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Sample records for y-family polymerases bypass

  1. Quantitative Analysis of the Mutagenic Potential of 1-Aminopyrene-DNA Adduct Bypass Catalyzed by Y-Family DNA Polymerases

    Science.gov (United States)

    Sherrer, Shanen M.; Taggart, David J.; Pack, Lindsey R.; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

    2012-01-01

    N- (deoxyguanosin-8-yl)-1-aminopyrene (dGAP) is the predominant nitro polyaromatic hydrocarbon product generated from the air pollutant 1-nitropyrene reacting with DNA. Previous studies have shown that dGAP induces genetic mutations in bacterial and mammalian cells. One potential source of these mutations is the error-prone bypass of dGAP lesions catalyzed by the low-fidelity Y-family DNA polymerases. To provide a comparative analysis of the mutagenic potential of the translesion DNA synthesis (TLS) of dGAP, we employed short oligonucleotide sequencing assays (SOSAs) with the model Y-family DNA polymerase from Sulfolobus solfataricus, DNA Polymerase IV (Dpo4), and the human Y-family DNA polymerases eta (hPolη), kappa (hPolκ), and iota (hPolι). Relative to undamaged DNA, all four enzymes generated far more mutations (base deletions, insertions, and substitutions) with a DNA template containing a site-specifically placed dGAP. Opposite dGAP and at an immediate downstream template position, the most frequent mutations made by the three human enzymes were base deletions and the most frequent base substitutions were dAs for all enzymes. Based on the SOSA data, Dpo4 was the least error-prone Y-family DNA polymerase among the four enzymes during the TLS of dGAP. Among the three human Y-family enzymes, hPolκ made the fewest mutations at all template positions except opposite the lesion site. hPolκ was significantly less error-prone than hPolι and hPolη during the extension of dGAP bypass products. Interestingly, the most frequent mutations created by hPolι at all template positions were base deletions. Although hRev1, the fourth human Y-family enzyme, could not extend dGAP bypass products in our standing start assays, it preferentially incorporated dCTP opposite the bulky lesion. Collectively, these mutagenic profiles suggest that hPolkk and hRev1 are the most suitable human Y-family DNA polymerases to perform TLS of dGAP in humans. PMID:22917544

  2. Kinetic Analysis of the Bypass of a Bulky DNA Lesion Catalyzed by Human Y-family DNA Polymerases

    Science.gov (United States)

    Sherrer, Shanen M.; Sanman, Laura E.; Xia, Cynthia X.; Bolin, Eric R.; Malik, Chanchal K.; Efthimiopoulos, Georgia; Basu, Ashis K.; Suo, Zucai

    2012-01-01

    1-Nitropyrene (1-NP), a mutagen and potential carcinogen, is the most abundant nitro polyaromatic hydrocarbon in diesel exhaust, which reacts with DNA to form predominantly N-(deoxyguanosin-8-yl)-1-aminopyrene (dGAP). If not repaired, this DNA lesion is presumably bypassed in vivo by any of human Y-family DNA polymerases kappa (hPolκ), iota (hPolτ), eta (hPolη), and Rev1 (hRev1). Our running start assays demonstrated that each of these enzymes was indeed capable of traversing a site-specifically placed dGAP on a synthetic DNA template but hRev1 was stopped after lesion bypass. The time required to bypass 50% of the dGAP sites (t50bypass ) encountered by hPolη, hPolκ and hPolτ was determined to be 2.5 s, 4.1 s, and 106.5 s, respectively. The efficiency order of catalyzing translesion synthesis of dGAP (hPolη > hPolκ > hPolτ >> hRev1) is the same as the order for these human Y-family enzymes to elongate undamaged DNA. Although hPolη bypassed dGAP efficiently, replication by both hPolκ and hPolτ was strongly stalled at the lesion site and at a site immediately downstream from dGAP. By employing pre-steady state kinetic methods, a kinetic basis was established for polymerase pausing at these DNA template sites. Besides efficiency of bypass, the fidelity of those low-fidelity polymerases at these pause sites was also significantly decreased. Thus, if the translesion DNA synthesis of dGAP in vivo is catalyzed by a human Y-family DNA polymerase, e.g. hPolη, the process is certainly mutagenic. PMID:22324639

  3. Structural insight into dynamic bypass of the major cisplatin-DNA adduct by Y-family polymerase Dpo4

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    Wong, Jimson H.Y.; Brown, Jessica A.; Suo, Zucai; Blum, Paul; Nohmi, Takehiko; Ling, Hong (OSU); (NINA-Japan); (UNL); (UWO)

    2010-08-23

    Y-family DNA polymerases bypass Pt-GG, the cisplatin-DNA double-base lesion, contributing to the cisplatin resistance in tumour cells. To reveal the mechanism, we determined three structures of the Y-family DNA polymerase, Dpo4, in complex with Pt-GG DNA. The crystallographic snapshots show three stages of lesion bypass: the nucleotide insertions opposite the 3{prime}G (first insertion) and 5{prime}G (second insertion) of Pt-GG, and the primer extension beyond the lesion site. We observed a dynamic process, in which the lesion was converted from an open and angular conformation at the first insertion to a depressed and nearly parallel conformation at the subsequent reaction stages to fit into the active site of Dpo4. The DNA translocation-coupled conformational change may account for additional inhibition on the second insertion reaction. The structures illustrate that Pt-GG disturbs the replicating base pair in the active site, which reduces the catalytic efficiency and fidelity. The in vivo relevance of Dpo4-mediated Pt-GG bypass was addressed by a dpo-4 knockout strain of Sulfolobus solfataricus, which exhibits enhanced sensitivity to cisplatin and proteomic alterations consistent with genomic stress.

  4. Recent Insight into the Kinetic Mechanisms and Conformational Dynamics of Y-Family DNA Polymerases

    OpenAIRE

    Maxwell, Brian A.; Suo, Zucai

    2014-01-01

    The kinetic mechanisms by which DNA polymerases catalyze DNA replication and repair have long been areas of active research. Recently discovered Y-family DNA polymerases catalyze the bypass of damaged DNA bases that would otherwise block replicative DNA polymerases and stall replication forks. Unlike DNA polymerases from the five other families, the Y-family DNA polymerases have flexible, solvent-accessible active sites that are able to tolerate various types of damaged template bases and all...

  5. Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y-Family DNA Polymerase

    Science.gov (United States)

    Vyas, Rajan; Efthimiopoulos, Georgia; Tokarsky, E. John; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

    2015-01-01

    1-Nitropyrene (1-NP), an environmental pollutant, induces DNA damage in vivo and is considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall replicative DNA polymerases but are presumably bypassed by error-prone Y-family DNA polymerases at the expense of replication fidelity and efficiency in vivo. Our running start assays confirmed that a site-specifically placed 8-(deoxyguanosin-N2-yl)-1-aminopyrene (dG1,8), one of the DNA adducts derived from 1-NP, can be bypassed by Sulfolobus solfataricus DNA polymerase IV (Dpo4), although this representative Y-family enzyme was paused strongly by the lesion. Pre-steady-state kinetic assays were employed to determine the low nucleotide incorporation fidelity and establish a minimal kinetic mechanism for the dG1,8 bypass by Dpo4. To reveal a structural basis for dCTP incorporation opposite dG1,8, we solved the crystal structures of the complexes of Dpo4 and DNA containing a templating dG1,8 lesion in the absence or presence of dCTP. The Dpo4·DNA-dG1,8 binary structure shows that the aminopyrene moiety of the lesion stacks against the primer/template junction pair, while its dG moiety projected into the cleft between the Finger and Little Finger domains of Dpo4. In the Dpo4·DNA-dG1,8·dCTP ternary structure, the aminopyrene moiety of the dG1,8 lesion, is sandwiched between the nascent and junction base pairs, while its base is present in the major groove. Moreover, dCTP forms a Watson–Crick base pair with dG, two nucleotides upstream from the dG1,8 site, creating a complex for “-2” frameshift mutation. Mechanistically, these crystal structures provide additional insight into the aforementioned minimal kinetic mechanism. PMID:26327169

  6. Mechanistic Investigation of the Bypass of a Bulky Aromatic DNA Adduct Catalyzed by a Y-family DNA Polymerase

    Science.gov (United States)

    Gadkari, Varun V.; Tokarsky, E. John; Malik, Chanchal K.; Basu, Ashis K.; Suo, Zucai

    2014-01-01

    3-Nitrobenzanthrone (3-NBA), a nitropolyaromatic hydrocarbon (NitroPAH) pollutant in diesel exhaust, is a potent mutagen and carcinogen. After metabolic activation, the primary metabolites of 3-NBA react with DNA to form dG and dA adducts. One of the three major adducts identified is N-(2’-deoxyguanosin-8-yl)-3-aminobenzanthrone (dGC8-N-ABA). This bulky adduct likely stalls replicative DNA polymerases but can be traversed by lesion bypass polymerases in vivo. Here, we employed running start assays to show that a site-specifically placed dGC8-N-ABA is bypassed in vitro by Sulfolobus solfataricus DNA polymerase IV (Dpo4), a model Y-family DNA polymerase. However, the nucleotide incorporation rate of Dpo4 was significantly reduced opposite both the lesion and the template position immediately downstream from the lesion site, leading to two strong pause sites. To investigate the kinetic effect of dGC8-N-ABA on polymerization, we utilized pre-steady-state kinetic methods to determine the kinetic parameters for individual nucleotide incorporations upstream, opposite, and downstream from the dGC8-N-ABA lesion. Relative to the replication of the corresponding undamaged DNA template, both nucleotide incorporation efficiency and fidelity of Dpo4 were considerably decreased during dGC8-N-ABA lesion bypass and the subsequent extension step. The lower nucleotide incorporation efficiency caused by the lesion is a result of a significantly reduced dNTP incorporation rate constant and modestly weaker dNTP binding affinity. At both pause sites, nucleotide incorporation followed biphasic kinetics with a fast and a slow phase and their rates varied with nucleotide concentration. In contrast, only the fast phase was observed with undamaged DNA. A kinetic mechanism was proposed for the bypass of dGC8-N-ABA bypass catalyzed by Dpo4. PMID:25048879

  7. (1)H, (13)C, and (15)N backbone resonance assignments of the full-length 40 kDa S. acidocaldarius Y-family DNA polymerase, dinB homolog.

    Science.gov (United States)

    Moro, Sean L; Cocco, Melanie J

    2015-10-01

    The dinB homolog (Dbh) is a member of the Y-family of translesion DNA polymerases, which are specialized to accurately replicate DNA across from a wide variety of lesions in living cells. Lesioned bases block the progression of high-fidelity polymerases and cause detrimental replication fork stalling; Y-family polymerases can bypass these lesions. The active site of the translesion synthesis polymerase is more open than that of a replicative polymerase; consequently Dbh polymerizes with low fidelity. Bypass polymerases also have low processivity. Short extension past the lesion allows the high-fidelity polymerase to switch back onto the site of replication. Dbh and the other Y-family polymerases have been used as structural models to investigate the mechanisms of DNA polymerization and lesion bypass. Many high-resolution crystal structures of Y-family polymerases have been reported. NMR dynamics studies can complement these structures by providing a measure of protein motions. Here we report the (15)N, (1)H, and (13)C backbone resonance assignments at two temperatures (35 and 50 °C) for Sulfolobus acidocaldarius Dbh polymerase. Backbone resonance assignments have been obtained for 86 % of the residues. The polymerase active site is assigned as well as the majority of residues in each of the four domains.

  8. Global conformational dynamics of a Y-family DNA polymerase during catalysis.

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    Cuiling Xu

    2009-10-01

    Full Text Available Replicative DNA polymerases are stalled by damaged DNA while the newly discovered Y-family DNA polymerases are recruited to rescue these stalled replication forks, thereby enhancing cell survival. The Y-family DNA polymerases, characterized by low fidelity and processivity, are able to bypass different classes of DNA lesions. A variety of kinetic and structural studies have established a minimal reaction pathway common to all DNA polymerases, although the conformational intermediates are not well defined. Furthermore, the identification of the rate-limiting step of nucleotide incorporation catalyzed by any DNA polymerase has been a matter of long debate. By monitoring time-dependent fluorescence resonance energy transfer (FRET signal changes at multiple sites in each domain and DNA during catalysis, we present here a real-time picture of the global conformational transitions of a model Y-family enzyme: DNA polymerase IV (Dpo4 from Sulfolobus solfataricus. Our results provide evidence for a hypothetical DNA translocation event followed by a rapid protein conformational change prior to catalysis and a subsequent slow, post-chemistry protein conformational change. Surprisingly, the DNA translocation step was induced by the binding of a correct nucleotide. Moreover, we have determined the directions, rates, and activation energy barriers of the protein conformational transitions, which indicated that the four domains of Dpo4 moved in a synchronized manner. These results showed conclusively that a pre-chemistry conformational change associated with domain movements was too fast to be the rate-limiting step. Rather, the rearrangement of active site residues limited the rate of correct nucleotide incorporation. Collectively, the conformational dynamics of Dpo4 offer insights into how the inter-domain movements are related to enzymatic function and their concerted interactions with other proteins at the replication fork.

  9. Mechanistic Studies with DNA Polymerases Reveal Complex Outcomes following Bypass of DNA Damage

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    Robert L. Eoff

    2010-01-01

    Full Text Available DNA is a chemically reactive molecule that is subject to many different covalent modifications from sources that are both endogenous and exogenous in origin. The inherent instability of DNA is a major obstacle to genomic maintenance and contributes in varying degrees to cellular dysfunction and disease in multi-cellular organisms. Investigations into the chemical and biological aspects of DNA damage have identified multi-tiered and overlapping cellular systems that have evolved as a means of stabilizing the genome. One of these pathways supports DNA replication events by in a sense adopting the mantra that one must “make the best of a bad situation” and tolerating covalent modification to DNA through less accurate copying of the damaged region. Part of this so-called DNA damage tolerance pathway involves the recruitment of specialized DNA polymerases to sites of stalled or collapsed replication forks. These enzymes have unique structural and functional attributes that often allow bypass of adducted template DNA and successful completion of genomic replication. What follows is a selective description of the salient structural features and bypass properties of specialized DNA polymerases with an emphasis on Y-family members.

  10. DNA polymerase eta participates in the mutagenic bypass of adducts induced by benzo[a]pyrene diol epoxide in mammalian cells.

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    Alden C Klarer

    Full Text Available Y-family DNA-polymerases have larger active sites that can accommodate bulky DNA adducts allowing them to bypass these lesions during replication. One member, polymerase eta (pol eta, is specialized for the bypass of UV-induced thymidine-thymidine dimers, correctly inserting two adenines. Loss of pol eta function is the molecular basis for xeroderma pigmentosum (XP variant where the accumulation of mutations results in a dramatic increase in UV-induced skin cancers. Less is known about the role of pol eta in the bypass of other DNA adducts. A commonly encountered DNA adduct is that caused by benzo[a]pyrene diol epoxide (BPDE, the ultimate carcinogenic metabolite of the environmental chemical benzo[a]pyrene. Here, treatment of pol eta-deficient fibroblasts from humans and mice with BPDE resulted in a significant decrease in Hprt gene mutations. These studies in mammalian cells support a number of in vitro reports that purified pol eta has error-prone activity on plasmids with site-directed BPDE adducts. Sequencing the Hprt gene from this work shows that the majority of mutations are G>T transversions. These data suggest that pol eta has error-prone activity when bypassing BPDE-adducts. Understanding the basis of environmental carcinogen-derived mutations may enable prevention strategies to reduce such mutations with the intent to reduce the number of environmentally relevant cancers.

  11. Backbone assignment of the little finger domain of a Y-family DNA polymerase.

    Science.gov (United States)

    Ma, Dejian; Fowler, Jason D; Suo, Zucai

    2011-10-01

    Sulfolobus solfataricus DNA polymerase IV (Dpo4), a prototype Y-family DNA polymerase, contains a unique little finger domain besides a catalytic core. Here, we report the chemical shift assignments for the backbone nitrogens, α and β carbons, and amide protons of the little finger domain of Dpo4. This work and our published backbone assignment for the catalytic core provide the basis for investigating the conformational dynamics of Dpo4 during catalysis using solution NMR spectroscopy.

  12. Bypass of a psoralen DNA interstrand cross-link by DNA polymerases beta, iota, and kappa in vitro

    Science.gov (United States)

    Smith, Leigh A.; Makarova, Alena V.; Samson, Laura; Thiesen, Katherine E.; Dhar, Alok; Bessho, Tadayoshi

    2012-01-01

    Repair of DNA inter-strand cross-links in mammalian cells involves several biochemically distinctive processes, including the release of one of the cross-linked strands and translesion DNA synthesis (TLS). In this report, we investigated in vitro TLS activity of psoralen DNA inter-strand cross-link by three DNA repair polymerases, DNA polymerase beta, kappa and iota. DNA polymerase beta is capable of bypassing a psoralen cross-link with a low efficiency. Cell extracts prepared from DNA polymerase beta knockout mouse embryonic fibroblast showed a reduced bypass activity of the psoralen cross-link and purified DNA polymerase beta restored the bypass activity. In addition, DNA polymerase iota mis-incorporated thymine across the psoralen cross-link and DNA polymerase kappa extended these mis-paired primer ends, suggesting that DNA polymerase iota may serve as an inserter and DNA polymerase kappa may play a role as an extender in the repair of psoralen DNA inter-strand cross-links. The results demonstrated here indicate that multiple DNA polymerases could participate in TLS steps in mammalian DNA inter-strand cross-link repair. PMID:23106263

  13. Following DNA chain extension and protein conformational changes in crystals of a Y-family DNA polymerase via Raman crystallography.

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    Espinoza-Herrera, Shirly J; Gaur, Vineet; Suo, Zucai; Carey, Paul R

    2013-07-23

    Y-Family DNA polymerases are known to bypass DNA lesions in vitro and in vivo. Sulfolobus solfataricus DNA polymerase (Dpo4) was chosen as a model Y-family enzyme for investigating the mechanism of DNA synthesis in single crystals. Crystals of Dpo4 in complexes with DNA (the binary complex) in the presence or absence of an incoming nucleotide were analyzed by Raman microscopy. (13)C- and (15)N-labeled d*CTP, or unlabeled dCTP, were soaked into the binary crystals with G as the templating base. In the presence of the catalytic metal ions, Mg(2+) and Mn(2+), nucleotide incorporation was detected by the disappearance of the triphosphate band of dCTP and the retention of *C modes in the crystal following soaking out of noncovalently bound C(or *C)TP. The addition of the second coded base, thymine, was observed by adding cognate dTTP to the crystal following a single d*CTP addition. Adding these two bases caused visible damage to the crystal that was possibly caused by protein and/or DNA conformational change within the crystal. When d*CTP is soaked into the Dpo4 crystal in the absence of Mn(2+) or Mg(2+), the primer extension reaction did not occur; instead, a ternary protein·template·d*CTP complex was formed. In the Raman difference spectra of both binary and ternary complexes, in addition to the modes of d(*C)CTP, features caused by ring modes from the template/primer bases being perturbed and from the DNA backbone appear, as well as features from perturbed peptide and amino acid side chain modes. These effects are more pronounced in the ternary complex than in the binary complex. Using standardized Raman intensities followed as a function of time, the C(*C)TP population in the crystal was maximal at ∼20 min. These remained unchanged in the ternary complex but declined in the binary complexes as chain incorporation occurred.

  14. Identification of an Unfolding Intermediate for a DNA Lesion Bypass Polymerase

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    Sherrer, Shanen M.; Maxwell, Brian A.; Pack, Lindsey R.; Fiala, Kevin A.; Fowler, Jason D.; Zhang, Jun; Suo, Zucai

    2012-01-01

    Sulfolobus solfataricusDNA Polymerase IV (Dpo4), a prototype Y-family DNA polymerase, has been well characterized biochemically and biophysically at 37 °C or lower temperatures. However, the physiological temperature of the hyperthermophile S. solfataricus is approximately 80 °C. With such a large discrepancy in temperature, the in vivo relevance of these in vitro studies of Dpo4 has been questioned. Here, we employed circular dichroism spectroscopy and fluorescence-based thermal scanning to investigate the secondary structural changes of Dpo4 over a temperature range from 26 to 119 °C. Dpo4 was shown to display a high melting temperature characteristic of hyperthermophiles. Unexpectedly, the Little Finger domain of Dpo4, which is only found in the Y-family DNA polymerases, was shown to be more thermostable than the polymerase core. More interestingly, Dpo4 exhibited a three-state cooperative unfolding profile with an unfolding intermediate. The linker region between the Little Finger and Thumb domains of Dpo4 was found to be a source of structural instability. Through site-directed mutagenesis, the interactions between the residues in the linker region and the Palm domain were identified to play a critical role in the formation of the unfolding intermediate. Notably, the secondary structure of Dpo4 was not altered when the temperature was increased from 26 to 87.5 °C. Thus, in addition to providing structural insights into the thermal stability and an unfolding intermediate of Dpo4, our work also validated the relevance of the in vitro studies of Dpo4 performed at temperatures significantly lower than 80 °C. PMID:22667759

  15. Analysis of UV-induced mutation spectra in Escherichia coli by DNA polymerase {eta} from Arabidopsis thaliana

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    Santiago, Maria Jesus [Departamento de Genetica, Facultad de Ciencias, Edificio Gregor Mendel, Campus Rabanales, Universidad de Cordoba (Spain); Alejandre-Duran, Encarna [Departamento de Genetica, Facultad de Ciencias, Edificio Gregor Mendel, Campus Rabanales, Universidad de Cordoba (Spain); Ruiz-Rubio, Manuel [Departamento de Genetica, Facultad de Ciencias, Edificio Gregor Mendel, Campus Rabanales, Universidad de Cordoba (Spain)]. E-mail: ge1rurum@uco.es

    2006-10-10

    DNA polymerase {eta} belongs to the Y-family of DNA polymerases, enzymes that are able to synthesize past template lesions that block replication fork progression. This polymerase accurately bypasses UV-associated cis-syn cyclobutane thymine dimers in vitro and therefore may contributes to resistance against sunlight in vivo, both ameliorating survival and decreasing the level of mutagenesis. We cloned and sequenced a cDNA from Arabidopsis thaliana which encodes a protein containing several sequence motifs characteristics of Pol{eta} homologues, including a highly conserved sequence reported to be present in the active site of the Y-family DNA polymerases. The gene, named AtPOLH, contains 14 exons and 13 introns and is expressed in different plant tissues. A strain from Saccharomyces cerevisiae, deficient in Pol{eta} activity, was transformed with a yeast expression plasmid containing the AtPOLH cDNA. The rate of survival to UV irradiation in the transformed mutant increased to similar values of the wild type yeast strain, showing that AtPOLH encodes a functional protein. In addition, when AtPOLH is expressed in Escherichia coli, a change in the mutational spectra is detected when bacteria are irradiated with UV light. This observation might indicate that AtPOLH could compete with DNA polymerase V and then bypass cyclobutane pyrimidine dimers incorporating two adenylates.

  16. A Crystallographic Study of the Role of Sequence Context in Thymine Glycol Bypass by a Replicative DNA Polymerase Serendipitously Sheds Light on the Exonuclease Complex

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    Aller, Pierre; Duclos, Stéphanie; Wallace, Susan S.; Doublié, Sylvie (Vermont)

    2012-06-27

    Thymine glycol (Tg) is the most common oxidation product of thymine and is known to be a strong block to replicative DNA polymerases. A previously solved structure of the bacteriophage RB69 DNA polymerase (RB69 gp43) in complex with Tg in the sequence context 5'-G-Tg-G shed light on how Tg blocks primer elongation: The protruding methyl group of the oxidized thymine displaces the adjacent 5'-G, which can no longer serve as a template for primer elongation [Aller, P., Rould, M. A., Hogg, M, Wallace, S. S. and Doublie S. (2007). A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol. Proc. Natl. Acad. Sci. USA, 104, 814-818.]. Several studies showed that in the sequence context 5'-C-Tg-purine, Tg is more likely to be bypassed by Klenow fragment, an A-family DNA polymerase. We set out to investigate the role of sequence context in Tg bypass in a B-family polymerase and to solve the crystal structures of the bacteriophage RB69 DNA polymerase in complex with Tg-containing DNA in the three remaining sequence contexts: 5'-A-Tg-G, 5'-T-Tg-G, and 5'-C-Tg-G. A combination of several factors - including the associated exonuclease activity, the nature of the 3' and 5' bases surrounding Tg, and the cis-trans interconversion of Tg - influences Tg bypass. We also visualized for the first time the structure of a well-ordered exonuclease complex, allowing us to identify and confirm the role of key residues (Phe123, Met256, and Tyr257) in strand separation and in the stabilization of the primer strand in the exonuclease site.

  17. Pre-Steady-State Kinetic Analysis of Truncated and Full-Length Saccharomyces cerevisiae DNA Polymerase Eta

    Science.gov (United States)

    Brown, Jessica A.; Zhang, Likui; Sherrer, Shanen M.; Taylor, John-Stephen; Burgers, Peter M. J.; Suo, Zucai

    2010-01-01

    Understanding polymerase fidelity is an important objective towards ascertaining the overall stability of an organism's genome. Saccharomyces cerevisiae DNA polymerase η (yPolη), a Y-family DNA polymerase, is known to efficiently bypass DNA lesions (e.g., pyrimidine dimers) in vivo. Using pre-steady-state kinetic methods, we examined both full-length and a truncated version of yPolη which contains only the polymerase domain. In the absence of yPolη's C-terminal residues 514–632, the DNA binding affinity was weakened by 2-fold and the base substitution fidelity dropped by 3-fold. Thus, the C-terminus of yPolη may interact with DNA and slightly alter the conformation of the polymerase domain during catalysis. In general, yPolη discriminated between a correct and incorrect nucleotide more during the incorporation step (50-fold on average) than the ground-state binding step (18-fold on average). Blunt-end additions of dATP or pyrene nucleotide 5′-triphosphate revealed the importance of base stacking during the binding of incorrect incoming nucleotides. PMID:20798853

  18. Pre-Steady-State Kinetic Analysis of Truncated and Full-Length Saccharomyces cerevisiae DNA Polymerase Eta

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    Jessica A. Brown

    2010-01-01

    Full Text Available Understanding polymerase fidelity is an important objective towards ascertaining the overall stability of an organism's genome. Saccharomyces cerevisiae DNA polymerase η (yPolη, a Y-family DNA polymerase, is known to efficiently bypass DNA lesions (e.g., pyrimidine dimers in vivo. Using pre-steady-state kinetic methods, we examined both full-length and a truncated version of yPolη which contains only the polymerase domain. In the absence of yPolη's C-terminal residues 514–632, the DNA binding affinity was weakened by 2-fold and the base substitution fidelity dropped by 3-fold. Thus, the C-terminus of yPolη may interact with DNA and slightly alter the conformation of the polymerase domain during catalysis. In general, yPolη discriminated between a correct and incorrect nucleotide more during the incorporation step (50-fold on average than the ground-state binding step (18-fold on average. Blunt-end additions of dATP or pyrene nucleotide 5′-triphosphate revealed the importance of base stacking during the binding of incorrect incoming nucleotides.

  19. Dynamic conformational change regulates the protein-DNA recognition: an investigation on binding of a Y-family polymerase to its target DNA.

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    Xiakun Chu

    2014-09-01

    Full Text Available Protein-DNA recognition is a central biological process that governs the life of cells. A protein will often undergo a conformational transition to form the functional complex with its target DNA. The protein conformational dynamics are expected to contribute to the stability and specificity of DNA recognition and therefore may control the functional activity of the protein-DNA complex. Understanding how the conformational dynamics influences the protein-DNA recognition is still challenging. Here, we developed a two-basin structure-based model to explore functional dynamics in Sulfolobus solfataricus DNA Y-family polymerase IV (DPO4 during its binding to DNA. With explicit consideration of non-specific and specific interactions between DPO4 and DNA, we found that DPO4-DNA recognition is comprised of first 3D diffusion, then a short-range adjustment sliding on DNA and finally specific binding. Interestingly, we found that DPO4 is under a conformational equilibrium between multiple states during the binding process and the distributions of the conformations vary at different binding stages. By modulating the strength of the electrostatic interactions, the flexibility of the linker, and the conformational dynamics in DPO4, we drew a clear picture on how DPO4 dynamically regulates the DNA recognition. We argue that the unique features of flexibility and conformational dynamics in DPO4-DNA recognition have direct implications for low-fidelity translesion DNA synthesis, most of which is found to be accomplished by the Y-family DNA polymerases. Our results help complete the description of the DNA synthesis process for the Y-family polymerases. Furthermore, the methods developed here can be widely applied for future investigations on how various proteins recognize and bind specific DNA substrates.

  20. The beta subunit modulates bypass and termination at UV lesions during in vitro replication with DNA polymerase III holoenzyme of Escherichia coli

    International Nuclear Information System (INIS)

    Shavitt, O.; Livneh, Z.

    1989-01-01

    The cycling time of DNA polymerase III holoenzyme during replication of UV-irradiated single-stranded (ss) DNA was longer than with unirradiated DNA (8 versus 3 min, respectively), most likely due to slow dissociation from lesion-terminated nascent DNA strands. Initiation of elongation on primed ssDNA was not significantly inhibited by the presence of UV lesions as indicated by the identical distribution of replication products synthesized at early and late reaction times and by the identical duration of the initial synthesis bursts on both unirradiated and UV-irradiated DNA templates. When replication was performed with DNA polymerase III* supplemented with increasing quantities of purified beta 2 subunit, the cycling time on UV-irradiated DNA decreased from 14.8 min at 1.7 nM beta 2 down to 6 min at 170 nM beta 2, a concentration in which beta 2 was in large excess over the polymerase. In parallel to the reduction in cycling time, also the bypass frequency of cyclobutane-photodimers decreased with increasing beta 2 concentration, and at 170 nM beta 2, bypass of photodimers was essentially eliminated. It has been shown that polymerase complexes with more than one beta 2 per polymerase molecule were formed at high beta 2 concentrations. It is plausible that polymerase complexes obtained under high beta 2 concentration dissociate from lesion-terminated primers faster than polymerase complexes formed at a low beta 2 concentration. This is expected to favor termination over bypass at pyrimidine photodimers and thus decrease their bypass frequency. These results suggest that the beta 2 subunit might act as a sensor for obstacles to replication caused by DNA damage, and that it terminates elongation at these sites by promoting dissociation. The intracellular concentration of beta 2 was estimated to be 250 nM

  1. Nutrient deficiency and obstetrical outcomes in pregnant women following Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Hammeken, Lianna Hede; Betsagoo, Ramsina; Jensen, Ann Nygaard

    2017-01-01

    OBJECTIVE: Roux-en-Y gastric bypass surgery and small-for-gestational-age births are known to be associated although the etiology is not fully understood. This study aimed to investigate pregnancy outcomes and maternal nutritional status among pregnant women with a history of Roux-en-Y gastric...... obstetric clinic at Aalborg University Hospital in Denmark and gave birth between 1 January 2010 and 31 December 2013 were included. Each Roux-en-Y-gastric-bypass-operated woman was closely matched with a non-Roux-en-Y-gastric-bypass-operated woman. Primary outcomes were small-for-gestational-age birth.......169) between women with a history of Roux-en-Y gastric bypass (11.51kg±8.97 standard deviation (SD)) and non- Roux-en-Y-gastric-bypass-operated women (12.18kg±6.28 SD). CONCLUSION: A history of Roux-en-Y gastric bypass surgery increases the risk of small-for-gestational-age birth and anemia, while a finding...

  2. An In Vitro Model for Studying Neutrophil Activation During Cardiopulmonary Bypass by Using a Polymerase Chain Reaction Thermocycler

    NARCIS (Netherlands)

    Tang, Min; Zhao, Xiao-Gang; Gu, Y. John; Chen, Chang-Zhi

    The accurate temperature control of a polymerase chain reaction (PCR) thermocycler was exploited in developing an in vitro model to study neutrophil activation during cardiopulmonary bypass. Neutrophils from 12 volunteers underwent temperature changes in a PCR thermocycler (37 degrees C for 30

  3. Gastric bypass: why Roux-en-Y? A review of experimental data.

    Science.gov (United States)

    Collins, Brendan J; Miyashita, Tomoharu; Schweitzer, Michael; Magnuson, Thomas; Harmon, John W

    2007-10-01

    To highlight the clinical and experimental rationales that support why the Roux-en-Y limb is an important surgical principle for bariatric gastric bypass. We reviewed PubMed citations for open Roux-en-Y gastric bypass (RYGBP), laparoscopic RYGBP, loop gastric bypass, chronic alkaline reflux gastritis, and duodenoesophageal reflux. We reviewed clinical and experimental articles. Clinical articles included prospective, retrospective, and case series of patients undergoing RYGBP, laparoscopic RYGBP, or loop gastric bypass. Experimental articles that were reviewed included in vivo and in vitro models of chronic duodenoesophageal reflux and its effect on carcinogenesis. No formal data extraction was performed. We reviewed published operative times, lengths of stay, and anastomotic leak rates for laparoscopic RYGBP and loop gastric bypass. For in vivo and in vitro experimental models of duodenoesophageal reflux, we reviewed the kinetics and potential molecular mechanisms of carcinogenesis. Recent data suggest that laparoscopic loop gastric bypass, performed without the creation of a Roux-en-Y gastroenterostomy, is a faster surgical technique that confers similarly robust weight loss compared with RYGBP or laparoscopic RYGBP. In the absence of a Roux limb, the long-term effects of chronic alkaline reflux are unknown. Animal models and in vitro analyses of chronic alkaline reflux suggest a carcinogenic effect.

  4. The effect of laparoscopic Roux-en-Y gastric bypass on fibromyalgia.

    Science.gov (United States)

    Saber, Alan A; Boros, Michael J; Mancl, Tara; Elgamal, Mohamed H; Song, Susrap; Wisadrattanapong, Therawat

    2008-06-01

    Fibromyalgia is a chronic debilitating disorder affecting 3-5% of the US population. Treatment of this disorder is a challenge. The incidental finding of improvement of fibromyalgia following laparoscopic Roux-en-Y gastric bypass stimulated us to study this phenomenon. A retrospective chart review of patients with fibromyalgia who underwent laparoscopic Roux-en-Y gastric bypass. Postoperative decrease in median of BMI from 49.4 to 29.7 was significant (p value = 0.0010). This was associated with statistically significant improvement in median of pain score (p value = 0.0010) and median points of tenderness (p value = 0.0010). Significant weight loss following laparoscopic Roux-en-Y gastric bypass is associated with resolution or improvement of fibromyalgia. Consequently, the bariatric surgeon should be a member of the multidisciplinary team approach for treating fibromyalgia.

  5. Accommodation of an N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adduct in the active site of human DNA polymerase iota: Hoogsteen or Watson-Crick base pairing?

    Science.gov (United States)

    Donny-Clark, Kerry; Shapiro, Robert; Broyde, Suse

    2009-01-13

    Bypass across DNA lesions by specialized polymerases is essential for maintenance of genomic stability. Human DNA polymerase iota (poliota) is a bypass polymerase of the Y family. Crystal structures of poliota suggest that Hoogsteen base pairing is employed to bypass minor groove DNA lesions, placing them on the spacious major groove side of the enzyme. Primer extension studies have shown that poliota is also capable of error-free nucleotide incorporation opposite the bulky major groove adduct N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF). We present molecular dynamics simulations and free energy calculations suggesting that Watson-Crick base pairing could be employed in poliota for bypass of dG-AAF. In poliota with Hoogsteen-paired dG-AAF the bulky AAF moiety would reside on the cramped minor groove side of the template. The Hoogsteen-capable conformation distorts the active site, disrupting interactions necessary for error-free incorporation of dC opposite the lesion. Watson-Crick pairing places the AAF rings on the spacious major groove side, similar to the position of minor groove adducts observed with Hoogsteen pairing. Watson-Crick-paired structures show a well-ordered active site, with a near reaction-ready ternary complex. Thus our results suggest that poliota would utilize the same spacious region for lesion bypass of both major and minor groove adducts. Therefore, purine adducts with bulk on the minor groove side would use Hoogsteen pairing, while adducts with the bulky lesion on the major groove side would utilize Watson-Crick base pairing as indicated by our MD simulations for dG-AAF. This suggests the possibility of an expanded role for poliota in lesion bypass.

  6. How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

    Science.gov (United States)

    Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

    2015-11-01

    To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal

  7. Viewing Human DNA Polymerase β Faithfully and Unfaithfully Bypass an Oxidative Lesion by Time-Dependent Crystallography

    Science.gov (United States)

    Vyas, Rajan; Reed, Andrew J.; Tokarsky, E. John; Suo, Zucai

    2015-01-01

    One common oxidative DNA lesion, 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG), is highly mutagenic in vivo due to its anti-conformation forming a Watson–Crick base pair with correct deoxycytidine 5′-triphosphate (dCTP) and its syn-conformation forming a Hoogsteen base pair with incorrect deoxyadenosine 5′-triphosphate (dATP). Here, we utilized time-resolved X-ray crystallography to follow 8-oxoG bypass by human DNA polymerase β (hPolβ). In the 12 solved structures, both Watson–Crick (anti-8-oxoG:anti-dCTP) and Hoogsteen (syn-8-oxoG:anti-dATP) base pairing were clearly visible and were maintained throughout the chemical reaction. Additionally, a third Mg2+ appeared during the process of phosphodiester bond formation and was located between the reacting α- and β-phosphates of the dNTP, suggesting its role in stabilizing reaction intermediates. After phosphodiester bond formation, hPolβ reopened its conformation, pyrophosphate was released, and the newly incorporated primer 3′-terminal nucleotide stacked, rather than base paired, with 8-oxoG. These structures provide the first real-time pictures, to our knowledge, of how a polymerase correctly and incorrectly bypasses a DNA lesion. PMID:25825995

  8. Role of exonucleolytic processing and polymerase-DNA association in bypass of lesions during replication in vitro. Significance for SOS-targeted mutagenesis

    International Nuclear Information System (INIS)

    Shwartz, H.; Shavitt, O.; Livneh, Z.

    1988-01-01

    The role of exonuclease activity in trans-lesion DNA replication with Escherichia coli DNA polymerase III holoenzyme was investigated. RecA protein inhibited the 3'----5' exonuclease activity of the polymerase 2-fold when assayed in the absence of replication and had no effect on turnover of dNTPs into dNMPs. In contrast, single-stranded DNA-binding protein, which had no effect on the exonuclease activity in the absence of replication, showed a pronounced 7-fold suppression of the 3'----5' exonuclease activity during replication. The excision of incorporated dNMP alpha S residues from DNA by the 3'----5' exonuclease activity of DNA polymerase III holoenzyme was inhibited 10-20-fold; still no increase in bypass of pyrimidine photodimers was observed. Thus, in agreement with our previous results in which the exonuclease activity was inhibited at the protein level, inhibition at the DNA level also did not increase bypass of photodimers. Fractionation of the replication mixture after termination of DNA synthesis on a Bio-Gel A-5m column under conditions which favor polymerase-DNA binding yielded a termination complex which could perform turnover of dNTPs into dNMPs. Adding challenge-primed single-stranded DNA to the complex yielded a burst of DNA synthesis which was promoted most likely by DNA polymerase III holoenzyme molecules transferred from the termination complex to the challenge DNA thus demonstrating the instability of the polymerase-DNA association. Addition of a fresh sample of DNA polymerase III holoenzyme to purified termination products, which consist primarily of partially replicated molecules with nascent chains terminated at UV lesions, did not result in any net DNA synthesis as expected

  9. Accommodation of an N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adduct in the active site of human DNA polymerase ι: Hoogsteen or Watson-Crick base pairing?†

    Science.gov (United States)

    Donny-Clark, Kerry; Shapiro, Robert; Broyde, Suse

    2009-01-01

    Bypass across DNA lesions by specialized polymerases is essential for maintenance of genomic stability. Human DNA polymerase ι (polι) is a bypass polymerase of the Y family. Crystal structures of polι suggest that Hoogsteen base pairing is employed to bypass minor groove DNA lesions, placing them on the spacious major groove side of the enzyme. Primer extension studies have shown that polι is also capable of error-free nucleotide incorporation opposite the bulky major groove adduct N-(deoxyguanosin-8-yl)-2-acetyl-aminofluorene (dG-AAF). We present molecular dynamics simulations and free energy calculations suggesting that Watson-Crick base pairing could be employed in polι for bypass of dG-AAF. In polι with Hoogsteen paired dG-AAF the bulky AAF moiety would reside on the cramped minor groove side of the template. The Hoogsteen-capable conformation distorts the active site, disrupting interactions necessary for error-free incorporation of dC opposite the lesion. Watson-Crick pairing places the AAF rings on the spacious major groove side, similar to the position of minor groove adducts observed with Hoogsteen pairing. Watson-Crick paired structures show a well-ordered active site, with a near reaction-ready ternary complex. Thus our results suggest that polι would utilize the same spacious region for lesion bypass of both major and minor groove adducts. Therefore, purine adducts with bulk on the minor groove side would use Hoogsteen pairing, while adducts with the bulky lesion on the major groove side would utilize Watson-Crick base pairing as indicated by our MD simulations for dG-AAF. This suggests the possibility of an expanded role for polι in lesion bypass. PMID:19072536

  10. Bypass of a nick by the replisome of bacteriophage T7.

    Science.gov (United States)

    Zhu, Bin; Lee, Seung-Joo; Richardson, Charles C

    2011-08-12

    DNA polymerase and DNA helicase are essential components of DNA replication. The helicase unwinds duplex DNA to provide single-stranded templates for DNA synthesis by the DNA polymerase. In bacteriophage T7, movement of either the DNA helicase or the DNA polymerase alone terminates upon encountering a nick in duplex DNA. Using a minicircular DNA, we show that the helicase · polymerase complex can bypass a nick, albeit at reduced efficiency of 7%, on the non-template strand to continue rolling circle DNA synthesis. A gap in the non-template strand cannot be bypassed. The efficiency of bypass synthesis depends on the DNA sequence downstream of the nick. A nick on the template strand cannot be bypassed. Addition of T7 single-stranded DNA-binding protein to the complex stimulates nick bypass 2-fold. We propose that the association of helicase with the polymerase prevents dissociation of the helicase upon encountering a nick, allowing the helicase to continue unwinding of the duplex downstream of the nick.

  11. Bypass of a Nick by the Replisome of Bacteriophage T7*

    Science.gov (United States)

    Zhu, Bin; Lee, Seung-Joo; Richardson, Charles C.

    2011-01-01

    DNA polymerase and DNA helicase are essential components of DNA replication. The helicase unwinds duplex DNA to provide single-stranded templates for DNA synthesis by the DNA polymerase. In bacteriophage T7, movement of either the DNA helicase or the DNA polymerase alone terminates upon encountering a nick in duplex DNA. Using a minicircular DNA, we show that the helicase·polymerase complex can bypass a nick, albeit at reduced efficiency of 7%, on the non-template strand to continue rolling circle DNA synthesis. A gap in the non-template strand cannot be bypassed. The efficiency of bypass synthesis depends on the DNA sequence downstream of the nick. A nick on the template strand cannot be bypassed. Addition of T7 single-stranded DNA-binding protein to the complex stimulates nick bypass 2-fold. We propose that the association of helicase with the polymerase prevents dissociation of the helicase upon encountering a nick, allowing the helicase to continue unwinding of the duplex downstream of the nick. PMID:21701044

  12. Replisome-mediated Translesion Synthesis and Leading Strand Template Lesion Skipping Are Competing Bypass Mechanisms*

    Science.gov (United States)

    Gabbai, Carolina B.; Yeeles, Joseph T. P.; Marians, Kenneth J.

    2014-01-01

    A number of different enzymatic pathways have evolved to ensure that DNA replication can proceed past template base damage. These pathways include lesion skipping by the replisome, replication fork regression followed by either correction of the damage and origin-independent replication restart or homologous recombination-mediated restart of replication downstream of the lesion, and bypass of the damage by a translesion synthesis DNA polymerase. We report here that of two translesion synthesis polymerases tested, only DNA polymerase IV, not DNA polymerase II, could engage productively with the Escherichia coli replisome to bypass leading strand template damage, despite the fact that both enzymes are shown to be interacting with the replicase. Inactivation of the 3′ → 5′ proofreading exonuclease of DNA polymerase II did not enable bypass. Bypass by DNA polymerase IV required its ability to interact with the β clamp and act as a translesion polymerase but did not require its “little finger” domain, a secondary region of interaction with the β clamp. Bypass by DNA polymerase IV came at the expense of the inherent leading strand lesion skipping activity of the replisome, indicating that they are competing reactions. PMID:25301949

  13. Bypass of a 5',8-cyclopurine-2'-deoxynucleoside by DNA polymerase β during DNA replication and base excision repair leads to nucleotide misinsertions and DNA strand breaks.

    Science.gov (United States)

    Jiang, Zhongliang; Xu, Meng; Lai, Yanhao; Laverde, Eduardo E; Terzidis, Michael A; Masi, Annalisa; Chatgilialoglu, Chryssostomos; Liu, Yuan

    2015-09-01

    5',8-Cyclopurine-2'-deoxynucleosides including 5',8-cyclo-dA (cdA) and 5',8-cyclo-dG (cdG) are induced by hydroxyl radicals resulting from oxidative stress such as ionizing radiation. 5',8-cyclopurine-2'-deoxynucleoside lesions are repaired by nucleotide excision repair with low efficiency, thereby leading to their accumulation in the human genome and lesion bypass by DNA polymerases during DNA replication and base excision repair (BER). In this study, for the first time, we discovered that DNA polymerase β (pol β) efficiently bypassed a 5'R-cdA, but inefficiently bypassed a 5'S-cdA during DNA replication and BER. We found that cell extracts from pol β wild-type mouse embryonic fibroblasts exhibited significant DNA synthesis activity in bypassing a cdA lesion located in replication and BER intermediates. However, pol β knock-out cell extracts exhibited little DNA synthesis to bypass the lesion. This indicates that pol β plays an important role in bypassing a cdA lesion during DNA replication and BER. Furthermore, we demonstrated that pol β inserted both a correct and incorrect nucleotide to bypass a cdA at a low concentration. Nucleotide misinsertion was significantly stimulated by a high concentration of pol β, indicating a mutagenic effect induced by pol β lesion bypass synthesis of a 5',8-cyclopurine-2'-deoxynucleoside. Moreover, we found that bypass of a 5'S-cdA by pol β generated an intermediate that failed to be extended by pol β, resulting in accumulation of single-strand DNA breaks. Our study provides the first evidence that pol β plays an important role in bypassing a 5',8-cyclo-dA during DNA replication and repair, as well as new insight into mutagenic effects and genome instability resulting from pol β bypassing of a cdA lesion. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase η.

    Science.gov (United States)

    O'Flaherty, D K; Patra, A; Su, Y; Guengerich, F P; Egli, M; Wilds, C J

    2016-08-01

    DNA lesions that elude repair may undergo translesion synthesis catalyzed by Y-family DNA polymerases. O 4 -Alkylthymidines, persistent adducts that can result from carcinogenic agents, may be encountered by DNA polymerases. The influence of lesion orientation around the C4- O 4 bond on processing by human DNA polymerase η (hPol η ) was studied for oligonucleotides containing O 4 -methylthymidine, O 4 -ethylthymidine, and analogs restricting the O 4 -methylene group in an anti -orientation. Primer extension assays revealed that the O 4 -alkyl orientation influences hPol η bypass. Crystal structures of hPol η •DNA•dNTP ternary complexes with O 4 -methyl- or O 4 -ethylthymidine in the template strand showed the nucleobase of the former lodged near the ceiling of the active site, with the syn - O 4 -methyl group engaged in extensive hydrophobic interactions. This unique arrangement for O 4 -methylthymidine with hPol η , inaccessible for the other analogs due to steric/conformational restriction, is consistent with differences observed for nucleotide incorporation and supports the concept that lesion conformation influences extension across DNA damage. Together, these results provide mechanistic insights on the mutagenicity of O 4 MedT and O 4 EtdT when acted upon by hPol η .

  15. Internal herniation after laparoscopic antecolic Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Kristensen, Sara Danshøj; Jess, Per; Floyd, Andrea Karen

    2016-01-01

    BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most common surgical treatment for morbid obesity in Denmark. Internal herniation (IH) or intermittent internal herniation (IIH) is a major late complication after LRYGB due to persistent mesenteric defects. However, the incidence...

  16. EARLY POSTOPERATIVE COMPLICATIONS IN ROUX-EN-Y GASTRIC BYPASS.

    Science.gov (United States)

    Stoll, Aluisio; Rosin, Leandro; Dias, Mariana Fernandes; Marquiotti, Bruna; Gugelmin, Giovana; Stoll, Gabriela Fanezzi

    Roux-en-Y gastric bypass is one of the most common bariatric surgery and leads to considerable weight loss in the first months. To quantify the main early postoperative complications in patients submitted to the gastric bypass. Observational retrospective cohort. Data of 1051 patients with class II obesity associated with comorbidities or class III obesity submitted to the gastric bypass with 30 days of follow-up starting from the date of the surgery. The age average was 36 years with a predominance of females (81.1%). The mean preoperative body mass index was 43 kg/m². The major complication was fistula (2.3%), followed by intestinal obstruction (0.5%) and pulmonary embolism (0.5%). Death occurred in 0.6% of the cases. In the period of 30 days after surgery the overall complication rate was 3.8%; reoperation was necessary in 2.6% and death occurred in 0.6%. Fistula was the main complication and the leading cause of hospitalization in intensive care unit, reoperation and death. Bypass gástrico em Y-de-Roux é uma das operações bariátricas mais comuns e leva a perdas consideráveis de peso já nos primeiros meses. Quantificar as principais complicações pós-operatórias precoces em pacientes submetidos ao bypass gástrico. Coorte retrospectiva observacional. Amostra de 1051 pacientes portadores de obesidade grau II associada à comorbidades ou grau III submetidos ao bypass gástrico com acompanhamento de 30 dias a partir da data da operação. A idade média dos pacientes foi de 36 anos com predominância de mulheres (81,1%). O índice de massa corporal pré-operatório médio foi de 43 kg/m². A principal complicação foi fístula (2,3%), seguida de obstrução intestinal (0,5%) e tromboembolismo pulmonar (0,5%). Óbito ocorreu em 0,6% dos casos. No período de 30 dias de pós-operatório a taxa geral de complicações foi de 3,8%; a de reoperação de 2,6% e óbito em 0,6%. A fístula foi a principal complicação e a principal causa de internamento em

  17. Replication of UV-irradiated single-stranded DNA by DNA polymerase III holoenzyme of Escherichia coli: evidence for bypass of pyrimidine photodimers

    International Nuclear Information System (INIS)

    Livneh, Z.

    1986-01-01

    Replication of UV-irradiated circular single-stranded phage M13 DNA by Escherichia coli RNA polymerase (EC 2.7.7.6) and DNA polymerase III holoenzyme (EC 2.7.7.7) in the presence of single-stranded DNA binding protein yielded full-length as well as partially replicated products. A similar result was obtained with phage G4 DNA primed with E. coli DNA primase, and phage phi X174 DNA primed with a synthetic oligonucleotide. The fraction of full-length DNA was several orders of magnitude higher than predicted if pyrimidine photodimers were to constitute absolute blocks to DNA replication. Recent models have suggested that pyrimidine photodimers are absolute blocks to DNA replication and that SOS-induced proteins are required to allow their bypass. Our results demonstrate that, under in vitro replication conditions, E. coli DNA polymerase III holoenzyme can insert nucleotides opposite pyrimidine dimers to a significant extent, even in the absence of SOS-induced proteins

  18. Interactions and Localization of Escherichia coli Error-Prone DNA Polymerase IV after DNA Damage.

    Science.gov (United States)

    Mallik, Sarita; Popodi, Ellen M; Hanson, Andrew J; Foster, Patricia L

    2015-09-01

    Escherichia coli's DNA polymerase IV (Pol IV/DinB), a member of the Y family of error-prone polymerases, is induced during the SOS response to DNA damage and is responsible for translesion bypass and adaptive (stress-induced) mutation. In this study, the localization of Pol IV after DNA damage was followed using fluorescent fusions. After exposure of E. coli to DNA-damaging agents, fluorescently tagged Pol IV localized to the nucleoid as foci. Stepwise photobleaching indicated ∼60% of the foci consisted of three Pol IV molecules, while ∼40% consisted of six Pol IV molecules. Fluorescently tagged Rep, a replication accessory DNA helicase, was recruited to the Pol IV foci after DNA damage, suggesting that the in vitro interaction between Rep and Pol IV reported previously also occurs in vivo. Fluorescently tagged RecA also formed foci after DNA damage, and Pol IV localized to them. To investigate if Pol IV localizes to double-strand breaks (DSBs), an I-SceI endonuclease-mediated DSB was introduced close to a fluorescently labeled LacO array on the chromosome. After DSB induction, Pol IV localized to the DSB site in ∼70% of SOS-induced cells. RecA also formed foci at the DSB sites, and Pol IV localized to the RecA foci. These results suggest that Pol IV interacts with RecA in vivo and is recruited to sites of DSBs to aid in the restoration of DNA replication. DNA polymerase IV (Pol IV/DinB) is an error-prone DNA polymerase capable of bypassing DNA lesions and aiding in the restart of stalled replication forks. In this work, we demonstrate in vivo localization of fluorescently tagged Pol IV to the nucleoid after DNA damage and to DNA double-strand breaks. We show colocalization of Pol IV with two proteins: Rep DNA helicase, which participates in replication, and RecA, which catalyzes recombinational repair of stalled replication forks. Time course experiments suggest that Pol IV recruits Rep and that RecA recruits Pol IV. These findings provide in vivo evidence

  19. Nutrient deficiency and obstetrical outcomes in pregnant women following Roux-en-Y gastric bypass: A retrospective Danish cohort study with a matched comparison group.

    Science.gov (United States)

    Hammeken, Lianna Hede; Betsagoo, Ramsina; Jensen, Ann Nygaard; Sørensen, Anne Nødgaard; Overgaard, Charlotte

    2017-09-01

    Roux-en-Y gastric bypass surgery and small-for-gestational-age births are known to be associated although the etiology is not fully understood. This study aimed to investigate pregnancy outcomes and maternal nutritional status among pregnant women with a history of Roux-en-Y gastric bypass using maternal anemia and gestational weight gain as indicators of micronutrient and macronutrient deficiency in pregnancy. The study was designed as a retrospective matched cohort study. All Roux-en-Y-gastric-bypass-operated pregnant women (n=151) who were followed in the outpatient obstetric clinic at Aalborg University Hospital in Denmark and gave birth between 1 January 2010 and 31 December 2013 were included. Each Roux-en-Y-gastric-bypass-operated woman was closely matched with a non-Roux-en-Y-gastric-bypass-operated woman. Primary outcomes were small-for-gestational-age birth, maternal anemia and gestational weight gain. The two groups (matched 1:1) were compared by paired tests on all measures, conditional logistic regression for paired binary data and the paired t-test or Wilcoxon signed-rank test for paired continuous data. The risk of small-for-gestational-age birth (odds ratio (OR)=2.67, 95% confidence interval (CI); 1.04-6.82) and maternal anemia (OR=3.0, 95% CI; 1.09-8.25) were significantly increased for the Roux-en-Y gastric bypass group compared to the non-Roux-en-Y gastric bypass group. No significant difference was found in gestational weight gain (p=0.169) between women with a history of Roux-en-Y gastric bypass (11.51kg±8.97 standard deviation (SD)) and non- Roux-en-Y-gastric-bypass-operated women (12.18kg±6.28 SD). A history of Roux-en-Y gastric bypass surgery increases the risk of small-for-gestational-age birth and anemia, while a finding of differences in gestational weight gain is uncorroborated. Our findings suggest a role of micronutrient deficiency rather than reduced gestational weight gain in the etiology of small-for-gestational-age birth among

  20. Role of polymerase η in mitochondrial mutagenesis of Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Nimrat; Pabla, Ritu [Dept. of Cell Biology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107 (United States); Siede, Wolfram, E-mail: wolfram.siede@unthsc.edu [Dept. of Cell Biology and Anatomy, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107 (United States)

    2013-02-08

    Highlights: ► DNA polymerase η is detectable in mitochondria of budding yeast. ► Pol η reduces UV-induced mitochondrial base pair substitutions and frameshifts. ► For UV-induced base pair substitutions, Pol η and Pol ζ interact epistatically. -- Abstract: DNA polymerase η mostly catalyzes an error-free bypass of the most frequent UV lesions, pyrimidine dimers of the cyclobutane-type. In addition to its nuclear localization, we show here for the first time its mitochondrial localization in budding yeast. In mitochondria, this polymerase improves bypass replication fidelity opposite UV damage as shown in base pair substitution and frameshift assays. For base pair substitutions, polymerase η appears to be related in function and epistatic to DNA polymerase ζ which, however, plays the opposite role in the nucleus.

