER,eukaryotes employ about 30 proteins to complete the same step.Here we summarize recent studies demonstrating that ubiquitination,a post-translational modification,plays critical roles in regulating the NER activity either dependent on or independent of ubiquitin-proteolysis.Several NER components have been shown as targets of ubiquitination while others are actively involved in the ubiquitination process.We argue through this analysis that ubiquitination serves to coordinate various steps of NER and meanwhile connect NER with other related pathways to achieve the efficient global DNA-damage response.

  1. Reshaping the eyebrow by follicular unit transplantation from excised eyebrow in extended infrabrow excision blepharoplasty

    Konishi, Kazuhito

    2012-01-01

    Kazuhito Konishi1, Isao Sugimoto2, Hirohiko Kakizaki3, Akihiro Ichinose41Kobe Academia Clinic, 2Division of Aesthetic Medical Science, Department of Plastic Surgery, Kobe University Graduate School of Medicine, 3Department of Ophthalmology, Aichi Medical University, Nagoya, Aichi, Japan; 4Department of Plastic Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, JapanPurpose: We report the reshaping of the eyebrow by follicular unit transplantation from excised eyebrow skin in ...

  2. Reshaping the eyebrow by follicular unit transplantation from excised eyebrow in extended infrabrow excision blepharoplasty

    Ichinose A

    2012-02-01

    Full Text Available Kazuhito Konishi1, Isao Sugimoto2, Hirohiko Kakizaki3, Akihiro Ichinose41Kobe Academia Clinic, 2Division of Aesthetic Medical Science, Department of Plastic Surgery, Kobe University Graduate School of Medicine, 3Department of Ophthalmology, Aichi Medical University, Nagoya, Aichi, Japan; 4Department of Plastic Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, JapanPurpose: We report the reshaping of the eyebrow by follicular unit transplantation from excised eyebrow skin in extended infrabrow excision blepharoplasty.Methods: The method was carried out in two patients with moderate or significant dermatochalasis. The areas to be excised from the infrabrow and intrabrow skin were decided upon and the area of hair transplantation was planned in the suprabrow area and the tail of the eyebrow. The skin was removed and the excised intrabrow skin was dissected into single follicular units. Tiny incisions were made with a scalpel, and grafts were inserted using fine forceps.Results: Almost all transplanted eyebrow follicles took successfully, resulting in eyebrows of a desirable shape as planned preoperatively. The reshaped eyebrows had a natural appearance since the transplanted hairs were similar to those of the original eyebrow. The eyelids still looked youthful rather than operated-on. Finally, the evidence of blepharoplasty was hardly visible and patient satisfaction was quite high. The patients felt more ease in opening their eyes and obtained a wider visual field.Conclusion: Our study demonstrated excellent results with hair transplantation from eyebrow to eyebrow, a finding which, to our knowledge, has not been previously reported. Our method can be used for selected patients, especially men, with moderate to severe dermatochalasis, who find a reduction or change in the shape of the eyebrow unacceptable.Keywords: blepharoplasty, dermatochalasis, follicular unit transplantation, eyebrow reconstruction

  3. 76 FR 46677 - Indoor Tanning Services; Cosmetic Services Excise Taxes

    2011-08-03

    ... Internal Revenue Service 26 CFR Parts 40 and 49 RIN 1545-BJ40 Indoor Tanning Services; Cosmetic Services Excise Taxes AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of public hearing on... providing guidance on the indoor tanning services excise tax imposed by the Patient Protection...

  4. 75 FR 33740 - Indoor Tanning Services; Cosmetic Services; Excise Taxes

    2010-06-15

    ... Internal Revenue Service 26 CFR Parts 40 and 49 RIN 1545-BJ40 Indoor Tanning Services; Cosmetic Services; Excise Taxes AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed rulemaking by... tanning services excise tax imposed by the Patient Protection and Affordable Care Act. These...

  5. Interference Excision in Spread Spectrum Communications Using Adaptive Positive Time-Frequency Analysis

    Krishnan Sridhar

    2007-01-01

    Full Text Available This paper introduces a novel algorithm to excise single and multicomponent chirp-like interferences in direct sequence spread spectrum (DSSS communications. The excision algorithm consists of two stages: adaptive signal decomposition stage and directional element detection stage based on the Hough-Radon transform (HRT. Initially, the received spread spectrum signal is decomposed into its time-frequency (TF functions using an adaptive signal decomposition algorithm, and the resulting TF functions are mapped onto the TF plane. We then use a line detection algorithm based on the HRT that operates on the image of the TF plane and detects energy varying directional elements that satisfy a parametric constraint. Interference is modeled by reconstructing the corresponding TF functions detected by the HRT, and subtracted from the received signal. The proposed technique has two main advantages: (i it localizes the interferences on the TF plane with no cross-terms, thus facilitating simple filtering techniques based on thresholding of the TF functions, and is an efficient way to excise the interference; (ii it can be used for the detection of any directional interferences that can be parameterized. Simulation results with synthetic models have shown successful performance with linear and quadratic chirp interferences for single and multicomponent interference cases. The proposed method excises the interference even under very low SNR conditions of  dB, and the technique could be easily extended to any interferences that could be represented by a parametric equation in the TF plane.

  6. State cigarette excise taxes - United States, 2010-2011.

    2012-03-30

    Increasing the price of cigarettes reduces the demand for cigarettes, thereby reducing youth smoking initiation and cigarette consumption and decreasing the prevalence of cigarette use in the United States overall, particularly among youths and young adults. The most common way governments have increased the price of cigarettes is by increasing cigarette excise taxes, which currently are imposed by all states and the District of Columbia. To update data on state cigarette excise taxes in 2009, CDC conducted a survey of changes in state cigarette excise taxes during 2010-2011. During that period, eight states increased their cigarette excise taxes, and one state decreased its tax; as a result, the mean state tax increased from $1.34 in 2009 to $1.46 in 2011. Previous evidence indicates that further increases in cigarette excise taxes would be expected to result in further reductions in demand for cigarettes, decreasing smoking and associated morbidity and mortality. PMID:22456118

  7. Resistance to Nucleotide Excision Repair of Bulky Guanine Adducts Opposite Abasic Sites in DNA Duplexes and Relationships between Structure and Function.

    Zhi Liu

    Full Text Available The nucleotide excision repair of certain bulky DNA lesions is abrogated in some specific non-canonical DNA base sequence contexts, while the removal of the same lesions by the nucleotide excision repair mechanism is efficient in duplexes in which all base pairs are complementary. Here we show that the nucleotide excision repair activity in human cell extracts is moderate-to-high in the case of two stereoisomeric DNA lesions derived from the pro-carcinogen benzo[a]pyrene (cis- and trans-B[a]P-N2-dG adducts in a normal DNA duplex. By contrast, the nucleotide excision repair activity is completely abrogated when the canonical cytosine base opposite the B[a]P-dG adducts is replaced by an abasic site in duplex DNA. However, base excision repair of the abasic site persists. In order to understand the structural origins of these striking phenomena, we used NMR and molecular spectroscopy techniques to evaluate the conformational features of 11mer DNA duplexes containing these B[a]P-dG lesions opposite abasic sites. Our results show that in these duplexes containing the clustered lesions, both B[a]P-dG adducts adopt base-displaced intercalated conformations, with the B[a]P aromatic rings intercalated into the DNA helix. To explain the persistence of base excision repair in the face of the opposed bulky B[a]P ring system, molecular modeling results suggest how the APE1 base excision repair endonuclease, that excises abasic lesions, can bind productively even with the trans-B[a]P-dG positioned opposite the abasic site. We hypothesize that the nucleotide excision repair resistance is fostered by local B[a]P residue-DNA base stacking interactions at the abasic sites, that are facilitated by the absence of the cytosine partner base in the complementary strand. More broadly, this study sets the stage for elucidating the interplay between base excision and nucleotide excision repair in processing different types of clustered DNA lesions that are substrates of

  8. Lingual Thyroid Excision with Transoral Robotic Surgery

    Elif Ersoy Callıoglu

    2015-01-01

    Full Text Available Ectopic thyroid gland may be detected at any place between foramen caecaum and normal thyroid localization due to inadequacy of the embryological migration of the thyroid gland. It has a prevalence varying between 1/10.000 and 1/100000 in the community. Usually follow-up without treatment is preferred except for obstructive symptoms, bleeding, and suspicion of malignity. Main symptoms are dysphagia, dysphonia, bleeding, dyspnea, and obstructive sleep apnea. In symptomatic cases, the first described method in surgical treatment is open approach since it is a region difficult to have access to. However, this approach has an increased risk of morbidity and postoperative complications. Transoral robotic surgery, which is a minimally invasive surgical procedure, has advantages such as larger three-dimensional point of view and ease of manipulation due to robotic instruments. In this report, a case at the age of 49 who presented to our clinic with obstructive symptoms increasing within the last year and was found to have lingual thyroid and underwent excision of ectopic thyroid tissue by da Vinci surgical system is presented.

  9. Nucleotide Excision Repair in Caenorhabditis elegans

    Hannes Lans

    2011-01-01

    Full Text Available Nucleotide excision repair (NER plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vitro and live cell experiments, particularly using model systems such as bacteria, yeast, and mammalian cell cultures. In recent years, the versatility of the nematode C. elegans to study DNA damage response (DDR mechanisms including NER has become increasingly clear. In particular, C. elegans seems to be a convenient tool to study NER during the UV response in vivo, to analyze this process in the context of a developing and multicellular organism, and to perform genetic screening. Here, we will discuss current knowledge gained from the use of C. elegans to study NER and the response to UV-induced DNA damage.

  10. Germicidal persistence of teat dips by modified excised teat procedure.

    Schmidt, A L; Oliver, S P; Fydenkevez, M E

    1985-01-01

    An excised teat protocol was modified to evaluate persistence of germicidal activity of teat dips over 8 h. Five teat dip formulations, iodophor (1%), chlorhexidine gluconate (.55%), linear dodecyl benzene sulfonic acid (1.94%), sodium chlorite-lactic acid in a water base, and sodium chlorite-lactic acid in a gel base were tested against Escherichia coli and Klebsiella oxytoca. Iodophor and chlorhexidine had high germicidal activity throughout 8 h, whereas dodecyl benzene sulfonic acid had little activity. Germicidal activity of both sodium chlorite-lactic acid teat dips was high initially but declined with time. The gel base dip, however, remained more germicidal than the water base dip. Results were similar for either organism for most teat dips. However, chlorhexidine was less effective and the gel base dip more effective against Klebsiella oxytoca than Escherichia coli. Standard errors often appeared higher for Klebsiella oxytoca than for Escherichia coli. These assays may prove useful for laboratory screening of teat dips to determine germicidal persistence over time. PMID:3884679

  11. Characteristics of thymine dimer excision from xeroderma pigmentosum chromatin

    We investigated thymine dimer excision from xeroderma pigmentosum (XP) chromatin in the cell-free reconstruction system. The normal-cell extract performed specific dimer excision from native chromatin and DNA isolated from 100 J/m2-irradiated cells. Such an excision in vitro was rapid and required high concentrations of extract. The extracts of XP group A, C and G cells were unable to excise from their own native-chromatin, but capable of excising from chromatin deprived of loosely bound nonhistone proteins with 0.35 M NaCl, as were from purified DNA. Thus, group A, C and G cells are most likely to be defective in the specific XP factors facilitating the excising activity under multicomponent regulation at the chromatin level. Further, either of group A, C and G extracts successfully complemented the native chromatin of the alternative groups. Uniquely, the XP group D extract excised dimers from native chromatin in the normal fashion under the condition. These results suggest that XP group A, C, D and G cells examined may not be defective in the dimer specific endonuclease and exonuclease per se. 19 references, 3 figures, 2 tables

  12. 77 FR 37806 - Disregarded Entities and the Indoor Tanning Services Excise Tax

    2012-06-25

    ... Services Excise Tax AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final and temporary... (including qualified subchapter S subsidiaries) and the indoor tanning services excise tax. These regulations affect disregarded entities responsible for collecting the indoor tanning services excise tax and...

  13. Effect of pterygium excision on pterygium induced astigmatism.

    Maheshwari Sejal

    2003-01-01

    Full Text Available Pterygium is known to affect refractive astigmatism, which can have a significant impact on vision. This study was undertaken to evaluate the effect of pterygium excision on refractive astigmatism. Thirty-six eyes with primary pterygium with astigmatism of 2D or more were analysed before and after pterygium excision. Astigmatism increased with the increase in the grade of pterygium (P = 0.000001. The preoperative refractive cylinder decreased from 4.60±2D to 2.20±2.04D (P = 0.00001 after pterygium excision.

  14. Laparoscopic choledochal cyst excision and Roux-en-Y hepaticojejunostomy.

    Kayaalp, Cüneyt; Soyer, Vural; Ersan, Veysel; Aydın, Cemalettin; Karagül, Servet

    2016-01-01

    Congenital choledochal cysts are rare in adults. Due to the risk of developing cholangiocarcinoma, the current standard of care is complete excision of the cyst and reconstruction with hepaticojejunostomy. So far, more than 200 laparoscopic resections have been reported in adults, the majority being from Far Eastern countries over the last five years. Herein, the technique of laparoscopic type I choledochal cyst excision and hepaticojejunostomy is presented in a 37-year-old male with an accompanying video. The advantages of laparoscopic surgery are applicable for choledochal cyst excision as well. We believe that teamwork, expertise on intracorporeal suturing and hepatobiliary surgery are central issues for this operation. PMID:27436941

  15. Global-genome Nucleotide Excision Repair Controlled by Ubiquitin/Sumo Modifiers

    Peter eRuethemann

    2016-04-01

    Full Text Available Global-genome nucleotide excision repair (GG-NER prevents genome instability by excising a wide range of structurally unrelated DNA base adducts and crosslinks induced by chemical carcinogens, ultraviolet (UV radiation or intracellular metabolic by-products. As a versatile damage sensor, xeroderma pigmentosum group C (XPC protein initiates this generic defense reaction by locating the damage and recruiting the subunits of a large lesion demarcation complex that, in turn, triggers the excision of aberrant DNA by endonucleases. In the very special case of a DNA repair response to UV radiation, the function of this XPC initiator is tightly controlled by the dual action of cullin-type CRL4DDB2 and sumo-targeted RNF111 ubiquitin ligases. This twofold protein ubiquitination system promotes GG-NER reactions by spatially and temporally regulating the interaction of XPC protein with damaged DNA across the nucleosome landscape of chromatin. In the absence of either CRL4DDB2 or RNF111, the DNA excision repair of UV lesions is inefficient, indicating that these two ubiquitin ligases play a critical role in mitigating the adverse biological effects of UV light in the exposed skin.