  1. Roles of the active site residues and metal cofactors in noncanonical base-pairing during catalysis by human DNA polymerase iota.

    Science.gov (United States)

    Makarova, Alena V; Ignatov, Artem; Miropolskaya, Nataliya; Kulbachinskiy, Andrey

    2014-10-01

    Human DNA polymerase iota (Pol ι) is a Y-family polymerase that can bypass various DNA lesions but possesses very low fidelity of DNA synthesis in vitro. Structural analysis of Pol ι revealed a narrow active site that promotes noncanonical base-pairing during catalysis. To better understand the structure-function relationships in the active site of Pol ι we investigated substitutions of individual amino acid residues in its fingers domain that contact either the templating or the incoming nucleotide. Two of the substitutions, Y39A and Q59A, significantly decreased the catalytic activity but improved the fidelity of Pol ι. Surprisingly, in the presence of Mn(2+) ions, the wild-type and mutant Pol ι variants efficiently incorporated nucleotides opposite template purines containing modifications that disrupted either Hoogsteen or Watson-Crick base-pairing, suggesting that Pol ι may use various types of interactions during nucleotide addition. In contrast, in Mg(2+) reactions, wild-type Pol ι was dependent on Hoogsteen base-pairing, the Y39A mutant was essentially inactive, and the Q59A mutant promoted Watson-Crick interactions with template purines. The results suggest that Pol ι utilizes distinct mechanisms of nucleotide incorporation depending on the metal cofactor and reveal important roles of specific residues from the fingers domain in base-pairing and catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Treatment of giant hiatal hernia by laparoscopic Roux-en-Y gastric bypass

    NARCIS (Netherlands)

    L.E. Duinhouwer (Lucia); L.U. Biter (L. Ulas); B.P.L. Wijnhoven (Bas); G.H.H. Mannaerts (Guido)

    2015-01-01

    textabstractIntroduction Obesity is a risk factor for hiatal hernia. In addition, much higher recurrence rates are reported after standard surgical treatment of hiatal hernia in morbidly obese patients. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is an effective surgical treatment for morbid

  3. Pregnant woman with fatal complication after laparoscopic Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Renault, Kristina; Gyrtrup, Hans Jørgen; Damgaard, Karen

    2012-01-01

    In Europe, an increasing number of women have bariatric surgery; therefore, obstetricians are likely to encounter these patients. We report a 22-year-old woman, who had previously undergone uncomplicated laparoscopic Roux-en-Y gastric bypass. She was admitted with severe abdominal pain at 35 weeks...

  4. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial.

    Science.gov (United States)

    Peterli, Ralph; Wölnerhanssen, Bettina Karin; Peters, Thomas; Vetter, Diana; Kröll, Dino; Borbély, Yves; Schultes, Bernd; Beglinger, Christoph; Drewe, Jürgen; Schiesser, Marc; Nett, Philipp; Bueter, Marco

    2018-01-16

    Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y

  5. The role of DNA polymerase {iota} in UV mutational spectra

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jun-Hyuk [Division of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States); Besaratinia, Ahmad [Division of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States); Lee, Dong-Hyun [Division of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States); Lee, Chong-Soon [Department of Biochemistry, College of Natural Sciences, Yeungnam University, Gyongsan 712-749 (Korea, Republic of); Pfeifer, Gerd P. [Division of Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010 (United States)]. E-mail: gpfeifer@coh.org

    2006-07-25

    UVB (280-320 nm) and UVC (200-280 nm) irradiation generate predominantly cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts in DNA. CPDs are thought to be responsible for most of the UV-induced mutations. Thymine-thymine CPDs, and probably also CPDs containing cytosine, are replicated in vivo in a largely accurate manner by a DNA polymerase {eta} (Pol {eta}) dependent process. Pol {eta} is a DNA damage-tolerant and error-prone DNA polymerase encoded by the POLH (XPV) gene in humans. Another member of the Y family of error-prone DNA polymerases is POLI encoding DNA polymerase iota (Pol {iota}). In order to clarify the specific role of Pol {iota} in UV mutagenesis, we have used an siRNA knockdown approach in combination with a supF shuttle vector which replicates in mammalian cells, similar as we have previously done for Pol {eta}. Synthetic RNA duplexes were used to efficiently inhibit Pol {iota} expression in 293T cells. The supF shuttle vector was irradiated with 254 nm UVC and replicated in 293T cells in presence of anti-Pol {iota} siRNA. Surprisingly, there was a consistent reduction of recovered plasmid from cells with Pol {iota} knockdown and this was independent of UV irradiation of the plasmid. The supF mutant frequency was unchanged in the siRNA knockdown cells relative to control cells confirming that Pol {iota} does not play an important role in UV mutagenesis. UV-induced supF mutants were sequenced from siRNA-treated cells and controls. Neither the type of mutations nor their distribution along the supF gene were significantly different between controls and siRNA knockdown cells and were predominantly C to T and CC to TT transitions at dipyrimidine sites. These results show that Pol {iota} has no significant role in UV lesion bypass and mutagenesis in vivo and provides some initial data suggesting that this polymerase may be involved in replication of extrachromosomal DNA.

  6. N-terminal domains of human DNA polymerase lambda promote primer realignment during translesion DNA synthesis

    Science.gov (United States)

    Taggart, David J.; Dayeh, Daniel M.; Fredrickson, Saul W.; Suo, Zucai

    2014-01-01

    The X-family DNA polymerases λ (Polλ) and β (Polβ) possess similar 5′-2-deoxyribose-5-phosphatelyase (dRPase) and polymerase domains. Besides these domains, Polλ also possesses a BRCA1 C-terminal (BRCT) domain and a proline-rich domain at its N terminus. However, it is unclear how these non-enzymatic domains contribute to the unique biological functions of Polλ. Here, we used primer extension assays and a newly developed high-throughput short oligonucleotide sequencing assay (HT-SOSA) to compare the efficiency of lesion bypass and fidelity of human Polβ, Polλ and two N-terminal deletion constructs of Polλ during the bypass of either an abasic site or a 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesion. We demonstrate that the BRCT domain of Polλ enhances the efficiency of abasic site bypass by approximately 1.6-fold. In contrast, deletion of the N-terminal domains of Polλ did not affect the efficiency of 8-oxodG bypass relative to nucleotide incorporations opposite undamaged dG. HT-SOSA analysis demonstrated that Polλ and Polβ preferentially generated −1 or −2 frameshift mutations when bypassing an abasic site and the single or double base deletion frequency was highly sequence dependent. Interestingly, the BRCT and proline-rich domains of Polλ cooperatively promoted the generation of −2 frameshift mutations when the abasic site was situated within a sequence context that was susceptible to homology-driven primer realignment. Furthermore, both N-terminal domains of Polλ increased the generation of −1 frameshift mutations during 8-oxodG bypass and influenced the frequency of substitution mutations produced by Polλ opposite the 8-oxodG lesion. Overall, our data support a model wherein the BRCT and proline-rich domains of Polλ act cooperatively to promote primer/template realignment between DNA strands of limited sequence homology. This function of the N-terminal domains may facilitate the role of Polλ as a gap-filling polymerase

  7. Two Family B DNA Polymerases From Aeropyrum pernix, Based on Revised Translational Frames

    Directory of Open Access Journals (Sweden)

    Katsuya Daimon

    2018-04-01

    Full Text Available Living organisms are divided into three domains, Bacteria, Eukarya, and Archaea. Comparative studies in the three domains have provided useful information to understand the evolution of the DNA replication machinery. DNA polymerase is the central enzyme of DNA replication. The presence of multiple family B DNA polymerases is unique in Crenarchaeota, as compared with other archaeal phyla, which have a single enzyme each for family B (PolB and family D (PolD. We analyzed PolB1 and PolB3 in the hyperthermophilic crenarchaeon, Aeropyrum pernix, and found that they are larger proteins than those predicted from the coding regions in our previous study and from public database annotations. The recombinant larger PolBs exhibited the same DNA polymerase activities as previously reported. However, the larger PolB3 showed remarkably higher thermostability, which made this enzyme applicable to PCR. In addition, the high tolerance to salt and heparin suggests that PolB3 will be useful for amplification from the samples with contaminants, and therefore it has a great potential for diagnostic use in the medical and environmental field.

  8. Many complications after Roux-en-Y gastric bypass surgery can be prevented and treated

    DEFF Research Database (Denmark)

    Gribsholt, Sigrid Bjerge; Richelsen, Bjørn

    2016-01-01

    A wide range of complications may occur after Roux-en-Y gastric bypass (RYGB) surgery, including surgical, medical/nutritional, and psychiatric complications. Some of the nutritional complications such as anaemia, dumping and hypoglycaemia may present rather unspecific symptoms that may easily no...

  9. Site-specifically modified oligodeoxyribonucleotides as templates for Escherichia coli DNA polymerase I

    International Nuclear Information System (INIS)

    O'Connor, D.; Stoehrer, G.

    1985-01-01

    Oligodeoxyribonucleotides with site-specific modifications have been used as substrates for Escherichia coli DNA polymerase I holoenzyme and Klenow fragment. Modifications included the bulky guanine-8-aminofluorene adduct and a guanine oxidation product resembling the product of photosensitized DNA oxidation. By a combination of primers and nick-mers, conditions of single-strand-directed DNA synthesis and nick-translation could be created. The results show that the polymerase can bypass both types of lesions. Bypass occurs on a single-stranded template but is facilitated on a nicked, double-stranded template. Only purines, with guanine more favored than adenine, are incorporated across both lesions. The results indicate that site-specifically modified oligonucleotides can be sensitive probes for the action of polymerases on damaged templates. They also suggest a function for polymerase I, in its nick-translation capacity, during DNA repair and mutagenesis

  10. Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase η

    OpenAIRE

    O’Flaherty, D. K.; Patra, A.; Su, Y.; Guengerich, F. P.; Egli, M.; Wilds, C. J.

    2016-01-01

    DNA lesions that elude repair may undergo translesion synthesis catalyzed by Y-family DNA polymerases. O4-Alkylthymidines, persistent adducts that can result from carcinogenic agents, may be encountered by DNA polymerases. The influence of lesion orientation around the C4-O4 bond on processing by human DNA polymerase η (hPol η) was studied for oligonucleotides containing O4-methylthymidine, O4-ethylthymidine, and analogs restricting the O4-methylene group in an anti-orientation. Primer extens...

  11. Solo Single-Incision Laparoscopic Resectional Roux-en-Y Gastric Bypass for Morbid Obesity with Metabolic Syndrome.

    Science.gov (United States)

    Kang, So Hyun; Lee, Yoontaek; Park, Young Suk; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung-Ho

    2017-12-01

    With the advancement of laparoscopic devices and surgical technology, the era of minimal invasive surgery has progressed to reduced-port surgery, and finally to single-incision laparoscopic surgery (SILS). Several reports show successful application of SILS to various types of bariatric surgery. Oftentimes, this requires a skilled and experienced scopist to perform the procedure. To overcome the technical difficulties of single-incision Roux-en-Y gastric bypass, a manual scope holder was used instead of an assistant scopist, greatly stabilizing the field of view. This allows the surgery to be performed at any time without being influenced by the need of a highly experienced scopist. In this report, we describe in detail the world's first solo single-incision laparoscopic resectional Roux-en-Y gastric bypass.

  12. Effect of Roux-en-Y gastric bypass on satiety and food likes: the role of genetics.

    Science.gov (United States)

    Thirlby, Richard C; Bahiraei, Frohar; Randall, Jim; Drewnoski, Adam

    2006-02-01

    Among factors influencing the outcome of bariatric surgery may be genetics and familial risk. The purpose of this study was to assess the etiology of obesity and its impact on hunger, satiety, and food likes in obese patients undergoing Roux-en-Y gastric bypass (RYGB). This study was based on 76 patients undergoing RYGB procedures performed by a single surgeon. A previously described 100-point obesity risk index (ORI) was used to assess familial obesity risk. Hunger and satiety were assessed using a standardized Visual Analog Scale "Snickers" test, and food preferences for regular vs. low-fat potato chips were measured preoperatively and postoperatively. Patients were stratified preoperatively into high ORI (n = 34) and low ORI (n = 42) groups. Before operation, high-ORI patients preferred high-fat (regular) potato chips to low-fat (baked) potato chips, whereas the low-ORI patients liked both food types equivalently (P food and a significantly prolonged drop in hunger ratings after a fast and after a standard 282 kcal meal. The success of bariatric surgery may be influenced by the etiology of obesity.

  13. Pancreatic and Intestinal Function Post Roux-en-Y Gastric Bypass Surgery for Obesity

    DEFF Research Database (Denmark)

    O'Keefe, Stephen J D; Rakitt, Tina; Ou, Junhai

    2017-01-01

    OBJECTIVES: Despite the fact that the most effective treatment for morbid obesity today is gastric bypass surgery, some patients develop life-threatening nutritional complications associated with their weight loss. METHODS: Here we examine the influence of the altered anatomy and digestive...... physiology on pancreatic secretion and fat absorption. Thirteen post Roux-en-Y gastric bypass (RYGB) patients who had lost >100 lbs in the first year following surgery and who gave variable histories of gastrointestinal (GI) dysfunction, were selected for study. Food-stimulated pancreatic enzyme secretion...... balance study when a normal diet was given containing ~100 g fat/d. RESULTS: Result showed that all patients had some fat malabsorption, but eight had coefficients of fat absorption associated with significantly lower feed-stimulated secretion rates of trypsin...

  14. Early 24-hour blood pressure response to Roux-en-Y gastric bypass in obese patients

    DEFF Research Database (Denmark)

    Pedersen, Julie S; Borup, Christian; Damgaard, Morten

    2017-01-01

    Recently, it has been proposed, that the blood pressure (BP) lowering effect of gastric bypass surgery not only is explained by the obtained weight loss, but that the anatomical rearrangement of the gut after 'malabsorptive' surgical techniques, such as the laparoscopic Roux-en-Y gastric bypass...... (LRYGB), may affect BP through a change in a putative 'entero-renal' axis. If so one could anticipate a reduction in BP even before a noticeable weight loss was obtained. The purpose of the present study was to investigate the very early BP response to LRYGB surgery. Ten severely obese hypertensive (mean...

  15. A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family

    Directory of Open Access Journals (Sweden)

    Jiqin Wu

    2015-06-01

    Full Text Available RNA-dependent RNA polymerases (RdRPs from the Flaviviridae family are representatives of viral polymerases that carry out RNA synthesis through a de novo initiation mechanism. They share a ≈ 600-residue polymerase core that displays a canonical viral RdRP architecture resembling an encircled right hand with palm, fingers, and thumb domains surrounding the active site. Polymerase catalytic motifs A–E in the palm and motifs F/G in the fingers are shared by all viral RdRPs with sequence and/or structural conservations regardless of the mechanism of initiation. Different from RdRPs carrying out primer-dependent initiation, Flaviviridae and other de novo RdRPs utilize a priming element often integrated in the thumb domain to facilitate primer-independent initiation. Upon the transition to the elongation phase, this priming element needs to undergo currently unresolved conformational rearrangements to accommodate the growth of the template-product RNA duplex. In the genera of Flavivirus and Pestivirus, the polymerase module in the C-terminal part of the RdRP protein may be regulated in cis by the N-terminal region of the same polypeptide. Either being a methyltransferase in Flavivirus or a functionally unclarified module in Pestivirus, this region could play auxiliary roles for the canonical folding and/or the catalysis of the polymerase, through defined intra-molecular interactions.

  16. Roux limb volvulus in laparoscopic Roux-en-Y gastric bypass due to Roux limb stabilization suture: case series.

    Science.gov (United States)

    Marr, Brendan; Yenumula, Panduranga

    2012-01-01

    Complications after laparoscopic Roux-en-Y gastric bypass surgery may be related to the type of surgical technique employed. One technique, the placement of a Roux limb stabilization suture, presumably prevents kink at the gastrojejunal anastomosis. However, it can have an adverse effect and we studied a series of cases presenting with intestinal obstruction secondary to this stitch. A retrospective review of a prospectively collected database of laparoscopic Roux-en-Y gastric bypass cases who had reoperations for Roux limb volvulus was performed at a single bariatric center by a single surgeon. Out of 199 patients who underwent laparoscopic Roux en Y gastric bypass with placement of Roux limb stabilization suture, 4 patients (2.01%) presented with Roux limb volvulus postoperatively. BMI was 45.35 ± 2.95. The postoperative time to presentation was 11 ± 10.6 months. All four patients required surgical exploration to reduce the volvulus. In all cases, the Roux limb volvulus was directly attributable to the presence of the stabilization suture. In subsequent 250 cases where this suture was eliminated, there was no volvulus of Roux limb seen. The use of a stabilization suture can result in volvulus of the Roux limb causing intestinal obstruction and this complication can be prevented by avoiding this suture.

  17. Medical image of the week: Dobhoff tube placement with Roux-en-Y gastric bypass

    Directory of Open Access Journals (Sweden)

    Ali H

    2018-04-01

    Full Text Available No abstract available. Article truncated after 150 words. Roux-en-Y gastric bypass is one of the most commonly performed bariatric operations in the United States. It involves partitioning a small gastric pouch off the proximal stomach and attaching that pouch directly to the intestine, thereby bypassing the large remainder of the stomach (1,2. Placing a Dobhoff tube (DHT and confirming its placement can be challenging due to the change in anatomy after the procedure. Here, we have a 65-year-old woman who presented to the hospital with acute encephalopathy and acute hypoxic respiratory failure due to multifocal pneumonia requiring intubation and prolonged ICU stay. A DHT was inserted after intubation for feeding purposes. An abdominal X-ray was obtained to confirm placement of the DHT (Figure 1. Normally the DHT tip should be placed in the 2nd to 3rd portion of the duodenum and would create a C-shaped tracing on the X-ray. However, in our patient who had history of Roux-en-Y

  18. Conformational Dynamics of a Y-Family DNA Polymerase during Substrate Binding and Catalysis As Revealed by Interdomain F?rster Resonance Energy Transfer

    OpenAIRE

    Maxwell, Brian A.; Xu, Cuiling; Suo, Zucai

    2014-01-01

    Numerous kinetic, structural, and theoretical studies have established that DNA polymerases adjust their domain structures to enclose nucleotides in their active sites and then rearrange critical active site residues and substrates for catalysis, with the latter conformational change acting to kinetically limit the correct nucleotide incorporation rate. Additionally, structural studies have revealed a large conformational change between the apoprotein and the DNA?protein binary state for Y-fa...

  19. Achalasia 5 years following Roux-en-y gastric bypass

    Directory of Open Access Journals (Sweden)

    Mehyar Hefazi Torghabeh

    2015-01-01

    Full Text Available Oesophageal achalasia is a rare, but serious condition in which the motility of the lower oesophageal sphincter (LES is inhibited. This disorder of idiopathic aetiology complicates the peristaltic function and relaxation of the LES that may cause symptoms such as dysphagia, epigastric pain, and regurgitation of an obstructed food. The following case describes achalasia in a patient 5 years following a laparoscopic Roux-en-Y gastric bypass (RYGB. The patient underwent a laparoscopic Heller myotomy without a fundoplication. Although achalasia seems to be a rare occurrence in obese patients, this is the third case documented in a patient who previously had an RYGB. The role of performing a fundoplication in these patients remains to be elucidated.

  20. ¿Cambio de paradigma desde el bypass gástrico Roux-en-Y al (mini) bypass gástrico debido a problemas de glucosa?

    OpenAIRE

    Himpens, Jaques

    2014-01-01

    El bypass gástrico Roux-en-Y funciona de la siguiente manera sobre la diabetes mellitus tipo 2: En obesos mórbidos la diabetes tipo2 inicia con la presencia de resistencia a la insulina con un incremento del péptido C, o sea incremento de las necesidades de insulina que los no obesos tienen para mantener el estado euglucemico. Cuando la secreción de insulina es insuficiente, se desarrolla la diabetes. Esta secreción de insulina está modulada por las incretinas y posiblemente por anti-incretin...

  1. Structure of human DNA polymerase iota and the mechanism of DNA synthesis.

    Science.gov (United States)

    Makarova, A V; Kulbachinskiy, A V

    2012-06-01

    Cellular DNA polymerases belong to several families and carry out different functions. Highly accurate replicative DNA polymerases play the major role in cell genome replication. A number of new specialized DNA polymerases were discovered at the turn of XX-XXI centuries and have been intensively studied during the last decade. Due to the special structure of the active site, these enzymes efficiently perform synthesis on damaged DNA but are characterized by low fidelity. Human DNA polymerase iota (Pol ι) belongs to the Y-family of specialized DNA polymerases and is one of the most error-prone enzymes involved in DNA synthesis. In contrast to other DNA polymerases, Pol ι is able to use noncanonical Hoogsteen interactions for nucleotide base pairing. This allows it to incorporate nucleotides opposite various lesions in the DNA template that impair Watson-Crick interactions. Based on the data of X-ray structural analysis of Pol ι in complexes with various DNA templates and dNTP substrates, we consider the structural peculiarities of the Pol ι active site and discuss possible mechanisms that ensure the unique behavior of the enzyme on damaged and undamaged DNA.

  2. Error-prone bypass of O6-methylguanine by DNA polymerase of Pseudomonas aeruginosa phage PaP1.

    Science.gov (United States)

    Gu, Shiling; Xiong, Jingyuan; Shi, Ying; You, Jia; Zou, Zhenyu; Liu, Xiaoying; Zhang, Huidong

    2017-09-01

    O 6 -Methylguanine (O 6 -MeG) is highly mutagenic and is commonly found in DNA exposed to methylating agents, generally leads to G:C to A:T mutagenesis. To study DNA replication encountering O 6 -MeG by the DNA polymerase (gp90) of P. aeruginosa phage PaP1, we analyzed steady-state and pre-steady-state kinetics of nucleotide incorporation opposite O 6 -MeG by gp90 exo - . O 6 -MeG partially inhibited full-length extension by gp90 exo - . O 6 -MeG greatly reduces dNTP incorporation efficiency, resulting in 67-fold preferential error-prone incorporation of dTTP than dCTP. Gp90 exo - extends beyond T:O 6 -MeG 2-fold more efficiently than C:O 6 -MeG. Incorporation of dCTP opposite G and incorporation of dCTP or dTTP opposite O 6 -MeG show fast burst phases. The pre-steady-state incorporation efficiency (k pol /K d,dNTP ) is decreased in the order of dCTP:G>dTTP:O 6 -MeG>dCTP:O 6 -MeG. The presence of O 6 -MeG at template does not affect the binding affinity of polymerase to DNA but it weakened their binding in the presence of dCTP and Mg 2+ . Misincorporation of dTTP opposite O 6 -MeG further weakens the binding affinity of polymerase to DNA. The priority of dTTP incorporation opposite O 6 -MeG is originated from the fact that dTTP can induce a faster conformational change step and a faster chemical step than dCTP. This study reveals that gp90 bypasses O 6 -MeG in an error-prone manner and provides further understanding in DNA replication encountering mutagenic alkylation DNA damage for P. aeruginosa phage PaP1. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Hedonic changes in food choices following Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Hansen, Thea Toft; Jakobsen, Tine Anette; Nielsen, Mette Søndergaard

    2016-01-01

    It has been suggested that a shift in food choices leading to a diet with a lower energy density plays an important role in successful weight loss after Roux-en-Y gastric bypass (RYGB) surgery. A decreased hedonic drive to consume highly palatable foods may explain these changes in eating behavio...... to consume highly palatable foods. Still, in order to fully understand the complexity of these changes, we need studies combining sociological and psychological approaches with objective measures of actual food choices examining different measures of hedonic drive....

  4. A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens.

    Science.gov (United States)

    Litschko, Christa; Oldrini, Davide; Budde, Insa; Berger, Monika; Meens, Jochen; Gerardy-Schahn, Rita; Berti, Francesco; Schubert, Mario; Fiebig, Timm

    2018-05-29

    Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called capsule polymerases. In this report, we describe a new family of polymerases that combine glycosyltransferase and hexose- and polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) and poly(glycosylpolyol phosphate) polymers, the latter of which display similarity to wall teichoic acid (WTA), a cell wall component of Gram-positive bacteria. Using modeling and multiple-sequence alignment, we showed homology between the predicted polymerase domains and WTA type I biosynthesis enzymes, creating a link between Gram-negative and Gram-positive cell wall biosynthesis processes. The polymerases of the new family are highly abundant and found in a variety of capsule-expressing pathogens such as Neisseria meningitidis , Actinobacillus pleuropneumoniae , Haemophilus influenzae , Bibersteinia trehalosi , and Escherichia coli with both human and animal hosts. Five representative candidates were purified, their activities were confirmed using nuclear magnetic resonance (NMR) spectroscopy, and their predicted folds were validated by site-directed mutagenesis. IMPORTANCE Bacterial capsules play an important role in the interaction between a pathogen and the immune system of its host. During the last decade, capsule polymerases have become attractive tools for the production of capsule polymers applied as antigens in glycoconjugate vaccine formulations. Conventional production of glycoconjugate vaccines requires the cultivation of the pathogen and thus the highest biosafety standards, leading to tremendous costs. With regard to animal husbandry, where vaccines could avoid the extensive use of antibiotics, conventional production is not sufficiently cost-effective. In contrast, enzymatic synthesis of capsule polymers is pathogen-free and fast, offers high stereo- and regioselectivity, and works with high efficacy

  5. Reconstruction Options for Pancreaticoduodenectomy in Patients with Prior Roux-en-Y Gastric Bypass.

    Science.gov (United States)

    Shah, Mihir M; Martin, Benjamin M; Stetler, Jamil L; Patel, Ankit D; Davis, S Scott; Sarmiento, Juan M; Lin, Edward

    2017-11-01

    Patients with prior Roux-en-Y gastric bypass (RYGB) operations for weight loss present reconstruction challenges during a pancreaticoduodenectomy (PD). With over 60,000 RYGB performed annually, the increasing odds of encountering such patients during a PD make it imperative to understand the RYGB anatomy and anticipate reconstruction options. This article describes the possible reconstruction options and their rationale. We reviewed our PD reconstruction options, compared them to what have been described in the literature, and derived a consensus from internal conferences comprising bariatric and hepatopancreatobiliary surgeons to describe known reconstruction options. In general, reconstruction options can include one of three options: (1) remnant gastrectomy, (2) preservation of gastric remnant, or (3) reversal of gastric bypass. This article describes individualized reconstruction options for RYGB patients undergoing PD. The reconstruction options can be tailored to the needs of the patient.

  6. Radiologic evaluation following Roux-en-Y gastric bypass surgery for morbid obesity

    Energy Technology Data Exchange (ETDEWEB)

    Carucci, Laura R. [Department of Radiology, Virginia Commonwealth University Medical Center, P.O. Box 980615, Richmond, VA 23298-0615 (United States)]. E-mail: lcarucci@vcu.edu; Turner, Mary Ann [Department of Radiology, Virginia Commonwealth University Medical Center, P.O. Box 980615, Richmond, VA 23298-0615 (United States)

    2005-03-01

    Morbid obesity is an increasing health problem, and bariatric surgery is becoming a popular treatment option. Radiologists must be familiar with performing and interpreting studies in this patient population. The typical postoperative findings of the Roux-en-Y gastric bypass (RYGBP) procedure for morbid obesity on upper gastrointestinal (UGI) series are presented. An overview of the potential complications that may be diagnosed with contrast studies and computed tomography (CT) is provided in addition to a description of potential pitfalls in interpreting these studies.

  7. Radiologic evaluation following Roux-en-Y gastric bypass surgery for morbid obesity

    International Nuclear Information System (INIS)

    Carucci, Laura R.; Turner, Mary Ann

    2005-01-01

    Morbid obesity is an increasing health problem, and bariatric surgery is becoming a popular treatment option. Radiologists must be familiar with performing and interpreting studies in this patient population. The typical postoperative findings of the Roux-en-Y gastric bypass (RYGBP) procedure for morbid obesity on upper gastrointestinal (UGI) series are presented. An overview of the potential complications that may be diagnosed with contrast studies and computed tomography (CT) is provided in addition to a description of potential pitfalls in interpreting these studies

  8. Biodistribution of technetium-99m pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

    International Nuclear Information System (INIS)

    Rego, Amalia Cinthia Meneses do; Jacome, Daniel Torres; Ramalho, Rachel de Alcantara Oliveira; Araujo-Filho, Irami; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha

    2010-01-01

    Purpose: The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na 99m Tc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na 99m Tc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gamma counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p 99m Tc - . (author)

  9. Roux-en-Y gastric bypass augments the feeding responses evoked by gastrin releasing peptides

    Science.gov (United States)

    Washington, Martha C.; Mhalhal, Thaer R.; Berger, Tanisha Johnson-Rouse Jose; Heath, John; Seeley, Randy; Sayegh, Ayman I.

    2016-01-01

    Background Roux-en-Y gastric bypass (RYGB) is the most effective method for the treatment of obesity and metabolic disease Roux-en-Y gastric bypass (RYGB) may reduce body weight by altering the feeding responses evoked by the short term satiety peptides. Materials and Methods Here, we measured meal size (MS, chow), intermeal interval (IMI) length and satiety ratio (SR, IMI/MS; food consumed per a unit of time) by the small and the large forms of gastrin releasing peptide (GRP) in rats, GRP-10 and GRP-29 (0, 0.1, 0.5 nmol/kg) infused in the celiac artery (CA, supplies stomach and upper duodenum) and the cranial mesenteric artery (CMA, supplies small and large intestine) in a RYGB rat model. Results GRP-10 reduced MS, prolonged the IMI and increased the SR only in the RYGB group, whereas GRP-29 evoked these responses by both routes and in both groups. Conclusion The RYGB procedure augments the feeding responses evoked by exogenous GRP, possibly by decreasing total food intake, increasing latency to the first meal, decreasing number of meals or altering the sites of action regulating MS and IMI length by the two peptides. PMID:27884350

  10. Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.

    Science.gov (United States)

    Lee, Young-Sam; Gregory, Mark T; Yang, Wei

    2014-02-25

    DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3-Rev7-PolD2-PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3-Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3' guanine and Pol ζ4 to extend the primers.

  11. Results of The Comparative Study of 200 Cases: One Anastomosis Gastric Bypass vs Roux-en-Y Gastric Bypass.

    Science.gov (United States)

    Navarrete, Salvador; Leyba, José Luis; Ll, Salvador Navarrete; Borjas, Guillermo; Tapia, José León; Alcázar, Ruben

    2018-05-01

    Obesity has experienced worldwide increase and surgery has become the treatment that has achieved the best results. Several techniques have been described; the most popular are vertical gastrectomy (GV) and the Roux-en-Y gastric bypass (RYGB). However, mini-gastric bypass/one anastomosis gastric bypass (MGB/OAGB) has gained popularity due to its simplicity and good results. To comparatively evaluate the results of MGB/OAGB with those of RYGB with 1-year follow-up. The paper presents a comparative case and control study of 100 patients that underwent MGB/OAGB surgery and another 100 with RYGB surgery, operated between 2008 and 2016. Patients were not submitted to revision surgery and had the following pre-operative variables: age 40.46 ± 12.4 vs. 39.43 ± 10.33 years; sex 64 and 54 women, 36 and 46 men; BMI 44.8 ± 12.06 and 45.29 ± 8.82 kg/m 2 ; 50 and 54 cases with comorbidities, respectively, these being non-significant differences. The surgical time was 69.01 ± 4.62 (OAGB) vs. 88.98 ± 3.44 min; the time of hospitalization was 2 days, reaching a BMI of 27.7 ± 7.85 and 29 ± 4.52 kg/m 2 , with an excess weight loss 1 year after surgery of 89.4 vs. 85.9%, respectively. The morbidity rates are 9% for OAGB and 11% for the RYGB. There was a comorbidity resolution of 84.4 and 83.7% respectively, without mortality. The results show the benefits of both techniques, OAGB being the easiest to perform and with less surgical time.

  12. Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery

    Directory of Open Access Journals (Sweden)

    Jaqueline Scholz Issa

    2000-07-01

    Full Text Available Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy, or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years showed a mean 30% reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease.

  13. Small-bowel volvulus in late pregnancy due to internal hernia after laparoscopic Roux-en-Y gastric bypass.

    Science.gov (United States)

    Naef, Markus; Mouton, Wolfgang G; Wagner, Hans E

    2010-12-01

    Internal hernias are a specific cause of acute abdominal pain and are a well-known complication after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Although internal hernias are a rare cause of intestinal obstruction, they may evolve towards serious complications, such as extensive bowel ischemia and gangrene, with the need for bowel resection and sometimes for a challenging reconstruction of intestinal continuity. The antecolic position of the Roux limb is associated with a decrease in the incidence of small-bowel obstruction and internal hernias. The best prevention of the formation of these hernias is probably by closure of potential mesenteric defects at the initial operation with a non-absorbable running suture. We present a patient in late pregnancy with a small-bowel volvulus following laparoscopic Roux-en-Y gastric bypass for morbid obesity and discuss the available literature. For a favorable obstetric and neonatal outcome, it is crucial not to delay surgical exploration and an emergency operation usually is mandatory.

  14. Roles of Saccharomyces cerevisiae DNA polymerases Poleta and Polzeta in response to irradiation by simulated sunlight.

    Science.gov (United States)

    Kozmin, Stanislav G; Pavlov, Youri I; Kunkel, Thomas A; Sage, Evelyne

    2003-08-01

    Sunlight causes lesions in DNA that if unrepaired and inaccurately replicated by DNA polymerases yield mutations that result in skin cancer in humans. Two enzymes involved in translesion synthesis (TLS) of UV-induced photolesions are DNA polymerase eta (Poleta) and polymerase zeta (Polzeta), encoded by the RAD30A and REV3 genes, respectively. Previous studies have investigated the TLS roles of these polymerases in human and yeast cells irradiated with monochromatic, short wavelength UVC radiation (254 nm). However, less is known about cellular responses to solar radiation, which is of higher and mixed wavelengths (310-1100 nm) and produces a different spectrum of DNA lesions, including Dewar photoproducts and oxidative lesions. Here we report on the comparative cytotoxic and mutagenic effects of simulated sunlight (SSL) and UVC radiation on yeast wild-type, rad30Delta, rev3Delta and rev3Delta rad30Delta strains. The results with SSL support several previous interpretations on the roles of these two polymerases in TLS of photodimers and (6-4) photoproducts derived from studies with UVC. They further suggest that Poleta participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polzeta is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polzeta, Poleta contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine.

  15. Nutrient re-routing and altered gut-islet cell crosstalk may explain early relief of severe postprandial hypoglycaemia after reversal of Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Svane, M S; Toft-Nielsen, M B; Kristiansen, V B

    2017-01-01

    BACKGROUND: Roux-en-Y gastric bypass is associated with an increased risk of postprandial hyperinsulinaemic hypoglycaemia, but the underlying pathophysiology remains poorly understood. We therefore examined the effect of re-routing of nutrient delivery on gut-islet cell crosstalk in a person...... insulin and glucagon-like peptide-1 hypersecretion and eliminated postprandial hypoglycaemia, which emphasizes the importance of altered gut-islet cell crosstalk for glucose metabolism after Roux-en-Y gastric bypass. This article is protected by copyright. All rights reserved....

  16. Analgesic Treatment in Laparoscopic Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenberg, Jacob

    2014-01-01

    This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines. The litera......This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines...

  17. DNA polymerase hybrids derived from the family-B enzymes of Pyrococcus furiosus and Thermococcus kodakarensis: improving performance in the polymerase chain reaction.

    Science.gov (United States)

    Elshawadfy, Ashraf M; Keith, Brian J; Ee Ooi, H'Ng; Kinsman, Thomas; Heslop, Pauline; Connolly, Bernard A

    2014-01-01

    The polymerase chain reaction (PCR) is widely applied across the biosciences, with archaeal Family-B DNA polymerases being preferred, due to their high thermostability and fidelity. The enzyme from Pyrococcus furiosus (Pfu-Pol) is more frequently used than the similar protein from Thermococcus kodakarensis (Tkod-Pol), despite the latter having better PCR performance. Here the two polymerases have been comprehensively compared, confirming that Tkod-Pol: (1) extends primer-templates more rapidly; (2) has higher processivity; (3) demonstrates superior performance in normal and real time PCR. However, Tkod-Pol is less thermostable than Pfu-Pol and both enzymes have equal fidelities. To understand the favorable properties of Tkod-Pol, hybrid proteins have been prepared. Single, double and triple mutations were used to site arginines, present at the "forked-point" (the junction of the exonuclease and polymerase channels) of Tkod-Pol, at the corresponding locations in Pfu-Pol, slightly improving PCR performance. The Pfu-Pol thumb domain, responsible for double-stranded DNA binding, has been entirely replaced with that from Tkod-Pol, again giving better PCR properties. Combining the "forked-point" and thumb swap mutations resulted in a marked increase in PCR capability, maintenance of high fidelity and retention of the superior thermostability associated with Pfu-Pol. However, even the arginine/thumb swap mutant falls short of Tkod-Pol in PCR, suggesting further improvement within the Pfu-Pol framework is attainable. The significance of this work is the observation that improvements in PCR performance are easily attainable by blending elements from closely related archaeal polymerases, an approach that may, in future, be extended by using more polymerases from these organisms.

  18. Trans-Lesion DNA Polymerases May Be Involved in Yeast Meiosis

    Science.gov (United States)

    Arbel-Eden, Ayelet; Joseph-Strauss, Daphna; Masika, Hagit; Printzental, Oxana; Rachi, Eléanor; Simchen, Giora

    2013-01-01

    Trans-lesion DNA polymerases (TLSPs) enable bypass of DNA lesions during replication and are also induced under stress conditions. Being only weakly dependent on their template during replication, TLSPs introduce mutations into DNA. The low processivity of these enzymes ensures that they fall off their template after a few bases are synthesized and are then replaced by the more accurate replicative polymerase. We find that the three TLSPs of budding yeast Saccharomyces cerevisiae Rev1, PolZeta (Rev3 and Rev7), and Rad30 are induced during meiosis at a time when DNA double-strand breaks (DSBs) are formed and homologous chromosomes recombine. Strains deleted for one or any combination of the three TLSPs undergo normal meiosis. However, in the triple-deletion mutant, there is a reduction in both allelic and ectopic recombination. We suggest that trans-lesion polymerases are involved in the processing of meiotic double-strand breaks that lead to mutations. In support of this notion, we report significant yeast two-hybrid (Y2H) associations in meiosis-arrested cells between the TLSPs and DSB proteins Rev1-Spo11, Rev1-Mei4, and Rev7-Rec114, as well as between Rev1 and Rad30. We suggest that the involvement of TLSPs in processing of meiotic DSBs could be responsible for the considerably higher frequency of mutations reported during meiosis compared with that found in mitotically dividing cells, and therefore may contribute to faster evolutionary divergence than previously assumed. PMID:23550131

  19. Accelerated protein digestion and amino acid absorption after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Anna Kirstine; Jacobsen, Siv H; Dirksen, Carsten

    2015-01-01

    BACKGROUND: Roux-en-Y gastric bypass (RYGB) involves exclusion of major parts of the stomach and changes in admixture of gastro-pancreatic enzymes, which could have a major impact on protein digestion and amino acid absorption. OBJECTIVE: We investigated the effect of RYGB on amino acid appearance......: RYGB accelerates caseinate digestion and amino acid absorption, resulting in faster and higher but more transient postprandial elevation of plasma amino acids. Changes are likely mediated by accelerated intestinal nutrient entry and clearly demonstrate that protein digestion is not impaired after RYGB...

  20. Improvement in health-related quality of life following Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Hansen, Nina Beck; Gudex, Claire; Støving, René Klinkby

    2014-01-01

    INTRODUCTION: This study explored whether health-related quality of life (HRQOL) changes following Roux-en-Y gastric bypass surgery were associated with identifiable socio-demographic or clinical characteristics, and it examined the impact on health outcomes of changes in the Danish criteria...... for bariatric surgery. MATERIAL AND METHODS: Participants (n = 55) completed the Short Form Health Survey v2 (SF-36) before and 22 ± 4.2 months after surgery. Information on socio-demographics, body mass index (BMI), co-morbidity and satisfaction with surgery were collected through patient questionnaires...

  1. [Simplified laparoscopic gastric bypass. Initial experience].

    Science.gov (United States)

    Hernández-Miguelena, Luis; Maldonado-Vázquez, Angélica; Cortes-Romano, Pablo; Ríos-Cruz, Daniel; Marín-Domínguez, Raúl; Castillo-González, Armando

    2014-01-01

    Obesity surgery includes various gastrointestinal procedures. Roux-en-Y gastric bypass is the prototype of mixed procedures being the most practiced worldwide. A similar and novel technique has been adopted by Dr. Almino Cardoso Ramos and Dr. Manoel Galvao called "simplified bypass," which has been accepted due to the greater ease and very similar results to the conventional technique. The aim of this study is to describe the results of the simplified gastric bypass for treatment of morbid obesity in our institution. We performed a descriptive, retrospective study of all patients undergoing simplified gastric bypass from January 2008 to July 2012 in the obesity clinic of a private hospital in Mexico City. A total of 90 patients diagnosed with morbid obesity underwent simplified gastric bypass. Complications occurred in 10% of patients; these were more frequent bleeding and internal hernia. Mortality in the study period was 0%. The average weight loss at 12 months was 72.7%. Simplified gastric bypass surgery is safe with good mid-term results and a loss of adequate weight in 71% of cases.

  2. Gastrointestinal complications of bariatric Roux-en-Y gastric bypass surgery

    Energy Technology Data Exchange (ETDEWEB)

    Sandrasegaran, Kumaresan; Rajesh, Arumugam; Lall, Chandana; Maglinte, Dean D. [Indiana University Medical Center, UH 0279, Department of Radiology, Indianapolis, IN (United States); Gomez, Gerardo A. [Wishard Memorial Hospital, Department of Surgery, Indianapolis (United States); Lappas, John C. [Wishard Memorial Hospital, Department of Radiology, Indianapolis (United States)

    2005-02-01

    Obesity is rapidly becoming the most important public health issue in USA and Europe. Roux-en-Y gastric bypass is now established as the gold standard for treating intractable morbid or super obesity. We reviewed the imaging findings following this surgery in 234 patients. In this pictorial essay we present the CT and upper gastrointestinal contrast study appearances of the expected postoperative anatomy as well as a range of abdominal complications. The complications are classified into leaks, fistula and obstruction. Postoperative gastric outlet and small bowel obstruction can be caused by anastomotic stenosis, mesocolic tunnel stenosis, adhesions, stomal ulcer, obturation, intussusception and internal or external hernia. Small bowel obstruction may be of a simple, closed loop and/or strangulating type. The radiologist should be able to diagnose the type and possible cause of obstruction. (orig.)

  3. Gastrointestinal complications of bariatric Roux-en-Y gastric bypass surgery

    International Nuclear Information System (INIS)

    Sandrasegaran, Kumaresan; Rajesh, Arumugam; Lall, Chandana; Maglinte, Dean D.; Gomez, Gerardo A.; Lappas, John C.

    2005-01-01

    Obesity is rapidly becoming the most important public health issue in USA and Europe. Roux-en-Y gastric bypass is now established as the gold standard for treating intractable morbid or super obesity. We reviewed the imaging findings following this surgery in 234 patients. In this pictorial essay we present the CT and upper gastrointestinal contrast study appearances of the expected postoperative anatomy as well as a range of abdominal complications. The complications are classified into leaks, fistula and obstruction. Postoperative gastric outlet and small bowel obstruction can be caused by anastomotic stenosis, mesocolic tunnel stenosis, adhesions, stomal ulcer, obturation, intussusception and internal or external hernia. Small bowel obstruction may be of a simple, closed loop and/or strangulating type. The radiologist should be able to diagnose the type and possible cause of obstruction. (orig.)

  4. Roles of Saccharomyces cerevisiae DNA polymerases Polη and Polζ in response to irradiation by simulated sunlight

    Science.gov (United States)

    Kozmin, Stanislav G.; Pavlov, Youri I.; Kunkel, Thomas A.; Sage, Evelyne

    2003-01-01

    Sunlight causes lesions in DNA that if unrepaired and inaccurately replicated by DNA polymerases yield mutations that result in skin cancer in humans. Two enzymes involved in translesion synthesis (TLS) of UV-induced photolesions are DNA polymerase η (Polη) and polymerase ζ (Polζ), encoded by the RAD30A and REV3 genes, respectively. Previous studies have investigated the TLS roles of these polymerases in human and yeast cells irradiated with monochromatic, short wavelength UVC radiation (254 nm). However, less is known about cellular responses to solar radiation, which is of higher and mixed wavelengths (310–1100 nm) and produces a different spectrum of DNA lesions, including Dewar photoproducts and oxidative lesions. Here we report on the comparative cytotoxic and mutagenic effects of simulated sunlight (SSL) and UVC radiation on yeast wild-type, rad30Δ, rev3Δ and rev3Δ rad30Δ strains. The results with SSL support several previous interpretations on the roles of these two polymerases in TLS of photodimers and (6–4) photoproducts derived from studies with UVC. They further suggest that Polη participates in the non-mutagenic bypass of SSL-dependent cytosine-containing Dewar photoproducts and 8-oxoguanine, while Polζ is mainly responsible for the mutagenic bypass of all types of Dewar photoproducts. They also suggest that in the absence of Polζ, Polη contributes to UVC- and SSL-induced mutagenesis, possibly by the bypass of photodimers containing deaminated cytosine. PMID:12888515

  5. Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Arora, Tulika; Seyfried, Florian; Docherty, Neil G

    2017-01-01

    Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance...... to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically......, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all...

  6. Characterization of family IV UDG from Aeropyrum pernix and its application in hot-start PCR by family B DNA polymerase.

    Directory of Open Access Journals (Sweden)

    Xi-Peng Liu

    Full Text Available Recombinant uracil-DNA glycosylase (UDG from Aeropyrum pernix (A. pernix was expressed in E. coli. The biochemical characteristics of A. pernix UDG (ApeUDG were studied using oligonucleotides carrying a deoxyuracil (dU base. The optimal temperature range and pH value for dU removal by ApeUDG were 55-65°C and pH 9.0, respectively. The removal of dU was inhibited by the divalent ions of Zn, Cu, Co, Ni, and Mn, as well as a high concentration of NaCl. The opposite base in the complementary strand affected the dU removal by ApeUDG as follows: U/C≈U/G>U/T≈U/AP≈U/->U/U≈U/I>U/A. The phosphorothioate around dU strongly inhibited dU removal by ApeUDG. Based on the above biochemical characteristics and the conservation of amino acid residues, ApeUDG was determined to belong to the IV UDG family. ApeUDG increased the yield of PCR by Pfu DNA polymerase via the removal of dU in amplified DNA. Using the dU-carrying oligonucleotide as an inhibitor and ApeUDG as an activator of Pfu DNA polymerase, the yield of undesired DNA fragments, such as primer-dimer, was significantly decreased, and the yield of the PCR target fragment was increased. This strategy, which aims to amplify the target gene with high specificity and yield, can be applied to all family B DNA polymerases.

  7. Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana

    Science.gov (United States)

    Kashiwagi, Sayo; Kuraoka, Isao; Fujiwara, Yoshie; Hitomi, Kenichi; Cheng, Quen J.; Fuss, Jill O.; Shin, David S.; Masutani, Chikahide; Tainer, John A.; Hanaoka, Fumio; Iwai, Shigenori

    2010-01-01

    Human DNA polymerase η (HsPolη) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-induced cis-syn cyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPolη from the thermophilic worm Alvinella pompejana, which inhabits deep-sea hydrothermal vent chimneys. ApPolη shares sequence homology with HsPolη and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrate Alvinella's environment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPolη is more thermostable than HsPolη, as expected from its habitat temperature. Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPolη provides a robust, human-like Polη that is more active after exposure to high temperatures and organic solvents. PMID:20936172

  8. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial.

    Science.gov (United States)

    Salminen, Paulina; Helmiö, Mika; Ovaska, Jari; Juuti, Anne; Leivonen, Marja; Peromaa-Haavisto, Pipsa; Hurme, Saija; Soinio, Minna; Nuutila, Pirjo; Victorzon, Mikael

    2018-01-16

    Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass. To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity. The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015). Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en-Y gastric bypass (n = 119). The primary end point was weight loss evaluated by percentage excess weight loss. Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were -9% to +9% excess weight loss. Secondary end points included resolution of comorbidities, improvement of quality of life (QOL), all adverse events (overall morbidity), and mortality. Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n

  9. Predictive Factors of Secondary Normocalcemic Hyperparathyroidism after Roux-en-Y Gastric Bypass

    Directory of Open Access Journals (Sweden)

    Claudio Casella

    2018-01-01

    Full Text Available Objective. Aim of this study is to evaluate determinants of secondary normocalcemic hyperparathyroidism (SNHPT persistence in patients who have undergone Roux-en-Y gastric bypass on vertical-banded gastroplasty. Methods. 226 consecutive patients submitted to bariatric surgery were prospectively enrolled and divided in two groups on the basis of preoperative presence of SNHPT. For each patient, we evaluated anthropometric and laboratory parameters. Calcium metabolism (calcemia, PTH, and 25-hydroxy vitamin D serum levels was studied before surgery and at 6-month intervals (6, 12, and 18 months as surgical follow-up. Results. Based on presurgical SNHPT presence or absence, we defined group 1—201 patients and group 2—25 patients, respectively. Among the group 1, 153 (76% recovered from this endocrinopathy within 6 months after surgery (group 3, while the remaining 48 patients (24% had persistent SNHPT (group 4. Comparing the anthropometric and laboratory data of group 3 with group 2, the only statistically significant factor was the elapsed time since a prior effective medically controlled diet that led to a steady and substantial weight loss. We found also a statistically significant difference (p<0.05 between group 3 and group 4 in term of % of weight loss and PTH levels. Conclusions. Patients suitable for bariatric surgery must have history of at least one efficient medically controlled diet, not dating back more than 5 years before surgery. This elapsed time represent the cut-off time within which it is possible to recover from SNHPT in the first semester after Roux-en-Y gastric bypass on vertical-banded gastroplasty. The treatment of vitamin D insufficiency and the evaluation of SNHPT before bariatric surgery should be recommended. The clinical significance of preoperative SNHPT and in particular SNHPT after bariatric surgery remains undefined and further studies are required.

  10. Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer

    Directory of Open Access Journals (Sweden)

    Anthony J. Berdis

    2017-11-01

    Full Text Available Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on describing the molecular mechanisms of these inhibitory effects against chromosomal and mitochondrial DNA polymerases. Discussions are also provided on the mechanisms associated with resistance to these therapeutic agents. A primary focus is toward understanding the roles of specialized DNA polymerases that by-pass DNA lesions produced by DNA damaging agents. Finally, a section is provided that describes emerging areas in developing new therapeutic strategies targeting specialized DNA polymerases.

  11. AGE AND GENDER MAY INFLUENCE THE RESULTS OF ROUX-EN-Y GASTRIC BYPASS? Metabolic syndrome parameters

    Directory of Open Access Journals (Sweden)

    Stephan Garcia ANDRADE-SILVA

    2014-09-01

    Full Text Available Context Severe obesity affects the body favoring the development of serious diseases, including hypertension, diabetes mellitus, atherosclerosis and non alcoholic fatty liver disease. Bariatric procedures increased in Brazil in the last decade. Objectives The purpose of this study was to verify if gender and age in date of procedure resulted significant differences in metabolic syndrome parameters after surgery. Methods The study involved 205 medical records of adult patients undergoing Roux-en-Y gastric bypass, stratified by gender and age groups and followed one year by a multidisciplinary team. Results It was observed significant decrease in body mass index, fasting glucose and insulin at all ages and both genders. Lipid profile showed significant improvements except high density lipoprotein cholesterol. Ectopic fat in the liver has decreased after 6 months in patients classified with steatosis at baseline. Patients classified as hypertensive blood pressure levels decreased 6 months after surgical intervention. Conclusions Roux-en-Y gastric bypass proved to be an important tool in remission of metabolic syndrome parameters. The reduction of body mass accompanied to decrease in insulin resistance resulted in lower prevalence of comorbidities associated with obesity. The benefits were similar and extended both genders and all age groups between 18 and 65 years old.

  12. Mechanism of replication of ultraviolet-irradiated single-stranded DNA by DNA polymerase III holoenzyme of Escherichia coli. Implications for SOS mutagenesis

    International Nuclear Information System (INIS)

    Livneh, Z.

    1986-01-01

    Replication of UV-irradiated oligodeoxynucleotide-primed single-stranded phi X174 DNA with Escherichia coli DNA polymerase III holoenzyme in the presence of single-stranded DNA-binding protein was investigated. The extent of initiation of replication on the primed single-stranded DNA was not altered by the presence of UV-induced lesions in the DNA. The elongation step exhibited similar kinetics when either unirradiated or UV-irradiated templates were used. Inhibition of the 3'----5' proofreading exonucleolytic activity of the polymerase by dGMP or by a mutD mutation did not increase bypass of pyrimidine photodimers, and neither did purified RecA protein influence the extent of photodimer bypass as judged by the fraction of full length DNA synthesized. Single-stranded DNA-binding protein stimulated bypass since in its absence the fraction of full length DNA decreased 5-fold. Termination of replication at putative pyrimidine dimers involved dissociation of the polymerase from the DNA, which could then reinitiate replication at other available primer templates. Based on these observations a model for SOS-induced UV mutagenesis is proposed

  13. Transient expression and activity of human DNA polymerase iota in loach embryos.

    Science.gov (United States)

    Makarova, Irina V; Kazakov, Andrey A; Makarova, Alena V; Khaidarova, Nella V; Kozikova, Larisa V; Nenasheva, Valentina V; Gening, Leonid V; Tarantul, Vyacheslav Z; Andreeva, Ludmila E

    2012-02-01

    Human DNA polymerase iota (Pol ι) is a Y-family DNA polymerase with unusual biochemical properties and not fully understood functions. Pol ι preferentially incorporates dGTP opposite template thymine. This property can be used to monitor Pol ι activity in the presence of other DNA polymerases, e.g. in cell extracts of tissues and tumors. We have now confirmed the specificity and sensitivity of the method of Pol ι activity detection in cell extracts using an animal model of loach Misgurnus fossilis embryos transiently expressing human Pol ι. The overexpression of Pol ι was shown to be accompanied by an increase in abnormalities in development and the frequency of pycnotic nuclei in fish embryos. Further analysis of fish embryos with constitutive or regulated Pol ι expression may provide insights into Pol ι functions in vertebrate animals.

  14. Hedonic Changes in Food Choices Following Roux-en-Y Gastric Bypass.

    Science.gov (United States)

    Hansen, Thea Toft; Jakobsen, Tine Anette; Nielsen, Mette Søndergaard; Sjödin, Anders; Le Roux, Carel W; Schmidt, Julie Berg

    2016-08-01

    It has been suggested that a shift in food choices leading to a diet with a lower energy density plays an important role in successful weight loss after Roux-en-Y gastric bypass (RYGB) surgery. A decreased hedonic drive to consume highly palatable foods may explain these changes in eating behavior. Here, we review the literature examining postoperative changes in mechanisms contributing to hedonic drive (food preferences, reinforcing value of food, dopamine signaling, and activity reward-related brain regions). The majority of studies reviewed support that RYGB decrease the hedonic drive to consume highly palatable foods. Still, in order to fully understand the complexity of these changes, we need studies combining sociological and psychological approaches with objective measures of actual food choices examining different measures of hedonic drive.

  15. Pre-Steady State Kinetic Investigation of the Incorporation of Anti-Hepatitis B Nucleotide Analogs Catalyzed by Non-Canonical Human DNA Polymerases

    Science.gov (United States)

    Brown, Jessica A.; Pack, Lindsey R.; Fowler, Jason D.; Suo, Zucai

    2011-01-01

    Antiviral nucleoside analogs have been developed to inhibit the enzymatic activities of the hepatitis B virus (HBV) polymerase, thereby preventing the replication and production of HBV. However, the usage of these analogs can be limited by drug toxicity because the 5′-triphosphates of these nucleoside analogs (nucleotide analogs) are potential substrates for human DNA polymerases to incorporate into host DNA. Although they are poor substrates for human replicative DNA polymerases, it remains to be established whether these nucleotide analogs are substrates for the recently discovered human X- and Y-family DNA polymerases. Using pre-steady state kinetic techniques, we have measured the substrate specificity values for human DNA polymerases β, λ, η, ι, κ, and Rev1 incorporating the active forms of the following anti-HBV nucleoside analogs approved for clinical use: adefovir, tenofovir, lamivudine, telbivudine, and entecavir. Compared to the incorporation of a natural nucleotide, most of the nucleotide analogs were incorporated less efficiently (2 to >122,000) by the six human DNA polymerases. In addition, the potential for entecavir and telbivudine, two drugs which possess a 3′-hydroxyl, to become embedded into human DNA was examined by primer extension and DNA ligation assays. These results suggested that telbivudine functions as a chain terminator while entecavir was efficiently extended by the six enzymes and was a substrate for human DNA ligase I. Our findings suggested that incorporation of anti-HBV nucleotide analogs catalyzed by human X- and Y-family polymerases may contribute to clinical toxicity. PMID:22132702

  16. Crohn’s disease after gastric bypass surgery

    OpenAIRE

    Janczewska, Izabella; Nekzada, Qayium; Kapraali, Marjo

    2011-01-01

    Bariatric surgery for the treatment of severe obesity has increased dramatically in recent years in the USA and parts of Western Europe. The most commonly used technique is the Roux-en Y gastric bypass (RYGBP). Several nutritional and gastrointestinal complications after bariatric surgery have been described during the last 10 years. The authors present two patients with diarrhoea and malnutrition; one after RYGBP and the other after jejunoileal bypass surgery. These patients were subsequentl...

  17. Emotional eating behavior hinders body weight loss in women after Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Novelli, Isabelle Romero; Fonseca, Laís Gomes; Gomes, Daniela Lopes; Dutra, Eliane Said; Baiocchi de Carvalho, Kênia Mara

    2018-05-01

    Successful weight loss and maintenance after Roux-en-Y gastric bypass (RYGB) may be related to eating behavior. The aim of this study was to assess the eating behavior domains that prevail in women during the RYGB postoperative period and their associations with surgery outcome. This cross-sectional study investigated eating behavior in 95 women (47.3 ± 9.8 y old)  ≥ 2 y after Roux-en-Y gastric bypass. Patients were grouped according to surgery outcome: successful group (SG; n = 67), defined as having lost ≥ 50% of the preoperative excess weight loss (EWL), and an unsuccessful group (UG; n = 28). Mean postoperative time was 59.5 ± 21.2 mo (55.7 ± 19.9 in the SG and 68.6 ± 21.9 in the UG). The short version of the Three-Factor Eating Questionnaire was used to assess cognitive restraint, emotional eating, and uncontrolled eating behaviors. Multivariate analysis was used to investigate associations between eating behavior scores and EWL. The highest score in both groups was for the cognitive restraint domain, followed by emotional and uncontrolled eating. Emotional eating was negatively associated with percentage of EWL (β = -0.286; P = 0.033), regardless of age, educational attainment, and postoperative time. The cognitive restraint domain was the main type of eating behavior observed, and patients with higher emotional eating score were at a higher risk for having insufficient weight loss after RYGB. These results indicate the relevance of monitoring emotional components during the long-term nutritional follow-up of bariatric patients to achieve better surgery outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Long-Term Effects of Laparoscopic Roux-en-Y Gastric Bypass on Diabetes Mellitus, Hypertension and Dyslipidaemia in Morbidly Obese Patients

    NARCIS (Netherlands)

    Dogan, K.; Betzel, B.; Homan, J.; Aarts, E.O.; Ploeger, N.; Boer, H. de; Aufenacker, T.J.; Laarhoven, C.J.H.M. van; Janssen, I.M.; Berends, F.J.

    2014-01-01

    BACKGROUND: Severely obese patients have an increased risk for developing metabolic complications such as type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and hypertension (HT). The aim of the present study is to research the effect of a primary laparoscopic Roux-en-Y gastric bypass (LRYGB) on

  19. Rates of secondary hyperparathyroidism after bypass operation for super-morbid obesity: An overlooked phenomenon.

    Science.gov (United States)

    White, Michael G; Ward, Marc A; Applewhite, Megan K; Wong, Harry; Prachand, Vivek; Angelos, Peter; Kaplan, Edwin L; Grogan, Raymon H

    2017-03-01

    With over 110,000 bariatric operations performed in the United States annually, it is important to understand the biochemical abnormalities causing endocrine dysfunction associated with these procedures. Here we compare 2 malabsorptive procedures, duodenal switch and Roux-en-Y gastric bypass, to determine the role malabsorption plays in secondary hyperparathyroidism in this population. Data from all super-obese patients undergoing duodenal switch or Roux-en-Y gastric bypass between August 2002 and October 2005 were prospectively collected. Postoperatively, all patients received 1,200 mg of calcium citrate and 1,000 IU vitamin D3 per American Society for Metabolic and Bariatric Surgery guidelines. Beginning in 2007, duodenal switch patients were instructed to add daily vitamin D3 10,000 IU. Statistical analyses included Student t test, multivariate, and univariate logistic regression. Of 283 patients with a body mass index ≥50, 170 (60.1%) underwent duodenal switch, while 113 (39.9%) underwent Roux-en-Y gastric bypass. Of 132 (46.6%) patients with secondary hyperparathyroidism, 101 (59.4%) had undergone duodenal switch and 31 (27.4%) had undergone Roux-en-Y gastric bypass. Symptoms were more common in the duodenal switch group (33 patients [19.4%]) than Roux-en-Y gastric bypass (11 patients [9.7%]). Multivariate logistic regression demonstrated that the extent of bypass and duration of follow-up were the only 2 independent predictive risk factors for developing secondary hyperparathyroidism. Although vitamin D levels improved with increased vitamin D3 supplementation in 2007, rates of secondary hyperparathyroidism increased. Despite routine postoperative calcium and vitamin D3 supplementation, secondary hyperparathyroidism is common after Roux-en-Y gastric bypass and duodenal switch. The degree of iatrogenic malabsorption correlates with the incidence of secondary hyperparathyroidism. These rates suggest current supplementation guidelines are not sufficient in

  20. Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase

    OpenAIRE

    Gaur, Vineet; Vyas, Rajan; Fowler, Jason D.; Efthimiopoulos, Georgia; Feng, Joy Y.; Suo, Zucai

    2014-01-01

    Considering that all natural nucleotides (D-dNTPs) and the building blocks (D-dNMPs) of DNA chains possess D-stereochemistry, DNA polymerases and reverse transcriptases (RTs) likely possess strongD-stereoselectivity by preferably binding and incorporating D-dNTPs over unnatural L-dNTPs during DNA synthesis. Surprisingly, a structural basis for the discrimination against L-dNTPs by DNA polymerases or RTs has not been established although L-deoxycytidine analogs (lamivudine and emtricitabine) a...

  1. Roux en Y gastric bypass hypoglycemia resolves with gastric feeding or reversal: Confirming a non-pancreatic etiology

    Directory of Open Access Journals (Sweden)

    Dawn Belt Davis

    2018-03-01

    Full Text Available Objective: Postprandial hypoglycemia is an infrequent but disabling complication of Roux-en-Y gastric bypass (RYGB surgery. Controversy still exists as to whether the postprandial hyperinsulinemia observed is due to inherent changes in pancreatic β-cell mass or function or to reversible alterations caused by RYGB anatomy. We aimed to determine if gastric feeding or reversal of RYGB would normalize postprandial glucose and hormone excursions in patients with symptomatic hypoglycemia. Methods: We completed a prospective study of six patients with severe symptomatic RYGB hypoglycemia who underwent RYGB reversal. An additional subject without hypoglycemia who underwent RYGB reversal was also studied prospectively. Mixed meal tolerance testing (MTT was done orally (RYGB anatomy, via gastrostomy tube in the excluded stomach in the setting of RYGB, and several months after RYGB reversal. Results: All subjects reported symptomatic improvement of hypoglycemia after reversal of RYGB. Weight gain after reversal was moderate and variable. Postprandial glucose, insulin, and GLP-1 excursions were significantly diminished with gastric feeding and after reversal. Insulin secretion changed proportional to glucose levels and insulin clearance increased after reversal. Glucagon/insulin ratios were similar throughout study. We further compared the impact of modified sleeve gastrectomy reversal surgery to those with restoration of complete stomach and found no significant differences in weight regain or in postprandial glucose or hormone levels. Conclusions: Reversal of RYGB is an effective treatment option for severe postprandial hypoglycemia. The pathophysiology of this disorder is primarily due to RYGB anatomy resulting in altered glucose, gut, and pancreatic hormone levels and decreased insulin clearance, rather than inherent β-cell hyperplasia or hyperfunction. Keywords: Hypoglycemia, Insulin, Glucagon-like peptide 1, Roux en Y gastric bypass, Gastric bypass

  2. Translesion Synthesis of the N2-2′-Deoxyguanosine Adduct of the Dietary Mutagen IQ in Human Cells: Error-Free Replication by DNA Polymerase κ and Mutagenic Bypass by DNA Polymerases η, ζ, and Rev1

    Science.gov (United States)

    2016-01-01

    Translesion synthesis (TLS) of the N2-2′-deoxyguanosine (dG-N2-IQ) adduct of the carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was investigated in human embryonic kidney 293T cells by replicating plasmid constructs in which the adduct was individually placed at each guanine (G1, G2, or G3) of the NarI sequence (5′-CG1G2CG3CC-3′). TLS efficiency was 38%, 29%, and 25% for the dG-N2-IQ located at G1, G2, and G3, respectively, which suggests that dG-N2-IQ is bypassed more efficiently by one or more DNA polymerases at G1 than at either G2 or G3. TLS efficiency was decreased 8–35% in cells with knockdown of pol η, pol κ, pol ι, pol ζ, or Rev1. Up to 75% reduction in TLS occurred when pol η, pol ζ, and Rev1 were simultaneously knocked down, suggesting that these three polymerases play important roles in dG-N2-IQ bypass. Mutation frequencies (MFs) of dG-N2-IQ at G1, G2, and G3 were 23%, 17%, and 11%, respectively, exhibiting a completely reverse trend of the previously reported MF of the C8-dG adduct of IQ (dG-C8-IQ), which is most mutagenic at G3 ((2015) Nucleic Acids Res.43, 8340−835126220181). The major type of mutation induced by dG-N2-IQ was targeted G → T, as was reported for dG-C8-IQ. In each site, knockdown of pol κ resulted in an increase in MF, whereas MF was reduced when pol η, pol ι, pol ζ, or Rev1 was knocked down. The reduction in MF was most pronounced when pol η, pol ζ, and Rev1 were simultaneously knocked down and especially when the adduct was located at G3, where MF was reduced by 90%. We conclude that pol κ predominantly performs error-free TLS of the dG-N2-IQ adduct, whereas pols η, pol ζ, and Rev1 cooperatively carry out the error-prone TLS. However, in vitro experiments using yeast pol ζ and κ showed that the former was inefficient in full-length primer extension on dG-N2-IQ templates, whereas the latter was efficient in both error-free and error-prone extensions. We believe that the observed differences between

  3. Five Vessel Coronary Arter Bypass Graft Surgery in a Case with Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Sureyya Talay

    2014-08-01

    Full Text Available We report a case of a rare and sypmtomatic familyal hypercholesterolemia case with an end-point of coronary artery bypass surgery at the age of 16. Patient was evaluated at the emergency department with chest pain and discomfort. Physical examination were within normal limits. The electrocardiogram showed a normal sinus rhythm for 108/ min. Arterial blood pressure was 90/60 mmHg. Lungs and heart were clear to auscultation. Patient was under treatment with a prior diagnosis of familial hypercholesterolemia (FH for one year by daily 40 mgs rosuvastatine. A coronary artery angiography was performed for chest pain. Multivessel coronary artery disease was diagnosed with a total occlusion of left anterior descending artery. Transthoracic echocardiography presented a left ventricular (LV ejection fraction 50%, LV diameters 44/26 mm, aneurysm formation at interatrial septum and mild dyskinesia of anterior wall. Thus, a five vessel emergent coronary artery graft bypass surgery was performed at this early age. FH is with a severe elevation in total cholesterol (TC and low density lipoprotein cholesterol (LDL in an autosomal dominant characteristic disorder that approximately occurs in 1 per 500 persons by its heterozygous form. FH is most certainly associated with premature coronary artery disease (CAD with catasthrophic early age results. [Cukurova Med J 2014; 39(4.000: 872-875

  4. Higher cytoplasmic and nuclear poly(ADP-ribose) polymerase expression in familial than in sporadic breast cancer

    NARCIS (Netherlands)

    Klauke, M.L.; Hoogerbrugge-van der Linden, N.; Budczies, J.; Bult, P.; Prinzler, J.; Radke, C.; van Krieken, J.H.; Dietel, M.; Denkert, C.; Muller, B.M.

    2012-01-01

    Poly(ADP-ribose) polymerase 1 (PARP) is a key element of the single-base excision pathway for repair of DNA single-strand breaks. To compare the cytoplasmic and nuclear poly(ADP-ribose) expression between familial (BRCA1, BRCA2, or non BRCA1/2) and sporadic breast cancer, we investigated 39 sporadic

  5. Current evidence for a role of GLP-1 in Roux-en-Y gastric bypass-induced remission of type 2 diabetes

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Vilsbøll, T; Knop, F K

    2012-01-01

    Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have proven efficient as means of decreasing excess body weight. Furthermore, some studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM) undergoing RYGB experience complete remission of their T2DM......-induced remission of T2DM are lacking. This article critically evaluates the current evidence for a role of GLP-1 in RYGB-induced remission of T2DM.......Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have proven efficient as means of decreasing excess body weight. Furthermore, some studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM) undergoing RYGB experience complete remission of their T2DM...... antidiabetic effects of GLP-1 are thought to be key mediators in RYGB-induced remission of T2DM. However, the published studies on the impact of RYGB on GLP-1 secretion are few, small and often not controlled properly. Furthermore, mechanistic studies delineating the role of endogenous GLP-1 secretion in RYGB...

  6. 8. Mujer joven con enfermedad de takayasu grave sintomática: bypass aortobicarotídeo en «y» de gore-tex

    Directory of Open Access Journals (Sweden)

    E. Rodríguez Caulo

    2010-01-01

    – La reconstrucción quirúrgica derivativa mediante bypass aortobicarotídeo se ha mostrado eficaz y segura hasta la fecha, cediendo la sintomatología de la paciente, por lo que podría utilizarse en casos similares de estenosis sintomáticas.

  7. Evolving a polymerase for hydrophobic base analogues.

    Science.gov (United States)

    Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

    2009-10-21

    Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity.

  8. The influence of nutrients, biliary-pancreatic secretions, and systemic trophic hormones on intestinal adaptation in a Roux-en-Y bypass model

    DEFF Research Database (Denmark)

    Taqi, Esmaeel; Wallace, Laurie E; de Heuvel, Elaine

    2010-01-01

    The signals that govern the upregulation of nutrient absorption (adaptation) after intestinal resection are not well understood. A Gastric Roux-en-Y bypass (GRYB) model was used to isolate the relative contributions of direct mucosal stimulation by nutrients, biliary-pancreatic secretions......, and systemic enteric hormones on intestinal adaptation in short bowel syndrome....

  9. Experimental bypass of Lake Reality, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

    International Nuclear Information System (INIS)

    1997-10-01

    Studies conducted by the Y-12 Reduction of Mercury in Plant Effluent (RMPE) Program and Y-12 Biological Monitoring and Abatement Program (BMAP) in 1995 and 1996 (Y/ER-251, Y/ER-277) identified concerns regarding Lake Reality's effect on the transport and transformation of mercury in East Fork Poplar Creek (EFPC). The pond appeared to have two potentially adverse effects on mercury transport. First, it acted as a biochemical reactor, converting inorganic mercury in inflowing water to methylmercury, a more toxic substance with extremely high bioaccumulation potential in aquatic environments. Second, the pond appeared to trap mercury associated with suspended particulates during periods of stormflow, and slowly released that mercury via the export of resuspended particles during periods of baseflow. The net effect was to raise the day-to-day exposure of aquatic life to mercury in the stream downstream from the pond, and add to the calculated mercury loading of the stream under baseflow conditions. Scientific investigations thus indicated that diversion of the flow of EFPC around Lake Reality had the potential to reduce time-averaged concentrations of methylmercury and total mercury in the creek below its discharge, but that such diversion might also interfere with possible beneficial effects of the retention pond. Therefore, an experimental bypass of the pond was undertaken in late 1996 to evaluate the consequences of such an action before embarking on a more permanent change

  10. Down-Regulation of Renal Gluconeogenesis in Type II Diabetic Rats Following Roux-en-Y Gastric Bypass Surgery: A Potential Mechanism in Hypoglycemic Effect

    Science.gov (United States)

    Wen, Yi; Lin, Ning; Yan, Hong-Tao; Luo, Hao; Chen, Guang-Yu; Cui, Jian-Feng; Shi, Li; Chen, Tao; Wang, Tao; Tang, Li-Jun

    2015-01-01

    Objective This study was initiated to evaluate the effects of Roux-en-Y gastric bypass surgery on renal gluconeogenesis in type 2 diabetic rats and its relationship with hormonal parameters. Methods Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ; 35 mg/kg) combined with a high-fat diet. They were then randomly divided into three groups: diabetes model group (DM group, n = 8), sham Roux-en-Y gastric bypass group (SRYGB group, n = 8), and Roux-en-Y gastric bypass group (RYGB group, n = 14). Another 8 normal rats comprised the normal control group (NC group, n = 8). Body weight, glucose, serum lipid, insulin, glucagon-like peptide-1 (GLP-1), leptin, and adiponectin were measured pre- and postoperatively. Glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), insulin receptor-α (IR-α), insulin receptor-β (IR-β), and glycogen synthase kinase 3 beta (Gsk3b) were measured in renal cortex by using RT-PCR and Western immune-blot analyses on the 4th week after operation. Results Following RYGB surgery, surgery-treated rats showed significantly improved oral glucose tolerance, dyslipidemia and insulin resistance as well as increased post-gavage insulin levels and serum circulating levels of GLP-1 and adiponectin. RT-PCR and Western immune-blot analyses showed PEPCK and G6Pase protein and mRNA to be significantly decreased in the renal cortex in the RYGB group (p insulin signal pathway in the renal cortex and increased circulating adiponectin concentrations may contribute to the decline of renal gluconeogenesis following RYGB surgery. PMID:25832593

  11. The Effect of Preoperative Type 2 Diabetes and Physical Fitness on Mental Health and Health-Related Quality of Life after Roux-en-Y Gastric Bypass

    DEFF Research Database (Denmark)

    Wimmelmann, Cathrine L.; Lund, Michael T.; Hansen, Merethe

    2016-01-01

    Objective: To investigate the predictive value of type 2 diabetes and lack of physical activity for mental health and health-related quality of life after Roux-en-Y gastric bypass. Method: Forty severely obese patients undergoing Roux-en-Y gastric bypass were included in the GASMITO study...... to physical fitness, mental distress, health-related quality of life, and weight-related body image (). The interaction between follow-up time and type 2 diabetes at baseline significantly predicted six of the thirteen psychological subscales () and, across the follow-ups, physical fitness level made modest...... contributions to variations in mental symptoms and HRQOL but not weight-related body image. Conclusion: The results suggest that baseline difference in mental symptoms and physical HRQOL between diabetic and nondiabetic patients declines across follow-ups and resolves around the time of surgery....

  12. Laparoscopic Roux-en-Y gastric bypass in super obese Göttingen minipigs

    DEFF Research Database (Denmark)

    Birck, Malene Muusfeldt; Vegge, Andreas; Støckel, Mikael

    2013-01-01

    Background: The specific mechanisms behind weight loss and comorbidity improvements in obese patients after Roux-en-Y gastric bypass (RYGBP) are still poorly understood. The aim of this study was to establish and evaluate the feasibility of a long-term survival RYGBP model in super obese Göttingen...... minipigs in order to improve the translational potential relative to current animal models. Methods: Eleven Göttingen minipigs with diet-induced obesity underwent laparoscopic RYGBP and were followed up to 9 months after surgery. Intra-and post-operative complications, body weight (BW), food intake......, biliary and common limb between minipigs. Conclusion: The use of obese Göttingen minipigs as a translational RYGBP model is feasible and has potential for the study of RYGBP-related changes in gut function, type-2 diabetes and appetite regulation. Still, the surgical procedure is technically highly...

  13. Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

    OpenAIRE

    Wu, Q; Li, JV; Seyfried, F; le Roux, CW; Ashrafian, H; Athanasiou, T; Fenske, W; Darzi, A; Nicholson, JK; Holmes, E; Gooderham, NJ

    2015-01-01

    Background/Objectives: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. Subjects/Methods: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. Results: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly ...

  14. Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Bojsen-Møller, Kirstine N; Jørgensen, Nils Bruun

    2013-01-01

    Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones...

  15. Preoperative β-cell function in patients with type 2 diabetes is important for the outcome of Roux-en-Y gastric bypass surgery

    DEFF Research Database (Denmark)

    Lund, Michael Taulo; Hansen, Merethe; Skaaby, Stinna

    2015-01-01

    INTRODUCTION: A major part of the patients with type 2 diabetes (T2DM) show remission after Roux-en-Y gastric bypass (RYGB). This is the result of increased postoperative insulin sensitivity and β-cell secretion. The aim of the present study was to elucidate the importance of the preoperative β-c...

  16. Prediction of Active Site and Distal Residues in E. coli DNA Polymerase III alpha Polymerase Activity.

    Science.gov (United States)

    Parasuram, Ramya; Coulther, Timothy A; Hollander, Judith M; Keston-Smith, Elise; Ondrechen, Mary Jo; Beuning, Penny J

    2018-02-20

    The process of DNA replication is carried out with high efficiency and accuracy by DNA polymerases. The replicative polymerase in E. coli is DNA Pol III, which is a complex of 10 different subunits that coordinates simultaneous replication on the leading and lagging strands. The 1160-residue Pol III alpha subunit is responsible for the polymerase activity and copies DNA accurately, making one error per 10 5 nucleotide incorporations. The goal of this research is to determine the residues that contribute to the activity of the polymerase subunit. Homology modeling and the computational methods of THEMATICS and POOL were used to predict functionally important amino acid residues through their computed chemical properties. Site-directed mutagenesis and biochemical assays were used to validate these predictions. Primer extension, steady-state single-nucleotide incorporation kinetics, and thermal denaturation assays were performed to understand the contribution of these residues to the function of the polymerase. This work shows that the top 15 residues predicted by POOL, a set that includes the three previously known catalytic aspartate residues, seven remote residues, plus five previously unexplored first-layer residues, are important for function. Six previously unidentified residues, R362, D405, K553, Y686, E688, and H760, are each essential to Pol III activity; three additional residues, Y340, R390, and K758, play important roles in activity.

  17. Biodistribution of technetium-{sup 99m} pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rego, Amalia Cinthia Meneses do; Jacome, Daniel Torres; Ramalho, Rachel de Alcantara Oliveira [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil); Araujo-Filho, Irami; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha, E-mail: aldo@ufrnet.b [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. of Surgery

    2010-01-15

    Purpose: The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na{sup 99m}Tc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na{sup 99m}Tc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gamma counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. Results: Significant reduction in mean %ATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in %ATI/g was observed between the two groups. Conclusion: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na{sup 99m}Tc{sup -}. (author)

  18. Heart bypass surgery

    Science.gov (United States)

    Off-pump coronary artery bypass; OPCAB; Beating heart surgery; Bypass surgery - heart; CABG; Coronary artery bypass graft; Coronary artery bypass surgery; Coronary bypass surgery; Coronary artery disease - CABG; CAD - CABG; Angina - ...

  19. Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Dirksen, C; Jørgensen, N B; Bojsen-Møller, K N

    2013-01-01

    Objective:To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB).Design:Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL 12 months after RYGB and a lean control group matched for...

  20. DNA polymerase catalysis in the absence of Watson-Crick hydrogen bonds

    Science.gov (United States)

    Potapova, Olga; Chan, Chikio; DeLucia, Angela M.; Helquist, Sandra A.; Kool, Eric T.; Grindley, Nigel D. F.; Joyce, Catherine M.

    2008-01-01

    We report the first pre-steady-state kinetic studies of DNA replication in the absence of hydrogen bonds. We have used nonpolar nucleotide analogues that mimic the shape of a Watson-Crick base pair in order to investigate the kinetic consequences of a lack of hydrogen bonds in the polymerase reaction catalyzed by the Klenow fragment of DNA Polymerase I from Escherichia coli. With a thymine isostere lacking hydrogen bonding ability in the nascent pair, the efficiency (kpol/Kd) of the polymerase reaction is decreased by 30-fold, affecting ground state (Kd) and transition state (kpol) approximately equally. When both thymine and adenine analogues in the nascent pair lack hydrogen bonding ability, the efficiency of the polymerase reaction is decreased by about 1000-fold, with most the decrease attributable to the transition state. Reactions using nonpolar analogues at the primer terminal base pair demonstrated the requirement for a hydrogen bond between the polymerase and the minor groove of the primer-terminal base. The R668A mutation of Klenow fragment abolished this requirement, identifying R668 as the probable hydrogen bond donor. Detailed examination of the kinetic data suggested that Klenow fragment has an extremely low tolerance of even minor deviations of the analogue base pairs from ideal Watson-Crick geometry. Consistent with this idea, some analogue pairings were better tolerated by Klenow fragment mutants having more spacious active sites. By contrast, the Y-family polymerase Dbh was much less sensitive to changes in base pair dimensions, and more dependent on hydrogen bonding between base-paired partners. PMID:16411765

  1. DNA polymerase preference determines PCR priming efficiency.

    Science.gov (United States)

    Pan, Wenjing; Byrne-Steele, Miranda; Wang, Chunlin; Lu, Stanley; Clemmons, Scott; Zahorchak, Robert J; Han, Jian

    2014-01-30

    Polymerase chain reaction (PCR) is one of the most important developments in modern biotechnology. However, PCR is known to introduce biases, especially during multiplex reactions. Recent studies have implicated the DNA polymerase as the primary source of bias, particularly initiation of polymerization on the template strand. In our study, amplification from a synthetic library containing a 12 nucleotide random portion was used to provide an in-depth characterization of DNA polymerase priming bias. The synthetic library was amplified with three commercially available DNA polymerases using an anchored primer with a random 3' hexamer end. After normalization, the next generation sequencing (NGS) results of the amplified libraries were directly compared to the unamplified synthetic library. Here, high throughput sequencing was used to systematically demonstrate and characterize DNA polymerase priming bias. We demonstrate that certain sequence motifs are preferred over others as primers where the six nucleotide sequences at the 3' end of the primer, as well as the sequences four base pairs downstream of the priming site, may influence priming efficiencies. DNA polymerases in the same family from two different commercial vendors prefer similar motifs, while another commercially available enzyme from a different DNA polymerase family prefers different motifs. Furthermore, the preferred priming motifs are GC-rich. The DNA polymerase preference for certain sequence motifs was verified by amplification from single-primer templates. We incorporated the observed DNA polymerase preference into a primer-design program that guides the placement of the primer to an optimal location on the template. DNA polymerase priming bias was characterized using a synthetic library amplification system and NGS. The characterization of DNA polymerase priming bias was then utilized to guide the primer-design process and demonstrate varying amplification efficiencies among three commercially

  2. [Laparoscopic Roux-en-Y gastric bypass surgery for morbid obesity. Experience at the Nacional de Ciencias Médicas y Nutrición Salvador Zubirán].

    Science.gov (United States)

    Romero-Lbargüengoitia, María Elena; Lerman-Garber, Israel; Herrera-Hernández, Miguel Francisco; Pablo-Pantoja, Juan; Sierra-Salazar, Mauricio; López-Rosales, Federico; Zamora-Barrón, Margarita; Vargas-Martínez, Angeles; García-García, Eduardo

    2009-01-01

    Morbid obesity is a serious health problem associated to a significant reduction in life expectancy. To evaluate the anthropometric and metabolic changes observed in obese patients, 3, 6 and 12 months after laparoscopic Roux-en-Y gastric bypass surgery and the complications associated with the procedure. Retrospective study that included 128 consecutive obese patients submitted for bariatric surgery at the INCMNSZ (2004-2006). Their mean age was 38 +/- 10 years, 83% were women with a BMI of 48 +/- 6 Kg/m2. 65% were hypertensives, 55% had hypertriglyceridemia and 34% diabetes. A year after surgery all patients had at least reduced 20% their body weight and the percentage of excess body weight loss was 73%. The prevalence of hypertension, hypertrigliceridemia and diabetes was reduced to 24%, 17% and 12%, respectively (p < 0.001). Four patients died (3%), all of them had a leak of the anastomosis and intra-abdominal abscess. One died because pulmonary embolism, another with a myocardial infarction (after surgical reinterventions) and the other two with sepsis. Laparoscopic Roux-en-Y gastric bypass surgery in morbid obese patients favors significant reductions in body weight and associated co morbidities. This surgery is not free of complications and mortality, reason why it must be done only by surgical and interdisciplinary groups with experience in these procedures.

  3. Internal hernia in late pregnancy after laparoscopic Roux-en-Y gastric bypass.

    Science.gov (United States)

    Gruetter, Florian; Kraljević, Marko; Nebiker, Christian A; Delko, Tarik

    2014-12-23

    A 27-year-old patient in late pregnancy presented to the department of obstetrics with crampy abdominal pain located in the right flank, 3 years after a laparoscopic Roux-en-Y gastric bypass. Clinical investigation showed tenderness on palpation in the upper abdomen without signs of peritonitis. The cardiotocogram and blood tests were normal. The ultrasound showed a hydronephrosis on the right side, and a pigtail catheter was inserted. The abdominal symptoms did not abate and the abdominal surgeon was consulted 36 hours after admission. Diagnostic laparoscopy was performed promptly because of high suspicion of internal hernia (IH). Laparoscopy showed IH at the mesojejunal intermesenteric defect with a herniated common channel and volvulus of the anastomosis. Conversion to open reduction and complete closure with non-absorbable interrupted sutures was performed. Small bowel resection was avoided. The patient was discharged 10 days after the operation and a healthy boy was born 4 weeks later. 2014 BMJ Publishing Group Ltd.

  4. Long-term hypovitaminosis D and secondary hyperparathyroidism outcomes of the Roux-en-Y gastric bypass: a systematic review.

    Science.gov (United States)

    Switzer, N J; Marcil, G; Prasad, S; Debru, E; Church, N; Mitchell, P; Billington, E O; Gill, R S

    2017-05-01

    Pre-operative Vitamin D deficiency is markedly prevalent in prospective bariatric surgery patients. While bariatric surgery leads to significant weight loss, it can exacerbate or prolong Vitamin D deficiency. We systematically reviewed the literature to assess whether secondary hyperparathyroidism is maintained in the medium to long term in patients following the Roux-en-Y gastric bypass. A comprehensive literature search was conducted through Medline, Embase, Scopus, Web of Science, Dare, Cochrane library and HTA database. The search terms used were bariatric surgery, gastric bypass and hyperparathyroidism. Fourteen studies were included (n = 2688 subjects). Parathyroid hormone levels rose gradually from a mean pre-operative level of 5.69 ± 1.2 pmol/L to 6.36 ± 0.77 pmol/L, 7.59 ± 0.73 pmol/L and 8.29 ± 1.41 pmol/L at 2 years, between 2 and 5 years, and beyond 5 years, respectively. Vitamin D levels slowly fell to a mean of 20.50 ± 4.37 ng/mL and 20.76 ± 3.80 ng/mL between follow-up intervals 2-5 years and beyond 5, respectively. It appears that hyperparathyroidism persists at 5-year follow-up after gastric bypass, despite most patients being supplemented with calcium and Vitamin D. © 2017 World Obesity Federation.

  5. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding

    DEFF Research Database (Denmark)

    Korner, Judith; Bessler, Marc; Inabnet, William

    2007-01-01

    BACKGROUND: The aim of this study was to measure the circulating levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon in patients who had undergone adjustable gastric banding (BND) or Roux-en-Y gastric bypass (RYGB) to understand the differences...

  6. Duodenal-jejunal bypass liner implantation provokes rapid weight loss and improved glycemic control, accompanied by elevated fasting ghrelin levels

    NARCIS (Netherlands)

    Koehestanie, P.; Dogan, K.; Berends, F.; Janssen, I.; Wahab, P.J.; Groenen, M.; Müller, M.R.; Wit, de N.J.W.

    2014-01-01

    Background and study aims: Endoscopic implantation of a duodenal-jejunal bypass liner (DJBL) is a novel bariatric technique to induce weight loss and remission of type 2 diabetes mellitus. Placement of the DJBL mimics the bypass component of the Roux-en-Y gastric bypass (RYGB) procedure. In this

  7. An unusual cause of chronic abdominal pain after laparoscopic Roux en Y gastric bypass: Case report of a penetrating fish bone causing adhesions at the biliary-digestive junction resulting in partial obstruction and chronic symptoms

    Directory of Open Access Journals (Sweden)

    Vincent Ochieng

    2016-01-01

    Conclusion: This case highlights the possibility of a missed fish bone perforation causing chronic postprandial abdominal pain and discomfort in a patient with a Roux-en-Y gastric bypass anatomy. Foreign body perforation is a rare cause of abdominal pain after gastric bypass that should be considered when evaluating chronic abdominal pain symptoms after LRYGP.

  8. Role of damage-specific DNA polymerases in M13 phage mutagenesis induced by a major lipid peroxidation product trans-4-hydroxy-2-nonenal

    Energy Technology Data Exchange (ETDEWEB)

    Janowska, Beata [Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw (Poland); Kurpios-Piec, Dagmara [Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097 Warsaw (Poland); Prorok, Paulina [Institute of Genetics and Biotechnology, Warsaw University, Pawinskiego 5a, 02-106 Warsaw (Poland); Szparecki, Grzegorz [Medical University of Warsaw, Zwirki i Wigury 61, 02-097 Warsaw (Poland); Komisarski, Marek [Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw (Poland); Kowalczyk, Pawel [Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Pawinskiego 5a, 02-106 Warsaw (Poland); Janion, Celina [Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw (Poland); Tudek, Barbara, E-mail: tudek@ibb.waw.pl [Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw (Poland); Institute of Genetics and Biotechnology, Warsaw University, Pawinskiego 5a, 02-106 Warsaw (Poland)

    2012-01-03

    One of the major lipid peroxidation products trans-4-hydroxy-2-nonenal (HNE), forms cyclic propano- or ethenoadducts bearing six- or seven-carbon atom side chains to G > C Much-Greater-Than A > T. To specify the role of SOS DNA polymerases in HNE-induced mutations, we tested survival and mutation spectra in the lacZ{alpha} gene of M13mp18 phage, whose DNA was treated in vitro with HNE, and which was grown in uvrA{sup -}Escherichia coli strains, carrying one, two or all three SOS DNA polymerases. When Pol IV was the only DNA SOS polymerase in the bacterial host, survival of HNE-treated M13 DNA was similar to, but mutation frequency was lower than in the strain containing all SOS DNA polymerases. When only Pol II or Pol V were present in host bacteria, phage survival decreased dramatically. Simultaneously, mutation frequency was substantially increased, but exclusively in the strain carrying only Pol V, suggesting that induction of mutations by HNE is mainly dependent on Pol V. To determine the role of Pol II and Pol IV in HNE induced mutagenesis, Pol II or Pol IV were expressed together with Pol V. This resulted in decrease of mutation frequency, suggesting that both enzymes can compete with Pol V, and bypass HNE-DNA adducts in an error-free manner. However, HNE-DNA adducts were easily bypassed by Pol IV and only infrequently by Pol II. Mutation spectrum established for strains expressing only Pol V, showed that in uvrA{sup -} bacteria the frequency of base substitutions and recombination increased in relation to NER proficient strains, particularly mutations at adenine sites. Among base substitutions A:T {yields} C:G, A:T {yields} G:C, G:C {yields} A:T and G:C {yields} T:A prevailed. The results suggest that Pol V can infrequently bypass HNE-DNA adducts inducing mutations at G, C and A sites, while bypass by Pol IV and Pol II is error-free, but for Pol II infrequent.

  9. Dynamics of translocation and substrate binding in individual complexes formed with active site mutants of {phi}29 DNA polymerase.

    Science.gov (United States)

    Dahl, Joseph M; Wang, Hongyun; Lázaro, José M; Salas, Margarita; Lieberman, Kate R

    2014-03-07

    The Φ29 DNA polymerase (DNAP) is a processive B-family replicative DNAP. Fluctuations between the pre-translocation and post-translocation states can be quantified from ionic current traces, when individual Φ29 DNAP-DNA complexes are held atop a nanopore in an electric field. Based upon crystal structures of the Φ29 DNAP-DNA binary complex and the Φ29 DNAP-DNA-dNTP ternary complex, residues Tyr-226 and Tyr-390 in the polymerase active site were implicated in the structural basis of translocation. Here, we have examined the dynamics of translocation and substrate binding in complexes formed with the Y226F and Y390F mutants. The Y226F mutation diminished the forward and reverse rates of translocation, increased the affinity for dNTP in the post-translocation state by decreasing the dNTP dissociation rate, and increased the affinity for pyrophosphate in the pre-translocation state. The Y390F mutation significantly decreased the affinity for dNTP in the post-translocation state by decreasing the association rate ∼2-fold and increasing the dissociation rate ∼10-fold, implicating this as a mechanism by which this mutation impedes DNA synthesis. The Y390F dissociation rate increase is suppressed when complexes are examined in the presence of Mn(2+) rather than Mg(2+). The same effects of the Y226F or Y390F mutations were observed in the background of the D12A/D66A mutations, located in the exonuclease active site, ∼30 Å from the polymerase active site. Although translocation rates were unaffected in the D12A/D66A mutant, these exonuclease site mutations caused a decrease in the dNTP dissociation rate, suggesting that they perturb Φ29 DNAP interdomain architecture.

  10. Bone structural changes after gastric bypass surgery evaluated by HR-pQCT

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram V; Støving, René Klinkby; Frederiksen, Katrine Hartmund

    2017-01-01

    OBJECTIVE, DESIGN AND METHODS: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiom......OBJECTIVE, DESIGN AND METHODS: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X...... of increased risk of developing osteoporosis and fragility fractures remain an important concern....

  11. Nucleotide-mimetic synthetic ligands for DNA-recognizing enzymes One-step purification of Pfu DNA polymerase.

    Science.gov (United States)

    Melissis, S; Labrou, N E; Clonis, Y D

    2006-07-28

    The commercial availability of DNA polymerases has revolutionized molecular biotechnology and certain sectors of the bio-industry. Therefore, the development of affinity adsorbents for purification of DNA polymerases is of academic interest and practical importance. In the present study we describe the design, synthesis and evaluation of a combinatorial library of novel affinity ligands for the purification of DNA polymerases (Pols). Pyrococcus furiosus DNA polymerase (Pfu Pol) was employed as a proof-of-principle example. Affinity ligand design was based on mimicking the natural interactions between deoxynucleoside-triphosphates (dNTPs) and the B-motif, a conserved structural moiety found in Pol-I and Pol-II family of enzymes. Solid-phase 'structure-guided' combinatorial chemistry was used to construct a library of 26 variants of the B-motif-binding 'lead' ligand X-Trz-Y (X is a purine derivative and Y is an aliphatic/aromatic sulphonate or phosphonate derivative) using 1,3,5-triazine (Trz) as the scaffold for assembly. The 'lead' ligand showed complementarity against a Lys and a Tyr residue of the polymerase B-motif. The ligand library was screened for its ability to bind and purify Pfu Pol from Escherichia coli extract. One immobilized ligand (oABSAd), bearing 9-aminoethyladenine (AEAd) and sulfanilic acid (oABS) linked on the triazine scaffold, displayed the highest purifying ability and binding capacity (0,55 mg Pfu Pol/g wet gel). Adsorption equilibrium studies with this affinity ligand and Pfu Pol determined a dissociation constant (K(D)) of 83 nM for the respective complex. The oABSAd affinity adsorbent was exploited in the development of a facile Pfu Pol purification protocol, affording homogeneous enzyme (>99% purity) in a single chromatography step. Quality control tests showed that Pfu Pol purified on the B-motif-complementing ligand is free of nucleic acids and contaminating nuclease activities, therefore, suitable for experimental use.

  12. Compression of the superior mesenteric vein - a sign of acute internal herniation in patients with antecolic laparoscopic Roux-en-Y gastric bypass

    International Nuclear Information System (INIS)

    Maier, Jens; Herrasti Gallego, Amaya; Floyd, Andrea K.

    2017-01-01

    To investigate whether compression of the superior mesenteric vein (SMV) on computed tomography (CT) can serve as a valid sign of internal herniation (IH) in patients with antecolic laparoscopic Roux-en-Y gastric bypass (LRYGBP). With institutional review board approval, we performed a retrospective analysis of 41 patients with antecolic LRYGBP referred for acute CT of the abdomen with suspicion of IH or another cause of acute abdomen. CT scans were randomly reviewed for signs of IH by two radiologists in a blinded manner, and the findings were correlated with the results of the patients' bariatric workup. Sensitivity, specificity, and inter-observer agreement were calculated for each sign. Five patients were classified as having intermittent IH and were excluded. Eighteen patients were found to have IH at laparoscopy and served as the study group; 18 patients served as the control group. SMV compression had the best sensitivity (67 % for both reviewers) and inter-observer agreement (kappa = 0.82) of all investigated signs. The swirl sign showed a lower sensitivity (39 and 50 % respectively) and kappa (0.37). SMV compression is a reliable sign of IH in patients with antecolic LRYGBP. circle CT can help detect internal herniation after laparoscopic Roux-en-Y gastric bypass. (orig.)

  13. Compression of the superior mesenteric vein - a sign of acute internal herniation in patients with antecolic laparoscopic Roux-en-Y gastric bypass

    Energy Technology Data Exchange (ETDEWEB)

    Maier, Jens; Herrasti Gallego, Amaya [Koege Sygehus, Department of Radiology, Koege (Denmark); Floyd, Andrea K. [Holbaek Sygehus, Department of Abdominal Surgery, Holbaek (Denmark)

    2017-04-15

    To investigate whether compression of the superior mesenteric vein (SMV) on computed tomography (CT) can serve as a valid sign of internal herniation (IH) in patients with antecolic laparoscopic Roux-en-Y gastric bypass (LRYGBP). With institutional review board approval, we performed a retrospective analysis of 41 patients with antecolic LRYGBP referred for acute CT of the abdomen with suspicion of IH or another cause of acute abdomen. CT scans were randomly reviewed for signs of IH by two radiologists in a blinded manner, and the findings were correlated with the results of the patients' bariatric workup. Sensitivity, specificity, and inter-observer agreement were calculated for each sign. Five patients were classified as having intermittent IH and were excluded. Eighteen patients were found to have IH at laparoscopy and served as the study group; 18 patients served as the control group. SMV compression had the best sensitivity (67 % for both reviewers) and inter-observer agreement (kappa = 0.82) of all investigated signs. The swirl sign showed a lower sensitivity (39 and 50 % respectively) and kappa (0.37). SMV compression is a reliable sign of IH in patients with antecolic LRYGBP. circle CT can help detect internal herniation after laparoscopic Roux-en-Y gastric bypass. (orig.)

  14. The Roles of Family B and D DNA Polymerases in Thermococcus Species 9°N Okazaki Fragment Maturation*

    Science.gov (United States)

    Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F.

    2015-01-01

    During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. PMID:25814667

  15. Structures of an Apo and a Binary Complex of an Evolved Archeal B Family DNA Polymerase Capable of Synthesising Highly Cy-Dye Labelled DNA

    Science.gov (United States)

    Wynne, Samantha A.; Pinheiro, Vitor B.; Holliger, Philipp; Leslie, Andrew G. W.

    2013-01-01

    Thermophilic DNA polymerases of the polB family are of great importance in biotechnological applications including high-fidelity PCR. Of particular interest is the relative promiscuity of engineered versions of the exo- form of polymerases from the Thermo- and Pyrococcales families towards non-canonical substrates, which enables key advances in Next-generation sequencing. Despite this there is a paucity of structural information to guide further engineering of this group of polymerases. Here we report two structures, of the apo form and of a binary complex of a previously described variant (E10) of Pyrococcus furiosus (Pfu) polymerase with an ability to fully replace dCTP with Cyanine dye-labeled dCTP (Cy3-dCTP or Cy5-dCTP) in PCR and synthesise highly fluorescent “CyDNA” densely decorated with cyanine dye heterocycles. The apo form of Pfu-E10 closely matches reported apo form structures of wild-type Pfu. In contrast, the binary complex (in the replicative state with a duplex DNA oligonucleotide) reveals a closing movement of the thumb domain, increasing the contact surface with the nascent DNA duplex strand. Modelling based on the binary complex suggests how bulky fluorophores may be accommodated during processive synthesis and has aided the identification of residues important for the synthesis of unnatural nucleic acid polymers. PMID:23940661

  16. Primer-Independent DNA Synthesis by a Family B DNA Polymerase from Self-Replicating Mobile Genetic Elements

    Directory of Open Access Journals (Sweden)

    Modesto Redrejo-Rodríguez

    2017-11-01

    Full Text Available Family B DNA polymerases (PolBs play a central role during replication of viral and cellular chromosomes. Here, we report the discovery of a third major group of PolBs, which we denote primer-independent PolB (piPolB, that might be a link between the previously known protein-primed and RNA/DNA-primed PolBs. PiPolBs are encoded by highly diverse mobile genetic elements, pipolins, integrated in the genomes of diverse bacteria and also present as circular plasmids in mitochondria. Biochemical characterization showed that piPolB displays efficient DNA polymerization activity that can use undamaged and damaged templates and is endowed with proofreading and strand displacement capacities. Remarkably, the protein is also capable of template-dependent de novo DNA synthesis, i.e., DNA-priming activity, thereby breaking the long-standing dogma that replicative DNA polymerases require a pre-existing primer for DNA synthesis. We suggest that piPolBs are involved in self-replication of pipolins and may also contribute to bacterial DNA damage tolerance.

  17. DNA polymerase inhibitors and heat alter fixation of postirradiation sublethal damage in L5178Y-S cells

    International Nuclear Information System (INIS)

    Kapiszewska, M.; Szumiel, I.; Lange, C.S.

    1988-01-01

    We have used the inhibitor of DNA polymerase alpha, aphidicolin (apc) (0.5 μg/ml for 1 h), or that of DNA polymerase beta, dideoxythymidine triphosphate (ddTTP) (5 μg/ml), as well as heat (15 min at 43 deg C) to examine fixation of sublethal damage (SLD) induced by X-rays in L5178Y-S (LY-S) cells. This cell line has the unique property of responding to split X-ray doses at 37 deg C by decreased survival. This effect was partly abolished by heating the cells before irradiation with the second dose; the protection was most pronounced when the cells were heated 30-120 min. after the first dose of radiation. Since similar changes in postirradiation survival occurred when ddTTP was applied, we suggest that heat induces a loss of polymerase beta activity. Apc gave a smaller protective effect. We interpreted these results as suggesting that mismatching takes place during DNA semiconservative replication or repair; inhibition of replication results in survival increase, by preventing misrepair. A proper timing of treatment with the inhibitors or heat is essential to obtain the sparing effect, i.e. to prevent SLD fixation. 27 refs., 3 figs., 1 tab. (author)

  18. Bowel habits after gastric bypass versus the duodenal switch operation.

    Science.gov (United States)

    Wasserberg, Nir; Hamoui, Nahid; Petrone, Patrizio; Crookes, Peter F; Kaufman, Howard S

    2008-12-01

    One of the perceived disadvantages of the biliopancreatic diversion with duodenal switch operation is diarrhea. The aim of this study was to compare the bowel habits of patients after duodenal switch operation or Roux-en-Y gastric bypass. A prospective comparative case series design was used. Forty-six patients who underwent duodenal switch (n=28) or gastric bypass (n=18) were asked to complete a daily diary for 14 days after losing least 50% of their excess body weight. Data were collected on number of bowel episodes, incontinence, urgency, stool consistency, and awakening from sleep to defecate. Background variables were recorded from the medical files. The duodenal switch group was heavier (body mass index 53.5 vs 47.0 kg/m(2), p=0.03) and older (47.5 vs 41.0 years, p=NS) than the gastric bypass group. Median time to 50% excess body weight loss was 22 months in the duodenal switch group compared to 10.0 months in the gastric bypass group (p=0.001). Patients after duodenal switch surgery reported a median of 23.5 bowel episodes over the 14-day study period compared to 16.5 in the gastric bypass group (p=NS). There was no between-group differences in any of the other bowel parameters studied. Although duodenal switch is associated with more bowel episodes than gastric bypass, the difference is not statistically significant. Bowel habits are similar in patients who achieve 50% estimated body weight loss with duodenal switch surgery or gastric bypass.

  19. The roles of family B and D DNA polymerases in Thermococcus species 9°N Okazaki fragment maturation.

    Science.gov (United States)

    Greenough, Lucia; Kelman, Zvi; Gardner, Andrew F

    2015-05-15

    During replication, Okazaki fragment maturation is a fundamental process that joins discontinuously synthesized DNA fragments into a contiguous lagging strand. Efficient maturation prevents repeat sequence expansions, small duplications, and generation of double-stranded DNA breaks. To address the components required for the process in Thermococcus, Okazaki fragment maturation was reconstituted in vitro using purified proteins from Thermococcus species 9°N or cell extracts. A dual color fluorescence assay was developed to monitor reaction substrates, intermediates, and products. DNA polymerase D (polD) was proposed to function as the replicative polymerase in Thermococcus replicating both the leading and the lagging strands. It is shown here, however, that it stops before the previous Okazaki fragments, failing to rapidly process them. Instead, Family B DNA polymerase (polB) was observed to rapidly fill the gaps left by polD and displaces the downstream Okazaki fragment to create a flap structure. This flap structure was cleaved by flap endonuclease 1 (Fen1) and the resultant nick was ligated by DNA ligase to form a mature lagging strand. The similarities to both bacterial and eukaryotic systems and evolutionary implications of archaeal Okazaki fragment maturation are discussed. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Análisis de predictores independientes del flujo del bypass coronario en pacientes intervenidos de revascularización miocárdica aislada

    Directory of Open Access Journals (Sweden)

    Stefano Urso

    2017-11-01

    Full Text Available Resumen: Introducción y objetivo: El medidor de flujo permite conocer 2 parámetros: el flujo medio del bypass coronario y el índice de pulsatilidad. Estos 2 parámetros, cuando están alterados, pueden indicar una estenosis de la anastomosis del bypass distal. Factores distintos de la suficiencia de la anastomosis, como la calidad de lecho coronario, pueden condicionar el flujo del bypass y dificultar su interpretación. El objetivo de nuestro estudio es analizar los predictores independientes del flujo de los bypass aorto-coronarios. Métodos: Recogimos de forma retrospectiva una serie consecutiva de 90 pacientes intervenidos de revascularización miocárdica aislada por el mismo cirujano desde enero del 2014 hasta agosto del 2016. A partir de esta serie, elaboramos una base de datos electrónica donde cada registro correspondía a un injerto. Construimos, por lo tanto, una base de datos de 185 injertos. De estos, 8 injertos no fueron analizados por no haberse medido el flujo correctamente. Por los tanto, los valores de flujo y de índice de pulsatilidad de 177 injertos fueron utilizados para nuestro análisis estadístico. Resultados: El análisis de regresión lineal múltiple detectó 2 predictores independientes del flujo de los bypasses: injerto de vena safena secuencial (valor r parcial: 0,32; p < 0,0001 e injerto arterial (valor r parcial: –0,23; p 0,0021. Por lo tanto, nuestro modelo objetivó una correlación directa entre la utilización de injerto de safena con técnica secuencial y flujo del bypass, y una correlación inversa entre la utilización de injerto arterial y flujo del bypass. Conclusiones: Los predictores del flujo de los bypasses aorto-coronarios son la utilización de un injerto arterial (coeficiente negativo y la utilización de un injerto venoso secuencial (coeficiente positivo. Nuestro modelo estadístico no ha identificado como predictor el SYNTAX score

  1. A nucleotide-analogue-induced gain of function corrects the error-prone nature of human DNA polymerase iota.

    Science.gov (United States)

    Ketkar, Amit; Zafar, Maroof K; Banerjee, Surajit; Marquez, Victor E; Egli, Martin; Eoff, Robert L

    2012-06-27

    Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol ι) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol ι through use of the fixed-conformation nucleotide North-methanocarba-2'-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol ι in complex with DNA containing a template 2'-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol ι inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle, which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol ι. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base-stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol ι by preventing the Hoogsteen base-pairing mode normally observed for hpol ι-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase.

  2. A nucleotide analogue induced gain of function corrects the error-prone nature of human DNA polymerase iota

    Science.gov (United States)

    Ketkar, Amit; Zafar, Maroof K.; Banerjee, Surajit; Marquez, Victor E.; Egli, Martin; Eoff, Robert L

    2012-01-01

    Y-family DNA polymerases participate in replication stress and DNA damage tolerance mechanisms. The properties that allow these enzymes to copy past bulky adducts or distorted template DNA can result in a greater propensity for them to make mistakes. Of the four human Y-family members, human DNA polymerase iota (hpol ι) is the most error-prone. In the current study, we elucidate the molecular basis for improving the fidelity of hpol ι through use of the fixed-conformation nucleotide North-methanocarba-2′-deoxyadenosine triphosphate (N-MC-dATP). Three crystal structures were solved of hpol ι in complex with DNA containing a template 2′-deoxythymidine (dT) paired with an incoming dNTP or modified nucleotide triphosphate. The ternary complex of hpol ι inserting N-MC-dATP opposite dT reveals that the adenine ring is stabilized in the anti orientation about the pseudo-glycosyl torsion angle (χ), which mimics precisely the mutagenic arrangement of dGTP:dT normally preferred by hpol ι. The stabilized anti conformation occurs without notable contacts from the protein but likely results from constraints imposed by the bicyclo[3.1.0]hexane scaffold of the modified nucleotide. Unmodified dATP and South-MC-dATP each adopt syn glycosyl orientations to form Hoogsteen base pairs with dT. The Hoogsteen orientation exhibits weaker base stacking interactions and is less catalytically favorable than anti N-MC-dATP. Thus, N-MC-dATP corrects the error-prone nature of hpol ι by preventing the Hoogsteen base-pairing mode normally observed for hpol ι-catalyzed insertion of dATP opposite dT. These results provide a previously unrecognized means of altering the efficiency and the fidelity of a human translesion DNA polymerase. PMID:22632140

  3. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    Science.gov (United States)

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  4. Structure and function of DNA polymerase μ

    International Nuclear Information System (INIS)

    Matsumoto, Takuro; Maezawa, So

    2013-01-01

    DNA polymerases are enzymes playing the central role in DNA metabolism, including DNA replication, DNA repair and recombination. DNA polymerase μ (pol μ DNA polymerase λ (pol λ) and terminal deoxynucleotidyltransferase (TdT) in X family DNA polymerases function in non-homologous end-joining (NHEJ), which is the predonmiant repair pathway for DNA double-strand breaks (DSBs). NHEJ involves enzymes that capture both ends of the broken DNA strand, bring them together in a synaptic DNA-protein complex, and repair the DSB. Pol μ and pol λ fill in the gaps at the junction to maintain the genomic integrity. TdT synthesizes N region at the junction during V(D)J recombination and promotes diversity of immunoglobulin or T-cell receptor gene. Among these three polymerases, the regulatory mechanisms of pol μ remain rather unclear. We have approached the mechanism of pol μ from both sides of structure and cellular dynamics. Here, we propose some new insights into pol μ and the probable NHEJ model including our findings. (author)

  5. NHS Gene Mutations in Ashkenazi Jewish Families with Nance-Horan Syndrome.

    Science.gov (United States)

    Shoshany, Nadav; Avni, Isaac; Morad, Yair; Weiner, Chen; Einan-Lifshitz, Adi; Pras, Eran

    2017-09-01

    To describe ocular and extraocular abnormalities in two Ashkenazi Jewish families with infantile cataract and X-linked inheritance, and to identify their underlying mutations. Seven affected members were recruited. Medical history, clinical findings, and biometric measurements were recorded. Mutation analysis of the Nance-Horan syndrome (NHS) gene was performed by direct sequencing of polymerase chain reaction-amplified exons. An unusual anterior Y-sutural cataract was documented in the affected male proband. Other clinical features among examined patients included microcorneas, long and narrow faces, and current or previous dental anomalies. A nonsense mutation was identified in each family, including a previously described 742 C>T, p.(Arg248*) mutation in Family A, and a novel mutation 2915 C>A, p.(Ser972*) in Family B. Our study expands the repertoire of NHS mutations and the related phenotype, including newly described anterior Y-sutural cataract and dental findings.