  16. Global-genome Nucleotide Excision Repair Controlled by Ubiquitin/Sumo Modifiers.

    Rüthemann, Peter; Balbo Pogliano, Chiara; Naegeli, Hanspeter

    2016-01-01

    Global-genome nucleotide excision repair (GG-NER) prevents genome instability by excising a wide range of different DNA base adducts and crosslinks induced by chemical carcinogens, ultraviolet (UV) light or intracellular side products of metabolism. As a versatile damage sensor, xeroderma pigmentosum group C (XPC) protein initiates this generic defense reaction by locating the damage and recruiting the subunits of a large lesion demarcation complex that, in turn, triggers the excision of aberrant DNA by endonucleases. In the very special case of a DNA repair response to UV radiation, the function of this XPC initiator is tightly controlled by the dual action of cullin-type CRL4(DDB2) and sumo-targeted RNF111 ubiquitin ligases. This twofold protein ubiquitination system promotes GG-NER reactions by spatially and temporally regulating the interaction of XPC protein with damaged DNA across the nucleosome landscape of chromatin. In the absence of either CRL4(DDB2) or RNF111, the DNA excision repair of UV lesions is inefficient, indicating that these two ubiquitin ligases play a critical role in mitigating the adverse biological effects of UV light in the exposed skin. PMID:27200078

  17. Clinical analysis of risk factors contributing to recurrence of pterygium after excision and graft surgery

    Sang; Won; Ha; Joon; Ho; Park; Im; Hee; Shin; Hong; Kyun; Kim

    2015-01-01

    AIM: To find the risk factors related to the reproliferation of the pterygial tissue after excision and graft surgery.METHODS: Charts of 130 eyes of 130 patients who had pterygial excision from March 2006 to April 2011 were reviewed. Preoperative pterygium morphology, surgical methods, and adjunctive treatments were statistically analyzed for their relationship with recurrence.RESULTS: During the follow-up period, recurrence was observed in 20 eyes(15.4%). None of the preoperative morphologic features were affected the rate of the recurrence. However, an age <40y [P =0.085, odds ratio(OR) 3.609, 95% confidence interval(CI) 0.838-15.540]and amniotic membrane graft instead of conjunctival autograft(P =0.002, OR 9.093, 95% CI 2.316-35.698) were statistically significant risk factors for recurrence.Multivariate analysis revealed that intraoperative mitomycin C(MMC)(P =0.072, OR 0.298, 95% CI 0.080-1.115)decreased the rate of recurrence. CONCLUSION: Younger age is a risk factor for reproliferation of pterygial tissue after excision and amniotic membrane transplantation(AMT) are less effective in preventing recurrence of pterygium after excision based on the comparison between conjunctival autograft and AMT. Intraoperative MMC application and conjunctival autograft reduce recurrence.

  18. [Face necrotizing fasciitis following spinocellular epithelioma excision].

    Gindre, S; Dellamonica, J; Couadau, E; Carles, M; Vandenbos, F; Delgiudice, P; Grimaud, D; Ichai, C

    2005-06-01

    Necrotizing fasciitis is a bacterial dermo-hypodermitis with superficial aponevrosis necrosis due to Streptococcus pyogenes. Head and neck region are some rare localization of this infection especially after surgery. We report herein a case of a face necrotizing fasciitis following minor face surgery. A 86 year-old Caucasian male without any antecedents, nor treatment, has been operated for a fronthead spinocellular epithelioma under local anesthesia. Twelve hours later, a severe pain localized to the face occurred, with sleeplessness, followed up with a face orbitary oedema and fever. Twenty-four hours later, an intravenous antibiotherapy was therefore started and surgical treatment was performed as soon as the diagnosis of necrotizing fasciitis was considered. An important inflammatory oedema was noticed, associated to a large necrotic softening of the face, the eyelid and the neck sub-cutaneous tissues. Then, the patient has been transferred in intensive care unit because multi-organ failure clinical and biological signs occurred. Pre-operatory bacteriological samples culture identified Streptococcus pyogenes. Repeated surgical explorations and debridement (excision, cleaning, draining and bandages recovery) were performed daily as needed until all the necrotic tissue was all eradicated. The antibiotherapy was prescribed to totalised 15 days. Our report underlines the importance of an early recognition of the diagnosis of soft tissue infection, because early surgical treatment has a better prognosis and antibiotic treatment alone is inefficient for the recovery. Alert is delivered by the local signs quickly followed up by skin changes. Anti-inflammatory therapy must be avoid in case of any soft tissue infection sign: they may increase the lesions, hide alarm signs and delay surgical treatment. PMID:15963844

  19. Proposal for a new comprehensive classification of V-Y plasty and its analogues: the pros and cons of inverted versus ordinary Burow's triangle excision.

    Suzuki, S; Matsuda, K; Nishimura, Y

    1996-11-01

    Burow's triangle excision is often used in V-Y plasty to facilitate the advancement of the V flap. The technique also seems to help reduce unsightly scarring. We devised an alternative technique to Burow's triangle excision, i.e., an inverted Burow's triangle excision. Sometimes the inverted Burow's triangle excision seems to be more effective for both purposes. In this paper we propose a new comprehensive classification of V-Y plasty and its analogues such as V-M, V-W, or five Z-plasty based on a new concept, the appropriate use of Burow's and inverted Burow's triangle excision and other criteria. The applications of these designs are discussed. PMID:8911471

  20. Subungual glomus tumors of the hand Treated by transungual excision

    Harshad Jawalkar

    2015-01-01

    Conclusions: The transungual approach provides good access to the entire lesion and facilitates complete excision. Contrary to reported literature, we did not find the development of any new nail deformity with this approach.

  1. Excise Tax Rates On Packs Of Cigarettes PDF Slides

    U.S. Department of Health & Human Services — Download the current excise tax rates on packs of cigarettes slides. These slides are available in PDF and PowerPoint formats. The PowerPoint version can be found...

  2. Teflon strip pneumostasis for excision of giant emphysematous bullae.

    Parmar, J M; Hubbard, W G; Matthews, H. R.

    1987-01-01

    Excision of giant emphysematous bullae commonly results in a persistent air leak that requires prolonged intercostal drainage and delays recovery. To minimise this we have used Teflon (polytetrafluoroethylene) strips to buttress the suture line and secure pneumostasis. During 1976-84 eight bullae were excised in seven patients. One patient had bilateral staged thoracotomies. All chest drains were removed within eight days (mean 4.5 days) and no patient developed pulmonary complications. At lo...

  3. Excision in algebraic K-theory and Karoubi's conjecture.

    Suslin, A A; Wodzicki, M

    1990-12-15

    We prove that the property of excision in algebraic K-theory is for a Q-algebra A equivalent to the H-unitality of the latter. Our excision theorem, in particular, implies Karoubi's conjecture on the equality of algebraic and topological K-theory groups of stable C*-algebras. It also allows us to identify the algebraic K-theory of the symbol map in the theory of pseudodifferential operators. PMID:11607130

  4. Low-dose formaldehyde delays DNA damage recognition and DNA excision repair in human cells.

    Andreas Luch

    Full Text Available OBJECTIVE: Formaldehyde is still widely employed as a universal crosslinking agent, preservative and disinfectant, despite its proven carcinogenicity in occupationally exposed workers. Therefore, it is of paramount importance to understand the possible impact of low-dose formaldehyde exposures in the general population. Due to the concomitant occurrence of multiple indoor and outdoor toxicants, we tested how formaldehyde, at micromolar concentrations, interferes with general DNA damage recognition and excision processes that remove some of the most frequently inflicted DNA lesions. METHODOLOGY/PRINCIPAL FINDINGS: The overall mobility of the DNA damage sensors UV-DDB (ultraviolet-damaged DNA-binding and XPC (xeroderma pigmentosum group C was analyzed by assessing real-time protein dynamics in the nucleus of cultured human cells exposed to non-cytotoxic (<100 μM formaldehyde concentrations. The DNA lesion-specific recruitment of these damage sensors was tested by monitoring their accumulation at local irradiation spots. DNA repair activity was determined in host-cell reactivation assays and, more directly, by measuring the excision of DNA lesions from chromosomes. Taken together, these assays demonstrated that formaldehyde obstructs the rapid nuclear trafficking of DNA damage sensors and, consequently, slows down their relocation to DNA damage sites thus delaying the excision repair of target lesions. A concentration-dependent effect relationship established a threshold concentration of as low as 25 micromolar for the inhibition of DNA excision repair. CONCLUSIONS/SIGNIFICANCE: A main implication of the retarded repair activity is that low-dose formaldehyde may exert an adjuvant role in carcinogenesis by impeding the excision of multiple mutagenic base lesions. In view of this generally disruptive effect on DNA repair, we propose that formaldehyde exposures in the general population should be further decreased to help reducing cancer risks.

  5. Genomic island excisions in Bordetella petrii

    Levillain Erwan

    2009-07-01

    Full Text Available Abstract Background Among the members of the genus Bordetella B. petrii is unique, since it is the only species isolated from the environment, while the pathogenic Bordetellae are obligately associated with host organisms. Another feature distinguishing B. petrii from the other sequenced Bordetellae is the presence of a large number of mobile genetic elements including several large genomic regions with typical characteristics of genomic islands collectively known as integrative and conjugative elements (ICEs. These elements mainly encode accessory metabolic factors enabling this bacterium to grow on a large repertoire of aromatic compounds. Results During in vitro culture of Bordetella petrii colony variants appear frequently. We show that this variability can be attributed to the presence of a large number of metastable mobile genetic elements on its chromosome. In fact, the genome sequence of B. petrii revealed the presence of at least seven large genomic islands mostly encoding accessory metabolic functions involved in the degradation of aromatic compounds and detoxification of heavy metals. Four of these islands (termed GI1 to GI3 and GI6 are highly related to ICEclc of Pseudomonas knackmussii sp. strain B13. Here we present first data about the molecular characterization of these islands. We defined the exact borders of each island and we show that during standard culture of the bacteria these islands get excised from the chromosome. For all but one of these islands (GI5 we could detect circular intermediates. For the clc-like elements GI1 to GI3 of B. petrii we provide evidence that tandem insertion of these islands which all encode highly related integrases and attachment sites may also lead to incorporation of genomic DNA which originally was not part of the island and to the formation of huge composite islands. By integration of a tetracycline resistance cassette into GI3 we found this island to be rather unstable and to be lost from

  6. "The lobbying strategy is to keep excise as low as possible" - tobacco industry excise taxation policy in Ukraine

    Krasovsky Konstantin S

    2010-01-01

    Abstract Background Tobacco taxes are one of the most effective ways to reduce tobacco use. Transnational tobacco companies (TTCs) claim they wish to develop and secure excise systems that benefit both governments and the profitability of the companies themselves. The objective of the paper is to use the case of Ukraine, with its inconsistent history of excise tax changes in 1992-2008, to explore tobacco industry taxation strategies and tactics, and their implications for governmental revenue...

  7. Adaptive Biorthogonal Local Discrete Cosine Transform for Interference Excision in Direct Sequence Spread Spectrum Communications

    朱丽平; 胡光锐; 朱义胜

    2005-01-01

    A novel time-frequency domain interference excision technique is proposed. The technique is based on adaptive biorthogonal local discrete cosine transform (BLDCT). It uses a redundant library of biorthogonal local discrete cosine bases and an efficient concave cost function to match the transform basis to the interfering signal. The main advantage of the algorithm over conventional transform domain excision algorithms is that the basis functions are not fixed but can be adapted to the time-frequency structure of the interfering signal. It is well suited to transform domain compression and suppression of various types of interference. Compared to the discrete wavelet transform (DWT) that provides logarithmic division of the frequency bands, the adaptive BLDCT can provide more flexible frequency resolution. Thus it is more insensitive to variations of jamming frequency. Simulation results demonstrate the improved bit error rate (BER) performance and the increased robustness of the receiver.

  8. Teaching elliptical excision skills to novice medical students: A randomized controlled study comparing low- and high-fidelity bench models

    Rafael Denadai

    2014-01-01

    Full Text Available Background: The search for alternative and effective forms of training simulation is needed due to ethical and medico-legal aspects involved in training surgical skills on living patients, human cadavers and living animals. Aims : To evaluate if the bench model fidelity interferes in the acquisition of elliptical excision skills by novice medical students. Materials and Methods: Forty novice medical students were randomly assigned to 5 practice conditions with instructor-directed elliptical excision skills′ training (n = 8: didactic materials (control; organic bench model (low-fidelity; ethylene-vinyl acetate bench model (low-fidelity; chicken legs′ skin bench model (high-fidelity; or pig foot skin bench model (high-fidelity. Pre- and post-tests were applied. Global rating scale, effect size, and self-perceived confidence based on Likert scale were used to evaluate all elliptical excision performances. Results : The analysis showed that after training, the students practicing on bench models had better performance based on Global rating scale (all P 0.05 between the groups that trained on bench models. The magnitude of the effect (basic cutaneous surgery skills′ training was considered large (>0.80 in all measurements. Conclusion : The acquisition of elliptical excision skills after instructor-directed training on low-fidelity bench models was similar to the training on high-fidelity bench models; and there was a more substantial increase in elliptical excision performances of students that trained on all simulators compared to the learning on didactic materials.

  9. Excision of IS492 Requires Flanking Target Sequences and Results in Circle Formation in Pseudoalteromonas atlantica

    Perkins-Balding, Donna; Duval-Valentin, Guy; Glasgow, Anna C.

    1999-01-01

    The gram-negative marine bacterium Pseudoalteromonas atlantica produces extracellular polysaccharide (EPS) that is important in biofilm formation by this bacterium. Insertion and precise excision of IS492 at a locus essential for extracellular polysaccharide production (eps) controls phase variation of EPS production in P. atlantica. Examination of IS492 transposition in P. atlantica by using a PCR-based assay revealed a circular form of IS492 that may be an intermediate in transposition or a...

  10. Mammary gland selective excision of c-jun identifies its role in mRNA splicing

    Katiyar, Sanjay; Jiao, Xuanmao; Addya, Sankar; Ertel, Adam; Rose, Vanessa; Casimiro, Mathew C.; Zhou, Jie; Lisanti, Michael P; Nasim, Talat; Fortina, Paolo; Pestell, Richard G.

    2011-01-01

    The c-jun gene regulates cellular proliferation and apoptosis via direct regulation of cellular gene expression. Alternative splicing of pre-mRNA increases the diversity of protein functions and alternate splicing events occur in tumors. Here, by targeting the excision of the endogenous c-jun gene within the mouse mammary epithelium, we have identified its selective role as an inhibitor of RNA splicing. Microarray-based assessment of gene expression, on laser capture micro-dissected c-jun−/− ...

  11. 29 CFR 779.262 - Excise taxes at the retail level.

    2010-07-01

    ... AS APPLIED TO RETAILERS OF GOODS OR SERVICES Employment to Which the Act May Apply; Enterprise Coverage Excise Taxes § 779.262 Excise taxes at the retail level. (a) Federal excise taxes are imposed at... 29 Labor 3 2010-07-01 2010-07-01 false Excise taxes at the retail level. 779.262 Section...

  12. Interference Excision in Spread Spectrum Communications Using Adaptive Positive Time-Frequency Analysis

    Sridhar Krishnan

    2007-07-01

    Full Text Available This paper introduces a novel algorithm to excise single and multicomponent chirp-like interferences in direct sequence spread spectrum (DSSS communications. The excision algorithm consists of two stages: adaptive signal decomposition stage and directional element detection stage based on the Hough-Radon transform (HRT. Initially, the received spread spectrum signal is decomposed into its time-frequency (TF functions using an adaptive signal decomposition algorithm, and the resulting TF functions are mapped onto the TF plane. We then use a line detection algorithm based on the HRT that operates on the image of the TF plane and detects energy varying directional elements that satisfy a parametric constraint. Interference is modeled by reconstructing the corresponding TF functions detected by the HRT, and subtracted from the received signal. The proposed technique has two main advantages: (i it localizes the interferences on the TF plane with no cross-terms, thus facilitating simple filtering techniques based on thresholding of the TF functions, and is an efficient way to excise the interference; (ii it can be used for the detection of any directional interferences that can be parameterized. Simulation results with synthetic models have shown successful performance with linear and quadratic chirp interferences for single and multicomponent interference cases. The proposed method excises the interference even under very low SNR conditions of −10 dB, and the technique could be easily extended to any interferences that could be represented by a parametric equation in the TF plane.

  13. Subungual glomus tumors of the hand: Treated by transungual excision

    Jawalkar, Harshad; Maryada, Venkateshwar Reddy; Brahmajoshyula, Venkatramana; Kotha, Guruvardhan Kumar V

    2015-01-01

    Background: Glomus tumors are benign hamartomas arising from the glomus body, mostly occurring in the subungual region of the digits. A triad of excruciating pain, localized tenderness and cold sensitivity is the key to diagnosing these tumors. Two surgical approaches are described in the literature for excision of subungual glomus tumors-transungual and periungual. We reviewed retrospectively the results of subungual glomus tumors of the hand treated by transungual excision. Materials and Methods: Twelve patients (9 females and 3 males) with histopathologically confirmed subungual glomus tumors of the hand were treated by transungual excision at our institute. The mean age of the patients was 40.5 years (range 28–63 years). All patients presented with pain in the nail bed and cold sensitivity. A bluish-brown discoloration was present in 6 patients. Love's pin test was positive in all and Hildreth's test was positive in 8 patients. The mean duration of followup was 38 months (range 8–72 months). Results: All patients had complete pain relief. There was no new nail deformity and no recurrence till last followup. One patient had deformity of the nail preoperatively due to previous surgery, which persisted after excision of the tumor. All of them returned to their preoperative occupation and regained full function of the hand. Conclusions: The transungual approach provides good access to the entire lesion and facilitates complete excision. Contrary to reported literature, we did not find the development of any new nail deformity with this approach. PMID:26229160

  14. APPROACHES REGARDING DELIVERY OPERATIONS ACCOUNTING BY THE MANUFACTURER OF EXCISABLE MERCHANDISE

    Anatol GRAUR

    2016-03-01

    Full Text Available This article describes the calculation of delivery operations accounting of goods subject to the excise duty. The author examines tax cases of the internal movement of excisable goods, while presenting the timing of the development of tax liability. The material analyses the Tax Code regulations concerning the excise duties in specialized stores. The author describes how to apply excise taxes on goods sold but not yet shipped outside of the excise premises.

  15. Genotypic and antimicrobial characterisation of Propionibacterium acnes isolates from surgically excised lumbar disc herniations

    Rollason, Jess; McDowell, Andrew; Albert, Hanne B;

    2013-01-01

    The anaerobic skin commensal Propionibacterium acnes is an underestimated cause of human infections and clinical conditions. Previous studies have suggested a role for the bacterium in lumbar disc herniation and infection. To further investigate this, five biopsy samples were surgically excised...... from each of 64 patients with lumbar disc herniation. P. acnes and other bacteria were detected by anaerobic culture, followed by biochemical and PCR-based identification. In total, 24/64 (38%) patients had evidence of P. acnes in their excised herniated disc tissue. Using recA and mAb typing methods...... isolate collection (63%) suggests that the role of P. acnes in lumbar disc herniation should not be readily dismissed....

  16. Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery

    Bertelsen, Claus Anders; Neuenschwander, Anders Ulrich; Jansen, Jens Erik; Wilhelmsen, Michael; Kirkegaard-Klitbo, Anders; Tenma, Jutaka Reilin; Bols, Birgitte; Ingeholm, Peter; Rasmussen, Leif Ahrenst; Jepsen, Lars Vedel; Iversen, Else Refsgaard; Kristensen, Bent; Gögenur, Ismail

    BACKGROUND: Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional...... colon resection. METHODS: Data for all patients who underwent elective resection for Union for International Cancer Control (UICC) stage I-III colon adenocarcinomas in the Capital Region of Denmark between June 1, 2008, and Dec 31, 2011, were retrieved for this population-based study. The CME group...... consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients...

  17. Co(acac)3/BMMImCl as a base-free catalyst system for clean syntheses of N,N’-disubstituted ureas from amines and CO2

    2010-01-01

    A base-free catalyst system Co(acac)3/BMMImCl was developed for the carbonylation of amines with CO2.45%-81% isolated yields for N,N’-dialkylureas and 6%-23% isolated yields for N,N-diarylureas were obtained.The catalyst system was recovered and reused without significant loss in activity.In this catalyst system,the base catalyst and chemical dehydrant were efficiently avoided.Different reaction conditions were also discussed and a postulated mechanism was proposed.

  18. Excision of oral mucocele by different wavelength lasers

    Umberto Romeo

    2013-01-01

    Full Text Available Background: Mucocele is a common benign neoplasm of oral soft tissues and the most common after fibroma. It generally occurs in the lower lip and its treatment includes excision of cyst and the responsible salivary gland, in order to prevent recurrences. Aims: To evaluate the capability of three different lasers in performing the excision of labial mucocele with two different techniques. Materials and Methods: In the presented cases, excision was performed using two different techniques (circumferential incision technique and mucosal preservation technique and three different laser wavelengths (Er,Cr:YSGG 2780 nm, diode 808 nm, and KTP 532 nm. Results: All the tested lasers, regardless of wavelength, showed many advantages (bloodless surgical field, no postoperative pain, relative speed, and easy execution. The most useful surgical technique depends on clinical features of the lesion. Conclusion: Tested lasers, with both techniques, are helpful in the management of labial mucocele.

  19. Boron-11 NMR spectroscopy of excised mouse tissues after infusion of boron compound used in neutron capture therapy

    Boron neutron capture therapy (BNCT) is based on selective boron uptake by the tumor and in situ activation by neutron beam. The authors propose the use of B-11 MR spectroscopy to noninvasively study boron uptake in animal tumor models. Sodium mercaptoundeca-hydrododecaborate was infused into female BALB/cJ mice and liver, brain, spleen, kidney, and tumor tissues were excised for MR (27.4MHz) and total boron content measurements. Boron-11 was easily detectable in tumor, liver, spleen, and skin. The results gave a very good correlation (correlation coefficient of .997) between B-11 MR measurements and total boron content of excised mouse tissues

  20. Effect of pterygium excision on pterygium induced astigmatism.

    Maheshwari Sejal

    2003-01-01

    Pterygium is known to affect refractive astigmatism, which can have a significant impact on vision. This study was undertaken to evaluate the effect of pterygium excision on refractive astigmatism. Thirty-six eyes with primary pterygium with astigmatism of 2D or more were analysed before and after pterygium excision. Astigmatism increased with the increase in the grade of pterygium (P = 0.000001). The preoperative refractive cylinder decreased from 4.60±2D to 2.20±2.04D (P = 0.0...

  1. Comparison of Adnexal Mass in Women Undergoing Mass Excision During the Antepartum Period and Cesarean Section

    Nafiseh Saghafi

    2016-05-01

    Full Text Available Objectives: The frequency of adnexal masses in pregnant women ranges from 0.1% to 4%. Selecting the right approach to manage the subsequent intervention remains one of the most controversial challenges among gynecologists. Our aim in this cross-sectional study was to clarify the clinical-pathological differences among the adnexal masses that are excised during either the antepartum period or cesarean section (CS. Methods: In this study, we assessed 11,000 pregnancy cases referred to the Qaem Hospital in the Mashhad University of Medical Sciences, Iran, between 2010 and 2014. In total, 53 pregnant women with adnexal masses (other than non-gynecological mass and ectopic pregnancy were selected for further investigation. We divided patients into two groups (group A and group B. Patients of group A had a diagnosed tumor that was excised antepartum while patients in group B had a mass taken out during CS. We then assembled data based on maternal age, parity, gestational age, surgery type, delivery mode, size and location of the tumor, complications, presentations, histopathological diagnosis, and ultrasonography findings for further analysis. Results: The major proportion of masses (62.3% were excised during CS whereas the remainder (37.7% were removed antepartum. The mean size of the detected tumor for benign and malignant cases was 10.0 cm and 13.8 cm in group A, and 8.0 cm and 9.3 cm in group B, respectively. There was a statistically significant difference observed between patients in the two groups regarding the benign/malignant status of the mass (p = 0.008, its size (p = 0.019 and simplicity/complexity (p = 0.004. Conclusions: The rate of malignant tumors was considerably higher in women who had antepartum mass excision compared to those with mass resection during CS. Also, tumors were larger (and more complex in patients in group A compared to group B.

  2. 75 FR 9359 - Drawback of Internal Revenue Excise Tax

    2010-03-02

    ... Federal Register (74 FR 52928) proposing changes to parts 113 and 191 within title 19 of the Code of... the Federal Register (74 FR 52928) on October 15, 2009, so that relevant issues involved in the... Parts 113 and 191 RIN 1505-AC18 Drawback of Internal Revenue Excise Tax AGENCY: Customs and...

  3. Structural basis of HIV-1 resistance to AZT by excision

    Tu, Xiongying; Das, Kalyan; Han, Qianwei; Bauman, Joseph D.; Clark, Jr., Arthur D.; Hou, Xiaorong; Frenkel, Yulia V.; Gaffney, Barbara L.; Jones, Roger A.; Boyer, Paul L.; Hughes, Stephen H.; Sarafianos, Stefan G.; Arnold, Eddy (Rutgers); (Clark); (NCI)

    2011-11-23

    Human immunodeficiency virus (HIV-1) develops resistance to 3'-azido-2',3'-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3' end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate (AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP- and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision.

  4. Nucleotide excision repair by dual incisions in plants.

    Canturk, Fazile; Karaman, Muhammet; Selby, Christopher P; Kemp, Michael G; Kulaksiz-Erkmen, Gulnihal; Hu, Jinchuan; Li, Wentao; Lindsey-Boltz, Laura A; Sancar, Aziz

    2016-04-26

    Plants use light for photosynthesis and for various signaling purposes. The UV wavelengths in sunlight also introduce DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts [(6-4)PPs] that must be repaired for the survival of the plant. Genome sequencing has revealed the presence of genes for both CPD and (6-4)PP photolyases, as well as genes for nucleotide excision repair in plants, such as Arabidopsis and rice. Plant photolyases have been purified, characterized, and have been shown to play an important role in plant survival. In contrast, even though nucleotide excision repair gene homologs have been found in plants, the mechanism of nucleotide excision repair has not been investigated. Here we used the in vivo excision repair assay developed in our laboratory to demonstrate that Arabidopsis removes CPDs and (6-4)PPs by a dual-incision mechanism that is essentially identical to the mechanism of dual incisions in humans and other eukaryotes, in which oligonucleotides with a mean length of 26-27 nucleotides are removed by incising ∼20 phosphodiester bonds 5' and 5 phosphodiester bonds 3' to the photoproduct. PMID:27071131

  5. Transient Allodynia Following Caudal Lipoma Excision: A Case Report

    Kalemci, Orhan; Ozer, Ercan; YUCESOY, Kemal; Arda, Mehmet Nuri; Erkin, Yüksel

    2011-01-01

    Allodynia is the sensation of pain due to non-painful stimuli. It usually occurs due to destructive lesions of the spinal cord or peripheral nerves. Allodynia following intradural lipoma surgery has been reported previously. We herein report a case of allodynia developed after microsurgical caudal lipoma excision without associated spinal cord injury.

  6. A Rat Excised Larynx Model of Vocal Fold Scar

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  7. 75 FR 33683 - Indoor Tanning Services; Cosmetic Services; Excise Taxes

    2010-06-15

    ... means a service employing any electronic product designed to incorporate one or more ultraviolet lamps... Internal Revenue Service 26 CFR Parts 40, 49, and 602 RIN 1545-BJ41 Indoor Tanning Services; Cosmetic Services; Excise Taxes AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Final and...

  8. Excise Taxes and the Price Elasticity of Demand.

    Gamble, Ralph C., Jr.