  6. The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model

    DEFF Research Database (Denmark)

    Lindqvist, Andreas; Ekelund, Mikael; Garcia-Vaz, Eliana

    2017-01-01

    BACKGROUND: A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover......, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. METHODS: In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two...... weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. RESULTS: A similar weight development in both groups of pigs...

  7. Enhanced glucose metabolism in cultured human skeletal muscle after Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Nascimento, Emmani B M; Riedl, Isabelle; Jiang, Lake Qunfeng; Kulkarni, Sameer S; Näslund, Erik; Krook, Anna

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) surgery rapidly increases whole body insulin sensitivity, with changes in several organs including skeletal muscle. Objectives were to determine whether improvements in insulin action in skeletal muscle may occur directly at the level of the myocyte or secondarily from changes in systemic factors associated with weight loss. Myotubes were derived before and after RYGB surgery. The setting was Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. Eight patients (body mass index (BMI) 41.8 kg/m(2); age 41 yr) underwent RYGB surgery. Before and 6 months after RYGB surgery, skeletal muscle biopsies were collected from vastus lateralis muscle. Satellite cells derived from skeletal muscle biopsies were propagated in vitro as myoblasts and differentiated into myotubes. Expression of myogenic markers is increased in myoblasts derived from biopsies taken 6 months after bypass surgery, compared with their respective presurgery condition. Furthermore, glycogen synthesis, tyrosine phosphorylation of insulin receptor (IRS)-1-Tyr612 and Interleukin (IL)-8 secretion were increased, while fatty acid oxidation and circulating IL8 levels remain unaltered. Myotubes derived from muscle biopsies obtained after RYGB surgery displayed increased insulin-stimulated phosphorylation of protein kinase B (PKB)-Thr308 and proline-rich Akt substrate of 40 kDa (PRAS40)-Thr246. RYGB surgery is accompanied by enhanced glucose metabolism and insulin signaling, altered IL8 secretion and changes in mRNA levels and myogenic markers in cultured skeletal muscle cells. Thus, RYGB surgery involves intrinsic reprogramming of skeletal muscle to increase peripheral insulin sensitivity and glucose metabolism. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  8. Dynamics of termination during in vitro replication of ultraviolet-irradiated DNA with DNA polymerase III holoenzyme of Escherichia coli

    International Nuclear Information System (INIS)

    Shwartz, H.; Livneh, Z.

    1987-01-01

    During in vitro replication of UV-irradiated single-stranded DNA with Escherichia coli DNA polymerase III holoenzyme termination frequently occurs at pyrimidine photodimers. The termination stage is dynamic and characterized by at least three different events: repeated dissociation-reinitiation cycles of the polymerase at the blocked termini; extensive hydrolysis of ATP to ADP and inorganic phosphate; turnover of dNTPs into dNMP. The reinitiation events are nonproductive and are not followed by further elongation. The turnover of dNTPs into dNMPs is likely to result from repeated cycles of insertion of dNMP residues opposite the blocking lesions followed by their excision by the 3'----5' exonucleolytic activity of the polymerase. Although all dNTPs are turned over, there is a preference for dATP, indicating that DNA polymerase III holoenzyme has a preference for inserting a dAMP residue opposite blocking pyrimidine photodimers. We suggest that the inability of the polymerase to bypass photodimers during termination is due to the formation of defective initiation-like complexes with reduced stability at the blocked termini

  9. Changes in hormones and biomarkers in polycystic ovarian syndrome treated with gastric bypass.

    Science.gov (United States)

    Eid, George M; McCloskey, Carol; Titchner, Rebecca; Korytkowski, Mary; Gross, Debra; Grabowski, Cynthia; Wilson, Mark

    2014-01-01

    Small retrospective studies have demonstrated reduction in weight and co-morbid hirsutism and diabetes in women with polycystic ovary syndrome (PCOS) treated with Roux-en-Y gastric bypass. The objective of this study was to prospectively determine clinical improvements in obese women with PCOS treated with gastric bypass and identify postoperative biomarker changes. Data were collected on obese women with PCOS undergoing Roux-en-Y gastric bypass over 1 year. Testosterone, follicle stimulating hormone, lutenizing hormone, insulin, fasting glucose, and lipid levels were obtained preoperatively at baseline, and 6 and 12 months after surgery. Testosterone was used as the primary hormonal biomarker. A physical examination for body mass index (BMI) and hirsutism, and information on menstrual pattern were collected at baseline and 3, 6, and 12 months after surgery. Data were available for 14 women. Mean BMI decreased from 44.8±5.9 kg/m(2) at baseline to 29.2±5.9 kg/m(2) at 12 months postoperatively. Significant improvements were seen in testosterone, fasting glucose, insulin, cholesterol, and triglyceride at 12 months (Pirregular menses were reported in 10 patients; all patients were experiencing regular menses 6 and 12 months after surgery. Hirsutism was present in 11 patients at baseline and only 7 patients at 12 months. Improvements in biomarkers, menstrual cycling, and hirsutism was not correlated with degree of weight change. Gastric bypass achieved significant reductions in BMI, testosterone, and markers of glucose and lipid metabolism. These data confirm reports of previous retrospective studies showing weight reduction and health improvement in women with PCOS treated with gastric bypass. Published by Elsevier Inc.

  10. Late intestinal obstruction due to an intestinal volvulus in a pregnant patient with a previous Roux-en-Y gastric bypass.

    Science.gov (United States)

    Gazzalle, Anajara; Braun, Débora; Cavazzola, Leandro Totti; Wendt, Luiz Roberto; Navarini, Daniel; Fauri, Marcelo de Azevedo; Vitola, Santo Pascual

    2010-12-01

    This is a case of a 33 weeks pregnant woman, presented 2 years after laparoscopic Roux-en-Y gastric bypass, with abdominal pain for 2 days. A laparoscopic cholecystectomy was performed 1 day earlier in another hospital, without improving the pain. She presented at our hospital with acute abdominal pain and clinical signs of intestinal obstruction, undergoing an exploratory laparotomy that revealed a volvulus and necrosis of the jejunum from the gastroenteroanastomosis through the lateral enteroenterostomy, which was resected with the reconstruction of the Roux-en-Y limb performed at the same operation. Patient and neonate presented with improvement after surgery and the patient was discharged on postoperative day 15. Internal hernias after bariatric surgery have been reported as the cause of acute abdomen problems during pregnancy, which may progress to necrosis and perforation. The delay of surgical intervention could have brought a tragic outcome for mother and neonate.

  11. Altered minor-groove hydrogen bonds in DNA block transcription elongation by T7 RNA polymerase.

    Science.gov (United States)

    Tanasova, Marina; Goeldi, Silvan; Meyer, Fabian; Hanawalt, Philip C; Spivak, Graciela; Sturla, Shana J

    2015-05-26

    DNA transcription depends upon the highly efficient and selective function of RNA polymerases (RNAPs). Modifications in the template DNA can impact the progression of RNA synthesis, and a number of DNA adducts, as well as abasic sites, arrest or stall transcription. Nonetheless, data are needed to understand why certain modifications to the structure of DNA bases stall RNA polymerases while others are efficiently bypassed. In this study, we evaluate the impact that alterations in dNTP/rNTP base-pair geometry have on transcription. T7 RNA polymerase was used to study transcription over modified purines and pyrimidines with altered H-bonding capacities. The results suggest that introducing wobble base-pairs into the DNA:RNA heteroduplex interferes with transcriptional elongation and stalls RNA polymerase. However, transcriptional stalling is not observed if mismatched base-pairs do not H-bond. Together, these studies show that RNAP is able to discriminate mismatches resulting in wobble base-pairs, and suggest that, in cases of modifications with minor steric impact, DNA:RNA heteroduplex geometry could serve as a controlling factor for initiating transcription-coupled DNA repair. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The RNA Template Channel of the RNA-Dependent RNA Polymerase as a Target for Development of Antiviral Therapy of Multiple Genera within a Virus Family

    NARCIS (Netherlands)

    van der Linden, Lonneke; Vives-Adrián, Laia; Selisko, Barbara; Ferrer-Orta, Cristina; Liu, Xinran; Lanke, Kjerstin; Ulferts, Rachel; De Palma, Armando M; Tanchis, Federica; Goris, Nesya; Lefebvre, David; De Clercq, Kris; Leyssen, Pieter; Lacroix, Céline; Pürstinger, Gerhard; Coutard, Bruno; Canard, Bruno; Boehr, David D; Arnold, Jamie J; Cameron, Craig E; Verdaguer, Nuria; Neyts, Johan; van Kuppeveld, Frank J M

    2015-01-01

    The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy.

  13. Effect of Roux-en-Y gastric bypass surgery on ventricular function and cardiac risk factors in obese patients: a systematic review

    Directory of Open Access Journals (Sweden)

    Alireza Abdollahi Moghaddam

    2016-03-01

    Full Text Available Introduction: Weight gain and obesity are two important public health problems, which are associated with many diseases such as cardiovascular disorders. Various policies such as bariatric surgery have been proposed for the treatment of morbid obesity. Methods: PubMed and Scopus were searched thoroughly with the following search terms (roux-en-y gastric bypass surgery AND (ventricular function, OR cardiac risk factors OR heart AND (BMI OR body mass index to find the articles in which the effect of roux-en-Y gastric bypass (RYGB surgery had been evaluated in severely obese patients.Result: Out of 120 articles which were found in PubMed, and 28 records which were found in Scopus, only 18 articles fully met the inclusion criteria. Out of 2740 participants in the included studied, 1706 were patients with body mass index (BMI over 40 kg/m2 who had undergone RYGB surgery, and 1034 were control participants. Results of the studies showed that RYGB surgery could reduce BMI, and cardiac risk factors, and improve diastolic function, systolic and diastolic blood pressures, and aortic function, postoperatively.Discussion: Obesity is associated with increased risk of cardiovascular diseases, impaired cardiac function, and hypertension. It is shown that RYGB surgery reduces the serum level of biochemical markers of cardiac diseases. Cardiac structure, parasympathetic indices of autonomic function, coronary circulatory function, hypertension, epicardial fat thickness, and ventricular performance improve after bariatric surgery.Conclusions: It is concluded that RYGB surgery is an effective strategy to improve ventricular function and cardiac risk factors in morbid obese patients.

  14. Variants of sequence family B Thermococcus kodakaraensis DNA polymerase with increased mismatch extension selectivity.

    Directory of Open Access Journals (Sweden)

    Claudia Huber

    Full Text Available Fidelity and selectivity of DNA polymerases are critical determinants for the biology of life, as well as important tools for biotechnological applications. DNA polymerases catalyze the formation of DNA strands by adding deoxynucleotides to a primer, which is complementarily bound to a template. To ensure the integrity of the genome, DNA polymerases select the correct nucleotide and further extend the nascent DNA strand. Thus, DNA polymerase fidelity is pivotal for ensuring that cells can replicate their genome with minimal error. DNA polymerases are, however, further optimized for more specific biotechnological or diagnostic applications. Here we report on the semi-rational design of mutant libraries derived by saturation mutagenesis at single sites of a 3'-5'-exonuclease deficient variant of Thermococcus kodakaraensis DNA polymerase (KOD pol and the discovery for variants with enhanced mismatch extension selectivity by screening. Sites of potential interest for saturation mutagenesis were selected by their proximity to primer or template strands. The resulting libraries were screened via quantitative real-time PCR. We identified three variants with single amino acid exchanges-R501C, R606Q, and R606W-which exhibited increased mismatch extension selectivity. These variants were further characterized towards their potential in mismatch discrimination. Additionally, the identified enzymes were also able to differentiate between cytosine and 5-methylcytosine. Our results demonstrate the potential in characterizing and developing DNA polymerases for specific PCR based applications in DNA biotechnology and diagnostics.

  15. Specialty Article: so You Think You Got a Bypass? A Case Series of Adventures in Bariatric Surgery.

    Science.gov (United States)

    Wang, Eugene Y; Shope, Timothy R

    2018-05-01

    To raise awareness for surgeons encountering bariatric patients with anatomy that deviates from the standard Roux-en-Y gastric bypass (RYGB). This is a single-institution retrospective case series over 12 years (2003-2014) involving patients who believed they received RYGBs, but actually did not. Data was obtained reviewing physician encounters, imaging, and operative reports. There were six cases with confusing clinical pictures, found to have aberrant RYGB anatomy: (1) gastric bypass with jejuno-jejunostomy only without gastrojejunostomy, (2) distal partial vertical gastrectomy without expected prosthetic band, (3) inverse vertical banded gastroplasty, (4) non-divided gastric bypass with no gastrojejunostomy, (5) 20-cm Roux limb, with gastro-gastric fistula, and (6) 200-cm bilio-pancreatic limb similar to the traditional Scopinaro procedure. There are cases of "Roux-en-Y gastric bypasses" that have no resemblance to the named procedure at all. Adjunctive upper gastrointestinal studies and upper endoscopies help surgeons make diagnoses that are incongruent with the surgical history. It is important to keep in mind that there could be anatomic or surgical variations which were born out of necessity or based on other surgeons' creativities.

  16. Changes in Gut Hormones After Roux en Y Gastric bypass, Sleeve Gastrectomy, and Adjustable Gastric Banding

    Directory of Open Access Journals (Sweden)

    Miroslav Ilić

    2015-12-01

    Full Text Available The obesity epidemic has burdened healthcare systems worldwide. Bariatric surgery is currently the most effective method for long-term weight loss in obese adults, but the exact mechanism of weight loss is poorly understood. Bariatric procedures were initially classified by their presumed mechanism of action into restrictive, malabsoptive, or mixed procedures; however, due to recent advancements in the field of neuroendocrinology, hormones are increasing being recognized as important regulators of satiation, hunger, and energy expenditure. Studies examining changes in gut hormones following bariatric surgery have yielded conflicting results and the relationship between these hormones and weight loss is nothing but clear. This review will summarize the effect of Roux en Y gastric bypass, sleeve gastrectomy and adjustable gastric banding on various gut hormones including ghrelin, cholecystokinin, glucagon-like polypeptide-1, peptide YY3, and pancreatic polypeptide. Furthermore, the relationship between these hormones and weight loss will be examined.

  17. Tier 3 multidisciplinary medical weight management improves outcome of Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Patel, P; Hartland, A; Hollis, A; Ali, R; Elshaw, A; Jain, S; Khan, A; Mirza, S

    2015-04-01

    In 2013 the Department of Health specified eligibility for bariatric surgery funded by the National Health Service. This included a mandatory specification that patients first complete a Tier 3 medical weight management programme. The clinical effectiveness of this recommendation has not been evaluated previously. Our bariatric centre has provided a Tier 3 programme six months prior to bariatric surgery since 2009. The aim of our retrospective study was to compare weight loss in two cohorts: Roux-en-Y gastric bypass only (RYGB only cohort) versus Tier 3 weight management followed by RYGB (Tier 3 cohort). A total of 110 patients were selected for the study: 66 in the RYGB only cohort and 44 in the Tier 3 cohort. Patients in both cohorts were matched for age, sex, preoperative body mass index and pre-existing co-morbidities. The principal variable was therefore whether they undertook the weight management programme prior to RYGB. Patients from both cohorts were followed up at 6 and 12 months to assess weight loss. The mean weight loss at 6 months for the Tier 3 cohort was 31% (range: 18-69%, standard deviation [SD]: 0.10 percentage points) compared with 23% (range: 4-93%, SD: 0.12 percentage points) for the RYGB only cohort (p=0.0002). The mean weight loss at 12 months for the Tier 3 cohort was 34% (range: 17-51%, SD: 0.09 percentage points) compared with 27% (range: 14-48%, SD: 0.87 percentage points) in the RYGB only cohort (p=0.0037). Our study revealed that in our matched cohorts, patients receiving Tier 3 specialist medical weight management input prior to RYGB lost significantly more weight at 6 and 12 months than RYGB only patients. This confirms the clinical efficacy of such a weight management programme prior to gastric bypass surgery and supports its inclusion in eligibility criteria for bariatric surgery.

  18. Is phonology bypassed in normal or dyslexic development?

    Science.gov (United States)

    Pennington, B F; Lefly, D L; Van Orden, G C; Bookman, M O; Smith, S D

    1987-01-01

    A pervasive assumption in most accounts of normal reading and spelling development is that phonological coding is important early in development but is subsequently superseded by faster, orthographic coding which bypasses phonology. We call this assumption, which derives from dual process theory, the developmental bypass hypothesis. The present study tests four specific predictions of the developmental bypass hypothesis by comparing dyslexics and nondyslexics from the same families in a cross-sectional design. The four predictions are: 1) That phonological coding skill develops early in normal readers and soon reaches asymptote, whereas orthographic coding skill has a protracted course of development; 2) that the correlation of adult reading or spelling performance with phonological coding skill is considerably less than the correlation with orthographic coding skill; 3) that dyslexics who are mainly deficient in phonological coding skill should be able to bypass this deficit and eventually close the gap in reading and spelling performance; and 4) that the greatest differences between dyslexics and developmental controls on measures of phonological coding skill should be observed early rather than late in development.None of the four predictions of the developmental bypass hypothesis were upheld. Phonological coding skill continued to develop in nondyslexics until adulthood. It accounted for a substantial (32-53 percent) portion of the variance in reading and spelling performance in adult nondyslexics, whereas orthographic coding skill did not account for a statistically reliable portion of this variance. The dyslexics differed little across age in phonological coding skill, but made linear progress in orthographic coding skill, surpassing spelling-age (SA) controls by adulthood. Nonetheless, they didnot close the gap in reading and spelling performance. Finally, dyslexics were significantly worse than SA (and Reading Age [RA]) controls in phonological coding skill

  19. Coronary Bypass Surgery in a 105-Year-Old Patient with Cardiopulmonary Bypass

    Directory of Open Access Journals (Sweden)

    Temucin Noyan Ogus

    2010-01-01

    Full Text Available Coronary artery bypass grafting is one of the routine daily surgical procedures in the current era. Parallel to the increasing life expectancy, cardiac surgery is commonly performed in octogenarians. However, literature consists of only seldom reports of coronary artery bypass grafting in patients above 90 years of age. In this report, we present our management strategy in a 105-year-old patient who underwent coronary artery bypass grafting at our institution.

  20. The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model

    DEFF Research Database (Denmark)

    Lindqvist, Andreas; Ekelund, Mikael; Garcia-Vaz, Eliana

    2017-01-01

    BACKGROUND: A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreov...... were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period......., RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. METHODS: In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two...... weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. RESULTS: A similar weight development in both groups of pigs...

  1. Your diet after gastric bypass surgery

    Science.gov (United States)

    Gastric bypass surgery - your diet; Obesity - diet after bypass; Weight loss - diet after bypass ... You had gastric bypass surgery. This surgery made your stomach smaller by closing off most of your stomach with staples. It changed the way your ...

  2. Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Alter the Gut-Brain Communication

    Directory of Open Access Journals (Sweden)

    L. A. Ballsmider

    2015-01-01

    Full Text Available This study investigated the anatomical integrity of vagal innervation of the gastrointestinal tract following vertical sleeve gastrectomy (VSG and Roux-en-Y gastric bypass (RYGB operations. The retrograde tracer fast blue (FB was injected into the stomach to label vagal neurons originating from nodose ganglion (NG and dorsal motor nucleus of the vagus (DMV. Microglia activation was determined by quantifying changes in the fluorescent staining of hindbrain sections against an ionizing calcium adapter binding molecule 1 (Iba1. Reorganization of vagal afferents in the hindbrain was studied by fluorescent staining against isolectin 4 (IB4. The density of Iba1- and IB4-immunoreactivity was analyzed using Nikon Elements software. There was no difference in the number of FB-labeled neurons located in NG and DMV between VSG and VSG-sham rats. RYGB, but not RYGB-sham rats, showed a dramatic reduction in number of FB-labeled neurons located in the NG and DMV. VSG increased, while the RYGB operation decreased, the density of vagal afferents in the nucleus tractus solitarius (NTS. The RYGB operation, but not the VSG procedure, significantly activated microglia in the NTS and DMV. Results of this study show that the RYGB, but not the VSG procedure, triggers microglia activation in vagal structures and remodels gut-brain communication.

  3. 75 FR 71145 - San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and...

    Science.gov (United States)

    2010-11-22

    ..., Eastside Bypass, and Mariposa Bypass Channel and Structural Improvements Project, Merced County, CA AGENCY... on the effects of the proposed Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and Structural... Mariposa Bypass with the San Joaquin River (generally referred to as Reach 4B1). The improvements will...

  4. Roux-en-Y gastric bypass increases intravenous ethanol self-administration in dietary obese rats.

    Directory of Open Access Journals (Sweden)

    James E Polston

    Full Text Available Roux-en-Y gastric bypass surgery (RYGB is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV administered ethanol (1%. For this purpose, high fat (60% kcal from fat diet-induced obese male Sprague Dawley rats were tested ~2 months after RYGB or sham surgery (SHAM using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.

  5. Discovery of cyanophage genomes which contain mitochondrial DNA polymerase.

    Science.gov (United States)

    Chan, Yi-Wah; Mohr, Remus; Millard, Andrew D; Holmes, Antony B; Larkum, Anthony W; Whitworth, Anna L; Mann, Nicholas H; Scanlan, David J; Hess, Wolfgang R; Clokie, Martha R J

    2011-08-01

    DNA polymerase γ is a family A DNA polymerase responsible for the replication of mitochondrial DNA in eukaryotes. The origins of DNA polymerase γ have remained elusive because it is not present in any known bacterium, though it has been hypothesized that mitochondria may have inherited the enzyme by phage-mediated nonorthologous displacement. Here, we present an analysis of two full-length homologues of this gene, which were found in the genomes of two bacteriophages, which infect the chlorophyll-d containing cyanobacterium Acaryochloris marina. Phylogenetic analyses of these phage DNA polymerase γ proteins show that they branch deeply within the DNA polymerase γ clade and therefore share a common origin with their eukaryotic homologues. We also found homologues of these phage polymerases in the environmental Community Cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA) database, which fell in the same clade. An analysis of the CAMERA assemblies containing the environmental homologues together with the filter fraction metadata indicated some of these assemblies may be of bacterial origin. We also show that the phage-encoded DNA polymerase γ is highly transcribed as the phage genomes are replicated. These findings provide data that may assist in reconstructing the evolution of mitochondria.

  6. Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2′-deoxyguanosine by Human DNA Polymerase η*

    Science.gov (United States)

    Patra, Amitraj; Zhang, Qianqian; Guengerich, F. Peter; Egli, Martin

    2016-01-01

    O6-Methyl-2′-deoxyguanosine (O6-MeG) is a ubiquitous DNA lesion, formed not only by xenobiotic carcinogens but also by the endogenous methylating agent S-adenosylmethionine. It can introduce mutations during DNA replication, with different DNA polymerases displaying different ratios of correct or incorrect incorporation opposite this nucleoside. Of the “translesion” Y-family human DNA polymerases (hpols), hpol η is most efficient in incorporating equal numbers of correct and incorrect C and T bases. However, the mechanistic basis for this specific yet indiscriminate activity is not known. To explore this question, we report biochemical and structural analysis of the catalytic core of hpol η. Activity assays showed the truncated form displayed similar misincorporation properties as the full-length enzyme, incorporating C and T equally and extending from both. X-ray crystal structures of both dC and dT paired with O6-MeG were solved in both insertion and extension modes. The structures revealed a Watson-Crick-like pairing between O6-MeG and 2"-deoxythymidine-5"-[(α, β)-imido]triphosphate (approximating dT) at both the insertion and extension stages with formation of two H-bonds. Conversely, both the structures with O6- MeG opposite dCTP and dC display sheared configuration of base pairs but to different degrees, with formation of two bifurcated H-bonds and two single H-bonds in the structures trapped in the insertion and extension states, respectively. The structural data are consistent with the observed tendency of hpol η to insert both dC and dT opposite the O6-MeG lesion with similar efficiencies. Comparison of the hpol η active site configurations with either O6-MeG:dC or O6-MeG:dT bound compared with the corresponding situations in structures of complexes of Sulfolobus solfataricus Dpo4, a bypass pol that favors C relative to T by a factor of ∼4, helps rationalize the more error-prone synthesis opposite the lesion by hpol η. PMID:27694439

  7. The Best Bypass Surgery Trial

    DEFF Research Database (Denmark)

    Møller, Christian H; Jensen, Birte Østergaard; Gluud, Christian

    2007-01-01

    Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have...

  8. Does the closure of mesenteric defects during laparoscopic gastric bypass surgery cause complications?

    DEFF Research Database (Denmark)

    Kristensen, Sara Danshøj; Floyd, Andrea Karen; Naver, Lars

    2015-01-01

    BACKGROUND: A well-known complication of laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) is bowel obstruction due to internal herniation (IH). Evidence suggests that mesenteric defects should be closed during LRYGB to reduce the risk of IH. Therefore, surgeons are now closing mesenteric...

  9. Avaliação da vitalidade fetal e resultados perinatais em gestações após gastroplastia com derivação em Y de Roux Assessment of fetal vitality and perinatal results in pregnancies after gastroplasty with Roux-en-Y gastric bypass

    Directory of Open Access Journals (Sweden)

    Roseli Mieko Yamamoto Nomura

    2010-01-01

    Full Text Available OBJETIVO: Analisar os resultados da avaliação da vitalidade fetal de gestações após gastroplastia com derivação em Y de Roux, verificando as complicações maternas e os resultados perinatais. MÉTODOS: No período de julho de 2001 a setembro de 2009, foram analisados, retrospectivamente, dados de prontuário de pacientes com gestação após gastroplastia com derivação em Y de Roux, acompanhadas em pré-natal especializado e cujo parto foi realizado na instituição. Foram analisados os exames de avaliação da vitalidade fetal (cardiotocografia, perfil biofísico fetal e dopplervelocimetria das artérias umbilicais realizada na semana anterior ao parto. As variáveis maternas investigadas foram: dados demográficos, complicações clínicas maternas, tipo de parto, complicações no parto e pós-parto, exames hematimétricos maternos e resultados perinatais. RESULTADOS: Trinta gestações após gastroplastia com derivação em Y de Roux foram identificadas e 24 delas foram submetidas à avaliação da vitalidade fetal. Todas as pacientes apresentaram resultados normais na cardiotocografia, no perfil biofísico fetal e na dopplervelocimetria das artérias umbilicais. Houve um caso de oligohidrâmnio. A principal complicação observada foi anemia materna (Hb OBJECTIVE: To study fetal vitality assessed in pregnancies after gastroplasty with Roux-en-Y gastric bypass'and verify maternal complications and perinatal results. METHODS: Hospital charts of all pregnancies after gastroplasty with Roux-en-Y gastric bypass were reviewed retrospectively. All cases followed at the specialized prenatal care that gave birth in this institution, between July 2001 and September 2009, were reviewed. The assessment of fetal vitality (cardiotocography, fetal biophysical profile and umbilical artery Doppler velocimetry performed in the last week before delivery were analyzed. The maternal variables investigated were: demographic data, maternal complications

  10. Optimal Bypass and Cream Skimming.

    OpenAIRE

    Laffont, Jean-Jacques; Tirole, Jean

    1990-01-01

    This paper develops a normative model of regulatory policy toward bypass and cream skimming. It analyzes the effects of bypass on second-degree price discrimination, on the rent of the regulated firm, and on the welfare of low-demand customers. It shows that pricing under marginal cost may be optimal for the regulated firm, excessive cream skimming occurs if access to the bypass technology is not regulated, and the prohibition of bypass may increase or decrease the regulated firm's rent. Copy...

  11. The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

    Science.gov (United States)

    Pournaras, Dimitri J.; Glicksman, Clare; Vincent, Royce P.; Kuganolipava, Shophia; Alaghband-Zadeh, Jamie; Mahon, David; Bekker, Jan H.R.; Ghatei, Mohammad A.; Bloom, Stephen R.; Walters, Julian R.F.; le Roux, Carel W.

    2012-01-01

    Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes. PMID:22673227

  12. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  13. Eukaryotic RNA polymerase subunit RPB8 is a new relative of the OB family.

    Science.gov (United States)

    Krapp, S; Kelly, G; Reischl, J; Weinzierl, R O; Matthews, S

    1998-02-01

    RNA polymerase II subunit RPB8 is an essential subunit that is highly conserved throughout eukaryotic evolution and is present in all three types of nuclear RNA polymerases. We report the first high resolution structural insight into eukaryotic RNA polymerase architecture with the solution structure of RPB8 from Saccharomyces cerevisiae. It consists of an eight stranded, antiparallel beta-barrel, four short helical regions and a large, unstructured omega-loop. The strands are connected in classic Greek-key fashion. The overall topology is unusual and contains a striking C2 rotational symmetry. Furthermore, it is most likely a novel associate of the oligonucleotide/oligosaccharide (OB) binding protein class.

  14. Ketamine has no effect on oxygenation indices following elective coronary artery bypass grafting under cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Parthasarathi Gayatri

    2011-01-01

    Full Text Available Cardiopulmonary bypass is known to elicit systemic inflammatory response syndrome and organ dysfunction. This can result in pulmonary dysfunction and deterioration of oxygenation after cardiac surgery and cardiopulmonary bypass. Previous studies have reported varying results on anti-inflammatory strategies and oxygenation after cardiopulmonary bypass. Ketamine administered as a single dose at induction has been shown to reduce the pro-inflammatory serum markers in patients undergoing cardiopulmonary bypass. Therefore we investigated if ketamine can result in better oxygenation in these patients. This was a prospective randomized blinded study. Eighty consecutive adult patients undergoing elective coronary artery bypass grafting under cardiopulmonary bypass were included in the study. Patients were divided into two groups. Patients in ketamine group received 1mg/kg of ketamine intravenously at induction of anesthesia. Control group patients received an equal volume of saline. All patients received standard anesthesia, operative and postoperative care.Paired t test and independent sample t test were used to compare the inter-group and between group oxygenation indices respectively. Oxygenation index and duration of ventilation were analyzed. Deterioration of oxygenation index was noted in both the groups after cardiopulmonary bypass. However, there was no significant difference in the oxygenation index at various time points after cardiopulmonary bypass or the duration of ventilation between the two groups. This study shows that the administered as a single dose at induction does not result in better oxygenation after cardiopulmonary bypass.

  15. Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery

    Directory of Open Access Journals (Sweden)

    Chen CH

    2015-03-01

    Full Text Available Chun-Han Chen,1,2 Cheng-Chih Chang,1 Tsung-Hsien Shih,2 Ibrahim A Aljuffali,3 Ta-Sen Yeh,4,5 Jia-You Fang6–8 1Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; 3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Department of Surgery, Chang Gung Memorial Hospital, 5School of Medicine, College of Medicine, 6Pharmaceutics Laboratory, Graduate Institute of Natural Products, 7Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, 8Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan Abstract: Roux-en-Y gastric bypass (RYGB is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence

  16. Mini-cardiopulmonary bypass impact on blood conservation strategy in coronary artery bypass grafting.

    Science.gov (United States)

    Abdel Aal, Mohamed; ElNahal, Nezar; Bakir, Bakir Moustafa; Fouda, Mohamed

    2011-04-01

    Cardiopulmonary bypass (CPB) using a closed circuit system with minimal priming volume can be a solution to ameliorate adverse effects of CPB. We hypothesize that the use of mini-bypass in routine coronary artery bypass grafting (CABG) reduces homologous blood product use and postoperative bleeding. The study is designed to determine the differences in blood loss and transfusion requirements associated with a minimized CPB circuit vs. a standard bypass circuit. From February 2009 to August 2009, 80 patients were prospectively randomized to undergo elective CABG. Group A included 40 patients who had the minimized bypass circuit (Medtronic Resting Heart Circuit). Group B had an equal number of patients who had the standard CPB circuit (Stockert III, SEC.BM). Laboratory parameters for hemoglobin, hematocrit and platelet count were measured at baseline after initiation of CPB and after bypass. Blood usage was controlled by study-specific protocol (transfusion for hemoglobin platelets (1.95±2.95 units vs. 3.23±2.85), and postoperative drainage in 24 hours (531.62±220.12 ml vs. 729±294.9 ml, P<0.05). The hematocrit was 33±5% in group A, and 27±1% in group B. There was statistical differences seen in the mean hemoglobin level which was 10.19±0.65 g/dl in group A, and 9.4±0.68 g/dl in group B. There was statistical difference in the duration of ventilation, length of ICU stay. The requirement of inotropic support was lower in group A. The adoption of mini-bypass significantly reduces morbidity including donor blood usage and postoperative bleeding in routine CABG patients.

  17. Identification of Critical Residues for the Tight Binding of Both Correct and Incorrect Nucleotides to Human DNA Polymerase λ

    Science.gov (United States)

    Brown, Jessica A.; Pack, Lindsey R.; Sherrer, Shanen M.; Kshetry, Ajay K.; Newmister, Sean A.; Fowler, Jason D.; Taylor, John-Stephen; Suo, Zucai

    2010-01-01

    DNA polymerase λ (Pol λ) is a novel X-family DNA polymerase that shares 34% sequence identity with DNA polymerase β (Pol β). Pre-steady state kinetic studies have shown that the Pol λ•DNA complex binds both correct and incorrect nucleotides 130-fold tighter on average than the Pol β•DNA complex, although, the base substitution fidelity of both polymerases is 10−4 to 10−5. To better understand Pol λ’s tight nucleotide binding affinity, we created single- and double-substitution mutants of Pol λ to disrupt interactions between active site residues and an incoming nucleotide or a template base. Single-turnover kinetic assays showed that Pol λ binds to an incoming nucleotide via cooperative interactions with active site residues (R386, R420, K422, Y505, F506, A510, and R514). Disrupting protein interactions with an incoming correct or incorrect nucleotide impacted binding with each of the common structural moieties in the following order: triphosphate ≫ base > ribose. In addition, the loss of Watson-Crick hydrogen bonding between the nucleotide and template base led to a moderate increase in the Kd. The fidelity of Pol λ was maintained predominantly by a single residue, R517, which has minor groove interactions with the DNA template. PMID:20851705

  18. Effect of Roux-en-Y gastric bypass on the distribution and hormone expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Rhee, Nicolai A; Wahlgren, Camilla D; Pedersen, Jens

    2015-01-01

    AIMS/HYPOTHESIS: We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes. METHODS: Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed...... of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of GHRL, SCT and GIP and increased expression of GCG....

  19. A high-throughput and quantitative method to assess the mutagenic potential of translesion DNA synthesis

    Science.gov (United States)

    Taggart, David J.; Camerlengo, Terry L.; Harrison, Jason K.; Sherrer, Shanen M.; Kshetry, Ajay K.; Taylor, John-Stephen; Huang, Kun; Suo, Zucai

    2013-01-01

    Cellular genomes are constantly damaged by endogenous and exogenous agents that covalently and structurally modify DNA to produce DNA lesions. Although most lesions are mended by various DNA repair pathways in vivo, a significant number of damage sites persist during genomic replication. Our understanding of the mutagenic outcomes derived from these unrepaired DNA lesions has been hindered by the low throughput of existing sequencing methods. Therefore, we have developed a cost-effective high-throughput short oligonucleotide sequencing assay that uses next-generation DNA sequencing technology for the assessment of the mutagenic profiles of translesion DNA synthesis catalyzed by any error-prone DNA polymerase. The vast amount of sequencing data produced were aligned and quantified by using our novel software. As an example, the high-throughput short oligonucleotide sequencing assay was used to analyze the types and frequencies of mutations upstream, downstream and at a site-specifically placed cis–syn thymidine–thymidine dimer generated individually by three lesion-bypass human Y-family DNA polymerases. PMID:23470999

  20. Decreased Cardiovascular Risk after Roux-en-Y Gastric Bypass Surgery in Chinese Diabetic Patients with Obesity.

    Science.gov (United States)

    Zhao, Xue; Duan, Wenyan; Sun, Chenglin; Li, Zhuo; Liu, Yujia; Xiao, Xianchao; Wang, Gang; Gang, Xiaokun; Wang, Guixia

    2017-01-01

    The influence of bariatric surgery on cardiovascular risks in Chinese diabetic patients remains unclear. Here, we aimed to explore the impact of Roux-en-Y gastric bypass surgery (RYGB) on cardiovascular risks in Chinese diabetic patients with obesity. Twenty Chinese patients with T2DM and obesity undergoing RYGB surgery were included in this study. Cardiovascular risk factors were measured before and 18 months after surgery. A 10-year cardiovascular risk was calculated by the UKPDS risk engine. Linear regression analysis was performed on CHD risk, stroke risk, and baseline metabolic parameters. The complete remission rate of diabetes was 90% after RYGB surgery, with significant improvements in blood pressure, BMI, glucose, and lipid metabolism ( P women,  5 years, using noninsulin therapy presented more obvious improvements in the 10-year cardiovascular risk after RYGB surgery. WHR, age, LDL-C, and HbA1c were the most important factors influencing CHD or stroke risk after RYGB surgery ( P treatment to reduce cardiovascular risk in Chinese diabetic patients with obesity.

  1. DNA polymerase η modulates replication fork progression and DNA damage responses in platinum-treated human cells

    Science.gov (United States)

    Sokol, Anna M.; Cruet-Hennequart, Séverine; Pasero, Philippe; Carty, Michael P.

    2013-11-01

    Human cells lacking DNA polymerase η (polη) are sensitive to platinum-based cancer chemotherapeutic agents. Using DNA combing to directly investigate the role of polη in bypass of platinum-induced DNA lesions in vivo, we demonstrate that nascent DNA strands are up to 39% shorter in human cells lacking polη than in cells expressing polη. This provides the first direct evidence that polη modulates replication fork progression in vivo following cisplatin and carboplatin treatment. Severe replication inhibition in individual platinum-treated polη-deficient cells correlates with enhanced phosphorylation of the RPA2 subunit of replication protein A on serines 4 and 8, as determined using EdU labelling and immunofluorescence, consistent with formation of DNA strand breaks at arrested forks in the absence of polη. Polη-mediated bypass of platinum-induced DNA lesions may therefore represent one mechanism by which cancer cells can tolerate platinum-based chemotherapy.

  2. α,β-D-constrained nucleic acids are strong terminators of thermostable DNA polymerases in polymerase chain reaction.

    Directory of Open Access Journals (Sweden)

    Olivier Martínez

    Full Text Available (S(C5', R(P α,β-D- Constrained Nucleic Acids (CNA are dinucleotide building blocks that can feature either B-type torsional angle values or non-canonical values, depending on their 5'C and P absolute stereochemistry. These CNA are modified neither on the nucleobase nor on the sugar structure and therefore represent a new class of nucleotide with specific chemical and structural characteristics. They promote marked bending in a single stranded DNA so as to preorganize it into a loop-like structure, and they have been shown to induce rigidity within oligonucleotides. Following their synthesis, studies performed on CNA have only focused on the constraints that this family of nucleotides introduced into DNA. On the assumption that bending in a DNA template may produce a terminator structure, we investigated whether CNA could be used as a new strong terminator of polymerization in PCR. We therefore assessed the efficiency of CNA as a terminator in PCR, using triethylene glycol phosphate units as a control. Analyses were performed by denaturing gel electrophoresis and several PCR products were further analysed by sequencing. The results showed that the incorporation of only one CNA was always skipped by the polymerases tested. On the other hand, two CNA units always stopped proofreading polymerases, such as Pfu DNA polymerase, as expected for a strong replication terminator. Non-proofreading enzymes, e.g. Taq DNA polymerase, did not recognize this modification as a strong terminator although it was predominantly stopped by this structure. In conclusion, this first functional use of CNA units shows that these modified nucleotides can be used as novel polymerization terminators of proofreading polymerases. Furthermore, our results lead us to propose that CNA and their derivatives could be useful tools for investigating the behaviour of different classes of polymerases.

  3. Can low BMI Chinese patients with type 2 diabetes benefit from laparoscopic Roux-en-Y gastric bypass surgery?

    Science.gov (United States)

    Wang, Guohui; Zhu, Liyong; Li, Weizheng; Yang, Xiangwu; Li, Pengzhou; Zhu, Shaihong

    2016-12-01

    The efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) in type 2 diabetes mellitus (T2D) is closely associated with the preoperative body mass index (BMI) of the patient. There is a lack of long-term and large sampling evidence on the efficacy of LRYGB in T2D patients with low BMI in China. This retrospective study aimed to evaluate the efficacy of surgical treatment in a Chinese population with T2D (especially patients with BMIBMI≥27.5 kg/m 2 in group 1 (high BMI group) had significant improvements in waist circumference, blood glucose levels, homeostasis model assessment-insulin resistance index, and C-peptide levels after LRYGB (PBMIBMI group, including 19 T2D patients with BMIBMI<27.5 kg/m 2 in China. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  4. Novel human CRYGD rare variant in a Brazilian family with congenital cataract

    Science.gov (United States)

    Giordano, Gabriel Gorgone; Tavares, Anderson; da Silva, Márcio José; de Vasconcellos, José Paulo Cabral; Arieta, Carlos Eduardo Leite; de Melo, Mônica Barbosa

    2011-01-01

    Purpose To describe a novel polymorphism in the γD-crystallin (CRYGD) gene in a Brazilian family with congenital cataract. Methods A Brazilian four-generation family was analyzed. The proband had bilateral lamellar cataract and the phenotypes were classified by slit lamp examination. Genomic DNA was extracted from peripheral blood and coding regions and intron/exon boundaries of the αA-crystallin (CRYAA), γC-crystallin (CRYGC), and CRYGD genes were amplified by polymerase chain reaction and directly sequenced. Results Sequencing of the coding regions of CRYGD showed the presence of a heterozygous A→G transversion at c.401 position, which results in the substitution of a tyrosine to a cysteine (Y134C). The polymorphism was identified in three individuals, two affected and one unaffected. Conclusions A novel rare variant in CRYGD (Y134C) was detected in a Brazilian family with congenital cataract. Because there is no segregation between the substitution and the phenotypes in this family, other genetic alterations are likely to be present. PMID:21866214

  5. Alternative splicing at exon 2 results in the loss of the catalytic activity of mouse DNA polymerase iota in vitro.

    Science.gov (United States)

    Kazachenko, Konstantin Y; Miropolskaya, Nataliya A; Gening, Leonid V; Tarantul, Vyacheslav Z; Makarova, Alena V

    2017-02-01

    Y-family DNA polymerase iota (Pol ι) possesses both DNA polymerase and dRP lyase activities and was suggested to be involved in DNA translesion synthesis and base excision repair in mammals. The 129 strain of mice and its derivatives have a natural nonsense codon mutation in the second exon of the Pol ι gene resulting in truncation of the Pol ι protein. These mice were widely used as a Pol ι-null model for in vivo studies of the Pol ι function. However whether 129-derived strains of mice are fully deficient in the Pol ι functions was a subject of discussion since Pol ι mRNA undergoes alternative splicing at exon 2. Here we report purification of mouse Pol ι lacking the region encoded by exon 2, which includes several conserved residues involved in catalysis. We show that the deletion abrogates both the DNA polymerase and dRP lyase activities of Pol ι in the presence of either Mg 2+ or Mn 2+ ions. Thus, 129-derived strains of mice express catalytically inactive alternatively spliced Pol ι variant, whose cellular functions, if any exist, remain to be established. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    DEFF Research Database (Denmark)

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J

    2015-01-01

    -surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery....... The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic......Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...

  7. MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

    Science.gov (United States)

    Stumpf, Jeffrey D; Copeland, William C

    2014-10-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  8. Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Zheng, Huiyuan; Shin, Andrew C; Lenard, Natalie R; Townsend, R Leigh; Patterson, Laurel M; Sigalet, David L; Berthoud, Hans-Rudolf

    2009-11-01

    Gastric bypass surgery efficiently and lastingly reduces excess body weight and reverses type 2 diabetes in obese patients. Although increased energy expenditure may also play a role, decreased energy intake is thought to be the main reason for weight loss, but the mechanisms involved are poorly understood. Therefore, the aim of this study was to characterize the changes in ingestive behavior in a rat model of Roux-en-Y gastric bypass surgery (RYGB). Obese (24% body fat compared with 18% in chow-fed controls), male Sprague-Dawley rats maintained for 15 wk before and 4 mo after RYGB or sham-surgery on a two-choice low-fat/high-fat diet, were subjected to a series of tests assessing energy intake, meal patterning, and food choice. Although sham-operated rats gained an additional 100 g body wt during the postoperative period, RYGB rats lost approximately 100 g. Intake of a nutritionally complete and palatable liquid diet (Ensure) was significantly reduced by approximately 50% during the first 2 wk after RYGB compared with sham surgery. Decreased intake was the result of greatly reduced meal size with only partial compensation by meal frequency, and a corresponding increase in the satiety ratio. Similar results were obtained with solid food (regular or high-fat chow) 6 wk after surgery. In 12- to 24-h two-choice liquid or solid diet paradigms with nutritionally complete low- and high-fat diets, RYGB rats preferred the low-fat choice (solid) or showed decreased acceptance for the high-fat choice (liquid), whereas sham-operated rats preferred the high-fat choices. A separate group of rats offered chow only before surgery completely avoided the solid high-fat diet in a choice paradigm. The results confirm anecdotal reports of "nibbling" behavior and fat avoidance in RYGB patients and provide a basis for more mechanistic studies in this rat model.

  9. Perforated marginal ulcers after laparoscopic gastric bypass.

    Science.gov (United States)

    Felix, Edward L; Kettelle, John; Mobley, Elijah; Swartz, Daniel

    2008-10-01

    Perforated marginal ulcer (PMU) after laparoscopic Roux-en-Y gastric bypass (LRYGB) is a serious complication, but its incidence and etiology have rarely been investigated. Therefore, a retrospective review of all patients undergoing LRYGB at the authors' center was conducted to determine the incidence of PMU and whether any causative factors were present. A prospectively kept database of all patients at the authors' bariatric center was retrospectively reviewed. The complete records of patients with a PMU were examined individually for accuracy and analyzed for treatment, outcome, and possible underlying causes of the marginal perforation. Between April 1999 and August 2007, 1% of the patients (35/3,430) undergoing laparoscopic gastric bypass experienced one or more perforated marginal ulcers 3 to 70 months (median, 18 months) after LRYGB. The patients with and without perforation were not significantly different in terms of mean age (37 vs 41 years), weight (286 vs 287 lb), body mass index (BMI) (46 vs 47), or female gender (89% vs 83%). Of the patients with perforations, 2 (6%) were taking steroids, 10 (29%) were receiving nonsteroidal antiinflammatory drugs (NSAIDs) at the time of the perforation, 18 (51%) were actively smoking, and 6 of the smokers also were taking NSAIDs. Eleven of the patients (31%) who perforated did not have at least one of these possible risk factors, but 4 (36%) of the 11 patients in this group had been treated after bypass for a marginal ulcer. Only 7 (20%) of the 35 patients who had laparoscopic bypass, or 7 (0.2%) in the entire group of 3,430 patients, perforated without any warning. There were no deaths, but three patients reperforated. The incidence of a marginal ulcer perforating after LRYGB was significant (>1%) and appeared to be related to smoking or the use of NSAIDs or steroids. Because only 0.2% of all patients acutely perforated without some risk factor or warning, long-term ulcer prophylaxis or treatment may be necessary

  10. Equilibrio trabajo-familia, apoyo familiar, autoeficacia parental y funcionamiento familiar percibidos por funcionarios públicos de Chile Work-Family Balance, Family Support, Parental Self Efficacy and Perceived Family Functioning in a Chilean Public Workers

    Directory of Open Access Journals (Sweden)

    Elizabeth Riquelme Orellana

    2012-06-01

    Full Text Available Se analiza la relación entre Equilibrio trabajo-familia, Apoyo familiar, y Autoeficacia parental en funcionarios públicos, determinado las diferencias entre hombres y mujeres. A 181 funcionarios profesionales les fueron aplicados tres instrumentos de medición de las variables referidas. Se observa que existen diferencias estadísticamente significativas en el nivel de equilibrio trabajo-familia entre hombres y mujeres, obteniendo un mayor equilibrio las mujeres. Por otra parte no se encontró diferencias en apoyo familiar, autoeficacia parental y en funcionamiento familiar. En cuanto a la relación entre dichas variables se encontró una relación estadísticamente significativa entre Apoyo familiar y autoeficacia parental (r=-0,333; pIt is analyzed the relationship between work-family balance, family support, parental self-efficacy and public officials, given the differences between men and women. A 181 professional staff We applied three instruments measuring variables related. It is noted that there were significant differences in the level of work-family balance among men and women, giving women a better balance. On the other hand there was no difference in family support, parental self-efficacy and family functioning. Regarding the relationship between these variables was found a statistically significant relationship between family support and parental self-efficacy (r =- 0.333, p <0.01 between family support and family functioning (r = 0.734, p <0.01, work-family balance and parental self-efficacy (r = 0.275, p<0.01 and between parental efficacy and family functioning (r =-0.276, P <0.01.

  11. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota

    DEFF Research Database (Denmark)

    Palleja, Albert; Kashani, Alireza; Allin, Kristine Højgaard

    2016-01-01

    Background: Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated......) to assimilate multiple energy sources using transporters and phosphotransferase systems, (ii) to use aerobic respiration, (iii) to shift from protein degradation to putrefaction, and (iv) to use amino acids and fatty acids as energy sources. Conclusions: Within 3 months after morbidly obese individuals had...... with obesity and some of its co-morbidities, like type 2 diabetes, and major changes of gut microbial communities have been hypothesized to mediate part of the beneficial metabolic effects observed after RYGB. Here we describe changes in gut microbial taxonomic composition and functional potential following...

  12. Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues

    DEFF Research Database (Denmark)

    Ten Kulve, Jennifer S; Veltman, Dick J; Gerdes, Victor E A

    2017-01-01

    of the GLP-1 receptor antagonist exendin 9-39 (Ex9-39) and placebo were assessed in 10 women before and after RYGB. We used functional MRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk), comparing results with Ex9-39 versus...... in response to visual and gustatory food cues may be mediated by central effects of GLP-1. Our findings provide further insights into the mechanisms underlying the weight-lowering effects of RYGB.......OBJECTIVE: It has been suggested that weight reduction and improvements in satiety after Roux-en-Y gastric bypass (RYGB) are partly mediated via postoperative neuroendocrine changes. Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted after food ingestion and is associated with appetite...

  13. Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota

    DEFF Research Database (Denmark)

    Palleja, Albert; Kashani, Alireza; Allin, Kristine Højgaard

    2016-01-01

    RYGB. Methods: We recruited 13 morbidly obese patients who underwent RYGB, carefully phenotyped them, and had their gut microbiomes quantified before (n = 13) and 3 months (n = 12) and 12 months (n = 8) after RYGB. Following shotgun metagenomic sequencing of the fecal microbial DNA purified from stools......Background: Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated...... with obesity and some of its co-morbidities, like type 2 diabetes, and major changes of gut microbial communities have been hypothesized to mediate part of the beneficial metabolic effects observed after RYGB. Here we describe changes in gut microbial taxonomic composition and functional potential following...

  14. Hybrid laparoscopic-robotic management of type IVa choledochal cyst in the setting of prior Roux-en-Y gastric bypass: video case report and review of the literature.

    Science.gov (United States)

    Chang, Julietta; Walsh, R Matthew; El-Hayek, Kevin

    2015-06-01

    Choledochal cysts are rare congenital disease of the biliary system. The recommended treatment of these lesions is surgical excision with biliary enteric reconstruction. In patients with normal anatomy, Roux-en-Y hepaticojejunostomy is preferred. However, different options in biliary reconstruction must be entertained in those with abnormal anatomy. Our patient is a 39-year-old female, who during workup for bariatric surgery two years prior to presentation, was found to have a 6 cm dilation of her common bile duct. She underwent a laparoscopic Roux-en-Y gastric bypass (LRYGB) in 2011 at an outside facility, with no planned intervention on her biliary tree. Ultimately, she developed right upper quadrant pain two years following her RYGB. Upon further workup including right upper quadrant ultrasound, an extrahepatic choledochal cyst was confirmed and she was referred to our institution for definitive care. The patient was taken to the operating room for resection of the choledochal cyst with hepatoenteric reconstruction. The dissection and resection of the cyst commenced laparoscopically. After performing a generous Kocher maneuver, we demonstrated that there was adequate mobilization of the duodenum to perform a tension free hepaticoduodenostomy, which was performed robotically. Her postoperative course was uneventful, and she was discharged home on postoperative day 3. At one month follow up, the patient was doing well with symptom resolution. Her final pathology revealed a choledochal cyst which was negative for dysplasia or carcinoma. Long-term follow up has been recommended with yearly alkaline phosphatase levels. Here we present a video of the technical considerations during a robot-assisted laparoscopic biliary reconstruction in a patient with a prior Roux-en-Y gastric bypass with a type IVA choledochal cyst.

  15. Alterações nos parâmetros pré e pós-operatórios de pacientes com síndrome metabólica, submetidos a Bypass gastrointestinal em Y de Roux Changes in the pre- and postoperative parameters in metabolic syndrome patients submitted to Roux-en-Y gastric bypass

    Directory of Open Access Journals (Sweden)

    Paulo Afonso Nunes Nassif

    2009-09-01

    Full Text Available RACIONAL: A epidemia mundial de sobrepeso e obesidade afeta aproximadamente 1,7 bilhão de pessoas, havendo aumento nos casos de obesidade mórbida de 80% para mulheres e de 400% para homens desde 1970. A síndrome metabólica é transtorno complexo relacionado com resistência à insulina e obesidade abdominal, provocando alterações no metabolismo da glicose em vários tecidos e hiperinsulinemia. OBJETIVO: Verificar as alterações nos parâmetros pré e pós-operatórios em pacientes obesos mórbidos com síndrome metabólica, submetidos a bypass gastrointestinal em Y de Roux. MÉTODO: Casuística de 74 pacientes obesos, que apresentavam síndrome metabólica e submetidos a procedimento cirúrgico. Foram avaliados, além do IMC, a relação cintura-quadril, pressão arterial, colesterol total, HDL, LDL, triglicerídeos, glicemia de jejum no pré-operatório e no 1º e 4º meses de pós-operatório. Para variáveis que apresentaram simetria na sua distribuição, foi usado o teste t de Student para amostras pareadas. Para variáveis com distribuição assimétrica, foi usado o teste não-paramétrico de Wilcoxon. Valores de PBACKGROUND: Overweight and obesity affects approximately 1.7 billion people, with increase in morbid obesity of 80% for women and 400% for men, since 1970. Metabolic syndrome is a complex disorder associated with insulin resistance and abdominal obesity, causing changes in glucose metabolism in various tissues and hyperinsulinemia. AIM: To verify changes in the pre and post-operative parameters in morbidly obese patients with metabolic syndrome who underwent to Roux-en-Y gastrointestinal bypass. METHOD: Seventy four patients with obesity with metabolic syndrome submitted to gastrointestinal bypass Roux-en-Y were included. All of them had measured waist-hip ratio, blood pressure, total cholesterol, HDL, LDL, triglycerides and fasting glucose pre-operatively and at the first and fourth month post-operatively. RESULTS: In

  16. Surgical Elimination of the Gastric Digestion by Roux-en-Y Gastric Bypass Impacts on Food Sensitisation-a Pilot Study.