    1989-01-01

    Points out that, although the analysis of the imposition of an excise tax is widely used in economics courses, the consequences of a change in the tax rate are different and ignored. This article presents an effective way to teach about such a change. (GG)

  9. Improved quality of care for patients undergoing an abdominoperineal excision for rectal cancer

    Bokkerink, G.M.J.; Buijs, E.F.; Ruijter, W. de; Rosman, C.; Sietses, C.; Strobel, R.; Heisterkamp, J.; Nagtegaal, I.D.; Bremers, A.J.A.; Wilt, J.H.W. de

    2015-01-01

    INTRODUCTION: New diagnostics, the emergence of total mesorectal excision and neoadjuvant treatments have improved outcome for patients with rectal cancer. Patients with distal rectal cancer undergoing an abdominoperineal excision seem to do worse compared to those treated with sphinctersparing tech

  10. Surgical problems in the excision and repair of radiated tissue

    Surgical procedures for tissues damaged by radiation are fraught with the possibility of multiple and serious complications. A knowledge of the altered pathophysiology of such tissues (chiefly diminished blood supply, fibrosis, and direct cellular reparative potential) is necessary for the surgeon to make a proper judgment. Recognition of the pathognomic signs in the skin is important. The possibility of malignant change must be kept in mind. Surgical treatment must include the excision of radiated tissues back to good blood supply, and then proper and adequate coverage by the simplest and best means. If the surrounding local tissues are so altered that they are unsuitable for coverage, structures from a distance must be used. Prior planning of the coverage before the excision pays dividends by preventing disastrous complications. (U.S.)

  11. The excision width in surgical treatment of basal cell carcinoma

    Mališ M.

    2006-01-01

    Full Text Available Basal cell carcinoma originates from pluripotent cells of basal layer of epiderm, external covering of hair follicles, sebaceous glands or other skin adnexa. It is characterized by local infiltrating and sometimes destructive growth. There are several types of basal cell carcinomas that may be manifested in over 12 clinical forms. Surgical treatment depends to a large extent on the histological type, localization and its clinical manifestation. The analysis included 250 patients of both gender and different age, operated for basal cell carcinoma. Clinical characteristics of basal cell carcinoma and the width of the excision were described. It was concluded that the width of the excision of basal cell cancer was in relation to histological type. .

  12. Anatomo surgical study on radical mesorectum excision in rectal cancer.

    Alejandro A. Gorodner

    2010-11-01

    Full Text Available Knowledge of surgical anatomy of the mesorectum is essential for cancer surgery in rectal cancer. Radical mesorectal excision allows an appropriate surgery, preserving the pelvic nerves of the autonomic system, preventing postsurgical morbidity. The aim of this paper is to describe the anatomy of the mesorectum as a cornerstone to achieve a careful and detailed technique on rectal cancer surgery. 10 (ten adult formalized cadavers were dissected (nine male and one female specimen. Anatomical elements, both nervous and vascular were explored, in order to recognize those elements that should be preserved in rectal cancer surgery with radical mesorectal excision. The dissection of corpses may be an experimental model to test this type of cancer surgery. Samples were photographed and compared with those made in vivo. Rectal resection with its corresponding mesorectum, accordingly to the location of the tumor improves survival of patients with rectal cancer. Knowledge of the anatomy of the pelvic neurovascular elements significantly reduces postsurgical morbidity.

  13. 77 FR 37838 - Disregarded Entities and the Indoor Tanning Services Excise Tax

    2012-06-25

    ... Services Excise Tax AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of proposed rulemaking... (including qualified subchapter S subsidiaries) and the indoor tanning services excise tax. These regulations affect disregarded entities responsible for collecting the indoor tanning services excise tax and...

  14. 29 CFR 779.263 - Excise taxes not at the retail level.

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Excise taxes not at the retail level. 779.263 Section 779... Coverage Excise Taxes § 779.263 Excise taxes not at the retail level. There are also a wide variety of taxes levied at the manufacturer's or distributor's level and not at the retail level. It should...

  15. Norwegian NOx emissions excise duty hits shipping and offshore industry

    The regulatory framework concerning the new excise duty appears as complex and unfinished, raising more questions than providing answers. The duty will entail a significant expense item for the businesses liable to register and it is therefore important to have an overview of how the regulatory framework should be understood. Errors made since 1 January 2007 may lead to future reassessments of duties, with interest (author) (ml)

  16. Excise levying on gold products on the Romanian territory

    I. Bostan

    2016-04-01

    Full Text Available As regards the trade operations with gold products, the tax regime is rather special. The current paper tackles the most significant aspects of excise levying of this products/jewels type in the Romanian system. The focus is on certain framework elements regarding the fiscal status of the operator with gold products. The study relies on the European and national regulations but it also refers to other works which highlight similar problems.

  17. Threshold to predict astigmatism reduction after pterygium excision

    Julio Morán, Gemma; de Carvalho Mendes Castanheira, Amélia Maria; Kostov, Belchin Adriyanov; Pujol Vives, Pere

    2014-01-01

    Purpose. To compare corneal astigmatism after pterygium excision, using limbal-conjunctival autograft (LCA) with and without mitomycin C (MMC) and to establish a threshold for postoperative astigmatism reduction.; Methods. Sixty-eight eyes with primary pterygium were consecutively sampled and assigned to LCA with MMC (MMC+) or LCA without MMC (MMC-). Corneal lesion length, corneal lesion area, preoperative corneal astigmatism (PRCA), and postoperative corneal astigmatism (POCA) at 1, 3, and 6...

  18. Tissue-specific accelerated aging in nucleotide excision repair deficiency

    Laura J. Niedernhofer

    2008-01-01

    Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helix-distorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transc...

  19. Summation by parts and dissipation for domains with excised regions

    Calabrese, G; Reula, O; Sarbach, O; Tiglio, M H; Calabrese, Gioel; Lehner, Luis; Reula, Oscar; Sarbach, Olivier; Tiglio, Manuel

    2003-01-01

    We extend and construct finite difference techniques for hyperbolic equations in non-trivial domains, as those that arise when simulating black hole spacetimes. We construct dissipative and difference operators that satisfy summation by parts in domains with excised multiple cubic regions. These techniques can be used to derive semi-discrete energy estimates for the associated initial-boundary value problem, and therefore, can be used to show numerical stability.

  20. Increased Ac excision (iae): Arabidopsis thaliana mutations affecting Ac transposition

    The maize transposable element Ac is highly active in the heterologous hosts tobacco and tomato, but shows very much reduced levels of activity in Arabidopsis. A mutagenesis experiment was undertaken with the aim of identifying Arabidopsis host factors responsible for the observed low levels of Ac activity. Seed from a line carrying a single copy of the Ac element inserted into the streptomycin phosphotransferase (SPT) reporter fusion, and which displayed typically low levels of Ac activity, were mutagenized using gamma rays. Nineteen mutants displaying high levels of somatic Ac activity, as judged by their highly variegated phenotypes, were isolated after screening the M2 generation on streptomycin-containing medium. The mutations fall into two complementation groups, iae1 and iae2, are unlinked to the SPT::Ac locus and segregate in a Mendelian fashion. The iae1 mutation is recessive and the iae2 mutation is semi-dominant. The iae1 and iae2 mutants show 550- and 70-fold increases, respectively, in the average number of Ac excision sectors per cotyledon. The IAE1 locus maps to chromosome 2, whereas the SPT::Ac reporter maps to chromosome 3. A molecular study of Ac activity in the iae1 mutant confirmed the very high levels of Ac excision predicted using the phenotypic assay, but revealed only low levels of Ac re-insertion. Analyses of germinal transposition in the iae1 mutant demonstrated an average germinal excision frequency of 3% and a frequency of independent Ac re-insertions following germinal excision of 22%. The iae mutants represents a possible means of improving the efficiency of Ac/Ds transposon tagging systems in Arabidopsis, and will enable the dissection of host involvement in Ac transposition and the mechanisms employed for controlling transposable element activity

  1. Summation by parts and dissipation for domains with excised regions

    Calabrese, Gioel [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Lehner, Luis [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Reula, Oscar [FaMAF, Universidad Nacional de Cordoba, Cordoba 5000 (Argentina); Sarbach, Olivier [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Tiglio, Manuel [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States)

    2004-12-21

    We discuss finite difference techniques for hyperbolic equations in non-trivial domains, as those that arise when simulating black-hole spacetimes. In particular, we construct dissipative and difference operators that satisfy the summation by parts property in domains with excised multiple cubic regions. This property can be used to derive semi-discrete energy estimates for the associated initial-boundary value problem which in turn can be used to prove numerical stability.

  2. Excise levying on gold products on the Romanian territory

    I. Bostan; T. Roman

    2016-01-01

    As regards the trade operations with gold products, the tax regime is rather special. The current paper tackles the most significant aspects of excise levying of this products/jewels type in the Romanian system. The focus is on certain framework elements regarding the fiscal status of the operator with gold products. The study relies on the European and national regulations but it also refers to other works which highlight similar problems.

  3. Robot-Assisted Laparoscopic Seminal Vesicle Cystadenoma Excision

    Mourmouris, Panagiotis; Tufek, İlter; Saglican, Yesim; Obek, Can; Kural, Ali Riza

    2015-01-01

    Abstract Background: Cystadenoma is an extremely rare benign tumor of the seminal vesicle. Diagnosis of these tumors and differential diagnosis from malignant ones may be challenging since most of the time symptoms do not occur. Management of these tumors remains debatable due to the limited data in the literature. We present the first robot-assisted laparoscopic excision of a cystadenoma of the seminal vesicle. Case Presentation: A 48-year-old man presented with diminished ejaculate volume and a 3.5 cm right seminal vesicle mass, which increased its size at 6 cm after the 3-month period. Transrectal ultrasound-guided biopsy revealed no malignancy. Robot-assisted laparoscopic excision of the tumor was performed. Port placement was the same as robot-assisted radical prostatectomy. Operative time and estimated blood loss were 240 minutes and 200 mL, respectively. Patient was discharged on postoperative day 3 without any complications. Final histopathologic examination revealed cystadenoma of the seminal vesicle. Conclusion: Surgical intervention may be considered when a cystadenoma of the seminal vesicle is diagnosed and symptoms or tumor growth occurs. Robot-assisted laparoscopic excision is an alternative in the management of these rare tumors.

  4. The Impact of Pterygium Excision on Corneal Astigmatism

    Objective: To compare the corneal astigmatism before and after the excision of pterygium and also to determine the correlation of pterygium size with the postoperative corneal astigmatism. Study Design: Cross-sectional interventional study. Place and Duration of Study: Eye Department, Combined Military Hospital, Abbottabad, from May 2011 to March 2012. Methodology: Thirty patients underwent pterygium excision. Pre-operatively Snellen visual acuity, manifest refraction and slit lamp examination was done. The size of the pterygium was recorded in mm by projecting a horizontal slit lamp beam from the limbus to the apex. All the pterygium were equal to or greater than 2.5 mm. Keratometry was performed with an automated keratometer. Keratometric data was recorded pre-operatively and at 28 days postoperatively. Wilcoxon signed rank test was used for comparing the pre-operative and the postoperative corneal astigmatism. Spearman's rank order was calculated to observe correlation of pterygium size with the postoperative astigmatism. Results: The median (mean rank) pre-operative astigmatism of 2.25 (15.50) reduced to a median (mean rank) postoperative astigmatism of 1.30 (14.96). This decrease in the postoperative astigmatism was statistically significant (p < 0.001). There was a statistically non-significant correlation between the postoperative astigmatism and the pterygium size (rs = -0.29, p = 0.12). Conclusion: Pterygium excision caused significant reduction in corneal astigmatism. (author)

  5. Staged Excision for Lentigo Maligna and Lentigo Maligna Melanoma

    Wilson, Joshua B.; Walling, Hobart W.; Scupham, Richard K.; Bean, Andrew K.; Ceilley, Roger I.

    2016-01-01

    Introduction: Lentigo maligna is a form of in situ melanoma that occurs commonly on sun-exposed skin of middle-aged to elderly adults. Margin-control surgery offers the highest cure rate for lentigo maligna/lentigo maligna melanoma. Materials and methods: Charts from the authors’ private office from the 20-year period from January 1986 to December 2005 were reviewed to identify patients with histologically confirmed lentigo maligna or lentigo maligna melanoma treated by staged excision. Results: Sixty-eight patients (39 men, 29 women; mean age at diagnosis 67.4±10.2 years, range 48-87 years) with 68 tumors were treated in the authors’ office for lentigo maligna (58) or lentigo maligna melanoma (10) between January 1986 and December 2005. After excision, patients were followed clinically for a minimum of three years. The mean follow-up duration was 138 months (median 139 months; range 37-330 months). The overall margin for tumor clearance was 7.0±0.55mm with a recurrence rate of 5.9 percent. Limitations: The limitations of this study include the retrospective nature of the authors’ review, and data collected from a single, private practice setting. Conclusion: The authors’ findings support staged excision as an effective method of treating lentigo maligna and lentigo maligna melanoma, offering a high cure rate while maximally preserving normal tissue. PMID:27386048

  6. State-specific liquor excise taxes and retail prices in 8 US states, 2012.

    Siegel, Michael; Grundman, Jody; DeJong, William; Naimi, Timothy S; King, Charles; Albers, Alison B; Williams, Rebecca S; Jernigan, David H

    2013-01-01

    The authors investigated the relationship between state excise taxes and liquor prices in 8 states, using 2012 data for 45 brands. The authors made 6042 price observations among 177 liquor stores with online prices. Using a hierarchical model, the authors examined the relationship between excise taxes and product prices. State excise taxes were significantly related to liquor prices, with an estimated pass-through rate of 0.93. The proportion of price accounted for by excise taxes averaged 7.0%. The authors find that excise taxes do increase the price of alcohol, but states are not taking advantage of this opportunity to reduce alcohol-related morbidity and mortality. PMID:24159914

  7. New insights about excisable pathogenicity islands in Salmonella and their contribution to virulence.

    Nieto, Pamela A; Pardo-Roa, Catalina; Salazar-Echegarai, Francisco J; Tobar, Hugo E; Coronado-Arrázola, Irenice; Riedel, Claudia A; Kalergis, Alexis M; Bueno, Susan M

    2016-05-01

    Pathogenicity islands (PAIs) are regions of the chromosome of pathogenic bacteria that harbor virulence genes, which were probably acquired by lateral gene transfer. Several PAIs can excise from the bacterial chromosome by site-specific recombination and in this review have been denominated "excisable PAIs". Here, the characteristic of some of the excisable PAIs from Salmonella enterica and the possible role and impact of the excision process on bacterial virulence is discussed. Understanding the role of PAI excision could provide important insights relative to the emergence, evolution and virulence of pathogenic enterobacteria. PMID:26939722

  8. Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats

    Chen Wei-Cheng

    2012-11-01

    Full Text Available Abstract Background Lonicera japonica Thunb. (Caprifoliaceae, a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE was investigated for its healing efficiency in a rat excision wound model. Methods Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w LJEE ointment, or the reference standard drug, 0.2% (w/w nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing. Results LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production. Conclusions The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair.