    Science.gov (United States)

    Shakeri-Leidenmühler, Soheila; Lukschal, Anna; Schultz, Cornelia; Bohdjalian, Arthur; Langer, Felix; Birsan, Tudor; Diesner, Susanne C; Greisenegger, Elli K; Scheiner, Otto; Kopp, Tamara; Jensen-Jarolim, Erika; Prager, Gerhard; Untersmayr, Eva

    2015-12-01

    Impairment of gastric digestion due to pH elevation increases the risk for food allergy induction. As patients after Roux-en-Y gastric bypass (RYGB) surgery have lower gastric acidity and less gastric gland secretion, we aimed to analyse in a prospective study the effect of limiting gastric digestion capacity by surgical intervention on the immune response towards allergens. Nine patients undergoing RYGB surgery for morbid obesity and one control patient having undergone surgery for treatment of an incisional hernia were enrolled in the study. Before and 1, 3, 6, 9 and 12 months after surgery, blood was collected for analysis of specific IgE antibodies, and patients were subjected to skin prick testing with 16 food and 18 aeroallergens. Skin prick test results revealed an increase of positive reactions indicating sensitisations towards the tested food and aeroallergens in 77.8 and 88.9 % of the patients, respectively, after surgical elimination of gastric digestion. These results were in line with elevated titers of food- and aeroallergen-specific IgE antibodies in 7 out of 9 (7/9) and 5/9 patients, respectively, after RYGB surgery. Serum cytokine levels revealed a mixed response for IFN-γ and were mostly beneath detection limit for IL-4. A change of IgE reactivity pattern occurred after impairment of gastric digestion due to surgical elimination underlining the important gastric gatekeeping function during oral sensitisation. Even though this study indicates an increased allergy risk for gastric bypass patients, further studies are needed to investigate in-depth the immunological changes associated with RYGB surgery.

  17. Intergenerational Learning (Between Generation X & Y) in Learning Families: A Narrative Inquiry

    Science.gov (United States)

    Ho, C. Y. Cherri

    2010-01-01

    The purpose of this study is to examine intergenerational learning behaviour within ten Hong Kong families between Generation X parents and their Generation Y children. It tries to investigate intergenerational knowledge exchange, identify the characteristics of learning behaviour and culture in their "learning families". A narrative…

  18. Investigating the effect of continuous care model on social health status of family caregivers in hospitalized patients undergoing coronary artery bypass graft surgery

    Directory of Open Access Journals (Sweden)

    T NasrAbadi

    2016-09-01

    Full Text Available Introduction: Chronic patient care causes  some problems, including pressure or burden of care, reducing the time for routine activities and self care, also causes compatibility decline in deal with stress and disorders of physical and mental health, emotional, social and financial prosperity of caregivers. The aim of this study was to determine the effect of continuous care model on social health status of  family caregivers in patients  underwent coronary artery bypass surgeries. Methods: This study was  one-group clinical trial research, the samples consisted 48 family caregiver of  the patients  underwent coronary artery bypass graft  surgeries, who  were selected using purposive sampling method. Data collection tools included the standard questionnaire Data collection tool was Novak and Guest caring burden inventory (CBI s as well as demographic questionnaire, which  was  measured at the baseline and 8 weeks after intervention.  Data were analyzed using  descriptive  and analytic statistic (paired t-test, and covariance analysis with SPSS version 16. Results: The mean score of  caring burden realated  to  the social health status before intervention was 3.86±6.11 and after intervention was 1.81±2.33. In examining five dimensions burden of care,  continuous care model had an impact on all aspects of the  caring burden and it led to the reduction of the burden of care  in  all aspects.  So,  it had a significant decrease  in the social health status (p <0.01. Conclusion: Implementation of continuous care model as the intervention of cheaper and available,  can be an effective step inreducing the burden of care of the  patients with  coronary artery disease in health status of social.

  19. Evaluation of the patency of an extracranial-intracranial bypass using magnetic resonance angiography with selective presaturation of bypass vessels

    Energy Technology Data Exchange (ETDEWEB)

    Mabuchi, Shoji; Nakayama, Naoki; Isu, Toyohiko; Harata, Tatsuo; Nanbu, Toshikazu [Kushiro Rousai Hospital, Hokkaido (Japan)

    1994-06-01

    Three-dimensional time-of-flight magnetic resonance (MR) angiography using radiofrequency presaturation pulses was used to evaluate the patency of extracranial-intracranial (EC/IC) bypass in 11 patients. Presaturation causes signal loss in the vascular territory supplied by the presaturated EC/IC bypass graft. In all patients with a patent EC/IC bypass graft confirmed on conventional angiography, disappearance of the signal of the middle cerebral artery receiving blood flow from the bypass graft was clearly observed on MR angiograms with presaturation, indicating patency of the EC/IC bypass graft. MR angiography with presaturation pulses is a noninvasive and repeatable method for evaluation of the function of an EC/IC bypass graft. (author).

  20. The RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden

    2015-03-01

    Full Text Available The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71 for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy. Nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. Most non-nucleoside inhibitors (NNIs target surface cavities, which are structurally more flexible than the nucleotide-binding pocket, and hence have a more narrow spectrum of activity and are more prone to resistance development. Here, we report a novel NNI, GPC-N114 (2,2'-[(4-chloro-1,2-phenylenebis(oxy]bis(5-nitro-benzonitrile with broad-spectrum activity against enteroviruses and cardioviruses (another genus in the picornavirus family. Surprisingly, coxsackievirus B3 (CVB3 and poliovirus displayed a high genetic barrier to resistance against GPC-N114. By contrast, EMCV, a cardiovirus, rapidly acquired resistance due to mutations in 3Dpol. In vitro polymerase activity assays showed that GPC-N114 i inhibited the elongation activity of recombinant CVB3 and EMCV 3Dpol, (ii had reduced activity against EMCV 3Dpol with the resistance mutations, and (iii was most efficient in inhibiting 3Dpol when added before the RNA template-primer duplex. Elucidation of a crystal structure of the inhibitor bound to CVB3 3Dpol confirmed the RNA-binding channel as the target for GPC-N114. Docking studies of the compound into the crystal structures of the compound-resistant EMCV 3Dpol mutants suggested that the resistant phenotype is due to subtle changes that interfere with the binding of GPC-N114 but not of the RNA template-primer. In conclusion, this study presents the first NNI that targets the RNA template channel of the picornavirus polymerase and identifies a new pocket that can be used for the design of broad-spectrum inhibitors. Moreover, this study provides important new insight

  1. The proofreading 3'→5' exonuclease activity of DNA polymerases: a kinetic barrier to translesion DNA synthesis

    International Nuclear Information System (INIS)

    Khare, Vineeta; Eckert, Kristin A.

    2002-01-01

    The 3'→5' exonuclease activity intrinsic to several DNA polymerases plays a primary role in genetic stability; it acts as a first line of defense in correcting DNA polymerase errors. A mismatched basepair at the primer terminus is the preferred substrate for the exonuclease activity over a correct basepair. The efficiency of the exonuclease as a proofreading activity for mispairs containing a DNA lesion varies, however, being dependent upon both the DNA polymerase/exonuclease and the type of DNA lesion. The exonuclease activities intrinsic to the T4 polymerase (family B) and DNA polymerase γ (family A) proofread DNA mispairs opposite endogenous DNA lesions, including alkylation, oxidation, and abasic adducts. However, the exonuclease of the Klenow polymerase cannot discriminate between correct and incorrect bases opposite alkylation and oxidative lesions. DNA damage alters the dynamics of the intramolecular partitioning of DNA substrates between the 3'→5' exonuclease and polymerase activities. Enzymatic idling at lesions occurs when an exonuclease activity efficiently removes the same base that is preferentially incorporated by the DNA polymerase activity. Thus, the exonuclease activity can also act as a kinetic barrier to translesion synthesis (TLS) by preventing the stable incorporation of bases opposite DNA lesions. Understanding the downstream consequences of exonuclease activity at DNA lesions is necessary for elucidating the mechanisms of translesion synthesis and damage-induced cytotoxicity

  2. Roux-en-Y gastric bypass in the treatment of non-classic congenital adrenal hyperplasia due to 11-hydroxylase deficiency.

    Science.gov (United States)

    Kalani, Amir; Thomas, Nithin; Sacerdote, Alan; Bahtiyar, Gül

    2013-03-18

    Non-classic adrenal hyperplasia (NCAH) has been associated with insulin resistance (IR). Therapies such as metformin, thiazolidinediones and lifestyle alterations improve IR and also ameliorate the biochemical and clinical abnormalities of NCAH, much as they do in polycystic ovarian syndrome (PCOS). More recently, bariatric surgery, such as Roux-en-Y gastric bypass (RYGBP), has also been associated with improvement in IR and amelioration of PCOS and may, therefore, be beneficial in NCAH. We report a case of a 39-year-old, deaf-mute, obese woman with NCAH due to 11-hydroxylase deficiency who underwent RYGBP followed by improvement of NCAH manifestations. She was initially treated with metformin and pioglitazone, which lowered serum 11-deoxycortisol from 198 ng/dl (irregular menses normalised as well. We conclude that RYGBP, like other interventions that reduce IR, may be another way of treating non-classic 11-hydroxylase deficiency in selected patients.

  3. Changes in Global Transcriptional Profiling of Women Following Obesity Surgery Bypass.

    Science.gov (United States)

    Pinhel, Marcela Augusta de Souza; Noronha, Natalia Yumi; Nicoletti, Carolina Ferreira; de Oliveira, Bruno Affonso Parente; Cortes-Oliveira, Cristiana; Pinhanelli, Vitor Caressato; Salgado Junior, Wilson; Machry, Ana Julia; da Silva Junior, Wilson Araújo; Souza, Dorotéia Rossi Silva; Marchini, Júlio Sérgio; Nonino, Carla Barbosa

    2018-01-01

    Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss. The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control. The gene expression levels were determined by microarray analysis. Significant differences in gene expression were validated by real-time quantitative polymerase chain reaction (RT-qPCR). Microarray analysis for comparison of the pre- and postoperative periods showed that 1366 genes were differentially expressed genes (DEGs). The main pathways were related to gene transcription; lipid, energy, and glycide metabolism; inflammatory and immunological response; cell differentiation; oxidative stress regulation; response to endogenous and exogenous stimuli; substrate oxidation; mTOR signaling pathway; interferon signaling; mitogen-activated protein kinases (MAPK), cAMP response element binding protein (CREB1), heat shock factor 1 (HSF1), and sterol regulatory element binding protein 1c (SREBP-1c) gene expression; adipocyte differentiation; and methylation. Six months after bariatric surgery and significant weight loss, many molecular pathways involved in obesity and metabolic diseases change. These findings are an important tool to identify potential targets for therapeutic intervention and clinical practice of nutritional genomics in obesity.

  4. Management of Excessive Weight Loss Following Laparoscopic Roux-en-Y Gastric Bypass: Clinical Algorithm and Surgical Techniques.

    Science.gov (United States)

    Akusoba, Ikemefuna; Birriel, T Javier; El Chaar, Maher

    2016-01-01

    There are no clinical guidelines or published studies addressing excessive weight loss and protein calorie malnutrition following a standard Roux-en-Y gastric bypass (RYGB) to guide nutritional management and treatment strategies. This study demonstrates the presentation, clinical algorithm, surgical technique, and outcomes of patients afflicted and successfully treated with excessive weight loss following a standard RYGB. Three patients were successfully reversed to normal anatomy after evaluation, management, and treatment by multidisciplinary team. Lowest BMI (kg/m(2)) was 18.9, 17.9, and 14.2, respectively. Twelve-month post-operative BMI (kg/m(2)) was 28.9, 22.8, and 26.1, respectively. Lowest weight (lbs) was 117, 128, and 79, respectively. Twelve-month post-operative weight (lbs) was 179, 161, and 145, respectively. Pre-reversal gastrostomy tube was inserted into the remnant stomach to demonstrate weight gain and improve nutritional status prior to reversal to original anatomy. We propose a practical clinical algorithm for the work-up and management of patients with excessive weight loss and protein calorie malnutrition after standard RYGB including reversal to normal anatomy.

  5. Integrated turbine bypass system

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.H.; Dickenson, R.J.; Parry, W.T.; Retzlaff, K.M.

    1982-07-01

    Turbine steam-flow bypasses have been used for years in various sizes and applications. Because of differing system requirements, their use has been more predominant in Europe than in the United States. Recently, some utilities and consulting engineers have been re-evaluating their need for various types of bypass operation in fossil-fuelled power plants.

  6. Macrophage Area Content and Phenotype in Hepatic and Adipose Tissue in Patients with Obesity Undergoing Roux-en-Y Gastric Bypass

    DEFF Research Database (Denmark)

    Kristensen, Marianne D; Lund, Michael Taulo; Hansen, Merethe

    2017-01-01

    OBJECTIVE: To investigate hepatic and adipose tissue macrophage content in subjects with obesity and the role of adipose tissue macrophages in weight loss-induced improved insulin sensitivity (IS). METHODS: A cross-sectional and a longitudinal study were combined to investigate the role...... of macrophages in subcutaneous (SAT) and visceral (VAT) adipose tissue and the liver in obesity-induced impaired IS and improvements with weight loss. Macrophage markers (CD68, CD163, and CD206) in SAT, VAT, and the liver from patients with obesity were investigated. The same macrophage markers were investigated...... in SAT from 18 patients with obesity before and ∼18 months after a diet- and Roux-en-Y gastric bypass-induced weight loss. RESULTS: SAT macrophage markers did not decrease with weight loss, but macrophage concentration may have increased, concomitant with improved IS. Hepatic macrophage markers did...

  7. Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

    Science.gov (United States)

    Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

    2007-11-01

    Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

  8. [Body weight evolution and classification of body weight in relation to the results of bariatric surgery: roux-en-Y gastric bypass].

    Science.gov (United States)

    Novais, Patrícia Fátima Sousa; Rasera Junior, Irineu; Leite, Celso Vieira de Souza; Oliveira, Maria Rita Marques de

    2010-03-01

    The objective of this study was to assess the evolution and classification of body weight in relation to the results of bariatric surgery in women who underwent the procedure more than two years ago. A total of 141 women underwent banded Roux-en-Y gastric bypass (RYGB). The participants were divided according to the time elapsed since surgery and the percentage of excess weight lost (%EWL): 75. The women in the group with %EWL 75 (36.2%) ranged from normal to pre-obese and presented lower late weight gain than the women in the other groups. Weight evolution two or more years after surgery showed the expected reductions, with some individuals responding better to surgery than others. This shows that it is necessary to monitor, investigate and intervene to obtain the desired results.

  9. Upper gastrointestinal series after Roux-en-Y gastric bypass for morbid obesity: effectiveness in leakage detection. a systematic review of the literature.

    Science.gov (United States)

    Quartararo, Giovanni; Facchiano, Enrico; Scaringi, Stefano; Liscia, Gadiel; Lucchese, Marcello

    2014-07-01

    The aim of this study is to evaluate the results of routine and selective postoperative upper gastrointestinal series (UGIS) after Roux-en-Y gastric bypass (RYGB) for morbid obesity in different published series to assessing its utility and cost-effectiveness. A search in PubMed's MEDLINE was performed for English-spoken articles published from January 2002 to December 2012. Keywords used were upper GI series, RYGB, and obesity. Only cases of anastomotic leaks were considered. A total of 22 studies have been evaluated, 15 recommended a selective use of postoperative UGIS. No differences in leakage detection or in clinical benefit between routine and selective approaches were found. Tachycardia and respiratory distress represent the best criteria to perform UGIS for early diagnosis of anastomotic leak after a RYGB.

  10. Evolution of nutritional, hematologic and biochemical changes in obese women during 8 weeks after Roux-en-Y gastric bypasss Evolución de los cambios nutricionales, hematológicos y bioquímicos en mujeres obesas durante 8 semanas después de bypass gástrico en Y de Roux

    OpenAIRE

    V. Custódio Afonso Rocha; L. Ramos de Arvelos; G. Pereira Felix; D. Nogueira Prado de Souza; M. Bernardino Neto; E. Santos Resende; N. Penha-Silva

    2012-01-01

    Obesity is a chronic disease of multifactorial origin and currently is a serious public health problem. The treatment of morbid obesity can be effectively done by bariatric surgery. The present study aimed to evaluate the influence of changes in food intake on body composition and some hematologic and biochemical variables in the period of eight weeks after Roux-en-Y gastric bypass (RYGB). The study included 22 women submitted to RYGB. We evaluated anthropometric, nutritional, hematologic and...

  11. Intraoperative echocardiographic imaging of coronary arteries and graft anastomoses during coronary artery bypass grafting without cardiopulmonary bypass.

    Science.gov (United States)

    Suematsu, Y; Takamoto, S; Ohtsuka, T

    2001-12-01

    No accepted approach exists for the intraoperative evaluation of the quality of coronary arteries and the technical adequacy of graft anastomoses during coronary artery bypass grafting without cardiopulmonary bypass. We assessed the accuracy of high-frequency epicardial echocardiography and power Doppler imaging in evaluating coronary arteries during coronary artery bypass grafting without cardiopulmonary bypass. To validate measurements of coronary arteries and graft anastomoses by high-frequency epicardial echocardiography and power Doppler imaging, we compared luminal diameters determined by these methods with diameters determined histologically in a study of off-pump coronary artery bypass grafting in 20 dogs. Technical errors were deliberately created in 10 grafts (stenosis group). The results of these animal validation studies showed that the maximum luminal diameters of coronary arteries and graft anastomoses measured by high-frequency epicardial echocardiography (HEE) and power Doppler imaging (PDI) correlated well with the histologic measurements: HEE = 1.027 x Histologic measurements + 0.005 (P anastomoses were examined intraoperatively by high-frequency epicardial echocardiography and power Doppler imaging, and luminal diameters determined by power Doppler imaging were compared with those determined by postoperative coronary angiography. The results demonstrated that graft anastomosis by power Doppler imaging correlated well with the angiographic measurements: PDI = 1.018 x Angiographic measurements - 0.106 (P anastomoses and can detect technical errors and inadequacies during coronary artery bypass grafting without cardiopulmonary bypass.

  12. Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery.

    Science.gov (United States)

    Zhu, Ying; Feng, Bing; He, Songmin; Su, Zuqing; Zheng, Guangjuan

    2018-02-01

    To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery. The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively. Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (P Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft. Copyright © 2018 Elsevier GmbH. All rights reserved.

  13. Impaired alcohol metabolism after gastric bypass surgery: a case-crossover trial.

    Science.gov (United States)

    Woodard, Gavitt A; Downey, John; Hernandez-Boussard, Tina; Morton, John M

    2011-02-01

    Severe obesity remains the leading public health crisis of the industrialized world, with bariatric surgery the only effective and enduring treatment. Poor psychological adjustment has been occasionally reported postoperatively. In addition, evidence suggests that patients can metabolize alcohol differently after gastric bypass. Preoperatively and at 3 and 6 months postoperatively, 19 Roux-en-Y gastric bypass (RYGB) patients' breath alcohol content (BAC) was measured every 5 minutes after drinking 5 oz red wine to determine peak BAC and time until sober in a case-crossover design preoperatively and at 6 months postoperatively. Patients reported symptoms experienced when intoxicated and answered a questionnaire of drinking habits. The peak BAC in patients after RYGB was considerably higher at 3 months (0.059%) and 6 months (0.088%) postoperatively than matched preoperative levels (0.024%). Patients also took considerably more time to return to sober at 3 months (61 minutes) and 6 months (88 minutes) than preoperatively (49 minutes). Postoperative intoxication was associated with lower levels of diaphoresis, flushing, and hyperactivity and higher levels of dizziness, warmth, and double vision. Postoperative patients reported drinking considerably less alcohol, fewer preferred beer, and more preferred wine than before surgery. This is the first study to match preoperative and postoperative alcohol metabolism in gastric bypass patients. Post-RYGB patients have much higher peak BAC after ingesting alcohol and require more time to become sober. Patients who drink alcohol after gastric bypass surgery should exercise caution. Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Polymerase Chain Reaction (PCR) provides a superior tool for the ...

    African Journals Online (AJOL)

    Polymerase Chain Reaction (PCR) provides a superior tool for the diagnosis of Pneumococcal Infection in Burkina Faso. Y Chaibou, M Congo/Ouedraogo, I Sanou, H Somlare, K Ouattara, CM Kienou, H Belem, E Sampo, SA Traore, R Traore/Ouedraogo, C Hatcher, L Mayer, X Wang, L Sangare ...

  15. DNA Polymerase κ Is a Key Cellular Factor for the Formation of Covalently Closed Circular DNA of Hepatitis B Virus.

    Directory of Open Access Journals (Sweden)

    Yonghe Qi

    2016-10-01

    Full Text Available Hepatitis B virus (HBV infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP, followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s that fills the gap in the plus strand of rcDNA remains to be determined. Here we conducted targeted genetic screening in combination with chemical inhibition to identify the cellular DNA polymerase(s responsible for cccDNA formation, and exploited recombinant HBV with capsid coding deficiency which infects HepG2-NTCP cells with similar efficiency of wild-type HBV to assure cccDNA synthesis is exclusively from de novo HBV infection. We found that DNA polymerase κ (POLK, a Y-family DNA polymerase with maximum activity in non-dividing cells, substantially contributes to cccDNA formation during de novo HBV infection. Depleting gene expression of POLK in HepG2-NTCP cells by either siRNA knockdown or CRISPR/Cas9 knockout inhibited the conversion of rcDNA into cccDNA, while the diminished cccDNA formation in, and hence the viral infection of, the knockout cells could be effectively rescued by ectopic expression of POLK. These studies revealed that POLK is a crucial host factor required for cccDNA formation during a de novo HBV infection and suggest that POLK may be a potential target for developing antivirals against HBV.

  16. Haemodynamics in axillobifemoral bypass grafts

    NARCIS (Netherlands)

    C.H. Wittens

    1992-01-01

    textabstractThis thesis is based on four publications on the subject of graft configuration and haemodynamics in axillobifemoral bypass grafts: 1. A clinical evaluation of 17 patients with axillobifemoral bypass graft operations, performed for various indications. Two important observations were

  17. Miscoding properties of 1,N{sup 6}-ethanoadenine, a DNA adduct derived from reaction with antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-03-05

    1,N{sup 6}-Ethanoadenine (EA) is an exocyclic adduct formed from DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). To understand the role of this adduct in the mechanism of mutagenicity or carcinogenicity by BCNU, an oligonucleotide with a site-specific EA was synthesized using phosphoramidite chemistry. We now report the in vitro miscoding properties of EA in translesion DNA synthesis catalyzed by mammalian DNA polymerases (pols) {alpha}, {beta}, {eta} and {iota}. These data were also compared with those obtained for the structurally related exocyclic adduct, 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using a primer extension assay, both pols {alpha} and {beta} were primarily blocked by EA or {var_epsilon}A with very minor extension. Pol {eta} a member of the Y family of polymerases, was capable of catalyzing a significant amount of bypass across both adducts. Pol {eta} incorporated all four nucleotides opposite EA and {var_epsilon}A, but with differential preferences and mainly in an error-prone manner. Human pol {iota}, a paralog of human pol {eta}, was blocked by both adducts with a very small amount of synthesis past {var_epsilon}A. It incorporated C and, to a much lesser extent, T, opposite either adduct. In addition, the presence of an A adduct, e.g. {var_epsilon}A, could affect the specificity of pol {iota} toward the template T immediately 3 feet to the adduct. In conclusion, the four polymerases assayed on templates containing an EA or {var_epsilon}A showed differential bypass capacity and nucleotide incorporation specificity, with the two adducts not completely identical in influencing these properties. Although there was a measurable extent of error-free nucleotide incorporation, all these polymerases primarily misincorporated opposite EA, indicating that the adduct, similar to {var_epsilon}A, is a miscoding lesion.

  18. DNA Repair Mechanisms and the Bypass of DNA Damage in Saccharomyces cerevisiae

    Science.gov (United States)

    Boiteux, Serge; Jinks-Robertson, Sue

    2013-01-01

    DNA repair mechanisms are critical for maintaining the integrity of genomic DNA, and their loss is associated with cancer predisposition syndromes. Studies in Saccharomyces cerevisiae have played a central role in elucidating the highly conserved mechanisms that promote eukaryotic genome stability. This review will focus on repair mechanisms that involve excision of a single strand from duplex DNA with the intact, complementary strand serving as a template to fill the resulting gap. These mechanisms are of two general types: those that remove damage from DNA and those that repair errors made during DNA synthesis. The major DNA-damage repair pathways are base excision repair and nucleotide excision repair, which, in the most simple terms, are distinguished by the extent of single-strand DNA removed together with the lesion. Mistakes made by DNA polymerases are corrected by the mismatch repair pathway, which also corrects mismatches generated when single strands of non-identical duplexes are exchanged during homologous recombination. In addition to the true repair pathways, the postreplication repair pathway allows lesions or structural aberrations that block replicative DNA polymerases to be tolerated. There are two bypass mechanisms: an error-free mechanism that involves a switch to an undamaged template for synthesis past the lesion and an error-prone mechanism that utilizes specialized translesion synthesis DNA polymerases to directly synthesize DNA across the lesion. A high level of functional redundancy exists among the pathways that deal with lesions, which minimizes the detrimental effects of endogenous and exogenous DNA damage. PMID:23547164

  19. A shared promoter region suggests a common ancestor for the human VCX/Y, SPANX, and CSAG gene families and the murine CYPT family

    DEFF Research Database (Denmark)

    Hansen, Martin A; Nielsen, John E; Retelska, Dorota

    2008-01-01

    , sequences corresponding to the shared promoter region of the CYPT family were identified at 39 loci. Most loci were located immediately upstream of genes belonging to the VCX/Y, SPANX, or CSAG gene families. Sequence comparison of the loci revealed a conserved CYPT promoter-like (CPL) element featuring TATA...... cell types. The genomic regions harboring the gene families were rich in direct and inverted segmental duplications (SD), which may facilitate gene conversion and rapid evolution. The conserved CPL and the common expression profiles suggest that the human VCX/Y, SPANX, and CSAG2 gene families together......Many testis-specific genes from the sex chromosomes are subject to rapid evolution, which can make it difficult to identify murine genes in the human genome. The murine CYPT gene family includes 15 members, but orthologs were undetectable in the human genome. However, using refined homology search...

  20. Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination.

    Science.gov (United States)

    Betz, U A; Vosshenrich, C A; Rajewsky, K; Müller, W

    1996-10-01

    The analysis of gene function based on the generation of mutant mice by homologous recombination in embryonic stem cells is limited if gene disruption results in embryonic lethality. Mosaic mice, which contain a certain proportion of mutant cells in all organs, allow lethality to be circumvented and the potential of mutant cells to contribute to different cell lineages to be analyzed. To generate mosaic animals, we used the bacteriophage P1-derived Cre-loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments. We generated nestin-cre transgenic mouse lines, which expressed the Cre recombinase under the control of the rat nestin promoter and its second intron enhancer. In crosses to animals carrying a loxP-flanked target gene, partial deletion of the loxP-flanked allele occurred before day 10.5 post coitum and was detectable in all adult organs examined, including germ-line cells. Using this approach, we generated mosaic mice containing cells deficient in the gamma-chain of the interleukin-2 receptor (IL-2R gamma); in these animals, the IL-2R gamma-deficient cells were underrepresented in the thymus and spleen. Because mice deficient in DNA polymerase beta die perinatally, we studied the effects of DNA polymerase beta deficiency in mosaic animals. We found that some of the mosaic polymerase beta-deficient animals were viable, but were often reduced in size and weight. The fraction of DNA polymerase beta-deficient cells in mosaic embryos decreased during embryonic development, presumably because wild-type cells had a competitive advantage. The nestin-cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes. By using mosaic animals, embryonic lethality can be bypassed and cell lineages for whose development a given target gene is critical can be identified. In the case of DNA polymerase beta, deficient cells are already

  1. Annotation, Phylogeny and Expression Analysis of the Nuclear Factor Y Gene Families in Common Bean (Phaseolus vulgaris

    Directory of Open Access Journals (Sweden)

    Carolina eRípodas

    2015-01-01

    Full Text Available In the past decade, plant nuclear factor Y (NF-Y genes have gained major interest due to their roles in many biological processes in plant development or adaptation to environmental conditions, particularly in the root nodule symbiosis established between legume plants and nitrogen fixing bacteria. NF-Ys are heterotrimeric transcriptional complexes composed of three subunits, NF-YA, NF-YB and NF-YC, which bind with high affinity and specificity to the CCAAT box, a cis element present in many eukaryotic promoters. In plants, NF-Y subunits consist of gene families with about ten members each. In this study, we have identified and characterized the NF-Y gene families of common bean (Phaseolus vulgaris, a grain legume of worldwide economical importance and the main source of dietary protein of developing countries. Expression analysis showed that some members of each family are up-regulated at early or late stages of the nitrogen fixing symbiotic interaction with its partner Rhizobium etli. We also showed that some genes are differentially accumulated in response to inoculation with high or less efficient R. etli strains, constituting excellent candidates to participate in the strain-specific response during symbiosis. Genes of the NF-YA family exhibit a highly structured intron-exon organization. Moreover, this family is characterized by the presence of upstream ORFs when introns in the 5' UTR are retained and miRNA target sites in their 3' UTR, suggesting that these genes might be subjected to a complex post-transcriptional regulation. Multiple protein alignments indicated the presence of highly conserved domains in each of the NF-Y families, presumably involved in subunit interactions and DNA binding. The analysis presented here constitutes a starting point to understand the regulation and biological function of individual members of the NF-Y families in different developmental processes in this grain legume.

  2. Longitudinal trends in hedonic hunger after Roux-en-Y gastric bypass in adolescents.

    Science.gov (United States)

    Cushing, Christopher C; Benoit, Stephen C; Peugh, James L; Reiter-Purtill, Jennifer; Inge, Thomas H; Zeller, Meg H

    2014-01-01

    Initial outcome studies have reported that Roux-en-Y gastric bypass (RYGB) is safe and efficacious for adolescents with extreme obesity. Although rapid weight loss is seen initially, data also show that modest weight regain typically occurs as early as the second postoperative year. The contribution of various psychological factors, including hedonic hunger, to postoperative weight regain has not previously been studied in adolescents. The objective of this study was to examine the variability in hedonic hunger and body mass index (BMI) over the initial 2-year period of weight loss and modest weight regain in adolescent RYGB recipients. A total of 16 adolescents completed the Power of Food Scale before surgery and at 3, 6, 12, 18, and 24 months postoperatively. Height and weight were measured at each time point, from which BMI was calculated. Nonlinear trends were observed for time on both overall hedonic hunger and hedonic hunger specifically related to food available in the adolescent's environment. The BMI reduction during the first 18 months postoperatively was paralleled by reduction in hedonic hunger; increases in hedonic hunger also paralleled the modest BMI increase at 24 months. In growth analysis, significant power gains are available to models using 4 or more points of data. However, only large effect sizes that are>.85 were detectable with a sample of 16 patients. These data provide preliminary evidence that hedonic hunger is in need of further study in adolescent patients receiving RYGB both preoperatively and postoperatively. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  3. Changes in eating behaviour and meal pattern following Roux-en-Y gastric bypass.

    Science.gov (United States)

    Laurenius, A; Larsson, I; Bueter, M; Melanson, K J; Bosaeus, I; Forslund, H Bertéus; Lönroth, H; Fändriks, L; Olbers, T

    2012-03-01

    Little is known about eating behaviour and meal pattern subsequent to Roux-en-Y gastric bypass (RYGB), knowledge important for the nutritional care process. The objective of the study was to obtain basic information of how meal size, eating rate, meal frequency and eating behaviour change upon the RYGB surgery. Voluntary chosen meal size and eating rate were measured in a longitudinal, within subject, cohort study of 43 patients, 31 women and 12 men, age 42.6 (s.d. 9.7) years, body mass index (BMI) 44.5 (4.9) kg m(-2). Thirty-one non-obese subjects, 37.8 (13.6) years, BMI 23.7 (2.7) kg m(-2) served as a reference group. All subjects completed a meal pattern questionnaire and the Three-Factor Eating Questionnaire (TFEQ-R21). Six weeks postoperatively meal size was 42% of the preoperative meal size, (Pmeal size increased but was still lower than preoperative size 57% (Pmeal duration was constant before and after surgery. Mean eating rate measured as amount consumed food per minute was 45% of preoperative eating rate 6 weeks postoperatively (Pmeals per day increased from 4.9 (95% confidence interval, 4.4,5.4) preoperatively to 6 weeks: 5.2 (4.9,5.6), (not significant), 1 year 5.8 (5.5,6.1), (P=0.003), and 2 years 5.4 (5.1,5.7), (not significant). Emotional and uncontrolled eating were significantly decreased postoperatively, (both Pmeal patterns, which may lead to sustained weight loss.

  4. Spiritual Bypass: A Preliminary Investigation

    Science.gov (United States)

    Cashwell, Craig S.; Glosoff, Harriet L.; Hammond, Cheree

    2010-01-01

    The phenomenon of spiritual bypass has received limited attention in the transpersonal psychology and counseling literature and has not been subjected to empirical inquiry. This study examines the phenomenon of spiritual bypass by considering how spirituality, mindfulness, alexithymia (emotional restrictiveness), and narcissism work together to…

  5. DNA Polymerases Drive DNA Sequencing-by-Synthesis Technologies: Both Past and Present

    Directory of Open Access Journals (Sweden)

    Cheng-Yao eChen

    2014-06-01

    Full Text Available Next-generation sequencing (NGS technologies have revolutionized modern biological and biomedical research. The engines responsible for this innovation are DNA polymerases; they catalyze the biochemical reaction for deriving template sequence information. In fact, DNA polymerase has been a cornerstone of DNA sequencing from the very beginning. E. coli DNA polymerase I proteolytic (Klenow fragment was originally utilized in Sanger's dideoxy chain terminating DNA sequencing chemistry. From these humble beginnings followed an explosion of organism-specific, genome sequence information accessible via public database. Family A/B DNA polymerases from mesophilic/thermophilic bacteria/archaea were modified and tested in today's standard capillary electrophoresis (CE and NGS sequencing platforms. These enzymes were selected for their efficient incorporation of bulky dye-terminator and reversible dye-terminator nucleotides respectively. Third generation, real-time single molecule sequencing platform requires slightly different enzyme properties. Enterobacterial phage ⱷ29 DNA polymerase copies long stretches of DNA and possesses a unique capability to efficiently incorporate terminal phosphate-labeled nucleoside polyphosphates. Furthermore, ⱷ29 enzyme has also been utilized in emerging DNA sequencing technologies including nanopore-, and protein-transistor-based sequencing. DNA polymerase is, and will continue to be, a crucial component of sequencing technologies.

  6. RNA-dependent RNA polymerase 1 in potato (Solanum tuberosum) and its relationship to other plant RNA-dependent RNA polymerases.

    Science.gov (United States)

    Hunter, Lydia J R; Brockington, Samuel F; Murphy, Alex M; Pate, Adrienne E; Gruden, Kristina; MacFarlane, Stuart A; Palukaitis, Peter; Carr, John P

    2016-03-16

    Cellular RNA-dependent RNA polymerases (RDRs) catalyze synthesis of double-stranded RNAs that can serve to initiate or amplify RNA silencing. Arabidopsis thaliana has six RDR genes; RDRs 1, 2 and 6 have roles in anti-viral RNA silencing. RDR6 is constitutively expressed but RDR1 expression is elevated following plant treatment with defensive phytohormones. RDR1 also contributes to basal virus resistance. RDR1 has been studied in several species including A. thaliana, tobacco (Nicotiana tabacum), N. benthamiana, N. attenuata and tomato (Solanum lycopersicum) but not to our knowledge in potato (S. tuberosum). StRDR1 was identified and shown to be salicylic acid-responsive. StRDR1 transcript accumulation decreased in transgenic potato plants constitutively expressing a hairpin construct and these plants were challenged with three viruses: potato virus Y, potato virus X, and tobacco mosaic virus. Suppression of StRDR1 gene expression did not increase the susceptibility of potato to these viruses. Phylogenetic analysis of RDR genes present in potato and in a range of other plant species identified a new RDR gene family, not present in potato and found only in Rosids (but apparently lost in the Rosid A. thaliana) for which we propose the name RDR7.

  7. Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning

    Science.gov (United States)

    Neinast, Michael D.; Frank, Aaron P.; Zechner, Juliet F.; Li, Quanlin; Vishvanath, Lavanya; Palmer, Biff F.; Aguirre, Vincent; Gupta, Rana K.; Clegg, Deborah J.

    2015-01-01

    Objective Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These ‘BRITE/beige’ adipocytes express uncoupling protein 1 (UCP1) and are associated with improvements in glucose homeostasis and protection from obesity. Interestingly, atrial and B-type natriuretic peptides (NPs) promote BRITE/beige adipocyte enrichment of WAT depots, an effect known as “browning.” Here, we investigate the effect of RYGB surgery on NP, NP receptors, and browning in the gonadal adipose tissues of female mice. We propose that such changes may lead to improvements in metabolic homeostasis commonly observed following RYGB. Methods Wild type, female, C57/Bl6 mice were fed a 60% fat diet ad libitum for six months. Mice were divided into three groups: Sham operated (SO), Roux-en-Y gastric bypass (RYGB), and Weight matched, sham operated (WM-SO). Mice were sacrificed six weeks following surgery and evaluated for differences in body weight, glucose homeostasis, adipocyte morphology, and adipose tissue gene expression. Results RYGB and calorie restriction induced similar weight loss and improved glucose metabolism without decreasing food intake. β3-adrenergic receptor expression increased in gonadal adipose tissue, in addition to Nppb (BNP), and NP receptors, Npr1, and Npr2. The ratio of Npr1:Npr3 and Npr2:Npr3 increased in RYGB, but not WM-SO groups. Ucp1 protein and mRNA, as well as additional markers of BRITE/beige adipose tissue and lipolytic genes increased in RYGB mice to a greater extent than calorie-restricted mice. Conclusions Upregulation of Nppb, Npr1, Npr2, and β3-adrenergic receptors in gonadal adipose tissue following RYGB was associated with increased markers of browning. This browning of gonadal adipose tissue may underpin the positive

  8. SIMPLIFIED LAPAROSCOPIC GASTRIC BYPASS WITH GASTROJEJUNAL LINEAR MECHANICAL ANASTOMOSIS: TECHNICAL ASPECTS.

    Science.gov (United States)

    Palermo, Mariano; Serra, Edgardo

    Gastric bypass is a restrictive and malabsorptive surgery. The restrictive part consists in the creation of a small gastric pouch. The gastrointestinal bypass serves as the malabsorptive element. To describe a simplified gastric bypass approach for morbid obese patients, showing our results, and also remarking the importance of this technique for reducing the learning curve. The patient is positioned in a split legs position and carefully strapped to the operating room table, with the surgeon between the patient's legs. Five trocars are inserted after pneumoperitoneum at the umbilicus. Dissection of the esophagogastric angle and lesser curvature is mandatory before the gastric pouch manufacturing. This pouch is done with two blue load staplers. Using a blue load linear stapler inserted only half way into the hole in the pouch is used to perform the gastrojejunal anastomosis and in order to create an anastomosis that is about 2 cm in length. A side-to-side jejunojejunostomy is done with a white load linear stapler. The last step of the gastric bypass consists in the cut of the jejunum between the two anastomosis with a white load linear stapler. Blue test is performed in order to detect leaks. From January 2012 to December 2015, 415 simplified RYGB were performed. Gender: 67% female and 33 % males. Average of BMI 44.7. Mean age was 42 years old. Mean operative time 79 min. 39 % of this sample had T2 diabetes. Regarding complications were observed, one fistula, one gastrojejunal stenosis and one obstruction due to a bezoar. The described technique is a simplified approach in which all the anastomosis are performed in the upper part of the abdomen, allowing the surgeons to be more systematized and avoiding them to make mistakes in the confection of the Roux-en-Y anastomosis. This simplified gastric bypass is a safe and reproducible technique. Bypass gástrico é cirurgia restritiva e malabsortiva. A parte restritiva consiste na criação de uma pequena bolsa g

  9. Research for structure and function of protein promoting mutation induction

    International Nuclear Information System (INIS)

    Nohmi, Takehiko; Gruz, P.; Shimizu, M.

    2004-01-01

    The nature of Y family DNA polymerase, which takes a damaged deoxynucleotide 3 phosphate (dNTP) into the template, was discussed in detail. Bacterial endoenzyme DNA pol Y1 took in the oxidized dNTP uniquely. The pol Y1 showed following singularity: (1) taking 2-OH-dGTP in opposite side of template A, (2) taking 2-OH-dATP in opposite side of template G and T, (3) not only taking in both of the oxidized dNTP, but also carrying out an elongation reaction of the dNTP, (4) after taking in the oxidized nucleotide continuously, the elongation reaction stopped. Human Y family DNA polymerase, hpol η showed the same nature of the preceding item (1) and (2), also. Above mentioned natures indicated possibility of common nature of Y family polymerase. (M. Suetake)

  10. Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas.

    Science.gov (United States)

    Spier, Isabel; Holzapfel, Stefanie; Altmüller, Janine; Zhao, Bixiao; Horpaopan, Sukanya; Vogt, Stefanie; Chen, Sophia; Morak, Monika; Raeder, Susanne; Kayser, Katrin; Stienen, Dietlinde; Adam, Ronja; Nürnberg, Peter; Plotz, Guido; Holinski-Feder, Elke; Lifton, Richard P; Thiele, Holger; Hoffmann, Per; Steinke, Verena; Aretz, Stefan

    2015-07-15

    In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome/HNPCC, no germline alteration in the APC, MUTYH, or mismatch repair (MMR) genes are found. Missense mutations in the polymerase genes POLE and POLD1 have recently been identified as rare cause of multiple colorectal adenomas and carcinomas, a condition termed polymerase proofreading-associated polyposis (PPAP). The aim of the present study was to evaluate the clinical relevance and phenotypic spectrum of polymerase germline mutations. Therefore, targeted sequencing of the polymerase genes POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3 and POLE4 was performed in 266 unrelated patients with polyposis or fulfilled Amsterdam criteria. The POLE mutation c.1270C>G;p.Leu424Val was detected in four unrelated patients. The mutation was present in 1.5% (4/266) of all patients, 4% (3/77) of all familial cases and 7% (2/30) of familial polyposis cases. The colorectal phenotype in 14 affected individuals ranged from typical adenomatous polyposis to a HNPCC phenotype, with high intrafamilial variability. Multiple colorectal carcinomas and duodenal adenomas were common, and one case of duodenal carcinoma was reported. Additionally, various extraintestinal lesions were evident. Nine further putative pathogenic variants were identified. The most promising was c.1306C>T;p.Pro436Ser in POLE. In conclusion, a PPAP was identified in a substantial number of polyposis and familial colorectal cancer patients. Screening for polymerase proofreading mutations should therefore be considered, particularly in unexplained familial cases. The present study broadens the phenotypic spectrum of PPAP to duodenal adenomas and carcinomas, and identified novel, potentially pathogenic variants in four polymerase genes. © 2014 UICC.

  11. Variable volume combustor with an air bypass system

    Science.gov (United States)

    Johnson, Thomas Edward; Ziminsky, Willy Steve; Ostebee, Heath Michael; Keener, Christopher Paul

    2017-02-07

    The present application provides a combustor for use with flow of fuel and a flow of air in a gas turbine engine. The combustor may include a number of micro-mixer fuel nozzles positioned within a liner and an air bypass system position about the liner. The air bypass system variably allows a bypass portion of the flow of air to bypass the micro-mixer fuel nozzles.

  12. Collins' bypass for the main ring

    International Nuclear Information System (INIS)

    Ohnuma, S.

    1982-01-01

    Design of the bypass for the main ring at Fermilab is discussed. Specific design features discussed include space, path length, geometric closure, matching of betatron functions, and external dispersion. Bypass parameters are given

  13. Brain microvascular function during cardiopulmonary bypass

    International Nuclear Information System (INIS)

    Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

    1987-01-01

    Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass

  14. Heart bypass surgery - minimally invasive - discharge

    Science.gov (United States)

    ... invasive direct coronary artery bypass - discharge; MIDCAB - discharge; Robot assisted coronary artery bypass - discharge; RACAB - discharge; Keyhole ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  15. Utility of barium studies for patients with recurrent weight gain after Roux-en-Y gastric bypass

    International Nuclear Information System (INIS)

    Wang, B.; Levine, M.S.; Rubesin, S.E.; Williams, N.N.; Dumon, K.; Raper, S.

    2015-01-01

    Aim: To determine the utility of barium studies for detecting abnormalities responsible for recurrent weight gain after gastric bypass surgery. Methods: A computerized search identified 42 patients who had undergone barium studies for recurrent weight gain after gastric bypass and 42 controls. The images were reviewed to determine the frequency of staple-line breakdown and measure the length/width of the pouch and gastrojejunal anastomosis. A large pouch exceeded 6 cm in length or 5 cm in width and a wide anastomosis exceeded 2 cm. Records were reviewed for the amount of recurrent weight gain and subsequent weight loss after additional treatment. Results: Staple-line breakdown was present in 6/42 patients (14%) with recurrent weight gain. When measurements were obtained, 13/35 patients (37%) with recurrent weight gain had a large pouch, three (9%) had a wide anastomosis, and four (11%) had both, whereas 22/42 controls (52%) had a large pouch, one (2%) had a wide anastomosis, and two (5%) had both. Ten patients (24%) with recurrent weight gain underwent staple-line repair (n = 3) or pouch/anastomosis revision (n = 7). These 10 patients had a mean weight loss of 38.1 lbs versus a mean loss of 8.6 lbs in 19 patients managed medically. Conclusion: Only 14% of patients with recurrent weight gain after gastric bypass had staple-line breakdown, whereas 57% had a large pouch, wide anastomosis, or both. Not all patients with abnormal anatomy had recurrent weight gain, but those who did were more likely to benefit from surgical intervention than from medical management. - Highlights: • Only 14% of patients with recurrent weight gain after gastric bypass had GGFs. • The majority of patients with recurrent weight gain had a large pouch/wide GJA. • Many patients without recurrent weight gain also had a large pouch/wide GJA. • Those with weight gain and a large pouch/wide GJA are likely to benefit from surgery

  16. Editing of misaligned 3'-termini by an intrinsic 3'-5' exonuclease activity residing in the PHP domain of a family X DNA polymerase.

    Science.gov (United States)

    Baños, Benito; Lázaro, José M; Villar, Laurentino; Salas, Margarita; de Vega, Miguel

    2008-10-01

    Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolX(Bs)), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolX(Bs) possesses an intrinsic 3'-5' exonuclease activity specialized in resecting unannealed 3'-termini in a gapped DNA substrate. Biochemical analysis of a PolX(Bs) deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3'-5' exonuclease activity of PolX(Bs) resides in its PHP domain. Furthermore, site-directed mutagenesis of PolX(Bs) His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3'-termini resection by the 3'-5' exonuclease activity of PolX(Bs) in the DNA repair context are discussed.

  17. PCR fidelity of pfu DNA polymerase and other thermostable DNA polymerases.

    Science.gov (United States)

    Cline, J; Braman, J C; Hogrefe, H H

    1996-09-15

    The replication fidelities of Pfu, Taq, Vent, Deep Vent and UlTma DNA polymerases were compared using a PCR-based forward mutation assay. Average error rates (mutation frequency/bp/duplication) increased as follows: Pfu (1.3 x 10(-6)) Pfu and UlTma (approximately 5 x 10(-5)). Buffer optimization experiments indicated that Pfu fidelity was highest in the presence of 2-3 mM MgSO4 and 100-300 microM each dNTP and at pH 8.5-9.1. Under these conditions, the error rate of exo- Pfu was approximately 40-fold higher (5 x 10(-5)) than the error rate of Pfu. As the reaction pH was raised from pH 8 to 9, the error rate of Pfu decreased approximately 2-fold, while the error rate of exo- Pfu increased approximately 9-fold. An increase in error rate with pH has also been noted for the exonuclease-deficient DNA polymerases Taq and exo- Klenow, suggesting that the parameters which influence replication error rates may be similar in pol l- and alpha-like polymerases. Finally, the fidelity of 'long PCR' DNA polymerase mixtures was examined. The error rates of a Taq/Pfu DNA polymerase mixture and a Klentaq/Pfu DNA polymerase mixture were found to be less than the error rate of Taq DNA polymerase, but approximately 3-4-fold higher than the error rate of Pfu DNA polymerase.

  18. Dynamic Cerebral Autoregulation after Cardiopulmonary Bypass

    DEFF Research Database (Denmark)

    Christiansen, Claus Behrend; Berg, Ronan M G; Plovsing, Ronni R

    2016-01-01

    Background Cerebral hemodynamic disturbances in the peri- or postoperative period may contribute to postoperative cognitive dysfunction (POCD) in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). We therefore examined dynamic cerebral autoregulation (d...

  19. Intestinal obstruction after Roux-en-Y gastric bypass by Higa's technique for treatment of morbid obesity: radiological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Labrunie, Ester Moraes [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia]. E-mail: emlabrunie@superig.com.br; Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia

    2007-05-15

    Objective: The aim of this study is to describe the main radiological aspects of postoperative intestinal obstruction in patients submitted to Roux-en-Y gastric bypass by means of the Higa's technique. Materials and methods: A total of 10 patients presenting with postoperative intestinal obstruction following a gastric reduction procedure were evaluated in the period between November 2001 and April 2006, in seven different medical centers. Results: In the ten patients, the obstruction occurred in the small bowel, five of them because of internal hernias, three because of adhesions, one because of an umbilical hernia and one because of intussusception. Four patients presented obstruction early in the postoperative period (by the seventh post-op day), and six, late in the postoperative period (between the third month and the fifth year). Conclusion: All of the cases of intestinal obstruction were found in the small bowel. Internal hernia was the most frequent cause, followed by adhesion. Other causes included umbilical hernia and intussusception. (author)

  20. Structural Analysis of Monomeric RNA-Dependent Polymerases: Evolutionary and Therapeutic Implications.

    Directory of Open Access Journals (Sweden)

    Rodrigo Jácome

    Full Text Available The crystal structures of monomeric RNA-dependent RNA polymerases and reverse transcriptases of more than 20 different viruses are available in the Protein Data Bank. They all share the characteristic right-hand shape of DNA- and RNA polymerases formed by the fingers, palm and thumb subdomains, and, in many cases, "fingertips" that extend from the fingers towards the thumb subdomain, giving the viral enzyme a closed right-hand appearance. Six conserved structural motifs that contain key residues for the proper functioning of the enzyme have been identified in all these RNA-dependent polymerases. These enzymes share a two divalent metal-ion mechanism of polymerization in which two conserved aspartate residues coordinate the interactions with the metal ions to catalyze the nucleotidyl transfer reaction. The recent availability of crystal structures of polymerases of the Orthomyxoviridae and Bunyaviridae families allowed us to make pairwise comparisons of the tertiary structures of polymerases belonging to the four main RNA viral groups, which has led to a phylogenetic tree in which single-stranded negative RNA viral polymerases have been included for the first time. This has also allowed us to use a homology-based structural prediction approach to develop a general three-dimensional model of the Ebola virus RNA-dependent RNA polymerase. Our model includes several of the conserved structural motifs and residues described in other viral RNA-dependent RNA polymerases that define the catalytic and highly conserved palm subdomain, as well as portions of the fingers and thumb subdomains. The results presented here help to understand the current use and apparent success of antivirals, i.e. Brincidofovir, Lamivudine and Favipiravir, originally aimed at other types of polymerases, to counteract the Ebola virus infection.

  1. Isolation, structural analysis, and expression characteristics of the maize nuclear factor Y gene families

    International Nuclear Information System (INIS)

    Zhang, Zhongbao; Li, Xianglong; Zhang, Chun; Zou, Huawen; Wu, Zhongyi

    2016-01-01

    NUCLEAR FACTOR-Y (NF-Y) has been shown to play an important role in growth, development, and response to environmental stress. A NF-Y complex, which consists of three subunits, NF-YA, NF-YB, and, NF-YC, binds to CCAAT sequences in a promoter to control the expression of target genes. Although NF-Y proteins have been reported in Arabidopsis and rice, a comprehensive and systematic analysis of ZmNF-Y genes has not yet been performed. To examine the functions of ZmNF-Y genes in this family, we isolated and characterized 50 ZmNF-Y (14 ZmNF-YA, 18 ZmNF-YB, and 18 ZmNF-YC) genes in an analysis of the maize genome. The 50 ZmNF-Y genes were distributed on all 10 maize chromosomes, and 12 paralogs were identified. Multiple alignments showed that maize ZmNF-Y family proteins had conserved regions and relatively variable N-terminal or C-terminal domains. The comparative syntenic map illustrated 40 paralogous NF-Y gene pairs among the 10 maize chromosomes. Microarray data showed that the ZmNF-Y genes had tissue-specific expression patterns in various maize developmental stages and in response to biotic and abiotic stresses. The results suggested that ZmNF-YB2, 4, 8, 10, 13, and 16 and ZmNF-YC6, 8, and 15 were induced, while ZmNF-YA1, 3, 4, 6, 7, 10, 12, and 13, ZmNF-YB15, and ZmNF-YC3 and 9 were suppressed by drought stress. ZmNF-YA3, ZmNF-YA8 and ZmNF-YA12 were upregulated after infection by the three pathogens, while ZmNF-YA1 and ZmNF-YB2 were suppressed. These results indicate that the ZmNF-Ys may have significant roles in the response to abiotic and biotic stresses. - Highlights: • We indicated a total of 50 members of ZmNF-Y gene family in maize genome. • We analyzed gene structure, protein architecture of ZmNF-Y genes. • Evolution pattern and phylogenic relationships were analyzed among 50 ZmNF-Y genes. • Expression pattern of ZmNF-Ys were detected in various maize tissues. • Transcript levels of ZmNF-Ys were measured under various abiotic and biotic stresses.

  2. Roux-en-Y gastric bypass surgery suppresses hypothalamic PTP1B protein level and alleviates leptin resistance in obese rats.

    Science.gov (United States)

    Liu, Jia-Yu; Mu, Song; Zhang, Shu-Ping; Guo, Wei; Li, Qi-Fu; Xiao, Xiao-Qiu; Zhang, Jun; Wang, Zhi-Hong

    2017-09-01

    The present study aimed to explore the effect of Roux-en-Y gastric bypass (RYGB) surgery on protein tyrosine phosphatase 1B (PTP1B) expression levels and leptin activity in hypothalami of obese rats. Obese rats induced by a high-fat diet (HFD) that underwent RYGB (n=11) or sham operation (SO, n=9), as well as an obese control cohort (Obese, n=10) and an additional normal-diet group (ND, n=10) were used. Food efficiency was measured at 8 weeks post-operation. Plasma leptin levels were evaluated and hypothalamic protein tyrosine phosphatase 1B (PTP1B) levels and leptin signaling activity were examined at the genetic and protein levels. The results indicated that food efficiency was typically lower in RYGB rats compared with that in the Obese and SO rats. In the RYGB group, leptin receptor expression and proopiomelanocortin was significantly higher, while Neuropeptide Y levels were lower than those in the Obese and SO groups. Furthermore, the gene and protein expression levels of PTP1B in the RYGB group were lower, while levels of phosphorylated signal transducer and activator of transcription 3 protein were much higher compared with those in the Obese and SO groups. In conclusion, RYGB surgery significantly suppressed hypothalamic PTP1B protein expression. PTP1B regulation may partially alleviate leptin resistance.

  3. Multi-slice CT angiography in evaluation of extracranial-intracranial bypass

    Energy Technology Data Exchange (ETDEWEB)

    Teksam, Mehmet E-mail: mehmetteksam@yahoo.com; McKinney, Alexander; Truwit, Charles L

    2004-12-01

    Multi-slice CT (MSCT) scanners provided significant improvement in vascular applications. In this study, our purpose was to determine the clinical utility of MSCTA in evaluation of extracranial-intracranial (EC-IC) bypass patency. Eleven (4 men and 7 women; mean age, 46 years; age range, 19-68 years) consecutive patients who underwent MSCTA and DSA after EC-IC bypass surgery were evaluated retrospectively. All patients underwent DSA within 3 weeks of MSCTA. The indications for EC-IC bypass were severe stenosis or occlusion of intracranial arteries in seven patients and therapeutic occlusion of intracranial artery for unclippable giant aneurysm in four patients. Ten patients underwent superficial temporal artery (STA)-middle cerebral artery (MCA) bypass and one patient underwent occipital artery-posterior cerebral artery (PCA) bypass. Eight STA-MCA bypasses in six patients were patent on MSCTA which were confirmed on DSA. Two MSCTA bypasses and one occipital artery-posterior cerebral artery (PCA) bypass were occluded in three patients on MSCTA and DSA. In one patient, minimal stenosis of the STA-MCA bypass was identified on MSCTA and DSA. In 1 patient, STA-MCA bypass was not well seen on MSCTA and suspected for occlusion. DSA identified the occlusion of bypass on this patient. MSCTA seems to be a very promising noninvasive technique in evaluation of EC-IC bypass.

  4. Multi-slice CT angiography in evaluation of extracranial-intracranial bypass

    International Nuclear Information System (INIS)

    Teksam, Mehmet; McKinney, Alexander; Truwit, Charles L.

    2004-01-01

    Multi-slice CT (MSCT) scanners provided significant improvement in vascular applications. In this study, our purpose was to determine the clinical utility of MSCTA in evaluation of extracranial-intracranial (EC-IC) bypass patency. Eleven (4 men and 7 women; mean age, 46 years; age range, 19-68 years) consecutive patients who underwent MSCTA and DSA after EC-IC bypass surgery were evaluated retrospectively. All patients underwent DSA within 3 weeks of MSCTA. The indications for EC-IC bypass were severe stenosis or occlusion of intracranial arteries in seven patients and therapeutic occlusion of intracranial artery for unclippable giant aneurysm in four patients. Ten patients underwent superficial temporal artery (STA)-middle cerebral artery (MCA) bypass and one patient underwent occipital artery-posterior cerebral artery (PCA) bypass. Eight STA-MCA bypasses in six patients were patent on MSCTA which were confirmed on DSA. Two MSCTA bypasses and one occipital artery-posterior cerebral artery (PCA) bypass were occluded in three patients on MSCTA and DSA. In one patient, minimal stenosis of the STA-MCA bypass was identified on MSCTA and DSA. In 1 patient, STA-MCA bypass was not well seen on MSCTA and suspected for occlusion. DSA identified the occlusion of bypass on this patient. MSCTA seems to be a very promising noninvasive technique in evaluation of EC-IC bypass

  5. Y.O.O. Rock Columbia County: development of a volunteer reference guide for families, children, and youth.

    Science.gov (United States)

    Waibel-Duncan, Mary Katherine; Benner, Eleanor; Weeks, Meghan

    2012-05-01

    Y.O.O. Rock Columbia County Youth Outreach Opportunities for Families Children, and Youth (Waibel-Duncan & Gillam, 2009) represents our nonurban county's first organized effort to systematically identify and promote awareness of volunteer and outreach opportunities for families, children, and youth. In addition to describing Y.O.O. Rock's development, this article summarizes feedback from parents, professionals, and paraprofessionals and outlines their recommendations for the second edition of the guide. Issue briefs from the Corporation for National & Community Service (2005, 2006, 2008) suggest the need for reference guides like Y.O.O. Rock insofar as they document limited volunteer and outreach opportunities for young children as well as the family's role in engaging children in service to others. This article will inform others who seek to increase families', children's, and youth's awareness of volunteer activities and outreach opportunities in their communities. © 2012 Wiley Periodicals, Inc.

  6. The Y chromosome of the Atelidae family (Platyrrhini): study by chromosome microdissection.

    Science.gov (United States)

    Gifalli-Iughetti, C; Koiffmann, C P

    2009-01-01

    In order to study the intergeneric variability of the Y chromosome, we describe the hybridization of the Y chromosome of Brachytelesarachnoides, obtained by microdissection, to metaphases of Atelesbelzebuthmarginatus, Lagothrixlagothricha, and Alouatta male specimens. Brachytelesarachnoides (Atelinae) has 62 chromosomes and a very small Y chromosome. Our results showed that the Brachytelesarachnoides Y chromosome probe hybridized to Lagothrixlagothricha metaphases yielding one hybridization signal on only the tiny Y chromosome, and when hybridized with Atelesbelzebuthmarginatus metaphases it yielded one hybridization signal on two thirds of the small acrocentric Y chromosome. However, no hybridization signal was observed in Alouatta metaphases (subfamily Alouattinae), a closely related genus in the Atelidae family. Furthermore, our data support a close phylogenetic relationship among Brachyteles, Ateles, and Lagothrix and their placement in the Atelinae subfamily, but exclude Alouatta from this group indicating its placement as basal to this group. Copyright 2009 S. Karger AG, Basel.

  7. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pump tubing. 870.4390 Section 870.4390 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is...

  8. 21 CFR 870.4240 - Cardiopulmonary bypass heat exchanger.

    Science.gov (United States)

    2010-04-01

    ... bypass heat exchanger. (a) Identification. A cardiopulmonary bypass heat exchanger is a device, consisting of a heat exchange system used in extracorporeal circulation to warm or cool the blood or... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass heat exchanger. 870.4240...

  9. Impact of Roux-en-Y Gastric Bypass on Metabolic Syndrome and Insulin Resistance Parameters

    Science.gov (United States)

    Gestic, Martinho Antonio; Utrini, Murillo Pimentel; Machado, Ricardo Rossetto; Geloneze, Bruno; Pareja, José Carlos; Chaim, Elinton Adami

    2014-01-01

    Abstract Background: Metabolic syndrome (MetS) is a complex association of clustering metabolic factors that increase risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Surgical treatment has become an important tool to achieve its control. The aim of this study was to evaluate the impact of Roux-en-Y gastric bypass (RYGB) on MetS and its individual components, clinical characteristics, and biochemical features. Subjects and Methods: The study is a retrospective cohort of 96 subjects with MetS who underwent RYGB and were evaluated at baseline and after surgery. Clinical and biochemical features were analyzed. Results: After surgery, significant rates of resolution for MetS (88.5%), T2DM (90.6%), hypertension (85.6%), and dyslipidemias (54.2%) were found. Significant decreases in levels of fasting glucose, fasting insulin, hemoglobin A1c, low-density lipoprotein, and triglycerides and an increase in high-density lipoprotein level were also shown. The decrease in insulin resistance evaluated by homeostasis model assessment (HOMA-IR) was consistent. MetS resolution was associated with postoperative glycemic control, decreases in levels of fasting glucose, hemoglobin A1c, HOMA-IR, and triglycerides and in antihypertensive usage, and percentage weight loss. Conclusions: This study found high rates of resolution for MetS, T2DM, hypertension, and dyslipidemias after RYGB in obese patients. This finding was consistent with current literature. Hence RYGB should be largely indicated for this group of subjects as it is a safe and powerful tool to achieve MetS control. PMID:24299427

  10. Interaction of gold nanoparticles with Pfu DNA polymerase and effect on polymerase chain reaction.

    Science.gov (United States)

    Sun, L-P; Wang, S; Zhang, Z-W; Ma, Y-Y; Lai, Y-Q; Weng, J; Zhang, Q-Q

    2011-03-01

    The interaction of gold nanoparticles with Pfu DNA polymerase has been investigated by a number of biological, optical and electronic spectroscopic techniques. Polymerase chain reaction was performed to show gold nanoparticles' biological effect. Ultraviolet-visible and circular dichroism spectra analysis were applied to character the structure of Pfu DNA polymerase after conjugation with gold nanoparticles. X-ray photoelectron spectroscopy was used to investigate the bond properties of the polymerase-gold nanoparticles complex. The authors demonstrate that gold nanoparticles do not affect the amplification efficiency of polymerase chain reaction using Pfu DNA polymerase, and Pfu DNA polymerase displays no significant changes of the secondary structure upon interaction with gold nanoparticles. The adsorption of Pfu DNA polymerase to gold nanoparticles is mainly through Au-NH(2) bond and electrostatic interaction. These findings may have important implications regarding the safety issue as gold nanoparticles are widely used in biomedical applications.

  11. Interventions in Infrainguinal Bypass Grafts

    International Nuclear Information System (INIS)

    Mueller-Huelsbeck, S.; Order, B.-M.; Jahnke, T.

    2006-01-01

    The interventional radiologist plays an important role in the detection and prevention of infrainguinal bypass failure. Early detection and evaluation of flow-limiting lesions effectively preserve graft (venous bypass and polyester or expanded polytetrafluoroethylene bypass) patency by identifying stenoses before occlusion occurs. Delay in treatment of the at-risk graft may result in graft failure and a reduced chance of successful revascularization. For this reason, surveillance protocols form an important part of follow-up after infrainguinal bypass surgery. As well as having an understanding of the application of imaging techniques including ultrasound, MR angiography, CT angiography and digital subtraction angiography, the interventional radiologist should have detailed knowledge of the minimally invasive therapeutic options. Percutaneous transluminal angioplasty (PTA), or alternatively cutting balloon angioplasty, is the interventional treatment of choice in prevention of graft failure and occlusion. Further alternatives include metallic stent placement, fibrinolysis, and mechanical thrombectomy. Primary assisted patency rates following PTA can be up to 65% at 5 years. When the endovascular approach is unsuccessful, these therapeutic options are complemented by surgical procedures including vein patch revision, jump grafting, or placement of a new graft

  12. Post-Bypass Extensive Ascites due to Splanchnic Bypass and the Effectiveness of Hyperalimentation Treatment

    Directory of Open Access Journals (Sweden)

    Veysel Temizkan

    2013-04-01

    Full Text Available Reperfusion edema may develop in the early periods of chronic ischemic tissue reperfusion. Reperfusion edema may be represented after the splanchnic bypass with ascites, abdominal distension, and liver and kidney function impairment. In this article, we are reporting the hyperalimentation treatment and its results for the common ascites and hepatorenal syndrome, after a coeliac and superior mesenteric artery bypass. [Arch Clin Exp Surg 2013; 2(2.000: 124-128

  13. Extra-intracranial standard bypass in the elderly

    DEFF Research Database (Denmark)

    Sandow, Nora; von Weitzel-Mudersbach, Paul; Rosenbaum, Sverre

    2013-01-01

    Patients with chronic atherosclerotic vessel occlusion and cerebrovascular hemodynamic insufficiency may benefit from extra-intracranial (EC-IC) bypass surgery. Due to demographic changes, an increasing number of elderly patients presents with cerebrovascular hemodynamic insufficiency. So far......, little data for EC-IC bypass surgery in elderly patients suffering occlusive cerebrovascular disease are available. We therefore designed a retrospective study to address the question whether EC-IC bypass is a safe and efficient treatment in a patient cohort ≥70 years....

  14. Roux-en Y gastric bypass surgery reduces hedonic hunger and improves dietary habits in severely obese subjects.

    Science.gov (United States)

    Ullrich, Jennifer; Ernst, Barbara; Wilms, Britta; Thurnheer, Martin; Schultes, Bernd

    2013-01-01

    Many obese subjects suffer from an increased hedonic drive to consume palatable foods, i.e., hedonic hunger, and often show unfavorable dietary habits. Here, we investigated changes in the hedonic hunger and dietary habits after Roux-en-Y gastric bypass (RYGB) surgery. Forty-four severely obese patients were examined before and on average 15.9 ± 0.9 months after RYGB surgery with the Power of Food Scale (PFS), a questionnaire that reliably measures an individual's motivation to consume highly palatable foods but not actual consumptive behavior. Dietary habits were assessed by a food frequency questionnaire. After the RYGB procedure, patients showed markedly lower aggregated PFS scores and sub-domain scores related to generally available, physically present, as well as tasted foods than before the surgery (all P habits after the surgery were characterized by a more frequent consumption of poultry, fish, eggs, and cooked vegetables (P habits characterized by an increased intake of protein-rich foods and vegetables and a reduced consumption of sugar-containing snacks and beverages after RYGB surgery. Based on these findings, it can be speculated that the reduction of the hedonic drive to consume palatable foods induced by RYGB surgery helps severely obese patients to establish healthier dietary habits.

  15. Gastrojejunal anastomosis stricture after laparoscopic gastric bypass: Our experience with 62 patients Estenosis de la anastomosis gastroyeyunal en el bypass gástrico laparoscópico: Nuestra experiencia con 62 pacientes

    Directory of Open Access Journals (Sweden)

    A. Campillo-Soto

    2010-03-01

    complicación nada desdeñable en la cirugía bariátrica por laparoscopia, llegándose, en algunas series, a alcanzar el 15%. Presentamos nuestra casuística en una serie de 62 casos consecutivos y el manejo realizado. Pacientes y método: desde enero-2004 a septiembre-2006 hemos realizado de manera consecutiva 62 bypass gástricos por laparoscopia según técnica de Wittgrove modificada. La anastomosis gastroyeyunal se realiza con material de autosutura tipo CEAA nº 21 término-lateral (ILS; Ethicon y después de comprobar la estanqueidad anastomótica se dan dos puntos de válvula tipo Hoffmeister a cada lado de la anastomosis. En 4 casos (6,45% se reconvirtió a laparotomía, realizándose la anastomosis de la misma manera. El seguimiento tiene un rango de 3-35 meses, realizado en 61 enfermos, pues un paciente falleció por tromboembolismo pulmonar en el postoperatorio inmediato tras reintervención, a las dos semanas del bypass gástrico, por necrosis de un pequeño fragmento del remanente gástrico. En todos los pacientes con intolerancia persistente a la alimentación se realizó tránsito baritado y/o gastroscopia. Cuando se evidenció estenosis gastroyeyunal se procedió a dilatación neumática endoscópica (recomendando dilatar la anastomosis hasta como máximo 1,5 cm. Resultados: en 5 casos (8,1% se desarrolló una estenosis gastroyeyunal, en 4 de estos casos el diagnóstico inicial fue por tránsito baritado y en 1 caso por endoscopia. Dos pacientes tenían antecedentes de HDA que precisaron esclerosis endoscópica de la lesión sangrante (esclerosis circunferencial a las 48 horas de la cirugía y esclerosis de puntos sangrantes. Todos los casos se resolvieron mediante dilatación endoscópica, precisando en dos casos dos sesiones de dilatación y el resto una. En el seguimiento no se han detectado re-estenosis. Conclusión: la estenosis gastroyeyunal es consecuencia de realizar una anastomosis de pequeño calibre (con vistas a evitar así el r

  16. The modeled structure of the RNA dependent RNA polymerase of GBV-C Virus suggests a role for motif E in Flaviviridae RNA polymerases

    Directory of Open Access Journals (Sweden)

    Dutartre Hélène

    2005-10-01

    Full Text Available Abstract Background The Flaviviridae virus family includes major human and animal pathogens. The RNA dependent RNA polymerase (RdRp plays a central role in the replication process, and thus is a validated target for antiviral drugs. Despite the increasing structural and enzymatic characterization of viral RdRps, detailed molecular replication mechanisms remain unclear. The hepatitis C virus (HCV is a major human pathogen difficult to study in cultured cells. The bovine viral diarrhea virus (BVDV is often used as a surrogate model to screen antiviral drugs against HCV. The structure of BVDV RdRp has been recently published. It presents several differences relative to HCV RdRp. These differences raise questions about the relevance of BVDV as a surrogate model, and cast novel interest on the "GB" virus C (GBV-C. Indeed, GBV-C is genetically closer to HCV than BVDV, and can lead to productive infection of cultured cells. There is no structural data for the GBV-C RdRp yet. Results We show in this study that the GBV-C RdRp is closest to the HCV RdRp. We report a 3D model of the GBV-C RdRp, developed using sequence-to-structure threading and comparative modeling based on the atomic coordinates of the HCV RdRp structure. Analysis of the predicted structural features in the phylogenetic context of the RNA polymerase family allows rationalizing most of the experimental data available. Both available structures and our model are explored to examine the catalytic cleft, allosteric and substrate binding sites. Conclusion Computational methods were used to infer evolutionary relationships and to predict the structure of a viral RNA polymerase. Docking a GTP molecule into the structure allows defining a GTP binding pocket in the GBV-C RdRp, such as that of BVDV. The resulting model suggests a new proposition for the mechanism of RNA synthesis, and may prove useful to design new experiments to implement our knowledge on the initiation mechanism of RNA

  17. 21 CFR 870.4350 - Cardiopulmonary bypass oxygenator.

    Science.gov (United States)

    2010-04-01

    ... bypass oxygenator. (a) Identification. A cardiopulmonary bypass oxygenator is a device used to exchange gases between blood and a gaseous environment to satisfy the gas exchange needs of a patient during open...

  18. Reduction in cardiovascular risk factors and insulin dose, but no beta-cell regeneration 1 year after Roux-en-Y gastric bypass in an obese patient with type 1 diabetes

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Jacobsen, Siv H; Bojsen-Møller, Kirstine N

    2013-01-01

    Experience with Roux-en-Y gastric bypass in patients with type 1 diabetes is very limited, despite an increasing prevalence of obesity also in this population. We describe changes in anthropometric measures, insulin dose, HbA1c, blood pressure, lipid status, and metabolic response to a liquid mixed...... meal throughout the first year after RYGB in an obese patient with type 1 diabetes. No change in HbA1c was observed, but a 48% reduction in weight-adjusted insulin dose and improvements in cardiovascular risk factors was seen 1 year after surgery. Exaggerated secretions of anorexigenic gut hormones...

  19. Variations in dietary intake after bypass surgery for obesity. Possible relation to development of fatty liver after jejunoileal bypass

    International Nuclear Information System (INIS)

    Rogus, J.; Blumenthal, S.A.

    1981-01-01

    Consumption of nutrients and food energy was compared, with concomitant chemical and radiologic measurements of hepatic fat content, preoperatively and postoperatively in 25 patients who underwent gastric or jejunoileal bypass for obesity. Patients in the two operative groups ingested similar quantities of food before surgery. After surgery, caloric intake from all sources decreased in both groups but to a significantly greater extent in the gastric bypass patients. During the first six months postoperatively, the 13 gastric bypass patients showed no changes in hepatic fat content, whereas substantial increases in liver fat uniformly occurred in the 12 patients who had jejunoileal bypasses. It is suggested that dietary carbohydrate may have contributed to the accretion of liver fat in these 12 patients

  20. Trends in Weight Regain Following Roux-en-Y Gastric Bypass (RYGB) Bariatric Surgery.

    Science.gov (United States)

    Cooper, Timothy C; Simmons, Elizabeth B; Webb, Kirsten; Burns, James L; Kushner, Robert F

    2015-08-01

    The primary purpose of this study was to assess weight loss and occurrence of weight regain among patients who underwent Roux-en-Y gastric bypass (RYGB) using categorical analysis. Study participants were selected from patients who underwent RYGB from a single institution. Participants (n = 300, mean procedure age = 45.6 ± 9.9) completed surveys for self-reported preoperative weight, current weight, and subsequent weights over postoperative years. Measured weights and confirmed procedure dates were acquired from patient medical records. Mean preoperative weight and BMI were 140.8 kg ± 32.1 and 49.7 ± 9.9, respectively, and mean years since surgery was 6.9 ± 4.9. Study subjects were mostly Caucasian (56.7 %) and female (80.3 %). Participants were stratified a priori into four cohorts based on percent of weight loss at 1 year, 35 % (n = 113). General linear model analyses were conducted to assess the effect of year one weight loss on percent weight regain. The mean weight regain for all patients was 23.4 % of maximum weight loss. Using categorical analysis, mean weight regain in the 35 % weight loss cohorts was 29.1, 21.9, 20.9, and 23.8 %, respectively. Excessive weight regain, defined as ≥25 % of total lost weight, occurred in 37 % of patients. Weight gain is a common complication following RYGB surgery. Despite the percentage of weight loss over the first year, all cohort patient groups regained on average between 21 and 29 % of lost weight. Excessive weight gain was experienced by over one third of patients. Greater initial absolute weight loss leads to more successful long-term weight outcomes.

  1. Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation

    DEFF Research Database (Denmark)

    Tremaroli, Valentina; Karlsson, Fredrik; Werling, Malin

    2015-01-01

    Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass...... or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls....... By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut...

  2. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

  3. On-pump versus off-pump coronary artery bypass surgery

    DEFF Research Database (Denmark)

    Houlind, Kim Christian

    2013-01-01

    Off pump coronary artery bypass surgery has been purported to be safer than conventional coronary artery bypass surgery performed using cardiopulmonary bypass. This theory was supported by a number of early series, but failed to be confirmed by a number of small, randomized controlled trials...

  4. EUS-directed Transgastric ERCP (EDGE) Versus Laparoscopy-assisted ERCP (LA-ERCP) for Roux-en-Y Gastric Bypass (RYGB) Anatomy: A Multicenter Early Comparative Experience of Clinical Outcomes.

    Science.gov (United States)

    Kedia, Prashant; Tarnasky, Paul R; Nieto, Jose; Steele, Stephen L; Siddiqui, Ali; Xu, Ming-Ming; Tyberg, Amy; Gaidhane, Monica; Kahaleh, Michel

    2018-04-17

    The standard of care for managing pancreaticobiliary disease in altered Roux-en-Y gastric bypass patients is laparoscopy-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP), but is limited by cost and adverse events. Recently a minimally invasive, completely endoscopic approach using endoscopic ultrasound (EUS) directed transgastric ERCP (EDGE) has been described. We aim to compare EDGE to LA-ERCP in this study. Patients from May 2005 to June 2017 with Roux-en-Y gastric bypass anatomy having undergone LA-ERCP or EDGE at 4 tertiary centers were captured in a registry. Patient demographics, procedural details, and clinical outcomes were measured for each group. Seventy-two patients (n=29 EDGE, n=43 LA-ERCP) were included in this study. There was no significant difference in the technical success of EDGE gastrogastric fistula (96.5%) versus LA-gastrostomy creation (100%). The success rate of achieving therapeutic ERCP (EDGE 96.5% vs. LA-ERCP 97.7%) and number of ERCP (EDGE 1.2 vs. LA-ERCP 1.02) needed to achieve clinical resolution was similar between both groups. Adverse event rate for EDGE, 24% (7/29) and LA-ERCP, 19% (8/43) was similar. The total procedure time (73 vs. 184 min) and length of hospital stay (0.8 vs. 2.65 d) was significantly shorter for EDGE compared to LA-ERCP. The overall weight change after EDGE was -6.6 lbs at an average 28-week follow-up. This study suggests that the EDGE procedure has similar technical success and adverse events compared with LA-ERCP with the benefit of significantly shorter procedure times and hospital stay. EDGE may offer a minimally invasive, effective option, with less resource utilization, and without significant weight gain.

  5. Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats

    DEFF Research Database (Denmark)

    Hankir, Mohammed K; Seyfried, Florian; Hintschich, Constantin A

    2017-01-01

    Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small int...

  6. Towards Spirituality After Coronary Artery bypass grafting: A Hermeneutic Phenomenological Study

    Directory of Open Access Journals (Sweden)

    Mohammad Abbasi

    2017-03-01

    Full Text Available Abstract Background and Objectives: Patients are oriented towards spirituality after coronary artery bypass grafting (CABG. The aim of this study was to explore the patients’ spiritual experiences after CABG. Methods: This qualitative study was conducted using hermeneutic phenomenology. 11 participants (7 males and 4 females were interviewed in Tehran Heart Center Hospital in 2013 using maximum variation along with purposive sampling methods. The interviews were recorded and then converted to texts word for word. The texts were analyzed using van Manen six-step method. Results: The main theme of the contents which were experienced by the participants was spirituality and its sub contents were: trust in God, Supplicating to the Prophet and Imams, and accepting the will of God. Conclusion: The findings showed that the participants who had undergone surgery on coronary artery bypass grafting had a rise in spirituality. They took advantage of spirituality to handle their problems. Using the research findings, members of the treatment team, especially nurses, can use this study to advance care planning and to train patients and their families better.

  7. Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

    Directory of Open Access Journals (Sweden)

    Mohamad Mokadem

    Full Text Available Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

  8. Comparison of Harmonic scalpel and Ligasure devices in laparoscopic Roux-en-Y gastric bypass.

    Science.gov (United States)

    Kirmizi, Serdar; Kayaalp, Cuneyt; Karagul, Servet; Tardu, Ali; Ertugrul, Ismail; Sumer, Fatih; Yagci, Mehmet Ali

    2017-01-01

    Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most preferred bariatric procedures in the world for surgical treatment of morbid obesity. The Harmonic scalpel (HS) and LigaSure (LS) are the most commonly used devices in laparoscopic surgery. As far as we know, there is no comparative study of the two energy devices in LRYGB for morbid obesity. To compare the intraoperative performances of the two energy devices in LRYGB for morbid obesity. The HS and LS were used in 43 and 42 cases, respectively. The patient demographics of both groups were comparable. The duration of the procedures (gastric pouch creation time and total operation time), quantity of bleeding (during gastric pouch creation and total quantities of bleeding) and the number of pneumoperitoneum desufflations due to smoking that impaired sight fields were recorded prospectively. Gastric pouch creation time (HS: 22.5 ±9.5 vs. LS: 19.5 ±9.7 min, p = 0.15), bleeding during gastric pouch preparation (HS: 15.3 ±30.5 vs. LS: 17.5 ±31.3 ml, p = 0.74), total operation time (HS: 183.2 ±47 vs. LS: 165.3 ±37.1 min, p = 0.06) and total bleeding (HS: 110 ±195.5 vs. LS: 102.5 ±70 ml, p = 0.81) were similar in the two groups. Only the mean number of pneumoperitoneum desufflations due to smoking was lower in the HS group (HS: 0.28 ±0.49 vs. LS: 0.57 ±0.78, p = 0.04). The HS and LS performed similarly in LRYGB, with fewer desufflations from smoking in the HS group.

  9. Effect of closure of the mesenteric defect during laparoscopic gastric bypass and prevention of internal hernia

    DEFF Research Database (Denmark)

    Kristensen, Sara Danshøj; Naver, Lars; Jess, Per

    2014-01-01

    INTRODUCTION: The aim of this study is to evaluate the benefits and disadvantages of closing the mesenteric defects during gastric bypass to avoid internal herniation (IH). MATERIAL AND METHODS: The study is performed as a single-centre, randomised, controlled, blinded trial. Patients are randomly...... assigned to either conventional laparoscopic Roux-en-Y gastric bypass (LRYGB) without closing the mesenteric defects (n = 250) or RYGB with closing of the defects with hernia clips (n = 250). Follow-up is conducted at six months, one year, two years and five years after RYGB. The primary endpoint......: The study was registered with the Danish Data Protection Agency (SN-10-2012) and The Central Denmark Regional Committees on Biomedical Research Ethics (1-01-83-0209-12, SJ-284). The study is registered with clinicaltrials.gov: NCT01595230....

  10. Relaciones trabajo-familia y salud en mujeres trabajadoras Work-family relationships and health in working women

    Directory of Open Access Journals (Sweden)

    Lya Feldman

    2008-12-01

    Full Text Available OBJETIVO: Estudiar la asociación existente entre las gratificaciones y las interferencias generadas en la relación trabajo-familia y su impacto en la salud de mujeres trabajadoras. MATERIAL Y MÉTODOS: Se utilizó un diseño no experimental correlacional. Se aplicó en Caracas, Venezuela, durante el año 2006, a un grupo de 402 mujeres trabajadoras con edades comprendidas entre 27 y 71 años, una batería de pruebas para medir relación trabajo-familia, autoestima, ansiedad, depresión, bienestar, percepción de salud y número de síntomas. RESULTADOS: Se encontró que las gratificaciones en la relación trabajo-familia están relacionadas con un mayor bienestar y autoestima, así como con menor depresión, ansiedad y síntomas reportados. Una mayor interferencia se asoció a una mayor depresión, ansiedad y número de síntomas. CONCLUSIONES: Los resultados permiten identificar algunos factores protectores y de riesgo para la salud de las mujeres con roles múltiples y sirven de base para el diseño de planes de intervención tanto en el plano individual como organizacional.OBJECTIVE: To study the relationship between gratifications and interferences generated in the work-family relationship and its impact on working women's health. MATERIAL AND METHODS: A non-experimental, correlational design was used. A group of 402 working women between 27 and 71 years of age were tested in Caracas, Venezuela during 2006, to measure work-family relationship, self-esteem, anxiety, depression, wellbeing, health perception and number of symptoms. RESULTS: It was found that the gratifications in the work-family relationship are related to better wellbeing and self-esteem, less depression, anxiety and symptom report. Presence of more interferences was associated with more depression, anxiety and number of symptoms. CONCLUSIONS: These results give an indication of protective and risk factors for multiple-role women's health and could provide some guidelines

  11. Multisubunit DNA-Dependent RNA Polymerases from Vaccinia Virus and Other Nucleocytoplasmic Large-DNA Viruses: Impressions from the Age of Structure.

    Science.gov (United States)

    Mirzakhanyan, Yeva; Gershon, Paul D

    2017-09-01

    The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus. The first half of this review surveys the recently determined structural biology of cellular RNA polymerases for a microbiology readership. The second half discusses a reannotation of MSDDRP subunits from NCLDV families and the apparent specialization of these enzymes by virus family and by subunit with regard to subunit or domain loss, subunit dissociability, endogenous control of polymerase arrest, and the elimination/customization of regulatory interactions that would confer higher-order cellular control. Some themes are apparent in linking subunit function to structure in the viral world: as with cellular RNA polymerases I and III and unlike cellular RNA polymerase II, the viral enzymes seem to opt for speed and processivity and seem to have eliminated domains associated with higher-order regulation. The adoption/loss of viral RNA polymerase proofreading functions may have played a part in matching intrinsic mutability to genome size. Copyright © 2017 American Society for Microbiology.

  12. Are There Mutator Polymerases?

    Directory of Open Access Journals (Sweden)

    Miguel Garcia-Diaz

    2003-01-01

    Full Text Available DNA polymerases are involved in different cellular events, including genome replication and DNA repair. In the last few years, a large number of novel DNA polymerases have been discovered, and the biochemical analysis of their properties has revealed a long list of intriguing features. Some of these polymerases have a very low fidelity and have been suggested to play mutator roles in different processes, like translesion synthesis or somatic hypermutation. The current view of these processes is reviewed, and the current understanding of DNA polymerases and their role as mutator enzymes is discussed.

  13. Assessing Patient bypass Behavior Using Taxi Trip Origin–Destination (OD Data

    Directory of Open Access Journals (Sweden)

    Gege Yang

    2016-09-01

    Full Text Available Many patients prefer to use the best hospitals even if there are one or more other hospitals closer to their homes; this behavior is called “hospital bypass behavior”. Because this behavior can be problematic in urban areas, it is important that it be reduced. In this paper, the taxi GPS data of Beijing and Suzhou were used to measure hospital bypass behavior. The “bypass behavior index” (BBI represents the bypass behavior for each hospital. The results indicated that the mean hospital bypass trip distance value ranges from 5.988 km to 9.754 km in Beijing and from 4.168 km to 10.283 km in Suzhou. In general, the bypass shares of both areas show a gradually increasing trend. The following hospitals exhibited significant patient bypass behavior: the 301 Hospital, Beijing Children’s Hospital, the Second Affiliated Hospital of Soochow University and the Suzhou Hospital of Traditional Chinese Medicine. The hospitals’ reputation, transport accessibility and spatial distribution were found to be the main factors affecting patient bypass behavior. Although the hospital bypass phenomena generally appeared to be more pronounced in Beijing, the bypass trip distances between hospitals were found to be more significant in Suzhou.

  14. 21 CFR 870.4300 - Cardiopulmonary bypass gas control unit.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass gas control unit. 870.4300... bypass gas control unit. (a) Identification. A cardiopulmonary bypass gas control unit is a device used to control and measure the flow of gas into the oxygenator. The device is calibrated for a specific...

  15. Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

    Directory of Open Access Journals (Sweden)

    Loqmane Seridi

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective way to lose weight and reverse type 2 diabetes. We profiled the metabolome of 18 obese patients (nine euglycemic and nine diabetics that underwent RYGB surgery and seven lean subjects. Plasma samples from the obese patients were collected before the surgery and one week and three months after the surgery. We analyzed the metabolome in association to five hormones (Adiponectin, Insulin, Ghrelin, Leptin, and Resistin, four peptide hormones (GIP, Glucagon, GLP1, and PYY, and two cytokines (IL-6 and TNF. PCA showed samples cluster by surgery time and many microbially driven metabolites (indoles in particular correlated with the three months after the surgery. Network analysis of metabolites revealed a connection between carbohydrate (mannosamine and glucosamine and glyoxylate and confirms glyoxylate association to diabetes. Only leptin and IL-6 had a significant association with the measured metabolites. Leptin decreased immediately after RYGB (before significant weight loss, whereas IL-6 showed no consistent response to RYGB. Moreover, leptin associated with tryptophan in support of the possible role of leptin in the regulation of serotonin synthesis pathways in the gut. These results suggest a potential link between gastric leptin and microbial-derived metabolites in the context of obesity and diabetes.

  16. Fluid distribution kinetics during cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Mattias Törnudd

    2014-08-01

    Full Text Available OBJECTIVE: The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. METHODS: Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. RESULTS: The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02. The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. CONCLUSIONS: The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur.

  17. Nuclear DNA polymerase beta from Leishmania infantum. Cloning, molecular analysis and developmental regulation

    Science.gov (United States)

    Taladriz, Soraya; Hanke, Tobias; Ramiro, María J.; García-Díaz, Miguel; Lacoba, Mario García de; Blanco, Luis; Larraga, Vicente

    2001-01-01

    We have identified a novel polymerase beta (Pol β)-like enzyme from Leishmania infantum, a parasite protozoon causing disease in humans. This protein, named Li Pol β, shows a nuclear localization that contrasts with the mitochondrial localization of Pol β from Crithidia fasciculata, a closely related parasite, the only polymerase β described so far in Trypanosomatidae. Li Pol β, that belongs to the DNA polymerase X family, displays an evolutionarily conserved Pol β-type DNA polymerase core, in which most of the key residues involved in DNA binding, nucleotide binding, dRPase and polymerization catalysis are conserved. In agreement with this, Li Pol β, overproduced in Escherichia coli, displayed intrinsic DNA polymerase activity. Cell synchronization experiments showed a correlation between both Li Pol β mRNA and protein levels along the parasite cell cycle. Analysis of these parameters at the different growth phases of the parasite, from the proliferative (non-infective) logarithmic phase to the non-dividing (highly infectious) stationary phase, showed high levels of Li Pol β at the infective phase of the parasite. The data suggest a role of Li Pol β in base excision repair in L.infantum, a parasite usually affected by oxygen stress environments into the macrophage host cells. PMID:11557814

  18. The influence of core bypass flow during SBLOCA

    International Nuclear Information System (INIS)

    Maselj, A.; Jurkovic, M.

    1996-01-01

    Many parameters affect the behaviour of a NPP during a Small Break Loss of Coolant Accident (SBLOCA). The bypass flow between the core side and the downcomer is one of them. Different PWRs have different values of core bypass flow. In spite of the complexity of the real situation in the primary system during SBLOCA, some fundamental details of the phenomena can be explained with simplified mathematical models, which relate on basic parameters of the primary coolant. These models define the conditions for loop seal clearance and final results are confirmed with measured values. The analysis presented in the paper refers to Bethsy Test 9.1.b SB LOCA scenario, with variation of core bypass flow. Basic RELAP5 input model calculation results show very good agreement with the experimental data. The core liquid level depression before loop seal clearance is lower in case of smaller core bypass flow. This affects the fuel clad temperature because of different heat transfer mechanisms. Time of loop seal clearance is delayed with larger core bypass flow and consequently lower differential pressure between downcomer and core. (author)

  19. Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Yu, Elaine W; Wewalka, Marlene; Ding, Su-Ann

    2016-01-01

    CONTEXT: Roux-en-Y gastric bypass (RYGB) leads to high-turnover bone loss, but little is known about skeletal effects of laparoscopic adjustable gastric banding (LAGB) or mechanisms underlying bone loss after bariatric surgery. OBJECTIVE: To evaluate effects of RYGB and LAGB on fasting and postpr......CONTEXT: Roux-en-Y gastric bypass (RYGB) leads to high-turnover bone loss, but little is known about skeletal effects of laparoscopic adjustable gastric banding (LAGB) or mechanisms underlying bone loss after bariatric surgery. OBJECTIVE: To evaluate effects of RYGB and LAGB on fasting...... and postprandial indices of bone remodeling. DESIGN AND SETTING: Ancillary investigation of a prospective study at 2 academic institutions. PARTICIPANTS: Obese adults aged 21-65 years with type 2 diabetes who underwent RYGB (n=11) or LAGB (n=8). OUTCOMES: Serum C-terminal telopeptide (CTX), procollagen type 1 (P1......NP), and parathyroid hormone (PTH) were measured during a mixed meal tolerance test at baseline, 10 days and 1 year after surgery. Changes in 25-hydroxyvitamin D, polypeptide YY (PYY), glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and insulin were also assessed. RESULTS: Fasting...

  20. Molecular diagnosis of hemophilia A and B. Report of five families from Costa Rica

    Directory of Open Access Journals (Sweden)

    Lizbeth Salazar-Sánchez

    2004-09-01

    Full Text Available Hemophilia Aand B are X-chromosome linked bleeding disorders caused by deficiency of the respective coagulation factor VIII and IX. Affected individuals develop a variable phenotype of hemorrhage caused by a broad range of mutations within the Factor VIII or Factor IX gene. Here, were report the results of the molecular diagnosis in a five Costa Rican families affected with Hemophilia. Methods of indirect and direct molecular diagnosis are applied in three Hemophilia A and two Hemophilia B families from Costa Rica as well as preconditions, practicability and facilities of this diagnosis. In two families with Hemophilia A and both families with Hemophilia B the causative mutation could be detected by Southern blotting, polymerase chain reaction or sequence analysis. One Hemophilia A family could only analyzed by linkage analysis using genomic markers. Rev. Biol. Trop. 52(3: 521-530. Epub 2004 Dic 15.La hemofilia A y B es una enfermedad hemorrágica hereditaria ligada al cromosoma X, producida por la deficiencia del factor VIII o IX, respectivamente. Los individuso afectados presentan un fenotipo de hemorragia variable causada por el amplio espectro de mutacionesdentro del gen del factor VIII o IX. Se reportan los resultados preliminares del diagnóstico molecular de familias hemofilicas costarricenses. Se demuestran los hallazgos obtenidos por medio de diagnóstico molecular directo e indirecto en tres familias con hemofilia A y dos con hemofilia B; así como las precondiciones y facilidad de este diagnóstico. En dos familias con hemofilia A y dos con hemofilia B, la mutación responsable pudo ser detectada por medio de Southern Blot, por la reacción en cadena de la polimerasa o por secuenciación genética. Una familia con hemofilia A pudo ser analizada solamente por medio de análisis indirecto por medio de marcadores genéticos intragénicos y extragénicos.

  1. Cardiometabolic health among gastric bypass surgery patients with polycystic ovarian syndrome.

    Science.gov (United States)

    Gomez-Meade, Carley A; Lopez-Mitnik, Gabriela; Messiah, Sarah E; Arheart, Kristopher L; Carrillo, Adriana; de la Cruz-Muñoz, Nestor

    2013-06-15

    To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome (PCOS). Retrospective medical chart review identified women (n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical practice. Separate repeated measures linear mixed models were fit using the MIXED procedure to assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic, non-Hispanic black (NHB) and white (NHW)]. The majority of the sample was Hispanic (66%, 25% NHB, 9% NHW). Mean body mass index significantly improved 1 year post-surgery for all ethnic groups (45.5 to 35.5 kg/m(2) for Hispanics, 46.8 to 37.7 kg/m(2) for NHB and 45.7 to 36.7 kg/m(2) for NHW, P cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any outcome. Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women.

  2. Gastric bypass surgery

    Science.gov (United States)

    ... your body will not get all of the calories from the food you eat. ... to a small hole in your pouch. The food you eat will now travel ... absorb fewer calories. Gastric bypass can be done in two ways. ...

  3. Passage of downstream migrant American eels through an airlift-assisted deep bypass

    Science.gov (United States)

    Haro, Alexander J.; Watten, Barnaby J.; Noreika, John

    2016-01-01

    Traditional downstream guidance and bypass facilities for anadromous fishes (i.e., surface bypasses, surface guidance structures, and behavioral barriers) have frequently been ineffective for anguillid eels. Because eels typically spend the majority of their time near the bottom in the vicinity of intake structures, deep bypass structures with entrances near the bottom hold promise for increased effectiveness, thereby aiding in the recovery of this important species. A new design of a deep bypass system that uses airlift technology (the Conte Airlift Bypass) to induce flow in a bypass pipe was tested in a simulated intake entrance environment under controlled laboratory conditions. Water velocities of 0.9–1.5 m s−1 could be generated at the bypass entrance (opening with 0.073 m2 area), with corresponding flows through the bypass pipe of 0.07–0.11 m3 s−1. Gas saturation and hydrostatic pressure within the bypass pipe did not vary appreciably from a control (no air) condition under tested airflows. Migratory silver-phase American eels (Anguilla rostrata) tested during dark conditions readily located, entered, and passed through the bypass; initial avoidance rates (eels approaching but not entering the bypass entrance) were lower at higher entrance velocities. Eels that investigated the bypass pipe entrance tended to enter headfirst, but those that then exited the pipe upstream did so more frequently at lower entrance velocities. Eels appeared to swim against the flow while being transported downstream through the pipe; median transit times through the bypass for each test velocity ranged from 5.8 to 12.2 s, with transit time decreasing with increasing entrance velocity. Eels did not show strong avoidance of the vertical section of the pipe which contained injected air. No mortality or injury of bypassed eels was observed, and individual eels repeatedly passed through the bypass at rates of up to 40 passes per hour, suggesting that individuals do not

  4. Bioinformatic prediction of polymerase elements in the rotavirus VP1 protein

    Directory of Open Access Journals (Sweden)

    RODRIGO VÁSQUEZ-DEL CARPIÓ

    2006-01-01

    Full Text Available Rotaviruses are the major cause of acute gastroenteritis in infants world-wide. The genome consists of eleven double stranded RNA segments. The major segment encodes the structural protein VP1, the viral RNA-dependent RNA polymerase (RdRp, which is a minor component of the viral inner core. This study is a detailed bioinformatic assessment of the VP1 sequence. Using various methods we have identified canonical motifs within the VP1 sequence which correspond to motifs previously identified within RdRps of other positive strand, double-strand RNA viruses. The study also predicts an overall structural conservation in the middle region that may correspond to the palm subdomain and part of the fingers and thumb subdomains, which comprise the polymerase core of the protein. Based on this analysis, we suggest that the rotavirus replicase has the minimal elements to function as an RNA-dependent RNA polymerase. VP1, besides having common RdRp features, also contains large unique regions that might be responsible for characteristic features observed in the Reoviridae family

  5. No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial

    DEFF Research Database (Denmark)

    Møller, Christian H; Perko, Mario J; Lund, Jens T

    2010-01-01

    Off-pump coronary artery bypass grafting compared with coronary revascularization with cardiopulmonary bypass seems safe and results in about the same outcome in low-risk patients. Observational studies indicate that off-pump surgery may provide more benefit in high-risk patients. Our objective...... was to compare 30-day outcomes in high-risk patients randomized to coronary artery bypass grafting without or with cardiopulmonary bypass....

  6. Aortic valve bypass

    DEFF Research Database (Denmark)

    Lund, Jens T; Jensen, Maiken Brit; Arendrup, Henrik

    2013-01-01

    In aortic valve bypass (AVB) a valve-containing conduit is connecting the apex of the left ventricle to the descending aorta. Candidates are patients with symptomatic aortic valve stenosis rejected for conventional aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). ...

  7. Circulating and Urinary miR-210 and miR-16 Increase during Cardiac Surgery Using Cardiopulmonary Bypass - A Pilot Study.

    Science.gov (United States)

    Mazzone, Annette L; Baker, Robert A; McNicholas, Kym; Woodman, Richard J; Michael, Michael Z; Gleadle, Jonathan M

    2018-03-01

    A pilot study to measure and compare blood and urine microRNAs miR-210 and miR-16 in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting surgery. Frequent serial blood and urine samples were taken from patients undergoing cardiac surgery with CPB (n = 10) and undergoing off-pump cardiac surgery (n = 5) before, during, and after surgery. Circulating miR-210 and miR-16 levels were determined by relative quantification real-time polymerase chain reaction. Levels of plasma-free haemoglobin (fHb), troponin-T, creatine kinase, and creatinine were measured. Perioperative serum miR-210 and miR-16 were elevated significantly compared to preoperative levels in patients undergoing cardiac surgery with CPB (CPB vs. Pre Op and Rewarm vs. Pre Op; p Octopus on vs. Pre Op); however, the release was less marked when compared to cardiac surgery with CPB. A significant association was observed between both miR-16 and miR-210 and plasma fHb when CPB was used ( r = -.549, p red cell, and renal injury during cardiac surgery.

  8. DNA Polymerases ImuC and DinB Are Involved in DNA Alkylation Damage Tolerance in Pseudomonas aeruginosa and Pseudomonas putida.

    Science.gov (United States)

    Jatsenko, Tatjana; Sidorenko, Julia; Saumaa, Signe; Kivisaar, Maia

    2017-01-01

    Translesion DNA synthesis (TLS), facilitated by low-fidelity polymerases, is an important DNA damage tolerance mechanism. Here, we investigated the role and biological function of TLS polymerase ImuC (former DnaE2), generally present in bacteria lacking DNA polymerase V, and TLS polymerase DinB in response to DNA alkylation damage in Pseudomonas aeruginosa and P. putida. We found that TLS DNA polymerases ImuC and DinB ensured a protective role against N- and O-methylation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in both P. aeruginosa and P. putida. DinB also appeared to be important for the survival of P. aeruginosa and rapidly growing P. putida cells in the presence of methyl methanesulfonate (MMS). The role of ImuC in protection against MMS-induced damage was uncovered under DinB-deficient conditions. Apart from this, both ImuC and DinB were critical for the survival of bacteria with impaired base excision repair (BER) functions upon alkylation damage, lacking DNA glycosylases AlkA and/or Tag. Here, the increased sensitivity of imuCdinB double deficient strains in comparison to single mutants suggested that the specificity of alkylated DNA lesion bypass of DinB and ImuC might also be different. Moreover, our results demonstrated that mutagenesis induced by MMS in pseudomonads was largely ImuC-dependent. Unexpectedly, we discovered that the growth temperature of bacteria affected the efficiency of DinB and ImuC in ensuring cell survival upon alkylation damage. Taken together, the results of our study disclosed the involvement of ImuC in DNA alkylation damage tolerance, especially at low temperatures, and its possible contribution to the adaptation of pseudomonads upon DNA alkylation damage via increased mutagenesis.

  9. Bypass flow rate control method

    International Nuclear Information System (INIS)

    Kiyama, Yoichi.

    1997-01-01

    In a PWR type reactor, bypass flow rate is controlled by exchanging existent jetting hole plugs of a plurality of nozzles disposed to the upper end of incore structures in order to flow a portion of primary coolants as a bypass flow to the upper portion of the pressure vessel. Two kinds of exchange plugs, namely, a first plug and a second plug each having a jetting out hole of different diameter are used as exchange plugs. The first plug has the diameter as that of an existent plug and the second plug has a jetting out hole having larger diameter than that of the existent plug. Remained extent plugs are exchanged to a combination of the first and the second plugs without exchanging existent plugs having seizing with the nozzles, in which the number and the diameter of the jetting out holes of the second plugs are previously determined based on predetermined total bypass flow rate to be jetted from the entire plugs after exchange of plugs. (N.H.)

  10. 21 CFR 870.4260 - Cardiopulmonary bypass arterial line blood filter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass arterial line blood filter... Cardiopulmonary bypass arterial line blood filter. (a) Identification. A cardiopulmonary bypass arterial line blood filter is a device used as part of a gas exchange (oxygenator) system to filter nonbiologic...

  11. 21 CFR 870.4360 - Nonroller-type cardiopulmonary bypass blood pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nonroller-type cardiopulmonary bypass blood pump... Nonroller-type cardiopulmonary bypass blood pump. (a) Identification. A nonroller-type cardiopulmonary bypass blood pump is a device that uses a method other than revolving rollers to pump the blood through...

  12. 21 CFR 870.4370 - Roller-type cardiopulmonary bypass blood pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Roller-type cardiopulmonary bypass blood pump. 870... Roller-type cardiopulmonary bypass blood pump. (a) Identification. A roller-type cardiopulmonary bypass blood pump is a device that uses a revolving roller mechanism to pump the blood through the...

  13. Roux-en-Y Gastric Bypass Surgery Increases Respiratory Quotient and Energy Expenditure during Food Intake.

    Directory of Open Access Journals (Sweden)

    Malin Werling

    Full Text Available The mechanisms determining long-term weight maintenance after Roux-en-Y gastric bypass (RYGB remain unclear. Cross sectional studies have suggested that enhanced energy expenditure (EE may play a significant role and the aim of this study was to reveal the impact of RYGB on each major component constituting total EE.Six obese female subjects, without other co-morbidities, were assessed before and at 10 days, 3 and 20 months after RYGB. Indirect calorimetry in a metabolic chamber was used to assess 24 h EE at each study visit. Other measurements included body composition by DEXA, gut hormone profiles and physical activity (PA using high sensitivity accelerometers.Median Body Mass Index decreased from 41.1 (range 39.1-44.8 at baseline to 28 kg/m2 (range 22.3-30.3 after 20 months (p<0.05. Lean tissue decreased from 55.9 (range 47.5-59.3 to 49.5 (range 41.1-54.9 kg and adipose tissue from 61 (range 56-64.6 to 27 (range 12-34.3 kg (both p<0.05. PA over 24 h did not change after surgery whereas 24 h EE and basal metabolic rate (BMR decreased. EE after a standard meal increased after surgery when adjusted for total tissue (p<0.05. After an initial drop, RQ (respiratory quotient had increased at 20 months, both as measured during 24 h and after food intake (p<0.05.RYGB surgery up-regulates RQ and EE after food intake resulting in an increased contribution to total EE over 24 h when corrected for total tissue.

  14. Carotid intima-media thickness is reduced 12 months after gastric bypass surgery in obese patients with type 2 diabetes or impaired glucose tolerance

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Tarnow, Lise; Hansen, Dorte L

    2014-01-01

    AIM: To investigate whether Roux-en-Y gastric bypass surgery (RYGB) - an in vivo model for normalisation of hyperglycaemia - improves carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: Observati...

  15. Cardiopulmonary bypass: development of John Gibbon's heart-lung machine

    Directory of Open Access Journals (Sweden)

    Andréia Cristina Passaroni

    2015-04-01

    Full Text Available AbstractObjective:To provide a brief review of the development of cardiopulmonary bypass.Methods:A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation.Results:The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from various degrees of tissue injury to multiple organ dysfunction syndrome. Investigators have long researched the ways in which cardiopulmonary bypass may insult the human body. Potential solutions arose and laid the groundwork for development of safer postoperative care strategies.Conclusion:Steady progress has been made in cardiopulmonary bypass in the decades since it was first conceived of by Gibbon. Despite the constant evolution of cardiopulmonary bypass techniques and attempts to minimize their complications, it is still essential that clinicians respect the particularities of each patient's physiological function.

  16. Crystal structure of Pfu, the high fidelity DNA polymerase from Pyrococcus furiosus.

    Science.gov (United States)

    Kim, Suhng Wook; Kim, Dong-Uk; Kim, Jin Kwang; Kang, Lin-Woo; Cho, Hyun-Soo

    2008-05-01

    We have determined a 2.6A resolution crystal structure of Pfu DNA polymerase, the most commonly used high fidelity PCR enzyme, from Pyrococcus furiosus. Although the structures of Pfu and KOD1 are highly similar, the structure of Pfu elucidates the electron density of the interface between the exonuclease and thumb domains, which has not been previously observed in the KOD1 structure. The interaction of these two domains is known to coordinate the proofreading and polymerization activity of DNA polymerases, especially via H147 that is present within the loop (residues 144-158) of the exonuclease domain. In our structure of Pfu, however, E148 rather than H147 is located at better position to interact with the thumb domain. In addition, the structural analysis of Pfu and KOD1 shows that both the Y-GG/A and beta-hairpin motifs of Pfu are found to differ with that of KOD1, and may explain differences in processivity. This information enables us to better understand the mechanisms of polymerization and proofreading of DNA polymerases.

  17. Preserving Duodenal-Jejunal (Foregut) Transit Does Not Impair Glucose Tolerance and Diabetes Remission Following Gastric Bypass in Type 2 Diabetes Sprague-Dawley Rat Model.

    Science.gov (United States)

    Dolo, Ponnie R; Yao, Libin; Li, Chao; Zhu, Xiaocheng; Shi, Linsen; Widjaja, Jason

    2017-11-02

    Possible mechanisms underlying diabetes remission following Roux-en-Y gastric bypass (RYGB) include eradication of putative factor(s) with duodenal-jejunal bypass. The objective of this study is to observe the effects of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass rat model. In order to verify the effect of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass, 22 type 2 diabetes Sprague-Dawley rat models established through high-fat diet and low-dose streptozotocin (STZ) administered intraperitoneally were assigned to one of three groups: gastric bypass with duodenal-jejunal transit (GB-DJT n = 8), gastric bypass without duodenal-jejunal transit (RYGB n = 8), and sham (n = 6). Body weight, food intake, blood glucose, as well as meal-stimulated insulin, and incretin hormone responses were assessed to ascertain the effect of surgery in all groups. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted three and 7 weeks after surgery. Comparing our GB-DJT to the RYGB group, we saw no differences in the mean decline in body weight, food intake, and blood glucose 8 weeks after surgery. GB-DJT group exhibited immediate and sustained glucose control throughout the study. Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels were also significantly increased from preoperative level in the GB-DJT group (p transit does not impede glucose tolerance and diabetes remission after gastric bypass in type-2 diabetes Sprague-Dawley rat model.