  9. Female urogenital dysfunction following total mesorectal excision for rectal cancer

    Raja Ashraf

    2006-01-01

    Full Text Available Abstract Background The effect of Total Mesorectal Excision (TME on sexual function in the male is well documented. However, there is little literature in female patients. The aim of this study was to review the pelvic autonomic nervous anatomy in the female and to perform a retrospective audit of urinary and sexual function in women following surgery for rectal cancer where TME had been performed. Urogenital dysfunction was assessed through interview and questionnaire. Method Twenty-three questionnaires, eighteen returned, were sent to women with a mean age 65.5 yrs (range 34–86. All had undergone total mesorectal excision for rectal cancer between 1998–2001. Mean follow-up was 18.8 months (range 3–35. Results Preoperatively 5/18 (28% were sexually active, 3/18 (17% of patients described urinary frequency and nocturia and 7/18 (39% described symptoms of stress incontinence prior to surgery. Postoperatively all sexually active patients remained active although all described some discomfort with penetration. Two of the patients sexually active described reduced libido secondary to the stoma. Postoperative urinary symptoms developed with 59% reporting the development of nocturia, 18% developed stress incontinence and one patient required a permanent catheter. Of those with symptoms, 80% persisted longer than three months from surgery. Symptoms were predominant in those patients with low rectal cancers, particularly those undergoing abdomino-perineal excision and in those who had previously undergone abdominal hysterectomy. Conclusion The treatment of rectal cancer involves surgery to the pelvic floor. Despite nerve preservation this is associated with the development of worsening nocturia and stress incontinence. This is most marked in those patients who had previously undergone a hysterectomy. Further studies are warranted to assess the interaction with previous gynaecological surgery.

  10. Evidence implying DNA polymerase beta function in excision repair.

    Siedlecki, J A; Szyszko, J.; Pietrzykowska, I; Zmudzka, B

    1980-01-01

    Comparison was made of the ability of calf thymus DNA polymerases alpha and beta to replicate the following templates: native E. coli CR-34 DNA (T-DNA), calf thymus DNA activated by DNase I (act.DNA), BU-DNA (from E. coli CR-34 cells cultured on BUdR-containing medium) with damages resulting from incomplete excision repair, as well as thermally denatured act.DNA and BU-DNA (s.s.act.DNA and s.s.BU-DNA). 3H-TTP incorporation during extensive replication of act.DNA was similar for both enzymes, ...

  11. Microsurgical excision of hematoma of the lumbar ligamentum flavum.

    Takeno, Kenichi; Kobayashi, Shigeru; Miyazaki, Tsuyoshi; Yayama, Takafumi; Baba, Hisatoshi

    2010-07-01

    Hematoma of the lumbar ligamentum flavum is a very rare cause of sciatica. A 72-year-old man presented with left-sided sciatica and paresthesia of the lateral aspect of his left foot. From CT and MRI findings, he was diagnosed as having a hematoma embedded in the ligamentum flavum, which compressed the dura mater at the L5/S1 disc level. After an adequate surgical field was obtained with a microscope and a Casper retractor, the hematoma of the ligamentum flavum could be excised via a unilateral approach and satisfactory decompression of the cauda equina and nerve roots were obtained. PMID:20537575

  12. Successful surgical excision of primary right atrial angiosarcoma

    van der Horst Iwan CC

    2011-04-01

    Full Text Available Abstract Primary cardiac angiosarcoma is a rare and aggressive tumor with a high incidence of metastatic spread (up to 89% at the time of diagnosis, which restricts the indication for surgical resection to a small number of patients. We report the case of a 50-year old Caucasian woman with non-metastatic primary right atrial angiosarcoma, who underwent successful surgical excision of the tumor (with curative intent and reconstruction of the right atrium with a porcine pericardial patch. However, after a symptom-free survival of five months the patient presented with bone and liver metastases without evidence of local tumor recurrence.

  13. Successful excision of a massive bleeding schwannoma by thoracoscopic surgery.

    Ishibashi, Hironori; Takasaki, Chihiro; Okubo, Kenichi

    2016-06-01

    Massive intrathoracic bleeding caused by rupture of a benign schwannoma is extremely rare. A 73-year-old man was admitted to our emergency department because of chest pain and dyspnea. Computed tomography revealed massive pleural effusion and a posterior mediastinal tumor. Chest tube thoracostomy was performed, and the initial blood drainage was 1700 mL. Magnetic resonance imaging revealed that the tumor at the 8th costal level measured 46 × 60 mm. The tumor, located beside the 8th vertebra, had ruptured and caused the bleeding. It was successfully excised by thoracoscopic surgery and diagnosed as a benign schwannoma. PMID:27095705

  14. Use of Preputial Skin as Cutaneous Graft after Nevus Excision

    A. D'Alessio

    2010-01-01

    Full Text Available We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.

  15. Use of Preputial Skin as Cutaneous Graft after Nevus Excision

    A. D'Alessio; Piro, E; Brugnoni, M.; L. Abati

    2010-01-01

    We report a four-year-old boy with a nevus covering all the plantar side of his second finger on the left foot. He was also affected by congenital phimosis. Surgical excision of the nevus was indicated, but the skin defect would have been too large to be directly closed. The foreskin was taken as a full-thickness skin graft to cover the cutaneous defect of the finger. The graft intake was favourable and provided a functional repair with good aesthetic characteristic.

  16. Effect of the uvrD mutation on excision repair.

    Kuemmerle, N B; Masker, W E

    1980-01-01

    A pair of related Escherichia coli K-12 strains, one of which contains the uvrD101 mutation, were constructed and compared for ability to perform various steps in the excision repair of deoxyribonucleic acid damage inflicted by ultraviolet radiation. The results of this study indicated: (i) ultraviolet sensitivity in the uvrD101 mutant was greater than that of wild type but less than that measured in an incision-deficient uvrA mutant; (ii) host cell reactivation paralleled the survival data; ...

  17. Lobar pressure-volume characteristics of excised human lungs.

    Berend, N; Skoog, C; Thurlbeck, W. M.

    1981-01-01

    The pressure-volume (P-V) characteristics were investigated in 14 excised left human lungs and their individual lobes. Comparison of the upper and lower lobar P-V curves of the emphysema-free and emphysematous lungs showed no significant difference when plotted as per cent lobar volume at a transpulmonary pressure (PL) of 30 cm H2O (V30). However, when in the emphysematous lungs the more severely involved lobes were compared with the less severely involved lobes, significant differences in th...

  18. Chloroethyinitrosourea-derived ethano cytosine and adenine adducts are substrates for escherichia coli glycosylases excising analogous etheno adducts

    Guliaev, Anton B.; Singer, B.; Hang, Bo

    2004-05-05

    Exocyclic ethano DNA adducts are saturated etheno ring derivatives formed mainly by therapeutic chloroethylnitrosoureas (CNUs), which are also mutagenic and carcinogenic. In this work, we report that two of the ethano adducts, 3,N{sup 4}-ethanocytosine (EC) and 1,N{sup 6}-ethanoadenine (EA), are novel substrates for the Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug) and 3-methyladenine DNA glycosylase II (AlkA), respectively. It has been shown previously that Mug excises 3,N{sup 4}-ethenocytosine ({var_epsilon}C) and AlkA releases 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using synthetic oligonucleotides containing a single ethano or etheno adduct, we found that both glycosylases had a {approx}20-fold lower excision activity toward EC or EA than that toward their structurally analogous {var_epsilon}C or {var_epsilon}A adduct. Both enzymes were capable of excising the ethano base paired with any of the four natural bases, but with varying efficiencies. The Mug activity toward EC could be stimulated by E. coli endonuclease IV and, more efficiently, by exonuclease III. Molecular dynamics (MD) simulations showed similar structural features of the etheno and ethano derivatives when present in DNA duplexes. However, also as shown by MD, the stacking interaction between the EC base and Phe 30 in the Mug active site is reduced as compared to the {var_epsilon}C base, which could account for the lower EC activity observed in this study.

  19. Photoreversal-dependent release of thymidine and thymidine monophosphate from pyrimidine dimer-containing DNA excision fragments isolated from ultraviolet-damaged human fibroblasts

    To elucidate the enzymatic excision-repair process operative on cyclobutane-type pyrimidine photodimers in human dermal fibroblasts, we have examined excised dimer-containing material recovered in the trichloroacetic acid soluble fraction from far-ultraviolet-irradiated (254 nm, 40 J m-2) and incubated (24 h) cell cultures. The excised DNA photoproducts were found in oligonucleotide fragments with an estimated mean chain length of approximately 3.7 bases. Exposure of these isolated excision fragments, labeled with [3H]thymidine (dT), to a secondary, dimer-photoreversing fluence of far-UV (5.5 kJ m-2) resulted in the release of free dT and thymidine monophosphate (TMP). Photorelease of these two radioactive species was measured by high-performance liquid chromatography, with TMP being detected as the increase in dT following bacterial alkaline phosphatase treatment. These data imply that the photoliberated dT and TMP moieties were attached to the excision fragments solely by the cyclobutane ring of the dimer. No evidence was obtained for the photoliberation of free thymine, thus corroborating a conclusion reached by others that the excision of dimers in human cells is not initiated by scission of an intradimer N-glycosyl bond. The sum of the tritium label recovered in dT plus TMP corresponded to approximately 40% of that disappearing from thymine-containing dimers on photoreversal, suggesting that in about 80% of the isolated excision fragments the dimer is located at one end of the oligonucleotide and contains a break in its internal phosphodiester bond

  20. 26 CFR 55.4981-2 - Imposition of excise tax with respect to certain undistributed income of real estate investment...

    2010-04-01

    ... certain undistributed income of real estate investment trusts; calendar years beginning after December 31... (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) EXCISE TAX ON REAL ESTATE INVESTMENT TRUSTS AND REGULATED INVESTMENT COMPANIES Excise Tax on Real Estate Investment Trusts § 55.4981-2 Imposition of excise tax...

  1. Endoscopic Excision of Non-embolized Juvenile Nasopharyngeal Angiofibroma: Our Technique.

    Janakiram, Trichy Narayanan; Sharma, Shilpee Bhatia; Panicker, Vidya Bhargavan

    2016-09-01

    To approach Juvenile nasopharyngeal angiofibroma extending to the sphenoid sinus, pterygoid wedge and minimal involvement of the pterygopalatine fossa (Radkowski Stage 2 A) with an endoscopic technique without embolization with no recurrence and minimal morbidity and mortality. This is a retrospective, descriptive study based on the medical records of 15 patients with histologically confirmed JNA who underwent endoscopic binostril four handed endoscopic excision in our centre without embolisation between 2010 and 2015. All 15 patients were young males with a mean age of 14.13 years who underwent endoscopic excision of JNA without embolisation. Nasal obstruction (100 %) and epistaxis (100 %) were the most common symptoms. Average surgery length was 1 h 41 min. Mean blood loss was 67.2 ml and none of patients required blood transfusion. All patients had crusting and septal defect postoperatively, only 3 (20 %) had synechiae. Mean hospitalization time was 3.66 days. 2 (13.33 %) of our patients had a residual tumor and one (6.66 %) had a relapse in pterygoid wedge. There were no cases of death or significant morbidity. The follow up period was 1 year. Endoscopic endo nasal bi nostril four handed technique can achieve complete resection without embolization in case of small to medium sized JNA s in the hands of an experienced surgeon with minimal blood loss, low rates of recurrence and morbidity. PMID:27508124

  2. Nucleotide-excision repair of DNA in cell-free extracts of the yeast Saccharomyces cerevisiae

    A wide spectrum of DNA lesions are repaired by the nucleotide-excision repair (NER) pathway in both eukaryotic and prokaryotic cells. We have developed a cell-free system in Saccharomyces cerevisiae that supports NER. NER was monitored by measuring repair synthesis in DNA treated with cisplatin or with UV radiation. Repair synthesis in vitro was defective in extracts of rad1, rad2, and rad10 mutant cells, all of which have mutations in genes whose products are known to be required for NER in vivo. Additionally, repair synthesis was complemented by mixing different mutant extracts, or by adding purified Rad1 or Rad10 protein to rad1 or rad10 mutant extracts, respectively. The latter observation demonstrates that the Rad1 and Rad10 proteins directly participate in the biochemical pathway of NER. NER supported by nuclear extracts requires ATP and Mg2+ and is stimulated by polyethylene glycol and by small amounts of whole cell extract containing overexpressed Rad2 protein. The nuclear extracts also contain base-excision repair activity that is present at wild-type levels in rad mutant extracts. This cell-free system is expected to facilitate studies on the biochemical pathway of NER in S. cerevisiae

  3. Enzymic excision of ultraviolet-induced cytosine hydrates from left-handed DNA

    Ultraviolet irradiation of DNA produces a variety of pyrimidine modifications. These include cytosine hydrate (5,6-dihydro-6-hydroxycytosine), released as a free base by E. coli endonuclease III. The enzymic excision of cytosine hydrate by this purified enzyme was investigated by assaying release of labeled photoproduct from DNA into the ethanol-soluble fraction. Ultraviolet-irradiated poly(dG-dC):poly(dG-dC), radio-labeled in cytosines, was used as substrate. Shifts between the right-handed B-conformation and the left-handed Z-conformation were effected by heating the polymer in the presence of either Ni[II] or Co[II]. Conformational states were determined by ultraviolet circular dichroism. Rates of enzymic cytosine hydrate release did not differ between the different substrate conformations, B-DNA and Z-DNA. Irradiation of left-handed poly(dG-dC):poly(dG-dC) resulted in cytosine hydrate formation. Therefore, neither formation nor enzymic excision of ultraviolet-induced cytosine hydrates are substantially affected by the DNA conformational state. Cytosine hydrates are most likely to occur in alternating purine:pyrimidine sequences. Such segments can adopt the Z-conformation as a result of reactions with chemical carcinogens, the presence of metal ions, or negative superhelicity. These results indicate repair of cytosine hydrates to be likely, regardless of the DNA conformational state

  4. Excising terrestrial radio interference in low frequency radio astronomy

    Interference from terrestrial transmitters is a major problem in low-frequency radio astronomy. Experimental work is described in which a 22.25-MHz interferometer provided baseband signals from which 128-channel spectra were calculated in hardware by FFT and processed by a microcomputer. Narrow-band interference was identified and excised from the in-phase and quadrature cross-spectra and the auto-spectra in a 52-kHz band in real time. The observations were performed during winter near sun-spot maximum with the on-line microcomputer performing +- 4 σ iterative deletion of interference. Off-line, an algorithm was developed in which robust estimation was used to give protection from statistical outliers. The results showed consistently that 2 to 3 hr extra observing time were made possible per night. Low-level interference, which would not have been noticeable in records taken with a conventional receiving system, was detected and excised on most nights. (author)

  5. Effect of the uvrD mutation on excision repair

    A pair of related Escherichia coli K-12 strains, one of which contains the uvrD101 mutation, were constructed and compared for ability to perform various steps in the excision repair of deoxyribonucleic acid damage inflicted by ultraviolet radiation. The results of this study indicated: (i) ultraviolet sensitivity in the uvrD101 mutant was greater than that of wild type but less than that measured in an incision-deficient uvrA mutant; (ii) host cell reactivation paralleled the survival data; (iii) postirradiation deoxyribonucleic acid degradation was virtually identical in the two strains; (iv) incision, presumably at the sites of pyrimidine dimers, proceeded normally in the uvrD101 strain; (v) excision of pyrimidine dimers was markedly reduced in both rate and extent in the uvrD101 mutant; (vi) the amount of repair resynthesis was the same in both strains, and there was no evidence of abnormally long repair patches in the uvrD mutant; and (vii) rejoining of incision breaks was slow and incomplete in the uvrD strain. These data suggest that the ultraviolet sensitivity conferred by the uvrD mutation arises from inefficient removal of pyrimidine dimers or from failure to close incision breaks. The data are compatible with the notion that the uvrD+ gene product affects the conformation of incised deoxyribonucleic acid molecules

  6. Effect of the uvrD mutation on excision repair

    Kuemmerle, N.B.; Masker, W.E.