  18. Laparoscopic Roux-en-Y choledochojejunostomy.

    Science.gov (United States)

    Schöb, O M; Schmid, R A; Morimoto, A K; Largiadèr, F; Zucker, K A

    1997-04-01

    Although surgical biliary bypass for nonresectable periampullary tumors is superior to endoscopic stent placement, the latter has become popular because of the "minimally invasive" approach. Laparoscopic biliary bypass would appear to offer the advantages of both. However, this technique remains technically difficult using existing instrumentation. This study investigates the efficacy of a new endoscopic device designed for rapidly completing a small-diameter intestinal anastomosis under laparoscopic guidance. Eighteen female pigs (mean weight 35 kg, range 31 to 44) were randomly divided into three groups: animals undergoing handsewn (group H) or instrumental transient endoluminally stented anastomosis (TESA; groups P and D) laparoscopic Roux-en-Y choledochojejunostomy. For TESA two different reabsorbable stents were used, polyglycolic acid (PGA; group P) and polyurethane ester (Degrapol; group D). Blood chemistry, weight gain, and abdominal X-rays were taken weekly to document any possible migration or reabsorption of the radio-opaque stents. After 3 months, necropsy was performed. Patency of the biliary bypass and choledochojejunostomy were examined using fluoroscopy and measured by introducing graduated dilators into the anastomosis. Fluoroscopy revealed immediate passage of contrast through the anastomosis in all animals. Weight gain, bilirubin, and alkaline phosphatase were within normal range in all groups. Diameter of the bile duct (group H 10.7 +/- 2.9 mm/group P 9.5 +/- 3.6 mm/group D 11.0 +/- 4.6 mm) and choledochojejunostomy (group H 4.5 +/- 1.1 mm/group P 4.7 +/- 1.8 mm/group D 3.6 +/- 1.9 mm) did not differ. The time required to complete the biliary bypass was significantly decreased when TESA was applied (group H 152 +/- 13 min/group P 86 +/- 14 min, P stent placement with the functional results and lower readmission of conventional Roux-en-Y choledochojejunostomy.

  19. DNA polymerases beta and lambda mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Elena K Braithwaite

    2010-08-01

    Full Text Available Base excision repair (BER is a DNA repair pathway designed to correct small base lesions in genomic DNA. While DNA polymerase beta (pol beta is known to be the main polymerase in the BER pathway, various studies have implicated other DNA polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol lambda, was shown to be important in BER of oxidative DNA damage. To further explore roles of the X-family DNA polymerases lambda and beta in BER, we prepared a mouse embryonic fibroblast cell line with deletions in the genes for both pol beta and pol lambda. Neutral red viability assays demonstrated that pol lambda and pol beta double null cells were hypersensitive to alkylating and oxidizing DNA damaging agents. In vitro BER assays revealed a modest contribution of pol lambda to single-nucleotide BER of base lesions. Additionally, using co-immunoprecipitation experiments with purified enzymes and whole cell extracts, we found that both pol lambda and pol beta interact with the upstream DNA glycosylases for repair of alkylated and oxidized DNA bases. Such interactions could be important in coordinating roles of these polymerases during BER.

  20. Unequal rates of Y chromosome gene divergence during speciation of the family Ursidae.

    Science.gov (United States)

    Nakagome, Shigeki; Pecon-Slattery, Jill; Masuda, Ryuichi

    2008-07-01

    Evolution of the bear family Ursidae is well investigated in terms of morphological, paleontological, and genetic features. However, several phylogenetic ambiguities occur within the subfamily Ursinae (the family Ursidae excluding the giant panda and spectacled bear), which may correlate with behavioral traits of female philopatry and male-biased dispersal which form the basis of the observed matriarchal population structure in these species. In the process of bear evolution, we investigate the premise that such behavioral traits may be reflected in patterns of variation among genes with different modes of inheritance: matrilineal mitochondrial DNA (mtDNA), patrilineal Y chromosome, biparentally inherited autosomes, and the X chromosome. In the present study, we sequenced 3 Y-linked genes (3,453 bp) and 4 X-linked genes (4,960 bp) and reanalyzed previously published sequences from autosome genes (2,347 bp) in ursid species to investigate differences in evolutionary rates associated with patterns of inheritance. The results describe topological incongruence between sex-linked genes and autosome genes and between nuclear DNA and mtDNA. In more ancestral branches within the bear phylogeny, Y-linked genes evolved faster than autosome and X-linked genes, consistent with expectations based on male-driven evolution. However, this pattern changes among branches leading to each species within the lineage of Ursinae whereby the evolutionary rates of Y-linked genes have fewer than expected substitutions. This inconsistency between more recent nodes of the bear phylogeny with more ancestral nodes may reflect the influences of sex-biased dispersal as well as molecular evolutionary characteristics of the Y chromosome, and stochastic events in species natural history, and phylogeography unique to ursine bears.

  1. Two DNA polymerase sliding clamps from the thermophilic archaeon Sulfolobus solfataricus.

    Science.gov (United States)

    De Felice, M; Sensen, C W; Charlebois, R L; Rossi, M; Pisani, F M

    1999-08-06

    Herein, we report the identification and characterization of two DNA polymerase processivity factors from the thermoacidophilic archaeon Sulfolobus solfataricus. They, referred to as 039p (244 amino acid residues, 27 kDa) and 048p (249 amino acid residues, 27 kDa), present significant primary structure similarity to eukaryotic proliferating cell nuclear antigen (PCNA). We demonstrate that both 039p and 048p form oligomers in solution and are able to substantially activate the synthetic activity of the single-subunit family B DNA polymerase from S. solfataricus (Sso DNA pol B1) on poly(dA)-oligo(dT) as a primer-template. This stimulatory effect is the result of enhanced DNA polymerase processivity, as indicated by the analysis of the elongation products on polyacrylamide gels. Activation of Sso DNA pol B1 synthetic activity was also observed on linear primed single-stranded M13 mp18 DNA as a template. By immunoblot analysis using specific rabbit antisera, 039p and 048p were both detected in the logarithmic and stationary phases of S. solfataricus growth curve. This is the first report of the identification and biochemical characterization of two distinct DNA polymerase processivity factors from the same organism. The significance of these findings for the understanding of the DNA replication process in Archaea is discussed. Copyright 1999 Academic Press.

  2. Editing of misaligned 3′-termini by an intrinsic 3′–5′ exonuclease activity residing in the PHP domain of a family X DNA polymerase

    Science.gov (United States)

    Baños, Benito; Lázaro, José M.; Villar, Laurentino; de Vega, Miguel

    2008-01-01

    Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolXBs), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolXBs possesses an intrinsic 3′–5′ exonuclease activity specialized in resecting unannealed 3′-termini in a gapped DNA substrate. Biochemical analysis of a PolXBs deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3′–5′ exonuclease activity of PolXBs resides in its PHP domain. Furthermore, site-directed mutagenesis of PolXBs His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3′-termini resection by the 3′–5′ exonuclease activity of PolXBs in the DNA repair context are discussed. PMID:18776221

  3. Cooperation of terminal deoxynucleotidyl transferase with DNA polymerase α in the replication of ultraviolet-irradiated DNA

    International Nuclear Information System (INIS)

    Yoshida, S.; Masaki, S.; Nakamura, H.; Morita, T.

    1981-01-01

    The amount of DNA synthesis in vitro with the ultraviolet-irradiated poly(dT).oligo(rA) template initiators catalysed by DNA polymerase α (Masaki, S. and Yoshida, S., Biochim. Biophys. Acta 521, 74-88) decreased with the dose of ultraviolet-irradiation. The ultraviolet irradiation to the template, however, did not affect the rate of incorporation of incorrect deoxynucleotides into the newly synthesized poly(dA). The addition of terminal deoxynucleotidyl transferase to this system enhanced the DNA synthesis to a level which is comparable to that of the control and it concomitantly increased the incorporation of the mismatched deoxynucleotide into the newly synthesized poly(dA) strands. On the other hand, with an unirradiated template initiator, the misincorporation was only slightly enhanced by the addition of terminal deoxynucleotidyl transferase. The sizes of newly synthesized DNA measured by the sedimentation velocities were found to be smaller with the ultraviolet-irradiated templates but they increased to the control level with the addition of terminal deoxynucleotidyl transferase to the systems. These results suggest that terminal deoxynucleotidyl transferase can help DNA polymerase α to bypass thymine dimers in vitro by the formation of mismatched regions at the positions opposite to pyrimidine dimers on the template. (Auth.)

  4. The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model.

    Directory of Open Access Journals (Sweden)

    Andreas Lindqvist

    Full Text Available A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood.In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder.A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs.In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period.

  5. Differential effects of Roux-en-Y gastric bypass surgery on brown and beige adipose tissue thermogenesis.

    Science.gov (United States)

    Hankir, Mohammed K; Bronisch, Felix; Hintschich, Constantin; Krügel, Ute; Seyfried, Florian; Fenske, Wiebke K

    2015-10-01

    There are numerous reports of increased energy expenditure after Roux-en-Y gastric bypass (RYGB) surgery in humans and rodent models but the underlying mechanisms remain poorly understood. In the present study we assessed at the gene expression level whether RYGB leads to recruitment of brown adipose tissue (BAT) and/or beige adipose tissue (BeAT) as a means of enhanced facultative thermogenesis and increased energy expenditure after surgery. Diet-induced obese male Wistar rats were randomized into RYGB-operated (n=10), sham-operated ad libitum fed (Sham) (n=7) or sham-operated body weight matched (BWM) to RYGB groups (n=7). At a stage of postoperatively stabilized weight reduction, BAT (interscapular), subcutaneous (inguinal) and visceral (epididymal and perirenal) white adipose tissue (WAT) depots were collected in the fasted state. Expression of thermoregulatory genes (UCP1, CIDEA and PRDM16) in BAT and WAT as well as specific markers of BeAT (Ear2 and TMEM26) in WAT was analyzed using RT-qPCR. Compared to Sham rats, UCP1 mRNA expression in BAT was significantly reduced in BWM, but not in RYGB rats. No differences in mRNA expression were found for thermoregulatory proteins or for markers of BeAT in subcutaneous or visceral WAT depots between RYGB and Sham groups. The compensatory decrease in BAT thermogenic gene expression typically associated with body weight loss is attenuated after RYGB which, as opposed to recruitment of BeAT, may contribute to overall increases in energy expenditure and weight loss maintenance after surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Impact of Roux-en-Y Gastric Bypass Surgery on Pharmacokinetics of Administered Drugs: Implications and Perspectives.

    Science.gov (United States)

    Srinivas, Nuggehally R

    Obesity epidemic has grown out of proportion with increased heath cost because of comorbidity associated with obesity. Due to mediocre benefit from pharmacological interventions, bariatric surgery popularly known as Roux-en-Y gastric bypass (RYGB) surgery has been increasingly practiced. Although RYGB significantly reduces body mass index, it also alters the local gut environment leading to significant changes in the drug absorption and bioavailability. The focus of the review is to present and critically evaluate case studies pertaining to pharmacokinetic data gathered till date on subjects after RYGB. A large portion of the reviewed examples showed reduced area under the concentration versus time curve [area under curve (AUC)] of drugs after RYGB (44%), whereas equal number of investigations showed increased (26%) or unaltered AUC (26%) after RYGB. There was one instance (4%), where the AUC was highly variable and individual subject dependent. Examination of drugs that showed reduced bioavailability suggested that a complex interplay of various factors such as solubility, permeability, metabolic enzymes, and transporters may have contributed for the observed effect. The increased bioavailability seemed to be related to permeability enhancement and generally in drug classes that have reduced metabolism. Based on the review, there is a significant risk of therapy failure for certain drugs because of subtherapeutic plasma levels. The need to readjust doses immediately after RYGB may be considered based on the therapeutic drug monitoring (TDM) findings. It seems prudent to initiate TDM for certain disease areas or drug classes until stable doses are established after RYGB through the appropriate pharmacokinetic and/or pharmacodynamics surrogate, as appropriate.

  7. Predictions of the Bypass Flows in the HTR-PM Reactor Core

    International Nuclear Information System (INIS)

    Sun Jun; Chen Zhipeng; Zheng Yanhua; Shi Lei; Li Fu

    2014-01-01

    In the HTR-PM reactor core, the basic structure materials are large amount of graphite reflectors and carbon bricks. Small gaps among those graphite and carbon bricks are widespread in the reactor core so that the cold helium flow may be bypassed and not completely heated. The bypass flows in relative lower temperature would change the flow and temperature distributions in the reactor core, therefore, the accurate prediction of bypass flows need to be carried out carefully to evaluate the influence to the reactor safety. Based on the characteristics of the bypass flow problem, hybrid method of the flow network and the CFD tools was employed to represent the connections and calculate flow distributions of all the main flow and bypass flow paths. In this paper, the hybrid method was described and applied to specific bypass flow problem in the HTR-PM. Various bypass flow paths in the HTR-PM were reviewed, figured out, and modeled by the flow network and the CFD methods, including the axial vertical gaps in the side reflectors, control rod channels, absorber sphere channels and radial gap flow through keys around the hot helium plenum. The bypass flow distributions and its flow rate ratio to the total flow rate in the primary loop were also calculated, discussed and evaluated. (author)

  8. Effect of Roux-en-Y gastric bypass on liver mitochondrial dynamics in a rat model of obesity.

    Science.gov (United States)

    Sacks, Jessica; Mulya, Anny; Fealy, Ciaran E; Huang, Hazel; Mosinski, John D; Pagadala, Mangesh R; Shimizu, Hideharu; Batayyah, Esam; Schauer, Philip R; Brethauer, Stacy A; Kirwan, John P

    2018-02-01

    Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding. We assessed expression of mitochondrial proteins involved in fusion, fission, mitochondrial autophagy (mitophagy) and biogenesis, as well as differences in citrate synthase activity and markers of oxidative stress. Gene expression for mitochondrial fusion genes, mitofusin 1 (Mfn1; P fasting plasma insulin. In the RYGB group, citrate synthase activity was increased (P < 0.02) and reactive oxygen species (ROS) was decreased compared to the Sham control group (P < 0.05), although total antioxidant capacity was unchanged between groups. These data are the first to show an association between RYGB surgery and improved markers of liver mitochondrial dynamics. These observed improvements may be related to weight loss and reduced energetic demand on the liver, which could facilitate normalization of glucose homeostasis and protect against hepatic steatosis. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  9. Zinc nutritional status of morbidly obese patients before and after Roux-en-Y gastric bypass: a preliminary report.

    Science.gov (United States)

    Cominetti, Cristiane; Garrido, Arthur Belarmino; Cozzolino, Silvia Maria Franciscato

    2006-04-01

    Previous researchers have found that the nutritional zinc status in obese and diabetic subjects is altered: low zinc concentrations in plasma and erythrocytes with high urinary zinc excretion were observed. This study assessed the influence of the Roux-en-Y gastric bypass (RYGBP) on the plasma, erythrocyte and urinary zinc concentrations before the beginning of the mineral supplementation. 24 morbidly obese patients were studied before and 2 months after RYGBP (the period in which the patients were still not ingesting mineral supplements). Fast blood sample, 24-hour urine, and 3-day food records were collected in the pre- and postoperative phases. Zinc concentration in the samples was analyzed by flame atomic absorption spectrophotometry, and dietary analysis of the food records were performed using the software Virtual Nutri with the inclusion of zinc concentration in the database for regional foods. Pre- and postoperative results were respectively: plasma 68.0 and 66.3 microg/dL; erythrocytes 36.6 and 43.8 microg/g Hb; urine 884.7 microg/24h and 385.9 microg/24h; and zinc intake 10.5 and 6.7 mg/day. These results suggest that RYGBP changed mainly the zinc erythrocyte and urinary concentrations. As expected, the zinc intake was lower in the postoperative phase, which in the medium and long term, could cause problems for the patients.

  10. Rapid and specific identification of Yersinia pestis by using a nested polymerase chain reaction procedure.

    OpenAIRE

    Campbell, J; Lowe, J; Walz, S; Ezzell, J

    1993-01-01

    We developed a 4-h nested polymerase chain reaction assay that detected a region of the plasminogen activator gene of Yersinia pestis in 100% of 43 Y. pestis strains isolated from humans, rats, and fleas yet was unreactive with the closely related species Yersinia enterocolitica and Yersinia pseudotuberculosis.

  11. Early marginal ulcer following Roux-en-Y gastric bypass under proton pump inhibitor treatment: prospective multicentric study Úlcera perianastomótica após derivação gástrica em Y-de-Roux mesmo em uso de inibidor de bomba de prótons: estudo prospectivo multicêntrico

    Directory of Open Access Journals (Sweden)

    Arthur Belarmino Garrido Jr.

    2010-06-01

    Full Text Available CONTEXT: Causal factors of gastrojejunal ulcers after Roux-en-Y gastric bypass include peptic acid secretion from the gastric pouch. Esomeprazole is a potent inhibitor of acid secretion. OBJECTIVE: To assess the occurrence of dyspepsia and gastrojejunal ulcers within the first 2 months after Roux-en-Y gastric bypass during the use of esomeprazole. METHODS: One hundred eighteen morbid obese subjects were submitted to Roux-en-Y gastric bypass. Preoperative upper gastrointestinal tract endoscopy was negative for H. pylori. All subjects received esomeprazole for 60 days after surgery. RESULTS: Two weeks after surgery only 13 mild symptoms were reported. After 2 months, 17 also moderate complaints were registered. Endoscopy around the 60th day showed esophagitis in 10 (8.5%, hiatal hernia in 2 (1.7%, foreign body in the anastomotic line in 12 (10.2% and gastrojejunal ulcers was observed in 9 (7.6% subjects, 2 of which had a suture material or metallic staple granuloma in the gastrojejunostomy. Ten subjects took nonsteroidal anti-inflammatory drugs at least once during study, but none of them developed ulcer. None of the subjects with ulcer had dyspeptic symptoms. CONCLUSION: The incidence of ulcer in the gastrojejunal anastomosis within the first 2 months following Rouxen-Y gastric bypass under proton pump inhibitors is considerable. It was not related to the use of non-steroidal anti-inflammatory drugs, highlighting the possibility of ischemia and foreign body as causal factors. The ulcers were asymptomatic, and all post-surgical dyspeptic symptoms were moderate in severity.CONTEXTO: Sintomas dispépticos são comuns após derivação gástrica em Y-de-Roux. Podem decorrer de úlceras de boca anastomótica, cujos possíveis fatores causais incluem a secreção cloridropéptica da bolsa gástrica, isquemia, efeito de corpo estranho dos materiais de sutura e uso de antiinflamatórios não-esteróides. O esomeprazol é um redutor potente da secre

  12. Coronary Artery Bypass Grafting

    Science.gov (United States)

    ... lung bypass machine is used during this procedure. Robot-assisted technique. This type of procedure allows for ... driving after 3 to 8 weeks. Returning to work after 6 weeks is common unless your job ...

  13. X-Y Converter Family

    DEFF Research Database (Denmark)

    Bhaskar, Mahajan Sagar; Sanjeevikumar, Padmanaban; Wheeler, Patrick

    2016-01-01

    A New breed of a buck boost converter, named as the XY converter family is proposed in this article. In the XY family, 16 topologies are presented which are highly suitable for renewable energy applications which require a high ratio of DC-DC converter; such as a photovoltaic multilevel inverter...... system, high voltage automotive applications and industrial drives. Compared to the traditional boost converter and existing recent converters, the proposed XY converter family has the ability to provide a higher output voltage by using less number of power devices and reactive components. Other distinct...... features of the XY converter family are i) Single control switch ii) Provide negative output voltage iii) Non-isolated topologies iv) High conversion ratio without making the use of high duty cycle and v) modular structure. XY family is compared with the recent high step-up converters and the detailed...

  14. 21 CFR 870.4200 - Cardiopulmonary bypass accessory equipment.

    Science.gov (United States)

    2010-04-01

    ... Cardiopulmonary bypass accessory equipment. (a) Identification. Cardiopulmonary bypass accessory equipment is a... mounting bracket or system-priming equipment. (b) Classification. (1) Class I. The device is classified as class I if it does not involve an electrical connection to the patient. The device is exempt from the...

  15. Engineered split in Pfu DNA polymerase fingers domain improves incorporation of nucleotide γ-phosphate derivative

    Science.gov (United States)

    Hansen, Connie J.; Wu, Lydia; Fox, Jeffrey D.; Arezi, Bahram; Hogrefe, Holly H.

    2011-01-01

    Using compartmentalized self-replication (CSR), we evolved a version of Pyrococcus furiosus (Pfu) DNA polymerase that tolerates modification of the γ-phosphate of an incoming nucleotide. A Q484R mutation in α-helix P of the fingers domain, coupled with an unintended translational termination-reinitiation (split) near the finger tip, dramatically improve incorporation of a bulky γ-phosphate-O-linker-dabcyl substituent. Whether synthesized by coupled translation from a bicistronic (−1 frameshift) clone, or reconstituted from separately expressed and purified fragments, split Pfu mutant behaves identically to wild-type DNA polymerase with respect to chromatographic behavior, steady-state kinetic parameters (for dCTP), and PCR performance. Although naturally-occurring splits have been identified previously in the finger tip region of T4 gp43 variants, this is the first time a split (in combination with a point mutation) has been shown to broaden substrate utilization. Moreover, this latest example of a split hyperthermophilic archaeal DNA polymerase further illustrates the modular nature of the Family B DNA polymerase structure. PMID:21062827

  16. Engineered split in Pfu DNA polymerase fingers domain improves incorporation of nucleotide gamma-phosphate derivative.

    Science.gov (United States)

    Hansen, Connie J; Wu, Lydia; Fox, Jeffrey D; Arezi, Bahram; Hogrefe, Holly H

    2011-03-01

    Using compartmentalized self-replication (CSR), we evolved a version of Pyrococcus furiosus (Pfu) DNA polymerase that tolerates modification of the γ-phosphate of an incoming nucleotide. A Q484R mutation in α-helix P of the fingers domain, coupled with an unintended translational termination-reinitiation (split) near the finger tip, dramatically improve incorporation of a bulky γ-phosphate-O-linker-dabcyl substituent. Whether synthesized by coupled translation from a bicistronic (-1 frameshift) clone, or reconstituted from separately expressed and purified fragments, split Pfu mutant behaves identically to wild-type DNA polymerase with respect to chromatographic behavior, steady-state kinetic parameters (for dCTP), and PCR performance. Although naturally-occurring splits have been identified previously in the finger tip region of T4 gp43 variants, this is the first time a split (in combination with a point mutation) has been shown to broaden substrate utilization. Moreover, this latest example of a split hyperthermophilic archaeal DNA polymerase further illustrates the modular nature of the Family B DNA polymerase structure.

  17. Changes in the vessels following aorto-coronary bypass operation

    International Nuclear Information System (INIS)

    Goebel, N.; Pfluger, N.; Speiser, K.; Turina, M.; Rothlin, M.; Zurich Univ.; Zurich Univ.

    1983-01-01

    In a prospective study (238 men, mean age 53 years) the changes of the native vessels were studied 3 months after a-c-bypass operation and 5 months after preop. angiography. Progression was defined as increase of stenoses of at least 20% or new total occlusion. Progression was significantly more frequent in vessels with than without bypass and was located proximally to the anastomoses in most cases, less frequently at the anastomoses and very rarely distally to the anastomoses. Proximal progression was significantly more frequent with patent than with occluded bypasses. Stenoses at the anastomoses were significantly more frequent with occluded than with patent bypasses. Stenoses of higher degrees hat a stonger tendency for progression than slighter stenoses. Regression was rare and nearly always caused by surgery. (orig.) [de

  18. Off-Pump Versus On-Pump Coronary Artery Bypass Grafting

    DEFF Research Database (Denmark)

    Møller, Christian H; Steinbrüchel, Daniel A

    2014-01-01

    Coronary artery bypass grafting (CABG) remains the preferred treatment in patients with complex coronary artery disease. However, whether the procedure should be performed with or without the use of cardiopulmonary bypass, referred to as off-pump and on-pump CABG, is still up for debate....... Intuitively, avoidance of cardiopulmonary bypass seems beneficial as the systemic inflammatory response from extracorporeal circulation is omitted, but no single randomized trial has been able to prove off-pump CABG superior to on-pump CABG as regards the hard outcomes death, stroke or myocardial infarction....... In contrast, off-pump CABG is technically more challenging and may be associated with increased risk of incomplete revascularization. The purpose of the review is to summarize the current literature comparing outcomes of off-pump versus on-pump coronary artery bypass surgery....

  19. Sub-nuclear irradiation, in-vivo microscopy and single-molecule imaging to study a DNA Polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Soria, G; Mansilla, S; Belluscio, L; Speroni, J; D' Alessio, C; Gottifredi, V [Fundacion Leloir, Buenos Aires (Argentina); Essers, J; Kanaar, R [Erasmus Medical Center, Rotterdam (Netherlands)

    2009-07-01

    When the DNA is damaged in cells progressing through S phase, replication blockage can be avoided by TLS (Translesion DNA synthesis). This is an auxiliary replication mechanism that relies on the function of specialized polymerases that accomplish DNA damage bypass. An example of a classical TLS polymerase is Pol {eta} ({eta}). The current model implies that Pol {eta} activity is circumscribed to S-phase. Here we perform a systematic characterization of Pol {eta} behaviour after DNA-damage. We show that Pol {eta} is recruited to UV-induced DNA lesions in cells outside S phase including cells permanently arrested in G1. This observation was confirmed by different sub-nuclear damage strategies including global UV irradiation, local UV irradiation and local multi-photon laser irradiation of single nuclei in living cells. By local UV irradiation and alpha particle irradiation we evaluated the potential connection between Pol h recruitment to DNA lesions outside S phase and Homologous recombination repair (HRR) or Nucleotide excision repair (NER). Finally, we employ a single-molecule imaging approach (known as DNA fiber-assay) to determine how Pol h influences the progression of the replication fork. Our data reveals that the re-localization of Pol {eta} to DNA lesions might be temporally and mechanistically uncoupled from replicative DNA synthesis and from DNA damage processing. (authors)

  20. Sub-nuclear irradiation, in-vivo microscopy and single-molecule imaging to study a DNA Polymerase

    International Nuclear Information System (INIS)

    Soria, G.; Mansilla, S.; Belluscio, L.; Speroni, J.; D'Alessio, C.; Gottifredi, V.; Essers, J.; Kanaar, R.

    2009-01-01

    When the DNA is damaged in cells progressing through S phase, replication blockage can be avoided by TLS (Translesion DNA synthesis). This is an auxiliary replication mechanism that relies on the function of specialized polymerases that accomplish DNA damage bypass. An example of a classical TLS polymerase is Pol η (eta). The current model implies that Pol η activity is circumscribed to S-phase. Here we perform a systematic characterization of Pol η behaviour after DNA-damage. We show that Pol η is recruited to UV-induced DNA lesions in cells outside S phase including cells permanently arrested in G1. This observation was confirmed by different sub-nuclear damage strategies including global UV irradiation, local UV irradiation and local multi-photon laser irradiation of single nuclei in living cells. By local UV irradiation and alpha particle irradiation we evaluated the potential connection between Pol h recruitment to DNA lesions outside S phase and Homologous recombination repair (HRR) or Nucleotide excision repair (NER). Finally, we employ a single-molecule imaging approach (known as DNA fiber-assay) to determine how Pol h influences the progression of the replication fork. Our data reveals that the re-localization of Pol η to DNA lesions might be temporally and mechanistically uncoupled from replicative DNA synthesis and from DNA damage processing. (authors)

  1. Cystoviral polymerase complex protein P7 uses its acidic C-terminal tail to regulate the RNA-directed RNA polymerase P2.

    Science.gov (United States)

    Alphonse, Sébastien; Arnold, Jamie J; Bhattacharya, Shibani; Wang, Hsin; Kloss, Brian; Cameron, Craig E; Ghose, Ranajeet

    2014-07-15

    In bacteriophages of the cystovirus family, the polymerase complex (PX) encodes a 75-kDa RNA-directed RNA polymerase (P2) that transcribes the double-stranded RNA genome. Also a constituent of the PX is the essential protein P7 that, in addition to accelerating PX assembly and facilitating genome packaging, plays a regulatory role in transcription. Deletion of P7 from the PX leads to aberrant plus-strand synthesis suggesting its influence on the transcriptase activity of P2. Here, using solution NMR techniques and the P2 and P7 proteins from cystovirus ϕ12, we demonstrate their largely electrostatic interaction in vitro. Chemical shift perturbations on P7 in the presence of P2 suggest that this interaction involves the dynamic C-terminal tail of P7, more specifically an acidic cluster therein. Patterns of chemical shift changes induced on P2 by the P7 C-terminus resemble those seen in the presence of single-stranded RNA suggesting similarities in binding. This association between P2 and P7 reduces the affinity of the former toward template RNA and results in its decreased activity both in de novo RNA synthesis and in extending a short primer. Given the presence of C-terminal acidic tracts on all cystoviral P7 proteins, the electrostatic nature of the P2/P7 interaction is likely conserved within the family and could constitute a mechanism through which P7 regulates transcription in cystoviruses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Predictors of inotrope use in patients undergoing concomitant coronary artery bypass graft (CABG and aortic valve replacement (AVR surgeries at separation from cardiopulmonary bypass (CPB

    Directory of Open Access Journals (Sweden)

    Nelson William B

    2009-06-01

    Full Text Available Abstract Background Left ventricular dysfunction is common after coronary artery bypass graft and valve replacement surgeries and is often treated with inotropic drugs to maintain adequate hemodynamic status. In this study, we aimed to identify the demographic, clinical, laboratory, echocardiographic and hemodynamic factors that are associated with use of inotropic drugs in patients undergoing concomitant coronary artery bypass graft and aortic valve replacement surgery. Methods The study included 97 patients who had undergone concomitant coronary artery bypass graft and aortic valve replacement at Regions Hospital, University of Minnesota Medical School from January 2006 to December 2008. All data were collected retrospectively after reviewing electronic medical records. Inotropic support was defined as the use of dopamine [greater than or equal to] 5 ug/kg/min; any dose of epinephrine, norepinephrine, dobutamine, and milrinone at the separation from cardiopulmonary bypass. Results Inotropic support was used in a total of 50 patients (52% at the separation from cardiopulmonary bypass. Average age of the patients requiring inotropic support was 72.2 +/- 8.8 years. The study identified four significant, independent predictors of inotrope use: (1 Cardiac index [less than or equal to]2.5 L/min/m2, (2 LVEDP [greater than or equal to] 20 mm Hg, (3 LVEF [less than or equal to]40%, and (4 CKD stage 3 to 5. Conclusion We identified four independent risk factors for postoperative use of inotropic support in patients undergoing concomitant coronary artery bypass graft and arotic valve replacement surgery at the separation from cardiopulmonary bypass. The study results will be helpful to prospectively identify patients who will likely to require inotropic support at the separation from cardiopulmonary bypass.

  3. Improved crystallization of the coxsackievirus B3 RNA-dependent RNA polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Jabafi, Ilham; Selisko, Barbara; Coutard, Bruno; De Palma, Armando M.; Neyts, Johan; Egloff, Marie-Pierre; Grisel, Sacha; Dalle, Karen; Campanacci, Valerie; Spinelli, Silvia; Cambillau, Christian; Canard, Bruno; Gruez, Arnaud, E-mail: arnaud.gruez@maem.uhp-nancy.fr [Centre National de la Recherche Scientifique and Universités d’Aix-Marseille I et II, UMR 6098, Architecture et Fonction des Macromolécules Biologiques, Ecole Supérieure d’Ingénieurs de Luminy-Case 925, 163 Avenue de Luminy, 13288 Marseille CEDEX 9 (France)

    2007-06-01

    The first crystal of a coxsackievirus RNA-dependent RNA polymerase is reported. The Picornaviridae virus family contains a large number of human pathogens such as poliovirus, hepatitis A virus and rhinoviruses. Amongst the viruses belonging to the genus Enterovirus, several serotypes of coxsackievirus coexist for which neither vaccine nor therapy is available. Coxsackievirus B3 is involved in the development of acute myocarditis and dilated cardiomyopathy and is thought to be an important cause of sudden death in young adults. Here, the first crystal of a coxsackievirus RNA-dependent RNA polymerase is reported. Standard crystallization methods yielded crystals that were poorly suited to X-ray diffraction studies, with one axis being completely disordered. Crystallization was improved by testing crystallization solutions from commercial screens as additives. This approach yielded crystals that diffracted to 2.1 Å resolution and that were suitable for structure determination.

  4. Improved crystallization of the coxsackievirus B3 RNA-dependent RNA polymerase

    International Nuclear Information System (INIS)

    Jabafi, Ilham; Selisko, Barbara; Coutard, Bruno; De Palma, Armando M.; Neyts, Johan; Egloff, Marie-Pierre; Grisel, Sacha; Dalle, Karen; Campanacci, Valerie; Spinelli, Silvia; Cambillau, Christian; Canard, Bruno; Gruez, Arnaud

    2007-01-01

    The first crystal of a coxsackievirus RNA-dependent RNA polymerase is reported. The Picornaviridae virus family contains a large number of human pathogens such as poliovirus, hepatitis A virus and rhinoviruses. Amongst the viruses belonging to the genus Enterovirus, several serotypes of coxsackievirus coexist for which neither vaccine nor therapy is available. Coxsackievirus B3 is involved in the development of acute myocarditis and dilated cardiomyopathy and is thought to be an important cause of sudden death in young adults. Here, the first crystal of a coxsackievirus RNA-dependent RNA polymerase is reported. Standard crystallization methods yielded crystals that were poorly suited to X-ray diffraction studies, with one axis being completely disordered. Crystallization was improved by testing crystallization solutions from commercial screens as additives. This approach yielded crystals that diffracted to 2.1 Å resolution and that were suitable for structure determination

  5. Roux-en Y gastric bypass results in long-term remission of hepatocyte apoptosis and hepatic histological features of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Schneck

    2016-08-01

    Full Text Available The long-term effects of bariatric surgery on non alcoholic steatohepatitis (NASH, focusing on liver injury and hepatocyte apoptosis,are not well established. We here performed a longitudinal study with paired liver biopsies of 9 morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m2 with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB surgery. LRYGB surgery was associated with significant weight loss (median BMI loss –13.7 [–16.4; –9.5] kg/m2, improved hepatic steatosis in all patients (55.5% with total resolution, and resolution of hepatic inflammation and hepatocyte ballooning in 100% and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase 3levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.

  6. Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis.

    Science.gov (United States)

    Schneck, Anne-Sophie; Anty, Rodolphe; Patouraux, Stéphanie; Bonnafous, Stéphanie; Rousseau, Déborah; Lebeaupin, Cynthia; Bailly-Maitre, Beatrice; Sans, Arnaud; Tran, Albert; Gugenheim, Jean; Iannelli, Antonio; Gual, Philippe

    2016-01-01

    The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m(2)) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss -13.7 [-16.4; -9.5] kg/m(2)), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.

  7. La familia y su reconfiguración a partir del desplazamiento forzado The family and its configuration starting from the forced displacement

    Directory of Open Access Journals (Sweden)

    Gloria Marcela Gómez Builes

    2007-03-01

    Full Text Available Las familias que han llegado a Medellín en situación de desplazamiento forzado por la violencia, constituyen un colectivo humano con características y necesidades particulares. Objetivo: Describir las condiciones de vida de la población en situación de desplazamiento forzado del asentamiento El Palomar, del barrio Bello Oriente, de Medellín, Colombia, en los meses comprendidos entre mayo de 2004 y diciembre de 2005 y las transformaciones de la familia antes y a partir del desplazamiento Metodología: El presente estudio fue realizado desde un enfoque cualitativo, desde la perspectiva de la etnografía focalizada. Resultados: Se destacan los procesos de transformación que sufre la familia en relación con su dinámica y estructura, explicitando los cambios en cuanto a roles, funciones, contextos, posibilidades y limitaciones que se dan a partir del desplazamiento forzado. Conclusiones: La situación de desplazamiento implica la interacción de estas familias con el mundo urbano, que siendo ajeno a sus costumbres y formas de comprender el mundo, se impone y condiciona las posibilidades de desarrollo y realización de las familias y sus integrantes y aumenta la situación de vulnerabilidad, exclusión social y económica, concretándose en la violación del derecho a la familia.The families who have arrived to Medellín under a situation of displacement forced by the violence, constitutes a human group which expresses particular characteristics and needs. Objective: to describe life conditions of the population in forced situation displacement settled in "El palomar", in the district "Bello Oriente" of Medellín between May of 2004-December of 2005, and the changes in the family before and after the displacement. Methodology: The present study was made from a qualitative approach, under the view of focused ethnography. Results: they stand out the process of transformation in the family, according to their dynamic and structures, specifying

  8. Monsanto may bypass NIH in microbe test.

    Science.gov (United States)

    Sun, Marjorie

    1985-01-11

    The Monsanto Company is planning to ask the Environmental Protection Agency for clearance to field test a genetically engineered microbial pesticide, bypassing the traditional approval process of the National Institutes of Health. Although only federally funded institutions are required to obtain NIH approval for genetic engineering tests, Monsanto is the first company to bypass the NIH regulatory process, which has become mired in a lawsuit brought by Jeremy Rifkin.

  9. Gene structure, expression pattern and interaction of Nuclear Factor-Y family in castor bean (Ricinus communis).

    Science.gov (United States)

    Wang, Yue; Xu, Wei; Chen, Zexi; Han, Bing; Haque, Mohammad E; Liu, Aizhong

    2018-03-01

    Nuclear Factor-Y transcription factors, which function in regulating seed development (including storage reservoir accumulation) and responding to abiotic stresses, were identified and characterized in castor bean. Nuclear Factor-Y (NF-Y) transcription factors in plants contain three subunits (NF-YA, NF-YB and NF-YC), and function as a heterodimer or heterotrimer complex in regulating plant growth, development and response to stresses. Castor bean (Ricinus communis, Euphorbiaceae) one of the most economically important non-edible oilseed crops, able to grow in diverse soil conditions and displays high tolerance to abiotic stresses. Due to increasing demands for its seed oils, it is necessary to elucidate the molecular mechanism underlying the regulation of growth and development. Based on the available genome data, we identified 25 RcNF-Y members including six RcNF-YAs, 12 RcNF-YBs and seven RcNF-YCs, and characterized their gene structures. Yeast two-hybrid assays confirmed the protein-protein interactions among three subunits. Using transcriptomic data from different tissues, we found that six members were highly or specifically expressed in endosperms (in particular, two LEC1-type members RcNF-YB2 and RcNF-YB12), implying their involvement in regulating seed development and storage reservoir accumulation. Further, we investigated the expression changes of RcNF-Y members in two-week-old seedlings under drought, cold, hot and salt stresses. We found that the expression levels of 20 RcNF-Y members tested were changed and three RcNF-Y members might function in response to abiotic stresses. This study is the first reported on genomic characterization of NF-Y transcription factors in the family Euphorbiaceae. Our results provide the basis for improved understanding of how NF-Y genes function in the regulation of seed development and responses to abiotic stresses in both castor bean and other plants in this family.

  10. The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter.

    Directory of Open Access Journals (Sweden)

    Sarah L Noton

    Full Text Available Respiratory syncytial virus (RSV is an RNA virus in the Family Paramyxoviridae. Here, the activities performed by the RSV polymerase when it encounters the viral antigenomic promoter were examined. RSV RNA synthesis was reconstituted in vitro using recombinant, isolated polymerase and an RNA oligonucleotide template representing nucleotides 1-25 of the trailer complement (TrC promoter. The RSV polymerase was found to have two RNA synthesis activities, initiating RNA synthesis from the +3 site on the promoter, and adding a specific sequence of nucleotides to the 3' end of the TrC RNA using a back-priming mechanism. Examination of viral RNA isolated from RSV infected cells identified RNAs initiated at the +3 site on the TrC promoter, in addition to the expected +1 site, and showed that a significant proportion of antigenome RNAs contained specific nucleotide additions at the 3' end, demonstrating that the observations made in vitro reflected events that occur during RSV infection. Analysis of the impact of the 3' terminal extension on promoter activity indicated that it can inhibit RNA synthesis initiation. These findings indicate that RSV polymerase-promoter interactions are more complex than previously thought and suggest that there might be sophisticated mechanisms for regulating promoter activity during infection.

  11. Time-lapse crystallography snapshots of a double-strand break repair polymerase in action.

    Science.gov (United States)

    Jamsen, Joonas A; Beard, William A; Pedersen, Lars C; Shock, David D; Moon, Andrea F; Krahn, Juno M; Bebenek, Katarzyna; Kunkel, Thomas A; Wilson, Samuel H

    2017-08-15

    DNA polymerase (pol) μ is a DNA-dependent polymerase that incorporates nucleotides during gap-filling synthesis in the non-homologous end-joining pathway of double-strand break repair. Here we report time-lapse X-ray crystallography snapshots of catalytic events during gap-filling DNA synthesis by pol μ. Unique catalytic intermediates and active site conformational changes that underlie catalysis are uncovered, and a transient third (product) metal ion is observed in the product state. The product manganese coordinates phosphate oxygens of the inserted nucleotide and PP i . The product metal is not observed during DNA synthesis in the presence of magnesium. Kinetic analyses indicate that manganese increases the rate constant for deoxynucleoside 5'-triphosphate insertion compared to magnesium. The likely product stabilization role of the manganese product metal in pol μ is discussed. These observations provide insight on structural attributes of this X-family double-strand break repair polymerase that impact its biological function in genome maintenance.DNA polymerase (pol) μ functions in DNA double-strand break repair. Here the authors use time-lapse X-ray crystallography to capture the states of pol µ during the conversion from pre-catalytic to product complex and observe a third transiently bound metal ion in the product state.

  12. An Experimental Design of Bypass Magneto-Rheological (MR) damper

    Science.gov (United States)

    Rashid, MM; Aziz, Mohammad Abdul; Raisuddin Khan, Md.

    2017-11-01

    The magnetorheological (MR) fluid bypass damper fluid flow through a bypass by utilizing an external channel which allows the controllability of MR fluid in the channel. The Bypass MR damper (BMRD) contains a rectangular bypass flow channel, current controlled movable piston shaft arrangement and MR fluid. The static piston coil case is winding by a coil which is used inside the piston head arrangement. The current controlled coil case provides a magnetic flux through the BMRD cylinder for controllability. The high strength of alloy steel materials are used for making piston shaft which allows magnetic flux propagation throughout the BMRD cylinder. Using the above design materials, a Bypass MR damper is designed and tested. An excitation of current is applied during the experiment which characterizes the BMRD controllability. It is shown that the BMRD with external flow channel allows a high controllable damping force using an excitation current. The experimental result of damping force-displacement characteristics with current excitation and without current excitation are compared in this research. The BMRD model is validated by the experimental result at various frequencies and applied excitation current.

  13. 21 CFR 870.4410 - Cardiopulmonary bypass in-line blood gas sensor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass in-line blood gas sensor... Cardiopulmonary bypass in-line blood gas sensor. (a) Identification. A cardiopulmonary bypass in-line blood gas sensor is a transducer that measures the level of gases in the blood. (b) Classification. Class II...

  14. Predictors of weight regain in patients who underwent Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Shantavasinkul, Prapimporn Chattranukulchai; Omotosho, Philip; Corsino, Leonor; Portenier, Dana; Torquati, Alfonso

    2016-11-01

    Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for obesity and results in long-term weight loss and resolution of co-morbidities. However, weight regain may occur as soon as 1-2 years after surgery. This retrospective study aimed to investigate the prevalence of weight regain and possible preoperative predictors of this phenomenon after RYGB. An academic medical center in the United States. A total of 1426 obese patients (15.8% male) who underwent RYGB during January 2000 to 2012 and had at least a 2-year follow-up were reviewed. We included only patients who were initially successful, having achieved at least 50% excess weight loss at 1 year postoperatively. Patients were then categorized into either the weight regain group (WR) or sustained weight loss (SWL) group based upon whether they gained≥15% of their 1-year postoperative weight. Weight regain was observed in 244 patients (17.1%). Preoperative body mass index was similar between groups. Body mass index was significantly higher and percent excess weight loss was significantly lower in the WR group (Pweight regain was 19.5±9.3 kg and-.8±8.5 in the WR and SWL groups, respectively (Pweight loss. Moreover, a longer duration after RYGB was associated with weight regain. Multivariate analysis revealed that younger age was a significant predictor of weight regain even after adjusting for time since RYGB. The present study confirmed that a longer interval after RYGB was associated with weight regain. Younger age was a significant predictor of weight regain even after adjusting for time since RYGB. The findings of this study underscore the complexity of the mechanisms underlying weight loss and regain after RYGB. Future prospective studies are needed to further explore the prevalence, predictors, and mechanisms of weight regain after RYGB. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  15. Cardiopulmonary bypass and hemostasis

    NARCIS (Netherlands)

    Eijsman, Leon

    1992-01-01

    In chapter 1, we recalled that intracardiac defects can only be corrected when cardiopulmonary circulation is maintained by extracorporeal criculation and ventilation. To prevent clot formation in this artificial circuit, the socalled cardiopulmonary bypass (CPB), we completely depend on the

  16. Outcome after VAC® therapy for infected bypass grafts in the lower limb.

    Science.gov (United States)

    Acosta, S; Monsen, C

    2012-09-01

    To assess the outcome of vacuum-assisted wound closure (VAC(®)) therapy for infected bypass grafts. A retrospective 7-year review of patient records from 2004 to 2011 of all patients receiving VAC(®) therapy for infected bypass grafts. Thirty-seven patients with 42 wounds and 45 infected bypass (28 synthetic) grafts received VAC(®) treatment. Two serious bleeding episodes from the suture lines occurred. The median VAC(®) therapy time was 20 days. The proportion of patent bypass grafts was 91% (41/45) at a median time of 3.5 months from the start of VAC(®) therapy. Five patients with seven bypasses had persistent infection or re-infection, and the total graft preservation rate was 76% (34/45). The median follow-up time was 15 months. The presence of two infected bypass grafts in one groin wound was associated with an increased major amputation rate (hazard ratio (HR) 7.4 [95% confidence interval (CI) 2.0-27.5]), and synthetic graft infection (HR 5.0 [95% CI 1.5-17.4]) and non-healed wound (HR 3.6 [95% CI 1.5-8.7]) were associated with mortality. VAC(®) therapy of infected bypass grafts was able to induce effective wound healing without compromising the early bypass function. Two infected synthetic bypasses in the wound were associated with the highest risk of adverse outcome. Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  17. Comparison of circular- and linear-stapled gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass: a multicenter study.

    Science.gov (United States)

    Major, Piotr; Janik, Michał R; Wysocki, Michał; Walędziak, Maciej; Pędziwiatr, Michał; Kowalewski, Piotr K; Małczak, Piotr; Paśnik, Krzysztof; Budzyński, Andrzej

    2017-06-01

    Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a common, well-established procedure, but no consensus regarding selection of the gastrojejunostomy (GJ) technique has been reached, and standardization of this precise technique is far from being achieved. To compare circular-stapled and linear-stapled GJ in LRYGB in terms of operative time and postoperative complications. This retrospective case-control study compared the perioperative and postoperative outcomes of LRYGB with a circular-stapled (LRYGB-CS) versus linear-stapled (LRYGB-LS) gastrojejunostomy. All patients, operated on in two academic referral care centers for bariatric surgery, were enrolled from April 2013 to June 2016. 457 patients were included (255 and 202 respectively in the LRYGB-CS and LRYGB-LS groups). After matching the groups for age, sex, body mass index, arterial hypertension, and presence of type 2 diabetes in a 1 : 1 ratio, 99 patients were enrolled in each. The total operative time was longer in the LRYGB-LS group (140 vs. 85 min, p < 0.001). The postoperative hemorrhage and wound infection rates were lower in the LRYGB-LS group (2.1% vs. 10.3%, p = 0.021, and 1.0% vs. 9.3%, p = 0.011). The readmission rates were comparable (8.2% vs. 6.1%, p = 0.593). There was no significant difference in the incidence of gastrojejunostomy leakage, stricture, port-site hernia, or marginal ulcer. Both anastomosis types for LRYGB are safe and have low and comparable risks of postoperative complications. After LRYGB-CS, postoperative bleeding and wound infections are slightly more frequent; however, the operative time is shorter.

  18. Baseline Anthropometric and Metabolic Parameters Correlate with Weight Loss in Women 1-Year After Laparoscopic Roux-En-Y Gastric Bypass.

    Science.gov (United States)

    Sans, Arnaud; Bailly, Laurent; Anty, Rodolphe; Sielezenef, Igor; Gugenheim, Jean; Tran, Albert; Gual, Philippe; Iannelli, Antonio

    2017-11-01

    In this study, we explored in a prospective cohort of morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGP) correlations between baseline anthropometrics, metabolic parameters, resting energy expenditure (REE), body composition, and 1-year % excess body mass index loss (%EBMIL). We also investigated risk factors for insufficient %EBMIL. One hundred three consecutive women were prospectively evaluated at baseline (age 40.6 ± 11.2, weight 113.9 kg ± 15.3, BMI 43.3 ± 4.9 kg/m 2 ) and 1 year after LRYGP. Weight, excess weight, brachial circumference, waist circumference, fat mass (FM) and fat-free mass (FFM) (measured with bioelectrical impedance analysis), REE, inflammation, insulin resistance, and lipid disturbances were determined before and 1 year after LRYGP. At 1 year, mean weight loss was 39.8 kg ± 11.7 and mean EBMIL was 15.2 kg/m 2  ± 4.2. Mean %EBMIL was 86% ± 21% (range 30-146%). Baseline brachial circumference, waist circumference and triceps skinfold thickness decreased significantly at 1 year (P baseline body composition parameters, only preoperative FM was negatively correlated with %EBMIL (r = -0.23; p = 0.02). One year after surgery FM change was negatively correlated with EBMIL% (r = -0.49; P baseline blood glucose level (OR = 1.77; CI 95%: [1.3-2.4]) was the only predictive factor of EBMIL Baseline glucose level may be helpful in identifying poor responders to LRYGBP. NCT02820285y ( https://clinicaltrials.gov/ct2/show/NCT02820285?term=Characterization+of+Immune+Semaphorin+in+Non-Alcoholic+Fatty+Liver+Disease+and+NASH&rank=1 ).

  19. The impact of avoiding cardiopulmonary by-pass during coronary artery bypass surgery in elderly patients: the Danish On-pump Off-pump Randomisation Study (DOORS)

    DEFF Research Database (Denmark)

    Houlind, Kim; Kjeldsen, Bo Juul; Madsen, Susanne Nørgaard

    2009-01-01

    BACKGROUND: Coronary Artery Bypass Graft operation for ischemic heart disease provides improved quality of life and, in some patients, prolonged survival. Concern has, however, been raised about complications that may be related to the use of cardiopulmonary by-pass (CPB) and aortic cross......-clamping. It has been hypothesized that when coronary artery by-pass grafting is performed without the use of CPB, the rate of serious complications is reduced. METHODS/DESIGN: The trial is designed as an open, randomized, controlled, clinical trial with blinded assessment of end-points. Patients at or above 70...... years of age, referred for surgical myocardial revascularisation, are included and randomised to receive coronary artery by-pass grafting either with or without the use of CPB and aortic cross-clamping. Follow-up is performed by clinical, biochemical, electrocardiographic, and angiographic data...

  20. Demencia frontotemporal no familiar y epilepsia generalizada Frontotemporal dementia non familial and generalized epilepsy

    Directory of Open Access Journals (Sweden)

    Patricio Fuentes

    2005-12-01

    Full Text Available Se presenta un paciente de 62 años, sin antecedentes familiares de demencia, que a los 45 años debuta con crisis súbitas de disnea, visión borrosa, caída al suelo y movimientos repetitivos de brazos. Tratado por epilepsia con fenitoína y ácido valproico, repite esporádicamente crisis semejantes. Hace 4 años sus familiares notan cambios de personalidad, irritabilidad y conductas obsesivas. Hace 2 años aparecen episodios de desorientación de días de duración, algunos con alucinaciones auditivas y también fenómenos convulsivos. Ultimamente presenta crisis polimorfas, algunas con prolongada alteración de conciencia, estados catatoniformes y relajación esfinteriana. Examen físico y neurológico sin anormalidades. Evaluación neuropsicológica evidenció consistentes defectos en funciones frontales. EEG mostraron lentitud generalizada y actividad irritativa esporádica en regiones frontotemporales. Atrofia cortical de predominio anterior en CT scan e hipoperfusión fronto-temporal bilateral en SPECT. Exámenes de laboratorio y LCR normales. CONCLUSIÓN: La asociación de DFT con epilepsia, en forma no familiar, sugiere un síndrome neurodegenerativo cortical diferente.A 62 year-old patient is presented, without family antecedents of dementia who begins with 45 years of age with sudden crisis of dyspnea, blurred vision, fall to the floor and repetitive jerks of arms. Tried by epilepsy with phenytoin and valproate repeats similar crisis sporadically. Four years ago their relatives began to notice changes of personality, irritability and obsessive behaviors. Later on, are added episodes of disorientation of days of duration, some with auditory hallucinations and also convulsive manifestations. Finally appear polymorphic crisis, some with continue alteration of consciousness, catatonic states and sphincteric incontinence. Physical and neurological examination without abnormalities. Neuropsychological evaluation evidenced consistent

  1. Off-pump versus on-pump coronary artery bypass grafting for ischaemic heart disease

    DEFF Research Database (Denmark)

    Møller, Christian H; Penninga, Luit; Wetterslev, Jørn

    2012-01-01

    Coronary artery bypass grafting (CABG) is performed both without and with cardiopulmonary bypass, referred to as off-pump and on-pump CABG respectively. However, the preferable technique is unclear.......Coronary artery bypass grafting (CABG) is performed both without and with cardiopulmonary bypass, referred to as off-pump and on-pump CABG respectively. However, the preferable technique is unclear....

  2. Functional roles of DNA polymerases β and γ

    International Nuclear Information System (INIS)

    Huebscher, U.; Kuenzle, C.C.; Spadari, S.

    1979-01-01

    The physiological functions of DNA polymerases (deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC2.7.7.7)β and γ were investigated by using neuronal nuclei and synaptosomes isolated from rat brain. uv irradiation of neuronal nuclei from 60-day-old rats resulted in a 7- to 10-fold stimulation of DNA repair synthesis attributable to DNA polymerase β which, at this developmental stage, is virtually the only DNA polymerase present in the nuclei. No repair synthesis could be elicited by treating the nuclei with N-methyl-N-nitrosourea, but this was probably due to the inability of brain tissue to excise alkylated bases from DNA. The role of DNA polymerase γ was studied in synaptosomes by using a system mimicking in vivo mitochondrial DNA synthesis. By showing that under these conditions, DNA replication occurs in miatochondria, and exploiting the fact that DNA polymerase γ is the only DNA polymerase present in mitochondria, evidence was obtained for a role of DNA polymerase γ in mitochondrial DNA replication. Based on these results and on the wealth of literature on DNA polymerase α, we conclude that DNA polymerase α is mainly responsible for DNA replication in nuclei, DNA polymerase β is involved in nuclear DNA repair, and DNA polymerase γ is the mitochondrial replicating enzyme. However, minor roles for DNA polymerase α in DNA repair or for DNA polymerase β in DNA replication cannot be excluded

  3. A study on bypass flow gap distribution in a prismatic VHTR core

    International Nuclear Information System (INIS)

    Kim, M. H.; Jo, C. K.; Lim, H. S.

    2010-01-01

    Core bypass flow in VHTR is one of the key issues for core thermal margins and efficiency. The bypass flow in the prismatic core varies during core cycles due to the irradiation shrinkage and thermal expansion of the graphite blocks. A procedure to evaluate the local gap size variation between graphite blocks was developed and applied to a prismatic core VHTR. The influence of the core restraint mechanism on the bypass flow gap was evaluated. The predicted gap size is as much as 8 mm when the graphite block is exposed to its allowable limit of irradiation fluence. The analysis for the core bypass flow and hot spot was carried out based on the calculated gap distributions. The results indicate that the bypass flow and the location of core hot spots are closely related and a measure to reduce the bypass flow is necessary. (authors)

  4. Compartmentalized self-replication (CSR) selection of Thermococcus litoralis Sh1B DNA polymerase for diminished uracil binding.