    1980-05-01

    A pair of related Escherichia coli K-12 strains, one of which contains the uvrD101 mutation, were constructed and compared for ability to perform various steps in the excision repair of deoxyribonucleic acid damage inflicted by ultraviolet radiation. The results of this study indicated: (i) ultraviolet sensitivity in the uvrD101 mutant was greater than that of wild type but less than that measured in an incision-deficient uvrA mutant; (ii) host cell reactivation paralleled the survival data; (iii) postirradiation deoxyribonucleic acid degradation was virtually identical in the two strains; (iv) incision, presumably at the sites of pyrimidine dimers, proceeded normally in the uvrD101 strain; (v) excision of pyrimidine dimers was markedly reduced in both rate and extent in the uvrD101 mutant; (vi) the amount of repair resynthesis was the same in both strains, and there was no evidence of abnormally long repair patches in the uvrD mutant; and (vii) rejoining of incision breaks was slow and incomplete in the uvrD strain. These data suggest that the ultraviolet sensitivity conferred by the uvrD mutation arises from inefficient removal of pyrimidine dimers or from failure to close incision breaks. The data are compatible with the notion that the uvrD+ gene product affects the conformation of incised deoxyribonucleic acid molecules.

  7. EXCISE TAX AS EXTERNAL VARIABLE (ON TABACCO PRODUCTS AT STATE AND LOCAL COMMUNITIES IN BIH

    Dinko Primorac

    2012-01-01

    Full Text Available The subject of this paper is themovement and accounting for excise tax as aseparate subsystem of sales tax, with an emphasison tobacco products. Since the excise tax ontobacco products is a specific category of excisableproducts, it is possible to fully distance it fromother products. Unlike other excise goods, excisetaxes on tobacco products can not be distinguishedby the criterion of luxury and by the criterion ofharm to health. This paper explains the reasons,effects and the basic characteristics of excise taxes,and full adjustment of the special tax. The aim ofthe research paper is to present and analyze thesystem of excise tax revenue in Bosnia andHerzegovina, with special reference to the excisetax on tobacco products. Furthermore the aim is toexplore how the excise tax system in Bosnia andHerzegovina functions and how the funds fromexcise taxes are collected, and where exactly theyare expended.

  8. WOUND HEALING ACTIVITY OF ALCOHOLIC EXTRACT OF SOLANUM ERIANTHUM D.DON IN EXCISION AND INCISION METHOD

    Ch. Sudha Bhargavi

    2013-02-01

    Full Text Available Solanum erianthum D. Don is an unarmed shrub or small tree with dense indumentums of soft stellate hairs. Leaves are simple, ovate-elliptical; margin entire or slight wavy, base rounded to cuneate, and apex acute to acuminate. The leaves have been extensively used for leucorrhoea, piles, hemorrhoids, scrofula, headache, vertigo, digestive troubles and for wound healing purposes. Wistar albino rats of either sex weighing between 200 and 220g were topically treated with extract formulated in gel (10% and 20% which was applied once daily in excision and incision wound model. Rats of standard groups were treated with 5% w/w Povidone-Iodine ointment topically. The percentage of wound contraction was increased, epithelization period was decreased and wound breaking strength was increased with topical application of AESE (Alcoholic Extract of Solanum erianthum gel in excision and incision wound model. The experimental data revealed that the AESE displayed remarkable wound healing activity thus supports its traditional use.

  9. Did the single market cause competition in excise taxes?:evidence from EU countries

    Lockwood, B.; G Migali

    2009-01-01

    Tax competition theory predicts that the introduction of the EU Single Market in 1993 should have caused excise tax competition and thus increased strategic interaction in the setting of excise taxes among EU countries. We test this prediction using a panel data set of 12 EU countries over the period 1987–2004. We find that for excise duties on still and sparkling wine, beer and ethyl alcohol, strategic interaction significantly increased after 1993. There is weaker evidence of increased inte...

  10. How does knowledge of three-dimensional excision margins following breast conservation surgery impact upon clinical target volume definition for partial-breast radiotherapy?

    Background and purpose: To compare partial-breast clinical target volumes generated using a standard 15 mm margin (CTVstandard) with those generated using three-dimensional surgical excision margins (CTVtailored30) in women who have undergone wide local excision (WLE) for breast cancer. Material and methods: Thirty-five women underwent WLE with placement of clips in the anterior, deep and coronal excision cavity walls. Distances from tumour to each of six margins were measured microscopically. Tumour bed was defined on kV-CT images using clips. CTVstandard was generated by adding a uniform three-dimensional 15 mm margin, and CTVtailored30 was generated by adding 30 mm minus the excision margin in three-dimensions. Concordance between CTVstandard and CTVtailored30 was quantified using conformity (CoI), geographical-miss (GMI) and normal-tissue (NTI) indices. An external-beam partial-breast irradiation (PBI) plan was generated to cover 95% of CTVstandard with the 95% isodose. Percentage-volume coverage of CTVtailored30 by the 95% isodose was measured. Results: Median (range) coronal, superficial and deep excision margins were 15.0 (0.5-76.0) mm, 4.0 (0.0-60.0) mm and 4.0 (0.5-35.0) mm, respectively. Median CoI, GMI and NTI were 0.62, 0.16 and 0.20, respectively. Median coverage of CTVtailored30 by the PBI-plan was 97.7% (range 84.9-100.0%). CTVtailored30 was inadequately covered by the 95% isodose in 4/29 cases. In three cases, the excision margin in the direction of inadequate coverage was ≤2 mm. Conclusions: CTVs based on 3D excision margin data are discordant with those defined using a standard uniform 15 mm TB-CTV margin. In women with narrow excision margins, the standard TB-CTV margin could result in a geographical miss. Therefore, wider TB-CTV margins should be considered where re-excision does not occur.

  11. Excision repair in MUT-mutants of Proteus mirabilis after UV-irradiation

    The behaviour of MUT-mutants of P.mirabilis to perform certain steps of excision repair after U.V.-irradiation is described. MUT-mutants introduce single-strand breaks in the DNA immediately after U.V.-irradiation, but their ability to excise pyrimidine dimers from the DNA is very diminished. Moreover, they are not able to accomplish the excision repair by rejoining of the single-strand breaks. The connection between the incomplete excision repair and the mutator phenotype of these mutants is discussed. (author)

  12. State-Specific Liquor Excise Taxes and Retail Prices in Eight U.S. States, 2012

    Siegel, Michael; Grundman, Jody; DeJong, William; Naimi, Timothy S.; King, Charles; Albers, Alison B.; Williams, Rebecca S.; Jernigan, David H.

    2013-01-01

    We investigated the relationship between state excise taxes and liquor prices in eight states, using 2012 data for 45 brands. We made 6,042 price observations among 177 liquor stores with online prices. Using a hierarchical model, we examined the relationship between excise taxes and product prices. State excise taxes were significantly related to liquor prices, with an estimated pass-through rate of 0.93. The proportion of price accounted for by excise taxes averaged 7.0%. We find that excis...

  13. The yeast TFB1 and SSL1 genes, which encode subunits of transcription factor IIH, are required for nucleotide excision repair and RNA polymerase II transcription.

    Z. Wang; Buratowski, S; Svejstrup, J Q; Feaver, W J; Wu, X; Kornberg, R D; Donahue, T F; Friedberg, E C

    1995-01-01

    The essential TFB1 and SSL1 genes of the yeast Saccharomyces cerevisiae encode two subunits of the RNA polymerase II transcription factor TFIIH (factor b). Here we show that extracts of temperature-sensitive mutants carrying mutations in both genes (tfb1-101 and ssl1-1) are defective in nucleotide excision repair (NER) and RNA polymerase II transcription but are proficient for base excision repair. RNA polymerase II-dependent transcription at the CYC1 promoter was normal at permissive tempera...

  14. A comprehensive evaluation of the 8-gauge vacuum-assisted Mammotome® system for ultrasound-guided diagnostic biopsy and selective excision of breast lesions

    Jimenez Rafael E

    2007-07-01

    Full Text Available Abstract Background Minimally invasive breast biopsy technology is now considered a standard of care for the diagnostic evaluation of suspicious breast lesions. The aim of the current study was to present a comprehensive evaluation of the 8-gauge vacuum-assisted Mammotome® system for ultrasound-guided diagnostic biopsy and selective excision of breast lesions. Methods A retrospective analysis was conducted of a series of 304 consecutive 8-gauge Mammotome® procedures that were performed under ultrasound guidance by a single surgeon from March 2004 to December 2006. Multiple variables, including patient demographics, characteristics of the breast lesion (based on ultrasound and mammography, procedural and histopathology variables, and interval follow-up variables (based on ultrasound and mammography, were evaluated. Results Among 304 procedures, 235 (77% were performed with the presumption of complete excision of the ultrasound lesion during Mammotome® core acquisition, while 69 (23% were performed with only partial excision of the ultrasound lesion during Mammotome® core acquisition (diagnostic tissue sampling only. 100% of all ultrasound lesions were accurately diagnosed, demonstrating no apparent false-negative results among the 256 patients that were compliant with follow-up at a median interval follow-up duration of 11 months (range 1 to 37. Likewise, 89% of all appropriately selected ultrasound lesions were completely excised, as demonstrated on interval follow-up ultrasound at a median time of 6 months (range, 3 to 16. There were no independent predictors of successful complete excision of any given appropriately selected ultrasound lesion by the ultrasound-guided 8-gauge Mammotome® biopsy technique. Conclusion The 8-gauge vacuum-assisted Mammotome® system is highly accurate for ultrasound-guided diagnostic biopsy of suspicious breast lesions and is highly successful for complete excision of appropriately selected presumed benign

  15. Robot-assisted laparoscopic excision of a retroperitoneal paracaval tumor.

    Wei, Tzu-Chun; Chung, Hsiao-Jen; Lin, Alex T L; Chen, Kuang-Kuo

    2013-12-01

    During the past few years, robotic surgical systems have been rapidly developed. The progress and advantages of these systems include three-dimensional vision and enhanced ergonomics. These advantages have helped a new generation of minimally invasive surgery to evolve. The da Vinci Surgical System seems to greatly resolve problems (e.g., wide exposure and retraction of peritoneal organs) that are confronted by traditional laparoscopic surgeries for retroperitoneal tumors that are near great vessels. There have been few reported cases concerning laparoscopic excision of retroperitoneal tumors situated between the inferior vena cava, the right renal vessel, and the kidney. We report the use of a robotic surgical system for this type of treatment. A 54-year-old female patient had a hypoechoic lesion near the inferior vena cava and superior to the right renal vessels. It was incidentally found by ultrasound during a health check-up examination. The computed tomography (CT) scan revealed a heterogeneous contrast-enhanced retroperitoneal mass approximately 4.4 cm medial to the right kidney with the inferior vena cava slightly deviated to the left. Robot-assisted laparoscopic excision of the retroperitoneal tumor was performed on October 15, 2010 with an operation time of 135 minutes and an estimated blood loss of less than 30 mL. The J-Vac drainage tube was removed on postoperative Day 3, and the patient was discharged in a stable condition the following day. The pathology of the tumor was retroperitoneal schwannoma. A re-evaluation was arranged postoperatively for the 15-month ambulatory visit. No local recurrence or distal metastasis was present. PMID:24079977

  16. Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology

    Sarah C Shuck; Emily A Short; John J Turchi

    2008-01-01

    Repair of bulky DNA adducts by the nucleotide excision repair (NER) pathway is one of the more versatile DNA repair pathways for the removal of DNA lesions. There are two subsets of the NER pathway, global genomic-NER (GG-NER) and transcription-coupled NER (TC-NER), which differ only in the step involving recognition of the DNA lesion. Following recognition of the damage, the sub-pathways then converge for the incision/excision steps and subsequent gap filling and ligation steps. This review will focus on the GGR sub-pathway of NER while the TCR sub-pathway will be covered in another article in this issue. The ability of the NER pathway to repair a wide array of adducts stems, in part, from the mechanisms involved in the initial recognition step of the damaged DNA and results in NER impacting an equally wide array of human physiological responses and events. In this review, the impact of NER on carcinogenesis, neurological function, sensitivity to environmental factors and sensitivity to cancer therapeutics will be discussed. The knowledge generated in our understanding of the NER pathway over the past 40 years has resulted from advances in the fields of animal model systems, mammalian genetics and in vitro biochemistry, as well as from reconstitution studies and structural analyses of the proteins and enzymes that participate in this pathway. Each of these avenues of research has contributed significantly to our understanding of how the NER pathway works and how alterations in NER activity, both positive and negative, influence human biology.

  17. 碱基切除修复基因HOGG1特异性锤头状核酶表达载体的构建及其功能的初步研究%Constructing the Eukaryotic Expression Vector to Study Preliminarily the Functions of Hammerhead Ribozyme Targeting Base Excision Repair Gene HOGG1

    张遵真; 张勤; 吴媚

    2006-01-01

    Objective Adriamycin is widely used as an effective anti-tumor drug clinically treating a number of human cancers, but the effect of adriamycin is limited by drug resistance. The various kinds of investigations indicated that the anti-tumor activity of adriamycin resulted from drug-induced free radical formation. The free radicals could lead to oxidative DNA damage, and the lesion would be repaired by base excision repair (BER) pathway. Human 8-oxoguanine DNA glycosylase 1 (HOGG1) is a key enzyme on BER pathway. To study the influence and biological mechanism of the HOGG1 to adriamycin drug-sensitivity, the eukaryotic expression vector with gene of hammerhead ribozyme targeting HOGG1 mRNA would be constructed and identified, and then the change of drug-sensitivity in lung cancer A549 cells would be investigated. Methods According to computer design, two specific restriction site BamHⅠ and EcoRⅠ were added to both ends of the ribozyme gene, then the modified ribozyme gene was synthesized and cloned into the eukaryotic expression vector pcDNA3.1(+). The positive recombinants were screened by ampicillin resistance, and plasmids were extracted from the positive recombinants and digested by BamH Ⅰ and EcoR Ⅰ, and then were analyzed by agarose gel electrophoresis and DNA sequencing. The recombinants were transiently transfected into A549 cells. The positive recombinants were identified by reverse transcription-polymerase chain reaction (RT-PCR) targeting to NEO gene, which was a neomycin resistance gene for selection of stable cell lines and only existed in vectors. The changes of HOGG1 mRNA in A549 cells were detected by RT-PCR. Then the cellular sensitivity to adriamycin was tested by comparison between untransfected cells and transfected cells by MTT assay. The adriamycin-induced DNA damage was investigated by comet assay or single cell gel electrophoresis (SCGE) between untransfected and transfected cells. Results The recombinants containing the ribozyme gene

  18. Multicomponent Chirp-like Jammer Excision in DSSS Communication Systems Using Hilbert-Huang Hough Transform

    Yuan Ye

    2013-04-01

    Full Text Available A novel and efficient approach for multicomponent chirp-like jammer excision in direct sequence spread spectrum (DSSS communication systems using Hilbert-Huang Hough (HH-H transform is proposed, which is the generalization of marginal Hilbert spectrum. The approach iteratively decomposes the received signal into intrinsic mode functions (IMFs and applies Hilbert transform to each IMF to yield Hilbert spectrum (HS, by which the embedded jammers can be well concentrated in the time-frequency plane along their instantaneous frequency laws. By performing Hough transform over the HS and searching peaks in the parameter space, parameters estimation and components reconstruction of the multicomponent chirp-like jammer are implememted. Simulation results are presented showing performance comparison between the proposed method and the fractional Fourier transform (FrFT based method in the case of two chirp-like jammer components.

  19. New design of nucleotide excision repair (NER) inhibitors for combination cancer therapy.

    Gentile, Francesco; Tuszynski, Jack A; Barakat, Khaled H

    2016-04-01

    Many cancer chemotherapy agents act by targeting the DNA of cancer cells, causing substantial damage within their genome and causing them to undergo apoptosis. An effective DNA repair pathway in cancer cells can act in a reverse way by removing these drug-induced DNA lesions, allowing cancer cells to survive, grow and proliferate. In this context, DNA repair inhibitors opened a new avenue in cancer treatment, by blocking the DNA repair mechanisms from removing the chemotherapy-mediated DNA damage. In particular, the nucleotide excision repair (NER) involves more than thirty protein-protein interactions and removes DNA adducts caused by platinum-based chemotherapy. The excision repair cross-complementation group 1 (ERCC1)-xeroderma pigmentosum, complementation group A (XPA) protein (XPA-ERCC1) complex seems to be one of the most promising targets in this pathway. ERCC1 is over expressed in cancer cells and the only known cellular function so far for XPA is to recruit ERCC1 to the damaged point. Here, we build upon our recent advances in identifying inhibitors for this interaction and continue our efforts to rationally design more effective and potent regulators for the NER pathway. We employed in silico drug design techniques to: (1) identify compounds similar to the recently discovered inhibitors, but more effective at inhibiting the XPA-ERCC1 interactions, and (2) identify different scaffolds to develop novel lead compounds. Two known inhibitor structures have been used as starting points for two ligand/structure-hybrid virtual screening approaches. The findings described here form a milestone in discovering novel inhibitors for the NER pathway aiming at improving the efficacy of current platinum-based therapy, by modulating the XPA-ERCC1 interaction. PMID:26939044

  20. 77 FR 43157 - Disregarded Entities and the Indoor Tanning Services Excise Tax; Correction

    2012-07-24

    ... the Federal Register on June 25, 2012 (77 FR 37806) relating to disregarded entities (including qualified subchapter S subsidiaries) and the indoor tanning services excise tax. DATES: This correction is... Excise Tax; Correction AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Correcting...

  1. Periodontal plastic procedure for the management of the residual gingival defect after excision of an epulis

    Varun Choudhary

    2015-01-01

    Full Text Available Dentinal hypersensitivity and unesthetic appearance are common findings after excision of an epulis due to exposure of root and underlying bone. The simultaneous placement of subepithelial connective tissue grafting after excision of the lesion seems to be viable surgical option in such cases. Furthermore, this will avoid second surgical procedure for the management of the residual gingival defect.

  2. Surgical Site Infection After Skin Excisions in Children: Is Field Sterility Sufficient?

    Nuzzi, Laura C; Greene, Arin K; Meara, John G; Taghinia, Amir; Labow, Brian I

    2016-03-01

    Skin excisions are common procedures in children. They may be performed in the clinic using field sterility or the operating room with strict sterile technique. We compared the effect of these locations and the use of antibiotics on the incidence of surgical site infection (SSI) after skin excisions. Patients ages 0-18 years presenting to our department for the excision of lesions from 2006 to 2010 with complete medical records were included in our study. Records were reviewed for demographic characteristics, presentation, perioperative conditions, and postoperative SSI and other wound complications. Analyses were performed to estimate the costs associated with sterility technique and perioperative antibiotic use. We identified 700 patients with a mean age of 9.1 years. Of 872 lesions excised, 0.3% resulted in SSI and 1.8% had other wound complications. The incidence of SSI did not vary according to sterility technique, antibiotic usage, surgeon, age, or lesion size, type, or location. The equipment costs to excise a lesion in the operating room were 200% greater than in the clinic. The incidence of SSI after excision of benign lesions in children did not differ between those performed using clinic field sterility and those using the standard aseptic sterile technique in the operating room. A considerable cost savings could be realized by adopting field sterility for simple excisions performed in the operating room and avoiding routine perioperative antibiotics in pediatric skin excisions. PMID:25727412

  3. Aggressive Angiomyxoma of the Bladder Neck Requiring Local Excision and Mitrofanoff Formation

    Davari, M.; Lamb, B. W.; CHOWDHURY, S.; Jameson, C; Kelly, J.D. (James); Greenwell, T.

    2015-01-01

    Aggressive angiomyxoma is a rare mesenchymal tumour predominantly affecting the female pelvis and perineum but has also been described in males. This tumour can often present a diagnostic challenge and has a propensity for local recurrence after surgical excision. We present an unusual case of aggressive angiomyxoma arising from the bladder of a female patient which required local excision and Mitrofanoff formation.

  4. Oesophageal pseudodiverticulum after foregut duplication cyst excision: Case report and literature review

    Iuliana D Bobanga

    2016-01-01

    Full Text Available Oesophageal pseudodiverticula rarely occur after excision of benign oesophageal neoplasms. While management and outcomes have been reported in the adult leiomyoma literature, sparse data exist on the occurrence and management of pseudodiverticula after foregut duplication cyst excision. We discuss our experience with a paediatric patient and review relevant literature regarding operative techniques and surgical outcomes.

  5. Accurate DNA assembly and genome engineering with optimized uracil excision cloning

    Cavaleiro, Mafalda; Kim, Se Hyeuk; Seppala, Susanna;

    2015-01-01

    produces β-carotene to optimize assembly junctions and the uracil excision protocol. By combining uracil excision cloning with a genomic integration technology, we demonstrate that up to six DNA fragments can be assembled in a one-tube reaction for direct genome integration with high accuracy, greatly...

  6. Mechanisms of DNA Repair by Photolyase and Excision Nuclease (Nobel Lecture).

    Sancar, Aziz

    2016-07-18

    Ultraviolet light damages DNA by converting two adjacent thymines into a thymine dimer which is potentially mutagenic, carcinogenic, or lethal to the organism. This damage is repaired by photolyase and the nucleotide excision repair system in E. coli by nucleotide excision repair in humans. The work leading to these results is presented by Aziz Sancar in his Nobel Lecture. PMID:27337655

  7. Aerodynamic and Nonlinear Dynamic Acoustic Analysis of Tension Asymmetry in Excised Canine Larynges

    Devine, Erin E.; Bulleit, Erin E.; Hoffman, Matthew R.; McCulloch, Timothy M.; Jiang, Jack J.

    2012-01-01

    Purpose: To model tension asymmetry caused by superior laryngeal nerve paralysis (SLNP) in excised larynges and apply perturbation, nonlinear dynamic, and aerodynamic analyses. Method: SLNP was modeled in 8 excised larynges using sutures and weights to mimic cricothyroid (CT) muscle function. Weights were removed from one side to create tension…

  8. Development of a positron probe for localization and excision of brain tumours during surgery

    Bogalhas, F.; Charon, Y.; Duval, M.-A.; Lefebvre, F.; Palfi, S.; Pinot, L.; Siebert, R.; Ménard, L.

    2009-07-01

    The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for 18F was 1.1 cps kBq-1 ml-1 for the small head and 3.4 cps kBq-1 ml-1 for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The γ-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.

  9. Development of a positron probe for localization and excision of brain tumours during surgery

    The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for 18F was 1.1 cps kBq-1 ml-1 for the small head and 3.4 cps kBq-1 ml-1 for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The γ-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.

  10. Mammographic bi-dimensional product: a powerful predictor of successful excision of ductal carcinoma in situ

    Background: The aim of this analysis was to ascertain whether uni-dimensional measurement of mammographic microcalcification, the product of bi-dimensional measurement, calcification morphology, and pathological grade are helpful in predicting successful single therapeutic wide local excision (WLE) of ductal carcinoma in situ (DCIS). Methods: The study group comprised 505 patients whose mammograms showed the DCIS as calcification, and in whom a non-operative diagnosis had been obtained and WLE attempted. The extents of mammographic calcifications was measured in two planes at 90o on the oblique view, the appearances classified as comedo, granular, or punctate. DCIS was graded using cyto-nuclear characteristics. Results: Three hundred and forty-two patients had a successful first WLE and 163 patients had further surgery. A uni-dimensional measurement of 2 were associated with successful excision (69 versus 54%, p = 0.02 and 70 versus 27%, p = 0.0001, respectively). Mammographic calcification morphology and histological grade did not influence the likelihood of a successful first WLE. For high-grade DCIS, the upper limit of the bi-dimensional product associated with successful WLE was 800 mm2 (69 versus 24%, p = 0.0003). In contrast, for non-high-grade DCIS, the cut-off was 400 mm2 (73 versus 33%, p = 0.01). Analyses based on mammographic calcification morphology gave similar findings. Conclusion: The mammographic bi-dimensional product is a powerful predictor of successful WLE of DCIS when combined with histological grade and/or calcification morphology

  11. Measuring Rates of Herbicide Metabolism in Dicot Weeds with an Excised Leaf Assay.

    Ma, Rong; Skelton, Joshua J; Riechers, Dean E

    2015-01-01

    In order to isolate and accurately determine rates of herbicide metabolism in an obligate-outcrossing dicot weed, waterhemp (Amaranthus tuberculatus), we developed an excised leaf assay combined with a vegetative cloning strategy to normalize herbicide uptake and remove translocation as contributing factors in herbicide-resistant (R) and -sensitive (S) waterhemp populations. Biokinetic analyses of organic pesticides in plants typically include the determination of uptake, translocation (delivery to the target site), metabolic fate, and interactions with the target site. Herbicide metabolism is an important parameter to measure in herbicide-resistant weeds and herbicide-tolerant crops, and is typically accomplished with whole-plant tests using radiolabeled herbicides. However, one difficulty with interpreting biokinetic parameters derived from whole-plant methods is that translocation is often affected by rates of herbicide metabolism, since polar metabolites are usually not mobile within the plant following herbicide detoxification reactions. Advantages of the protocol described in this manuscript include reproducible, accurate, and rapid determination of herbicide degradation rates in R and S populations, a substantial decrease in the amount of radiolabeled herbicide consumed, a large reduction in radiolabeled plant materials requiring further handling and disposal, and the ability to perform radiolabeled herbicide experiments in the lab or growth chamber instead of a greenhouse. As herbicide resistance continues to develop and spread in dicot weed populations worldwide, the excised leaf assay method developed and described herein will provide an invaluable technique for investigating non-target site-based resistance due to enhanced rates of herbicide metabolism and detoxification. PMID:26383604

  12. Evaluation of 57 teat sanitizers using excised cow teats.

    Murdough, P A; Pankey, J W

    1993-07-01

    Fifty-seven teat dip formulations were tested for germicidal activity with an excised teat assay. Streptococcus agalactiae (ATCC 27956), Staphylococcus aureus (ATCC 29740), and Escherichia coli+ (a wild strain isolated from an Ohio cow 2956RR during the dry period) were used. Log reductions ranged from 5.6480 to 1.8330 for Strep. agalactiae compared with undipped controls. Staphylococcus aureus were reduced from 4.8972 to 1.0102. Escherichia coli were reduced from 5.8677 to 1.1450. The percentages of the products tested that had log reductions dip formulations contained 4% sodium hypochlorite; all were effective against Strep. agalactiae, Staph. aureus, and E. coli. The three formulations containing glutaraldehyde were effective against the three mastitis pathogens. Formulations containing 1 and .5% iodine were not consistently effective against Strep. agalactiae, Staph. aureus, or E. coli. Teat sanitizers containing .5% chlorhexidine also showed inconsistency. Variations in formulation for products containing iodine or chlorhexidine affected germicidal activity. PMID:8345130

  13. Screening of human bocavirus in surgically excised cancer specimens.

    Abdel-Moneim, Ahmed S; El-Fol, Hosam A; Kamel, Mahmoud M; Soliman, Ahmed S A; Mahdi, Emad A; El-Gammal, Ahmed S; Mahran, Taha Z M

    2016-08-01

    Human bocavirus (HBoV) is a prevalent virus worldwide and is mainly associated with respiratory disorders. Recently, it was detected in several disease conditions, including cancers. Colorectal cancer (CRC) is the third main cause of cancers worldwide. Risk factors that initiate cell transformation include nutritional, hereditary and infectious causes. The aim of the current study was to screen for the presence of HBoV in solid tumors of colorectal cancer and to determine the genotypes of the detected strains. Surgically excised and paraffin-embedded colorectal cancer tissue specimens from 101 male and female patients with and without metastasis were collected over the last four years. Pathological analysis and tumor stages were determined. The presence of HBoV was screened by polymerase chain reaction, and the genotype of the detected HBoV was determined by direct gene sequencing. Most of the examined specimens were adenocarcinoma with mucinous activity in many of them. Twenty-four out of 101 (23.8 %) CRC tissue specimens were found to contain HBoV-1. Low sequence diversity was recorded in the detected strains. The virus was detected in both male and female patients with an age range of 30-75 years. It is proposed that HBoV-1 could play a potential role in the induction of CRC. PMID:27155943

  14. Post-operative outcomes following the excision of dorsal wrist ganglions with/without the use of Methylene Blue

    Suleyman Tas

    2016-04-01

    Conclusions: The recurrence of cysts is rare after complete excision, particularly when rupture is prevented. Methylene blue injection is useful for ensuring complete excision and, therefore, to prevent recurrence. [Hand Microsurg 2016; 5(1.000: 1-6

  15. An unprecedented nucleic acid capture mechanism for excision of DNA damage

    Rubinson, Emily H.; Prakasha Gowda, A.S.; Spratt, Thomas E.; Gold, Barry; Eichmanbrand, Brandt F. (Pitt); (Vanderbilt); (Penn)

    2010-11-18

    DNA glycosylases that remove alkylated and deaminated purine nucleobases are essential DNA repair enzymes that protect the genome, and at the same time confound cancer alkylation therapy, by excising cytotoxic N3-methyladenine bases formed by DNA-targeting anticancer compounds. The basis for glycosylase specificity towards N3- and N7-alkylpurines is believed to result from intrinsic instability of the modified bases and not from direct enzyme functional group chemistry. Here we present crystal structures of the recently discovered Bacillus cereus AlkD glycosylase in complex with DNAs containing alkylated, mismatched and abasic nucleotides. Unlike other glycosylases, AlkD captures the extrahelical lesion in a solvent-exposed orientation, providing an illustration for how hydrolysis of N3- and N7-alkylated bases may be facilitated by increased lifetime out of the DNA helix. The structures and supporting biochemical analysis of base flipping and catalysis reveal how the HEAT repeats of AlkD distort the DNA backbone to detect non-Watson-Crick base pairs without duplex intercalation.

  16. Image-Guided Radiotherapy for Breast Cancer Patients: Surgical Clips as Surrogate for Breast Excision Cavity

    Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans. Methods and Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol. Retrospectively, the CBCT scans were registered to the planning CT scans, using gray-value registration of the excision cavity region and chamfer matching of the clips. Subsequently, residual setup errors (systematic [Σ] and random [σ]) of the excision cavity were estimated relative to the clips' registration. Finally, the stability of the clips' positions were quantified as the movement of each separate clip according to the center of gravity of the excision cavity. Results: When clips were used for online setup corrections, the residual errors of the excision cavity were Σleft-right = 1.2, σleft-right = 1.0; Σcranial-caudal = 1.3, σcranial-caudal = 1.2; and Σanterior-posterior = 0.7, σanterior-posterior = 0.9 mm. Furthermore, the average distance (over all patients) between the clips and centers of gravity of the excision cavities was 18.8 mm (on the planning CT) and was reduced to 17.4 mm (measured on the last CBCT scan). Conclusion: Clips move in the direction of the center of gravity of the excision cavity, on average, 1.4 mm. The clips are good surrogates for locating the excision cavity and providing small residual errors.

  17. Substrate overlap and functional competition between human nucleotide excision repair and Escherichia coli photolyase and (A)BC excision nuclease

    Human cell free extract prepared by the method of Manley et al. carries out repair synthesis on UV-irradiated DNA. Removal of pyrimidine dimers by photoreactivation with DNA photolyase reduces repair synthesis by about 50%. With excess enzyme in the reaction mixture photolyase reduced the repair signal by the same amount even in the absence of photoreactivating light, presumably by binding to pyrimidine dimers and interfering with the binding of human damage recognition protein. Similarly, the UvrB subunit of Escherichia coli (A)BC excinuclease when loaded onto UV-irradiated or psoralen-adducted DNA inhibited repair synthesis by cell-free extract by 75-80%. The opposite was true also as HeLa cell free extract specifically inhibited the photorepair of a thymine dimer by DNA photolyase and its removal by (A)BC excinuclease. Cell-free extracts from xeroderma pigmentosum (XP) complementation groups A and C were equally effective in blocking the E. coli repair proteins, while extracts from complementation groups D and E were ineffective in blocking the E. coli enzyme. These results suggest that XP-D and XP-E cells are defective in the damage recognition subunits(s) of human excision nuclease

  18. Copper-Controllable, Site-Specific DNA Excision in Transgenic Plants

    PENG Xiang-lei; LIANG Bin; CHEN Ming; HU Yuan-lei; LIN Zhong-ping

    2003-01-01

    A copper-inducible, Cre-loxP recombination-mediated DNA excision system has been developed in transgenic tobacco plants. The copper inducible system derived from yeast was used for the control of the expression of the Cre recombinase. Upon copper induction, the GUS reporter gene expression unit flanked by two direct lox sites was excised from the transgenic tobacco genome. Quantitative fluorometric GUS assays,Northern blot and PCR analyses showed a high-efficient, copper-dependent and Cre-loxP mediated DNA recombination in all the tested transgenic lines. The copper inducible foreign gene excision might be of great potential in genetic control of transgenic crops.

  19. Induction of the Tn10 Precise Excision in E. coli Cells after Accelerated Heavy Ions Irradiation

    Zhuravel, D V

    2003-01-01

    The influence of the irradiation of different kinds on the indication of the structural mutations in the bacteria Escherichia coli is considered. The regularities of the Tn10 precise excision after accelerated ^{4}He and ^{12}C ions irradiations with different linear energy transfer (LET) were investigated. Dose dependences of the survival and relative frequency of the Tn10 precise excision were obtained. It was shown, that the relative frequency of the Tn10 precise excision is the exponential function from the irradiation dose. Relative biological efficiency (RBE), and relative genetic efficiency (RGE) were calculated, and were treated as the function of the LET.

  20. Uptake and elimination of lanthanum by excised roots of Triticum aestivum

    In this paper, uptake and elimination of lanthanum by excised roots of Triticum aestivum L. in various conditions were studied. Lanthanum concentrations in the roots were determined by neutron activation analysis. Results showed that the uptake of La in the excised root was almost independent of vitality, and the bonding of La with the roots was tight, but could be removed by EDTA treatment. There was significant dose dependent accumulation of La in the excised roots within the experimental concentration (0-40 μmol/l). (author)

  1. Defective thymine dimer excision by cell-free extracts of xeroderma pigmentosum cells

    Crude extracts of normal human diploid fibroblasts and of human peripheral blood lymphocytes excise thymine dimers from purified ultraviolet-irradiated DNA, or from the DNA presumably present as chromatin in unfractionated cell-free preparations of cells that had been labeled with [3H]thymidine. Extracts of xeroderma pigmentosum cells from complementation groups A, C, and D also excise thymine dimers from purified DNA, but extracts of group A cells do not excise dimers from the DNA of radioactively labeled unfractionated cell-free preparations

  2. Keloid Management: A Retrospective Case Review on a New Approach Using Surgical Excision, Platelet-Rich Plasma, and In-office Superficial Photon X-ray Radiation Therapy

    Jones, Michael E.; Hardy, Cherrell; Ridgway, Julie

    2016-01-01

    ABSTRACT OBJECTIVE: The objective of this retrospective study was to evaluate the efficacy of the authors’ combination therapy protocol for keloid treatment. DESIGN: Retrospective. SETTING: Plastic surgery office-based outpatient setting in New York City. PATIENTS: Forty patients with 44 keloid scars requiring surgical excision. INTERVENTIONS: Keloid scars were treated using surgical excision, platelet-rich plasma, and postoperative in-office superficial photon X-ray radiation therapy. Intralesional triamcinolone injections were administered once to 4 patients with poor results on scar scale assessment. Patient follow-up visits ranged from 3 to 11 months to assess for evidence of recurrence and adverse effects. MAIN OUTCOME MEASURE(S): For the purpose of this study, recurrence was defined as any sign of extraordinary erythema, induration, and hypertrophy beyond the site of excision. MAIN RESULTS: In the 16 keloids treated with 2 fractions, there was no evidence of recurrence. One of 25 keloids treated with 3 fractions demonstrated evidence of recurrence. One of 3 keloids treated with a single fraction displayed signs of recurrence. Postirradiation hyperpigmentation was noted in all patients. CONCLUSIONS: Surgical excision combined with platelet-rich plasma and postoperative in-office superficial radiation therapy achieved a 95.5% nonrecurrence rate at 1- to 3-month follow-up. This protocol appears to be a safe and viable option in the management of keloids and merits further randomized controlled study of its comparative efficacy. PMID:27300360

  3. Short-term hypofractionated radiotherapy followed by total mesorectal excision

    As of December 1996 to March 1999, 34 patients with locally advanced rectal cancer have been irradiated preoperatively with 5 times 5 Gy. After CT-planning, radiotherapy was administered using a 3-field or 4-field box technique with 2 anterior-posterior fields or a posterior field of 9 ± 2 cm x 11.5 ± 2.4 cm and 2 opposed bilateral fields of 9 ± 1.5 cm x 11.5 ± 2 cm with 6- to 25-MV photons. Surgery was performed 14 ± 6 days after irradiation in 33/34 patients (82% anterior resection with total mesorectal excision, 18% abdomino-perineal resection). Patients with a positive lymph node status or pT3/4 lesions underwent adjuvant chemotherapy with 5-Fluorouracil (5-FU). The median follow-up period is 189 days (range: 15 to 548 days). Results: The following early side reactions were registered: Increased bowel movements (4/34), fatigue (2/34), pain in the groins (1/34), nausea and perianal smart (1/34), vertigo (1/34), temporary urinary obstruction (1/34). One patient with heart failure NYHA Grade III died of a heart attack after 21 days. Preoperative T and N categories showed a distribution of 3,29 and 2 for T4, T3 and unknown and 20, 11 and 3 for N+, N- and unknown; postoperative T and N categories showed a distribution of 3/19 and 11 for T4, T3 and T2 and 19 and 14 for N+ and N-. In 32 of 33 patients tumor free margins were achieved. One patient with peritoneal metastases had a R1 resection. In 3 patients metastases were detected intraoperatively. Perioperative complications were: 2 cases of leaking anastomosis and postoperative bowel atonia, 1 case with bowel obstruction, delayed wound healing, wound dehiscence and temporary renal dysfunction. (orig.)

  4. Quantitative characterization of pyrimidine dimer excision from UV-irradiated DNA (excision capacity) by cell-free extracts of the yeast Saccharomyces cerevisiae

    Cell-free extracts from wild-type yeast (RAD+) and from rad mutants belonging to the RAD3 epistatic group (rad1-1, rad2-1, rad3-1, rad4-1) contain activities catalyzing the excision of pyrimidine dimers (PD) from purified ultraviolet-irradiated DNA which was not pre-treated with exogenous UV-endonuclease. The level of these activities in cell-free extracts from rad mutants did not differ from that in wild-type extract and was close to the in vivo excision capacity of the latter calculated from the LD37 (about 104 PD per haploid genome). (Auth.)

  5. Incomplete excision repair process after UV-irradiation in MUT-mutants of Proteus mirabillis

    MUT-mutants of P. mirabilis seem to be able to perform the incision step in the course of excision repair. In contrast to the corresponding wildtype strains with MUT-mutants the number of single-strand breaks formed after UV-irradiation is independent of the UV-dose up to about 720 erg/mm2. Incubation in minimal medium over a longer time does not result in completion of excision repair; about 3-6 single-strand breaks in the DNA of these mutants remain open. Likewise, the low molecular weight of the newly synthesized daughter DNA confirms an incompletely proceeding or delayed repair process. As a possible reason for the mutator phenotype an alteration of the DNA-polymerase playing a role in excision and resynthesis steps of excision repair is discussed. (author)

  6. Excision of the urachal remnant using the abdominal wall-lift laparoscopy: A case report

    Kosuke Kobayashi

    2016-01-01

    Discussion and conclusion: Urachal sinus excision using the abdominal wall-lift laparoscopy seems to surpass the previously reported methods in term of safety, cosmetics, and adequacy of surgical procedures.

  7. Surgical Excision of Benign Papillomas Diagnosed with Core Biopsy: A Community Hospital Approach

    Our goal was to assess the value of surgical excision of benign papillomas of the breast diagnosed on percutaneous core biopsy by determining the frequency of upgrade to malignancies and high risk lesions on a final surgical pathology. We reviewed 67 patients who had biopsies yielding benign papilloma and underwent subsequent surgical excision. Surgical pathology of the excised lesions was compared with initial core biopsy pathology results. 54 patients had concordant benign core and excisional pathology. Cancer (ductal carcinoma in situ and invasive ductal carcinoma) was diagnosed in five (7%) patients. Surgery revealed high-risk lesions in 8 (12%) patients, including atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ. Cancer and high risk lesions accounted for 13 (19%) upstaging events from benign papilloma diagnosis. Our data suggests that surgical excision is warranted with core pathology of benign papilloma

  8. 76 FR 77053 - Proposed Collection; Income, Excise, and Estate and Gift Taxes Effective Dates, etc.

    2011-12-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Income, Excise, and Estate and Gift Taxes Effective Dates, etc. AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for...

  9. Excise Tax Rates On Packs Of Cigarettes PowerPoint Slides

    U.S. Department of Health & Human Services — Download the current cigarette excise tax rates on packs of cigarettes slides. These slides are available in PDF and PowerPoint formats. The PDF version can be...

  10. Evaluation of endoscopic laser excision of polypropylene mesh/sutures following anti-incontinence procedures.

    Davis, N F

    2012-11-01

    We reviewed our experience with and outcome of the largest series to our knowledge of patients who underwent endoscopic laser excision of eroded polypropylene mesh or sutures as a complication of previous anti-incontinence procedures.