    Science.gov (United States)

    Tubeleviciute, Agne; Skirgaila, Remigijus

    2010-08-01

    The thermostable archaeal DNA polymerase Sh1B from Thermococcus litoralis has a typical uracil-binding pocket, which in nature plays an essential role in preventing the accumulation of mutations caused by cytosine deamination to uracil and subsequent G-C base pair transition to A-T during the genomic DNA replication. The uracil-binding pocket recognizes and binds uracil base in a template strand trapping the polymerase. Since DNA replication stops, the repair systems have a chance to correct the promutagenic event. Archaeal family B DNA polymerases are employed in various PCR applications. Contrary to nature, in PCR the uracil-binding property of archaeal polymerases is disadvantageous and results in decreased DNA amplification yields and lowered sensitivity. Furthermore, in diagnostics qPCR, RT-qPCR and end-point PCR are performed using dNTP mixtures, where dTTP is partially or fully replaced by dUTP. Uracil-DNA glycosylase treatment and subsequent heating of the samples is used to degrade the DNA containing uracil and prevent carryover contamination, which is the main concern in diagnostic laboratories. A thermostable archaeal DNA polymerase with the abolished uracil binding would be a highly desirable and commercially interesting product. An attempt to disable uracil binding in DNA polymerase Sh1B from T. litoralis by generating site-specific mutants did not yield satisfactory results. However, a combination of random mutagenesis of the whole polymerase gene and compartmentalized self-replication was successfully used to select variants of thermostable Sh1B polymerase capable of performing PCR with dUTP instead of dTTP.

  5. The impact of gastric bypass surgery on sex hormones and menstrual cycles in premenopausal women

    DEFF Research Database (Denmark)

    Kjær, Mette Mandrup; Madsbad, Sten; Hougaard, David M.

    2017-01-01

    Obesity has adverse effects on ovulation, menstrual cyclicity and oocyte development leading to clinical symptoms such as infertility and menstrual disorders. The Roux-en-Y gastric bypass (RYGB) leads to weight loss, improved insulin sensitivity and may improve ovarian function. In 31 premenopausal...... women, 18 eu- and 13 oligo-/amenorrhoic, we followed the changes in follicular phase sex hormones 3, 6 and 12 month after RYGB. The average weight loss during the first postoperative year was 39.6 kg. The insulin sensitivity and serum insulin improved markedly especially within the first three...

  6. Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT

    DEFF Research Database (Denmark)

    Frederiksen, Katrine Diemer; Hanson, Stine; Hansen, Stinus

    2016-01-01

    Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density...... (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese...

  7. Thermal activation of dislocations in large scale obstacle bypass

    Science.gov (United States)

    Sobie, Cameron; Capolungo, Laurent; McDowell, David L.; Martinez, Enrique

    2017-08-01

    Dislocation dynamics simulations have been used extensively to predict hardening caused by dislocation-obstacle interactions, including irradiation defect hardening in the athermal case. Incorporating the role of thermal energy on these interactions is possible with a framework provided by harmonic transition state theory (HTST) enabling direct access to thermally activated reaction rates using the Arrhenius equation, including rates of dislocation-obstacle bypass processes. Moving beyond unit dislocation-defect reactions to a representative environment containing a large number of defects requires coarse-graining the activation energy barriers of a population of obstacles into an effective energy barrier that accurately represents the large scale collective process. The work presented here investigates the relationship between unit dislocation-defect bypass processes and the distribution of activation energy barriers calculated for ensemble bypass processes. A significant difference between these cases is observed, which is attributed to the inherent cooperative nature of dislocation bypass processes. In addition to the dislocation-defect interaction, the morphology of the dislocation segments pinned to the defects play an important role on the activation energies for bypass. A phenomenological model for activation energy stress dependence is shown to describe well the effect of a distribution of activation energies, and a probabilistic activation energy model incorporating the stress distribution in a material is presented.

  8. Platelet hyperreactivity in response to on- and off-pump coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Bochsen, Louise; Rosengaard, Lisbeth Bredahl; Nielsen, Allan Bybeck

    2009-01-01

    Hypercoagulability has been reported after off-pump coronary artery bypass grafting (OPCAB) compared with patients undergoing standard coronary artery bypass grafting (CABG) with cardiopulmonary bypass. The aim of this study was to evaluate the changes in platelet reactivity in response to cardiac...... and this study identified 23% of patients needing coronary bypass surgery to be at high risk for recurrent ischemic events at 1 month after surgery, based on the MA. These results suggest that a more aggressive antithrombotic treatment might be warranted for patients undergoing coronary artery bypass grafting...

  9. Blood utilization in neonates and infants undergoing cardiac surgery requiring cardiopulmonary bypass.

    Science.gov (United States)

    Wesley, Mark C; Yuki, Koichi; Daaboul, Dima G; Dinardo, James A

    2011-07-01

    Neonates and infants undergoing cardiac surgery with cardiopulmonary bypass are exposed to multiple blood products from different donors. The volume of the bypass circuit is often as large as the patient's total blood volume and asanguineous bypass primes are unusual. As a result, blood products are required for the cardiopulmonary bypass prime and are often used to treat the postbypass dilutional coagulopathy. We review clot formation and strength, cardiopulmonary bypass prime considerations, assessment of postbypass coagulopathy, component therapy use, ultrafiltration techniques, and use of antifibrinolytic medications. A combined approach including techniques to minimize the prime volume, utilization of ultrafiltration, administration of antifibrinolytics during surgery, and the proper treatment of the dilutional coagulopathy can limit the transfusion requirements.

  10. Insertion of the T3 DNA polymerase thioredoxin binding domain enhances the processivity and fidelity of Taq DNA polymerase

    OpenAIRE

    Davidson, John F.; Fox, Richard; Harris, Dawn D.; Lyons-Abbott, Sally; Loeb, Lawrence A.

    2003-01-01

    Insertion of the T3 DNA polymerase thioredoxin binding domain (TBD) into the distantly related thermostable Taq DNA polymerase at an analogous position in the thumb domain, converts the Taq DNA polymerase from a low processive to a highly processive enzyme. Processivity is dependent on the presence of thioredoxin. The enhancement in processivity is 20–50-fold when compared with the wild-type Taq DNA polymerase or to the recombinant polymerase in the absence of thioredoxin. The recombinant Taq...

  11. Gut hormones and gastric bypass

    DEFF Research Database (Denmark)

    Holst, Jens J.

    2016-01-01

    Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...

  12. Oil Bypass Filter Technology Performance Evaluation - First Quarterly Report

    Energy Technology Data Exchange (ETDEWEB)

    Zirker, L.R.; Francfort, J.E.

    2003-01-31

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  13. Graft type for femoro-popliteal bypass surgery.

    Science.gov (United States)

    Ambler, Graeme K; Twine, Christopher P

    2018-02-11

    Femoro-popliteal bypass is implemented to save limbs that might otherwise require amputation, in patients with ischaemic rest pain or tissue loss; and to improve walking distance in patients with severe life-limiting claudication. Contemporary practice involves grafts using autologous vein, polytetrafluoroethylene (PTFE) or Dacron as a bypass conduit. This is the second update of a Cochrane review first published in 1999 and last updated in 2010. To assess the effects of bypass graft type in the treatment of stenosis or occlusion of the femoro-popliteal arterial segment, for above- and below-knee femoro-popliteal bypass grafts. For this update, the Cochrane Vascular Information Specialist searched the Vascular Specialised Register (13 March 2017) and CENTRAL (2017, Issue 2). Trial registries were also searched. We included randomised trials comparing at least two different types of femoro-popliteal grafts for arterial reconstruction in patients with femoro-popliteal ischaemia. Randomised controlled trials comparing bypass grafting to angioplasty or to other interventions were not included. Both review authors (GKA and CPT) independently screened studies, extracted data, assessed trials for risk of bias and graded the quality of the evidence using GRADE criteria. We included nineteen randomised controlled trials, with a total of 3123 patients (2547 above-knee, 576 below-knee bypass surgery). In total, nine graft types were compared (autologous vein, polytetrafluoroethylene (PTFE) with and without vein cuff, human umbilical vein (HUV), polyurethane (PUR), Dacron and heparin bonded Dacron (HBD); FUSION BIOLINE and Dacron with external support). Studies differed in which graft types they compared and follow-up ranged from six months to 10 years.Above-knee bypassFor above-knee bypass, there was moderate-quality evidence that autologous vein grafts improve primary patency compared to prosthetic grafts by 60 months (Peto odds ratio (OR) 0.47, 95% confidence interval (CI

  14. 40 CFR 63.307 - Standards for bypass/bleeder stacks.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Standards for bypass/bleeder stacks. 63.307 Section 63.307 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Standards for Coke Oven Batteries § 63.307 Standards for bypass/bleeder stacks. (a)(1) Except as otherwise...

  15. A Time Interval of More Than 18 Months Between a Pregnancy and a Roux-en-Y Gastric Bypass Increases the Risk of Iron Deficiency and Anaemia in Pregnancy

    DEFF Research Database (Denmark)

    Crusell, Mie Korslund Wiinblad; Nilas, Lisbeth; Svare, Jens

    2016-01-01

    OBJECTIVE: The aim of the study is to explore the impact of time between Roux-en-Y gastric bypass (RYGB) and pregnancy on obstetrical outcome and nutritional derangements. METHODS: In a retrospective cross-sectional study of pregnant women admitted for antenatal care at two tertiary hospitals, we...... examined 153 women with RYGB and a singleton pregnancy of at least 24 weeks. The women were stratified according to a pregnancy nutritional parameters and glycated haemoglobin 1Ac (HbA1c) in second and third trimester...... of adverse pregnancy outcome or birth weight between the two groups. CONCLUSION: A long surgery-to-pregnancy time interval after a RYGB increases the risk of iron deficiency anaemia but not of other nutritional deficits. Time interval does not seem to have an adverse effect on the obstetrical outcome...

  16. Tidlige erfaringer med duplexovervågning af femoropopliteale og -krurale vene-bypass

    DEFF Research Database (Denmark)

    Nielsen, Tina G; von Jessen, Frants; Schroeder, T V

    1993-01-01

    Identification and correction of graft stenoses in femoropopliteal and -crural vein bypasses can prevent reconstruction failure. Sixty six consecutive vein bypasses entered a postoperative surveillance protocol, which implied clinical assessment, measurement of ankle blood pressure and duplex...... could not be reestablished. Of the 34 bypasses with normal duplex-scans only 2 (6%) thrombosed (p blood pressure measurement could reliably predict graft failure. This study indicates that duplex......-scanning effectively identifies grafts at risk and can be expected to improve long-term patency of infrainguinal vein bypasses....

  17. RNA polymerase II mediated transcription from the polymerase III promoters in short hairpin RNA expression vector

    International Nuclear Information System (INIS)

    Rumi, Mohammad; Ishihara, Shunji; Aziz, Monowar; Kazumori, Hideaki; Ishimura, Norihisa; Yuki, Takafumi; Kadota, Chikara; Kadowaki, Yasunori; Kinoshita, Yoshikazu

    2006-01-01

    RNA polymerase III promoters of human ribonuclease P RNA component H1, human U6, and mouse U6 small nuclear RNA genes are commonly used in short hairpin RNA (shRNA) expression vectors due their precise initiation and termination sites. During transient transfection of shRNA vectors, we observed that H1 or U6 promoters also express longer transcripts enough to express several reporter genes including firefly luciferase, green fluorescent protein EGFP, and red fluorescent protein JRed. Expression of such longer transcripts was augmented by upstream RNA polymerase II enhancers and completely inhibited by downstream polyA signal sequences. Moreover, the transcription of firefly luciferase from human H1 promoter was sensitive to RNA polymerase II inhibitor α-amanitin. Our findings suggest that commonly used polymerase III promoters in shRNA vectors are also prone to RNA polymerase II mediated transcription, which may have negative impacts on their targeted use

  18. Jubilación y vejez, su repercusión en la salud familiar Retirement and aging, their impact on family health

    Directory of Open Access Journals (Sweden)

    Patricia M Herrera Santi

    2008-12-01

    Full Text Available Se presenta el impacto en la salud familiar de la jubilación y la vejez, como eventos normativos propios de la etapa de contracción por la que atraviesa la familia en su ciclo vital. Se estudió la vejez en 58 familias que tenían en su seno, al menos, un integrante de la tercera edad, en el período comprendido entre septiembre de 2001 y diciembre de 2002; y la jubilación en 70 familias que tenían en su seno, al menos, un miembro con menos de un año de jubilación, en el período comprendido entre mayo de 2003 y junio de 2004. En ambos casos se realizaron estudios descriptivos y transversales. Se propuso como objetivo valorar la repercusión en la salud familiar de estos eventos. Se utilizó un instrumento que permite evaluar el nivel de repercusión del evento en la salud familiar. Mediante su aplicación logramos determinar que la ancianidad presentó una repercusión de leve a moderada, mientras que la jubilación presentó repercusión de elevada a moderada con sentido favorable ambas. Se observó que las áreas más comúnmente afectadas por la presencia de un adulto mayor fueron la socioeconómica y el funcionamiento familiar, mientras que en la jubilación fueron el área socioeconómica y estado de salud.The impact of retirement and aging on family health as normative events of the stage of contraction the family goes through in its vital cycle is presented. Aging was studied between September 2001 and December 2002 in 58 families who had at least an elderly among their members. Retirement was analyzed from May 2003 to June 2004 in 70 families who had al least a member with less than a year of retirement. In both cases, descriptive and cross-sectional studies were conducted aimed at assessing the repercussion of these events on family health. An instrument that allows to evaluate the level of repercussion of the event on family health was used. On applying it, it was possible to determine that aging showed a repercussion from mild

  19. Complications of Laparoscopic Retroperitoneal Sutureless and Clampless Aortobifemoral Bypass

    Directory of Open Access Journals (Sweden)

    B. Segers

    Full Text Available : Introduction: This report describes our experience with early complications that occurred in two patients who underwent sutureless aortobifemoral bypass using the EndoVascular REtroperitoneoScopic Technique (EVREST. Report: Two patients who underwent EVREST for aortoiliac TASC D lesions experienced a dislocation of the proximal assembly. The first dislocation occurred four hours post-operatively and led to the death of the patient, and the second occurred during surgery and led to open conversion. Conclusion: As a result of these serious complications, we recommend the use of anchorage stitches while using an endograft connector in a sutureless aortobifemoral bypass. Keywords: Early complications, Sutureless, Clampless, Retroperitoneoscopy, Aortobifemoral bypass

  20. Should Roux-en-Y gastric bypass biliopancreatic limb length be tailored to achieve improved diabetes outcomes?

    Science.gov (United States)

    Nora, Mário; Morais, Tiago; Almeida, Rui; Guimarães, Marta; Monteiro, Mariana P

    2017-12-01

    The objective is to access the role of Roux-en-Y gastric bypass (RYGB) biliopancreatic limb (BPL) length in type 2 diabetes (T2D) outcomes.RYGB is more effective than medical intervention for T2D treatment in obese patients. Despite the scarcity of available data, previous reports suggest that modifications of the RYGB limb lengths could improve the antidiabetic effects of the surgery.A cohort of obese T2D patients (n = 114) were submitted to laparoscopic RYGB, either with a standard BPL (SBPL) (n = 41; BPL 84 ± 2 cm) or long BPL (LBPL) (n = 73; BPL = 200 cm) and routinely monitored for weight loss and diabetic status up to 5 years after surgery.Baseline clinical features in the 2 patient subgroups were similar. After surgery, there was a significant reduction of body mass index (BMI) in both the groups, although the percentage of excess BMI loss (%EBMIL) after 5 years was higher for LBPL (75.50 ± 2.63 LBPL vs 65.90 ± 3.61 SBPL, P = .04). T2D remission rate was also higher (73% vs 55%, P < .05), while disease relapse rate (13.0% vs 32.5%; P < .05) and antidiabetic drug requirement in patients with persistent diabetes were lower after LBPL. Preoperative T2D duration predicted disease remission, but only for SBPL.RYGB with a longer BPL improves %EBMIL, T2D remission, and glycemic control in those with persistent disease, while it decreases diabetes relapse rate over time. The antidiabetic effects of LBPL RYGB also are less influenced by the preoperative disease duration. These data suggest the RYGB procedure could be tailored to improve T2D outcomes.

  1. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

    Directory of Open Access Journals (Sweden)

    Scott B Vafai

    Full Text Available Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS. Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

  2. Outcomes of lower extremity bypass performed for acute limb ischemia.

    Science.gov (United States)

    Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

    2013-10-01

    Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function

  3. Hemodynamic effect of bypass geometry on intracranial aneurysm: A numerical investigation.

    Science.gov (United States)

    Kurşun, Burak; Uğur, Levent; Keskin, Gökhan

    2018-05-01

    Hemodynamic analyzes are used in the clinical investigation and treatment of cardiovascular diseases. In the present study, the effect of bypass geometry on intracranial aneurysm hemodynamics was investigated numerically. Pressure, wall shear stress (WSS) and velocity distribution causing the aneurysm to grow and rupture were investigated and the best conditions were tried to be determined in case of bypassing between basilar (BA) and left/right posterior arteries (LPCA/RPCA) for different values of parameters. The finite volume method was used for numerical solutions and calculations were performed with the ANSYS-Fluent software. The SIMPLE algorithm was used to solve the discretized conservation equations. Second Order Upwind method was preferred for finding intermediate point values in the computational domain. As the blood flow velocity changes with time, the blood viscosity value also changes. For this reason, the Carreu model was used in determining the viscosity depending on the velocity. Numerical study results showed that when bypassed, pressure and wall shear stresses reduced in the range of 40-70% in the aneurysm. Numerical results obtained are presented in graphs including the variation of pressure, wall shear stress and velocity streamlines in the aneurysm. Considering the numerical results for all parameter values, it is seen that the most important factors affecting the pressure and WSS values in bypassing are the bypass position on the basilar artery (L b ) and the diameter of the bypass vessel (d). Pressure and wall shear stress reduced in the range of 40-70% in the aneurysm in the case of bypass for all parameters. This demonstrates that pressure and WSS values can be greatly reduced in aneurysm treatment by bypassing in cases where clipping or coil embolization methods can not be applied. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Cerebroprotective effect of piracetam in patients undergoing coronary bypass burgery.

    Science.gov (United States)

    Holinski, Sebastian; Claus, Benjamin; Alaaraj, Nour; Dohmen, Pascal Maria; Kirilova, Kremena; Neumann, Konrad; Uebelhack, Ralf; Konertz, Wolfgang

    2008-11-01

    Reduction of cognitive function is a possible side effect after cardiac surgery using cardiopulmonary bypass. We investigated the cerebroprotective effect of piracetam on cognitive performance in patients undergoing coronary artery bypass surgery under cardiopulmonary bypass. Patients scheduled for elective, primary and isolated coronary bypass surgery were randomised either to piracetam or placebo group. The study was performed in a double blind fashion. Patients received either 12 g piracetam or placebo at the beginning of the operation. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on the third postoperative day. To assess the overall cognitive function and the degree of cognitive decline across all tests after surgery we combined the six test-scores by principal component analysis. A total number of 120 patients were enrolled into the study. Preoperative overall cognitive function were not significantly different between the groups. The postoperative combined score of the neuropsychological tests showed a deterioration of cognitive function in both groups (placebo-pre: -0.06+/-0.99 vs placebo-post: -1.38+/-1.11; ppiracetam-pre: 0.06+/-1.02 vs piracetam-post: -0.65+/-0.93; ppiracetam patients performed significantly better compared to the placebo patients after the operation and had a less decline of overall cognitive function (pPiracetam has a cerebroprotective effect in patients undergoing coronary artery bypass surgery with the use of cardiopulmonary bypass. It reduces an early postoperative substantial decline of neuropsychological abilities.

  5. Obturator or "lateral" bypass in the management of infected vascular prostheses at the groin

    Directory of Open Access Journals (Sweden)

    Davidović Lazar B.

    2002-01-01

    Full Text Available The infection of the previously implanted vascular graft at the groin, is associated with great mortality and morbidity rate [1]. The authors present a retrospective study in which they analyzed management of infected vascular prostheses at the groin, using obturator bypass in 26 cases, and "lateral" bypass in 15 cases. The indications for obturator bypass reconstructions included: 20 infections of aorto-femoral grafts, two infected pse udoaneurysms in the groin after RTA of the superficial femoral artery, and 4 infections of iliac-femoral grafts. The indications for lateral bypass reconstructions were: infections after aorto-femoral reconstructions - 8 cases; infection after femora-popliteal reconstructions - 4 cases; infection after iliac-femoral reconstruction - 2 patients, and one infected pseudoaneurysm in the groin after RTA of the superficial femoral artery. In 3 subjects obturator bypass was performed using extraperitoneal approach while in other 23 patients transperitoneal approach was done by donor's artery. The obturator bypass was performed using a PTFE graft in 3 cases and Dacron graft in 23. The donor's artery used for obturator bypass was a noninfected proximal part of aortofemoral graft in 20 cases, and iliac artery in 6 patients. The superfical femoral artery was recipient artery for obturator bypass in 3 cases, deep femoral artery in one case, and above the knee popliteal artery in 22 cases (Figure 1. In two patients transperitoenal approach to donors artery for "lateral" bypass has been used, and in 13 cases extraperitoneal. The proximal noninfected part of aorto femoral graft was used as a donor's artery for lateral bypass in 8 patients, while common iliac artery in 7 subjects. In 5 cases recon structions were performed using PTFE grafts, in 3 using autologous saphenous vein grafts, and in 7 using Dacron grafts. The recipient artery for "lateral" bypass was deep femoral in 8 cases, superficial femoral in three patients and

  6. Effects of Sleeve Gastrectomy vs. Roux-en-Y Gastric Bypass on Eating Behavior and Sweet Taste Perception in Subjects with Obesity

    Directory of Open Access Journals (Sweden)

    Katie Nance

    2017-12-01

    Full Text Available The goal of this study was to test the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB has greater effects on taste perception and eating behavior than comparable weight loss induced by sleeve gastrectomy (SG. We evaluated the following outcomes in 31 subjects both before and after ~20% weight loss induced by RYGB (n = 23 or SG (n = 8: (1 sweet, savory, and salty taste sensitivity; (2 the most preferred concentrations of sucrose and monosodium glutamate; (3 sweetness palatability, by using validated sensory testing techniques; and (4 eating behavior, by using the Food Craving Inventory and the Dutch Eating Behavior Questionnaire. We found that neither RYGB nor SG affected sweetness or saltiness sensitivity. However, weight loss induced by either RYGB or SG caused the same decrease in: (1 frequency of cravings for foods; (2 influence of emotions and external food cues on eating behavior; and (3 shifted sweetness palatability from pleasant to unpleasant when repetitively tasting sucrose (all p-values ≤ 0.01. Therefore, when matched on weight loss, SG and RYGB cause the same beneficial effects on key factors involved in the regulation of eating behavior and hedonic component of taste perception.

  7. Posttraumatic growth in post-surgical coronary artery bypass graft patients

    Directory of Open Access Journals (Sweden)

    Catherine A Waight

    2015-02-01

    Full Text Available Recent research in posttraumatic growth has been applied to people with life-threatening illnesses to optimise recovery. There is a lack of research exploring posttraumatic growth in coronary artery bypass graft patients. This article describes the recovery experience of 14 coronary artery bypass graft patients (13 males and 1 female at their first outpatient review post-surgery. Grounded theory analysis was used to develop a model of distinct and shared pathways to growth depending on whether patients were symptomatic or asymptomatic pre-coronary artery bypass graft. Outcomes of posttraumatic growth in this sample included action-based healthy lifestyle growth and two forms of cognitive growth: appreciation of life and new possibilities. The model of posttraumatic growth developed in this study may be helpful in guiding future research into promoting posttraumatic growth and behaviour change in coronary artery bypass graft patients.

  8. S100A8/A9 (Calprotectin), Interleukin-6, and C-Reactive Protein in Obesity and Diabetes before and after Roux-en-Y Gastric Bypass Surgery

    DEFF Research Database (Denmark)

    Lylloff, Louise; Bathum, Lise; Madsbad, Sten

    2017-01-01

    Background: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin...... resistance and diabetes are few and contradictory. Methods: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory...... and diabetes-related markers were measured pre- A nd post-surgically. Results: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative...

  9. Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

    DEFF Research Database (Denmark)

    Thomsen, Stine Brinkløv; Rathcke, Camilla Noelle; Jørgensen, Nils Bruun

    2013-01-01

    Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states......, following Roux-en-Y gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose tolerance (NGT). Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year) RYGB. Results....... Fasting state MCP-1 levels decreased after RYGB in both groups (P values...

  10. Relación entre cefalea tensional y disfunción familiar en una unidad de medicina familiar Relation of tension headache and family dysfunction in a family medicine unit

    Directory of Open Access Journals (Sweden)

    Jorge Octavio Carvajal Rivera

    2009-03-01

    Full Text Available La cefalea tensional es la forma más frecuente de cefalea primaria. Este trabajo se realizó con el objetivo de estimar si existe asociación entre cefalea tensional y disfunción familiar. 60 pacientes evaluaron sus familias a través del cuestionario FF-SIL de funcionamiento familiar. La cefalea tensional fue más frecuente en miembros de familias disfuncionales que en aquellos que provenían de familias funcionales (p=.028. Fueron frecuentes las manifestaciones clínicas relacionadas con estrés postraumático en el paciente problema, existe un complejo y conflictual ambiente familiar que incluye a estos enfermos, lo que nos sugiere el uso de los recursos de la familia como opción terapéutica aún pobremente explorada.Tension headache is the more frequent presentation of primary cephalagia. Aim of this paper is to estimate if there is an association between tension headache and familial dysfunction. Sixty patients evaluated their families by through FF-SIL questionnaire of familial performance. Tension headache was more frequent in members of dysfunctional families than in those from functional families (p = .028. Clinical manifestations related to post-traumatic stress were frequent, there is a familial complex and difficult environment including these sick persons, suggesting us the use of family resources as therapeutical option not very explored yet.

  11. Error-Prone Translesion DNA Synthesis by Escherichia coli DNA Polymerase IV (DinB on Templates Containing 1,2-dihydro-2-oxoadenine

    Directory of Open Access Journals (Sweden)

    Masaki Hori

    2010-01-01

    Full Text Available Escherichia coli DNA polymerase IV (Pol IV is involved in bypass replication of damaged bases in DNA. Reactive oxygen species (ROS are generated continuously during normal metabolism and as a result of exogenous stress such as ionizing radiation. ROS induce various kinds of base damage in DNA. It is important to examine whether Pol IV is able to bypass oxidatively damaged bases. In this study, recombinant Pol IV was incubated with oligonucleotides containing thymine glycol (dTg, 5-formyluracil (5-fodU, 5-hydroxymethyluracil (5-hmdU, 7,8-dihydro-8-oxoguanine (8-oxodG and 1,2-dihydro-2-oxoadenine (2-oxodA. Primer extension assays revealed that Pol IV preferred to insert dATP opposite 5-fodU and 5-hmdU, while it inefficiently inserted nucleotides opposite dTg. Pol IV inserted dCTP and dATP opposite 8-oxodG, while the ability was low. It inserted dCTP more effectively than dTTP opposite 2-oxodA. Pol IV's ability to bypass these lesions decreased in the order: 2-oxodA > 5-fodU~5-hmdU > 8-oxodG > dTg. The fact that Pol IV preferred to insert dCTP opposite 2-oxodA suggests the mutagenic potential of 2-oxodA leading to A:T→G:C transitions. Hydrogen peroxide caused an ~2-fold increase in A:T→G:C mutations in E. coli, while the increase was significantly greater in E. coli overexpressing Pol IV. These results indicate that Pol IV may be involved in ROS-enhanced A:T→G:C mutations.

  12. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

    Science.gov (United States)

    Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M; Clements, Austin; Harmata, Emily E; Marks-Shulman, Pam; Gaylinn, Bruce D; Williams, Brandon; Clements, Ronald H; Albaugh, Vance L; Abumrad, Naji N

    2017-09-01

    Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg -1  min -1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB. © 2017 John Wiley & Sons Ltd.

  13. Comparison of circular- and linear-stapled gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass: a multicenter study

    Directory of Open Access Journals (Sweden)

    Piotr Major

    2017-03-01

    Full Text Available Introduction : Laparoscopic Roux-en-Y gastric bypass (LRYGB is a common, well-established procedure, but no consensus regarding selection of the gastrojejunostomy (GJ technique has been reached, and standardization of this precise technique is far from being achieved. Aim : To compare circular-stapled and linear-stapled GJ in LRYGB in terms of operative time and postoperative complications. Material and methods: This retrospective case-control study compared the perioperative and postoperative outcomes of LRYGB with a circular-stapled (LRYGB-CS versus linear-stapled (LRYGB-LS gastrojejunostomy. All patients, operated on in two academic referral care centers for bariatric surgery, were enrolled from April 2013 to June 2016. 457 patients were included (255 and 202 respectively in the LRYGB-CS and LRYGB-LS groups. After matching the groups for age, sex, body mass index, arterial hypertension, and presence of type 2 diabetes in a 1 : 1 ratio, 99 patients were enrolled in each. Results : The total operative time was longer in the LRYGB-LS group (140 vs. 85 min, p < 0.001. The postoperative hemorrhage and wound infection rates were lower in the LRYGB-LS group (2.1% vs. 10.3%, p = 0.021, and 1.0% vs. 9.3%, p = 0.011. The readmission rates were comparable (8.2% vs. 6.1%, p = 0.593. There was no significant difference in the incidence of gastrojejunostomy leakage, stricture, port-site hernia, or marginal ulcer. Conclusions : Both anastomosis types for LRYGB are safe and have low and comparable risks of postoperative complications. After LRYGB-CS, postoperative bleeding and wound infections are slightly more frequent; however, the operative time is shorter.

  14. Esophageal bypass after failed chemoradiotherapy for unresectable esophageal cancer

    International Nuclear Information System (INIS)

    Matono, Satoru; Tanaka, Toshiaki; Mori, Naoki; Nagano, Takeshi; Fujita, Hiromasa; Shirouzu, Kazuo

    2013-01-01

    Esophageal stenosis and/or fistula often occur after chemoradiotherapy (CRT) for unresectable esophageal cancer. In such patients, an esophageal stent can help achieve oral intake. However an esophageal stent cannot be inserted where there is complete stenosis or where the tumor is located. In such cases, esophageal bypass surgery may be necessary. Here, we investigated the clinical characteristics and outcomes in patients who underwent esophageal bypass surgery in our institution. We reviewed 10 cases of esophageal bypass surgery (gastric tube in 8 cases, colon in 2 cases) after CRT for unresectable esophageal cancer, between 2001 and 2009. There were 5 of stenosis-only cases, 4 fistula-only cases, and 1 case of stenosis and fistula. There were postoperative complications in 5 cases (50%), and all these were treated conservatively and healed. The median survival from surgery to peroral intake was 20 days (range 9-90 days), and the median survival after starting peroral intake was 130 days (range 48-293 days). Esophageal bypass surgery can achieve good performance status and improve peroral intake. (author)

  15. Emergency bypass post percutaneous atrial ablation: a case report.

    LENUS (Irish Health Repository)

    Hargrove, M

    2010-11-01

    A 34-year-old male undergoing percutaneous atrial ablation procedure for paroxysmal fibrillation required emergency sternotomy for cardiac tamponade. The patient had been anticoagulated and had received plavix and aspirin prior to and during the ablation procedure. Seven units of red cell concentrate had been transfused in the cardiac catherisation laboratory. On arrival in theatre, the patient was hypotensive, but was awake on induction of anaesthesia. No recordable blood pressure with non-invasive monitoring was observed. A sternotomy was immediately performed and, on evacuation of the pericardium, a bleeding site was not visible. The patient was commenced on cardiopulmonary bypass. Bleeding site was identified and the defect closed. The patient was weaned from cardiopulmonary bypass with minimal inotropic support and made an uneventful recovery. Bypass time was 38 minutes. A literature review showed a 1% incidence of post-ablation bleeding(1). The incidence of reverting to bypass for such an event has not been reported previously. During these procedures, it might be wise to have the cardiothoracic team notified while atrial ablation procedures are being performed in the cardiac catheterization laboratory.

  16. Aceptación y uso de herbolaria en medicina familiar Acceptance and use of therapeutic medical plants in family medical care

    Directory of Open Access Journals (Sweden)

    Genaro Armando Taddei-Bringas

    1999-05-01

    Full Text Available OBJETIVO. Explorar el grado de utilización de las plantas medicinales entre la población usuaria y el personal de salud en una unidad urbana de medicina familiar del Instituto Mexicano del Seguro Social. MATERIAL Y MÉTODOS. Se realizó un estudio transversal descriptivo. Se diseñó y validó un cuestionario que exploró aceptación y utilización. Se aplicó a 60 médicos familiares, a una muestra aleatoria de 130 trabajadores de la Unidad de Medicina Familiar y a otra de 264 usuarios-pacientes de la misma. El porcentaje de respuesta fue de 78%. RESULTADOS. Se encontró que 83% de los médicos aceptan la herbolaria y 75% la utilizan como recurso terapéutico. Entre el personal de salud, la aceptación y la utilización fue de 100% y, en el caso de los usuarios, 92% la aceptan y 90% la utilizan. Las diferencias entre grupos son significativas (pOBJECTIVE. To explore the degree of usage of therapeutic medical plants among the patients, physicans and health workers in a local Family Mediccal Care Unit of the Mexican Institute of Social Security (IMSS. MATERIAL AND METHODS. A transversal descriptive study was performed. A questionnaire focusing on two variables was designed and validated. It was applied to 60 family physicians, a randomized sample of 130 health workers and another of 264 patients of the Family Mediccal Care Unit. Response percentage was 78%. RESULTS. The study found that 83% of family physicians accept the therapeutic use of herbal medicine; moreover, 75% use it as a therapeutic resource. Among health workers, acceptance and use was 100%, while in patients the level of acceptance was of 92% and of use it was 90%. Differences between groups are significant (p<0.05. The more frequently used plants are Gordolobo (Gnaphalium sp., Eucalyptus (Eucalyptus sp., probably E. globulus, spearmint (Mentha sp., camomile (Matricaria chamomilla and prickly pear cladodes (the vegetative parts of the prickly pear, Opuntia sp. Probably Opuntia

  17. Fuel temperature prediction using a variable bypass gap size in the prismatic VHTR

    International Nuclear Information System (INIS)

    Lee, Sung Nam; Tak, Nam-il; Kim, Min Hwan

    2016-01-01

    Highlights: • The bypass flow of the prismatic very high temperature reactor is analyzed. • The bypass gap sizes are calculated considering the effect of the neutron fluences and thermal expansion. • The fuel hot spot temperature and temperature profiles are calculated using the variable gap size. • The BOC, MOC and EOC condition at the cycle 07 and 14 are applied. - Abstract: The temperature gradient and hot spot temperatures were calculated in the prismatic very high temperature reactor as a function of the variable bypass gap size. Many previous studies have predicted the temperature of the reactor core based on a fixed bypass gap size. The graphite matrix of the assemblies in the reactor core undergoes a dimensional change during the operation due to thermal expansion and neutron fluence. The expansion and shrinkage of the bypass gaps change the coolant flow fractions into the coolant channels, the control rod holes, and the bypass gaps. Therefore, the temperature of the assemblies may differ compared to those for the fixed bypass gap case. The temperature gradient and the hot spot temperatures are important for the design of reactor structures to ensure their safety and efficiency. In the present study, the temperature variation of the PMR200 is studied at the beginning (BOC), middle (MOC), and end (EOC) of cycles 07 and 14. CORONA code which has been developed in KAERI is applied to solve the thermal-hydraulics of the reactor core of the PMR200. CORONA solves a fluid region using a one-dimensional formulation and a solid region using a three-dimensional formulation to enhance the computational speed and still obtain a reasonable accuracy. The maximum temperatures in the fuel assemblies using the variable bypass gaps did not differ much from the corresponding temperatures using the fixed bypass gaps. However, the maximum temperatures in the reflector assemblies using the variable bypass gaps differ significantly from the corresponding temperatures

  18. Chromosomal location of the human gene for DNA polymerase β

    International Nuclear Information System (INIS)

    McBride, O.W.; Zmudzka, B.Z.; Wilson, S.H.

    1987-01-01

    Inhibition studies indicate that DNA polymerase β has a synthetic role in DNA repair after exposure of mammalian cells to some types of DNA-damaging agents. The primary structure of the enzyme is highly conserved in vertebrates, and nearly full-length cDNAs for the enzyme were recently cloned from mammalian cDNA libraries. Southern blot analysis of DNA from a panel of human-rodent somatic cell hybrids, using portions of the cDNA as probe, indicates that the gene for human DNA polymerase β is single copy and located on the short arm or proximal long arm of chromosome 8 (8pter-8q22). A restriction fragment length polymorphism (RFLP) was detected in normal individuals by using a probe from the 5' end of the cDNA, and this RFLP probably is due to an insertion or duplication of DNA in 20-25% of the population. This restriction site can be used as one marker for chromosome 8 genetic linkage studies and for family studies of traits potentially involving this DNA repair gene

  19. Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger.

    Science.gov (United States)

    Deloose, E; Janssen, P; Lannoo, M; Van der Schueren, B; Depoortere, I; Tack, J

    2016-07-01

    Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. Motilin may be an important regulator involved in the pathogenesis of obesity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Rankine cycle condenser pressure control using an energy conversion device bypass valve

    Science.gov (United States)

    Ernst, Timothy C; Nelson, Christopher R; Zigan, James A

    2014-04-01

    The disclosure provides a waste heat recovery system and method in which pressure in a Rankine cycle (RC) system of the WHR system is regulated by diverting working fluid from entering an inlet of an energy conversion device of the RC system. In the system, an inlet of a controllable bypass valve is fluidly coupled to a working fluid path upstream of an energy conversion device of the RC system, and an outlet of the bypass valve is fluidly coupled to the working fluid path upstream of the condenser of the RC system such that working fluid passing through the bypass valve bypasses the energy conversion device and increases the pressure in a condenser. A controller determines the temperature and pressure of the working fluid and controls the bypass valve to regulate pressure in the condenser.

  1. Active bypass flow control for a seal in a gas turbine engine

    Science.gov (United States)

    Ebert, Todd A.; Kimmel, Keith D.

    2017-01-10

    An active bypass flow control system for controlling bypass compressed air based upon leakage flow of compressed air flowing past an outer balance seal between a stator and rotor of a first stage of a gas turbine in a gas turbine engine is disclosed. The active bypass flow control system is an adjustable system in which one or more metering devices may be used to control the flow of bypass compressed air as the flow of compressed air past the outer balance seal changes over time as the outer balance seal between the rim cavity and the cooling cavity wears. In at least one embodiment, the metering device may include a valve formed from one or more pins movable between open and closed positions in which the one pin at least partially bisects the bypass channel to regulate flow.

  2. On-Pump Versus Off-Pump Coronary Artery Bypass Surgery in Elderly Patients

    DEFF Research Database (Denmark)

    Houlind, Kim; Kjeldsen, Bo Juul; Madsen, Susanne Nørgaard

    2012-01-01

    BACKGROUND: Conventional coronary artery bypass grafting performed with the use of cardiopulmonary bypass is a well-validated treatment for patients with ischemic heart disease. Off-pump coronary artery bypass grafting (OPCAB) has been suggested to reduce the number of perioperative complications......, especially in elderly patients. METHODS AND RESULTS: In a multicenter, randomized trial, we assigned 900 patients >70 years of age to conventional coronary artery bypass grafting or OPCAB surgery. After 30 days, a blinded end-point committee assessed whether a combined end point of death, stroke...... experiencing the combined end point within 30 days was 10.2% for conventional coronary artery bypass grafting and 10.7% for OPCAB. Implied risk difference of 0.4% (with a 95% confidence interval, -3.6 to 4.4) showed nonsignificance in a standard test for equality (P=0.83) and for noninferiority...

  3. Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity.

    Science.gov (United States)

    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2009-04-01

    The X-family DNA polymerases (PolXs) comprise a highly conserved DNA polymerase family found in all kingdoms. Mammalian PolXs are known to be involved in several DNA-processing pathways including repair, but the cellular functions of bacterial PolXs are less known. Many bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain at their C-termini in addition to a PolX core (POLXc) domain, and possess 3'-5' exonuclease activity. Although both domains are highly conserved in bacteria, their molecular functions, especially for a PHP domain, are unknown. We found Thermus thermophilus HB8 PolX (ttPolX) has Mg(2+)/Mn(2+)-dependent DNA/RNA polymerase, Mn(2+)-dependent 3'-5' exonuclease and DNA-binding activities. We identified the domains of ttPolX by limited proteolysis and characterized their biochemical activities. The POLXc domain was responsible for the polymerase and DNA-binding activities but exonuclease activity was not detected for either domain. However, the POLXc and PHP domains interacted with each other and a mixture of the two domains had Mn(2+)-dependent 3'-5' exonuclease activity. Moreover, site-directed mutagenesis revealed catalytically important residues in the PHP domain for the 3'-5' exonuclease activity. Our findings provide a molecular insight into the functional domain organization of bacterial PolXs, especially the requirement of the PHP domain for 3'-5' exonuclease activity.

  4. Advanced DVI for ECC direct bypass mitigation

    International Nuclear Information System (INIS)

    Kwon, Tae-Soon; Song, Chul-Hwa; Baek, Won-Pil

    2009-01-01

    An ECC direct bypass fraction during a late reflood phase of a LBLOCA is strongly dependent on the characteristics of the cross flow and the geometrical configuration of a DVI in the downcomer of a pressurized light water reactor. The important design parameters of a DVI are the elevation, the azimuthal angle, and the separator to prevent a steam-water interaction. An ECC sub-channel to separate or to isolate an ECC water from a high-speed cross flow is one of the important design features to mitigate the ECC bypass phenomena. A dual core barrel cylinder as an ECC flow separator is located between a reactor vessel and a core barrel outer wall in the downcomer annulus. A new narrow gap between the core barrel and the additional dual core barrel plays the role of a downward ECC flow channel or an ECC flow separator in a high-speed cross flow field of the downcomer annulus. The flow zone around a broken cold leg in the downcomer annulus has the role of a high ECC direct bypass due to a strong suction force while the wake zone of a hot leg has the role of an ECC penetration. Thus, the relative azimuthal angle of the DVI nozzle from the broken cold leg is an important design parameter. A large azimuthal angle from a cold leg to a hot leg needs to avoid a high suction flow zone when an ECC water is being injected. The other enhancing mechanism of an ECC penetration is a grooved core barrel which has small rectangular-shaped grooves vertically arranged on the core barrel wall of the reactor vessel downcomer annulus. These grooves have the role for a generation of a vortex induced by a high-speed cross flow. Since the stagnant flow in a lateral direction and rotational vortex provides the pulling force of an ECC drop or film to flow down into the lower downcomer annulus by gravity, the ECC direct bypass fraction is reduced when compared to the current design of a smoothed wall. An open channel of grooves generates a stagnant vortex, while a closed channel of grooves

  5. A case report and brief review of the literature on bilateral retinal infarction following cardiopulmonary bypass for coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    Trethowan Brian A

    2011-11-01

    Full Text Available Abstract Postoperative visual loss is a devastating perioperative complication. The commonest aetiologies are anterior ischaemic optic neuropathy (AION, posterior ischaemic optic neuropathy (PION, and central retinal artery occlusion (CRAO. These appear to be related to certain types of operation, most commonly spinal and cardiac bypass procedures; with the rest divided between: major trauma causing excessive blood loss; head/neck and nasal or sinus surgery; major vascular procedures (aortic aneurysm repair, aorto-bifemoral bypass; general surgery; urology; gynaecology; liposuction; liver transplantation and duration of surgery. The non-surgical risk factors are multifactorial: advanced age, prolonged postoperative anaemia, positioning (supine v prone, alteration of venous drainage of the retina, hypertension, smoking, atherosclerosis, hyperlipidaemia, diabetes, hypercoagulability, hypotension, blood loss and large volume resuscitation. Other important cardiac causes are septic emboli from bacterial endocarditis and emboli caused by atrial myxomata. The majority of AION cases occur during CPB followed by head/neck surgery and prone spine surgery. CPB is used to allow coronary artery bypass grafting on a motionless heart. It has many side-effects and complications associated with its use and we report here a case of bilateral retinal infarction during routine coronary artery bypass grafting in a young male patient with multiple risk factors for developing this complication despite steps to minimise its occurrence.

  6. Molecular typing of Lactobacillus brevis isolates from Korean food using repetitive element-polymerase chain reaction.

    Science.gov (United States)

    Kaur, Jasmine; Sharma, Anshul; Lee, Sulhee; Park, Young-Seo

    2018-06-01

    Lactobacillus brevis is a part of a large family of lactic acid bacteria that are present in cheese, sauerkraut, sourdough, silage, cow manure, feces, and the intestinal tract of humans and rats. It finds its use in food fermentation, and so is considered a "generally regarded as safe" organism. L. brevis strains are extensively used as probiotics and hence, there is a need for identifying and characterizing these strains. For identification and discrimination of the bacterial species at the subspecific level, repetitive element-polymerase chain reaction method is a reliable genomic fingerprinting tool. The objective of the present study was to characterize 13 strains of L. brevis isolated from various fermented foods using repetitive element-polymerase chain reaction. Repetitive element-polymerase chain reaction was performed using three primer sets, REP, Enterobacterial Repetitive Intergenic Consensus (ERIC), and (GTG) 5 , which produced different fingerprinting patterns that enable us to distinguish between the closely related strains. Fingerprinting patterns generated band range in between 150 and 5000 bp with REP, 200-7500 bp with ERIC, and 250-2000 bp with (GTG) 5 primers, respectively. The Jaccard's dissimilarity matrices were used to obtain dendrograms by the unweighted neighbor-joining method using genetic dissimilarities based on repetitive element-polymerase chain reaction fingerprinting data. Repetitive element-polymerase chain reaction proved to be a rapid and easy method that can produce reliable results in L. brevis species.

  7. Evaluation of Core Bypass Flow in the Prismatic VHTR with a Multi-block Experiment

    International Nuclear Information System (INIS)

    Lee, Jeong Hun; Yoon, Su Jong; Park, Goon Cherl; Kim, Min Hwan

    2010-01-01

    The core of Prismatic Modular Reactor (PMR) consists of assemblies of hexagonal graphite fuel and reflector elements. The core bypass flow of Very High Temperature Reactor (VHTR) is defined as the core flow that does not pass through the coolant channels but passes through the bypass gap between fuel elements. The increase in bypass flow makes the decrease in effective coolant flow. Since the core bypass flow has a negative impact on safety and efficiency of VHTR, core bypass phenomena have to be investigated to improve the core thermal margin of VHTR. For this purpose, the international project, I-NERI project, has been carried out since 2008. I-NERI project is collaborative project that KAERI and SNU of Korea side and INL, ANL and TAMU of U.S side are involved. In order to evaluate the core bypass flow, the multicolumn and multi-layer experimental facility is designed by SNU. In this experiment, the effect of cross-flow and local variation of bypass gap on the bypass flow distribution is investigated. Furthermore, the experimental data will be used for validation of CFD code or thermal hydraulic analysis codes such as GAMMA or GAS-NET

  8. Rural health care bypass behavior: how community and spatial characteristics affect primary health care selection.

    Science.gov (United States)

    Sanders, Scott R; Erickson, Lance D; Call, Vaughn R A; McKnight, Matthew L; Hedges, Dawson W

    2015-01-01

    (1) To assess the prevalence of rural primary care physician (PCP) bypass, a behavior in which residents travel farther than necessary to obtain health care, (2) To examine the role of community and non-health-care-related characteristics on bypass behavior, and (3) To analyze spatial bypass patterns to determine which rural communities are most affected by bypass. Data came from the Montana Health Matters survey, which gathered self-reported information from Montana residents on their health care utilization, satisfaction with health care services, and community and demographic characteristics. Logistic regression and spatial analysis were used to examine the probability and spatial patterns of bypass. Overall, 39% of respondents bypass local health care. Similar to previous studies, dissatisfaction with local health care was found to increase the likelihood of bypass. Dissatisfaction with local shopping also increases the likelihood of bypass, while the number of friends in a community, and commonality with community reduce the likelihood of bypass. Other significant factors associated with bypass include age, income, health, and living in a highly rural community or one with high commuting flows. Our results suggest that outshopping theory, in which patients bundle services and shopping for added convenience, extends to primary health care selection. This implies that rural health care selection is multifaceted, and that in addition to perceived satisfaction with local health care, the quality of local shopping and levels of community attachment also influence bypass behavior. © 2014 National Rural Health Association.

  9. The expanding polymerase universe.

    Science.gov (United States)

    Goodman, M F; Tippin, B

    2000-11-01

    Over the past year, the number of known prokaryotic and eukaryotic DNA polymerases has exploded. Many of these newly discovered enzymes copy aberrant bases in the DNA template over which 'respectable' polymerases fear to tread. The next step is to unravel their functions, which are thought to range from error-prone copying of DNA lesions, somatic hypermutation and avoidance of skin cancer, to restarting stalled replication forks and repairing double-stranded DNA breaks.

  10. Femoro-Supragenicular Popliteal Bypass with a Bridging Stent Graft in a Diffusely Diseased Distal Target Popliteal Artery: Alternative to Below-Knee Popliteal Polytetrafluoroethylene Bypass

    Directory of Open Access Journals (Sweden)

    Joung Hun Byun

    2017-10-01

    Full Text Available Background: Lesions in distal target arteries hinder surgical bypass procedures in patients with peripheral arterial occlusive disease. Methods: Between April 2012 and October 2015, 16 patients (18 limbs with lifestyle- limiting claudication (n=12 or chronic critical limb ischemia (n=6 underwent femoral–above-knee (AK polytetrafluoroethylene (PTFE bypass grafts with a bridging stent graft placement between the distal target popliteal artery and the PTFE graft. Ring-supported PTFE grafts were used in all patients with no available vein for graft material. Follow-up evaluations assessed clinical symptoms, the ankle-brachial index, ultrasonographic imaging and/or computed tomography angiography, the primary patency rate, and complications. Results: All procedures were successful. The mean follow-up was 12.6 months (range, 11 to 14 months, and there were no major complications. The median baseline ankle-brachial index of 0.4 (range, 0.2 to 0.55 significantly increased to 0.8 (range, 0.5 to 1.0 at 12 months (p<0.01. The primary patency rate at 12 months was 83.3%. The presenting symptoms resolved within 2 weeks. Conclusion: In AK bypasses with a diffusely diseased distal target popliteal artery or when below-knee (BK bypass surgery is impossible, this procedure could be clinically effective and safe when used as an alternative to femoral-BK bypass surgery.

  11. Concomitant coronary artery revascularization and right pneumonectomy without cardiopulmonary bypass

    NARCIS (Netherlands)

    Hensens, AG; Zeebregts, C.J.A.M.; Liem, TH; Gehlmann, H; Lacquet, LK

    Combined coronary artery bypass grafting (CABG) and pneumonectomy has a high morbidity and mortality rate, especially when the right lung has to be removed. A patient is described who underwent a CABG operation through a midline sternotomy without the use of cardiopulmonary bypass (CPB), and a right

  12. Severe scurvy after gastric bypass surgery and a poor postoperative diet

    DEFF Research Database (Denmark)

    Hansen, Esben P K; Metzsche, Carsten; Henningsen, Emil

    2012-01-01

    After bariatric gastric bypass surgery patients are at risk of developing micronutrient deficiencies. If gastric bypass surgery is followed by a vitamin deficient diet the patients have a risk of developing vitamin-C deficiency. When spontaneous ecchymosis is observed in the skin, in at......-risk patients, scurvy must be considered. When treated with large doses of vitamin-C the symptoms of scurvy rapidly improve even if the patient has developed multiple organ dysfunction syndrome. KEYWORDS: Scurvy; Gastric bypass surgery; Multiorgan dysfunction....

  13. Effect of STA-MCA bypass based on the motor activation SPECT

    International Nuclear Information System (INIS)

    Kawaguchi, Shoichiro; Uranishi, Ryunosuke; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime

    1999-01-01

    The effect of STA-MCA bypass for ischemic cerebrovascular diseases (CVDs) on pure motor function using motor activation SPECT was evaluated and analyzed, and this effect with the resting cerebral blood flow and reserved capacity was compared. Motor activation SPECT were carried out on 22 cases with STA-MCA bypass for symptomatic ischemic CVDs. All motors activation SPECT using the finger opposition task on the affected side were performed before bypass, at 1 month, and 3 months after the bypass. Visual inspection was used to determine whether the result of the motor activation SPECT was as negative or positive. The activated region was detected anatomically precisely by superimposing the SPECT on the MRI. Before this study, the same examination was performed on normal controls. In controls, 91% showed the activated area on the sensorimotor cortex after the finger opposition tasks. Before bypass, the resting SPECT revealed reduction of cerebral blood flow (CBF) on the affected side in all cases. All cases also showed a disturbed response to acetazolamide (ACZ). Nine cases were positive in the motor activation SPECT. One month after bypass, the resting CBF increased in 11 cases. Seven showed preoperative positive motor activation. Fifteen cases were positive in the motor activation SPECT. Three months after bypass, 20 cases showed improvement in the resting CBF, and 19 cases were positive in the motor activation SPECT. Ten cases were negative in the preoperative motor activation SPECT. At one month after surgery, ACZ activation SPECT was performed in 12 cases. Five showed improvement of the response to ACZ. At 3 months after surgery, 8 of 12 cases treated with ACZ activation SPECT showed improved response to ACZ. In most of the cases, improved response to ACZ could be seen after response to motor activation improved. STA-MCA bypass is useful not only for resting CBF but also for pure motor function based on motor activation SPECT. (K.H.)

  14. Effect of STA-MCA bypass based on the motor activation SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Shoichiro; Uranishi, Ryunosuke; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime [Nara Medical Univ., Kashihara (Japan)

    1999-07-01

    The effect of STA-MCA bypass for ischemic cerebrovascular diseases (CVDs) on pure motor function using motor activation SPECT was evaluated and analyzed, and this effect with the resting cerebral blood flow and reserved capacity was compared. Motor activation SPECT were carried out on 22 cases with STA-MCA bypass for symptomatic ischemic CVDs. All motors activation SPECT using the finger opposition task on the affected side were performed before bypass, at 1 month, and 3 months after the bypass. Visual inspection was used to determine whether the result of the motor activation SPECT was as negative or positive. The activated region was detected anatomically precisely by superimposing the SPECT on the MRI. Before this study, the same examination was performed on normal controls. In controls, 91% showed the activated area on the sensorimotor cortex after the finger opposition tasks. Before bypass, the resting SPECT revealed reduction of cerebral blood flow (CBF) on the affected side in all cases. All cases also showed a disturbed response to acetazolamide (ACZ). Nine cases were positive in the motor activation SPECT. One month after bypass, the resting CBF increased in 11 cases. Seven showed preoperative positive motor activation. Fifteen cases were positive in the motor activation SPECT. Three months after bypass, 20 cases showed improvement in the resting CBF, and 19 cases were positive in the motor activation SPECT. Ten cases were negative in the preoperative motor activation SPECT. At one month after surgery, ACZ activation SPECT was performed in 12 cases. Five showed improvement of the response to ACZ. At 3 months after surgery, 8 of 12 cases treated with ACZ activation SPECT showed improved response to ACZ. In most of the cases, improved response to ACZ could be seen after response to motor activation improved. STA-MCA bypass is useful not only for resting CBF but also for pure motor function based on motor activation SPECT. (K.H.)

  15. Transfusion requirements in elective cardiopulmonary bypass surgery patients

    DEFF Research Database (Denmark)

    Sivapalan, Praleene; Bäck, Anne Caroline; Ostrowski, Sisse Rye

    2017-01-01

    Managing haemostasis in patients undergoing cardiopulmonary bypass (CPB) surgery remains a challenge. There is no established laboratory test to predict transfusion requirements in cardiac surgery. We investigated whether preoperative Thromboelastography (TEG) with Platelet Mapping Assay (PMA......) or Multiple Electrode Aggrometry (MEA) could predict transfusion requirements in patients undergoing elective coronary artery bypass grafting (CABG) or combined CABG with aortic or mitral valve replacement. We prospectively investigated 199 patients undergoing elective CABG or combined procedures. PMA and MEA...

  16. Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy

    DEFF Research Database (Denmark)

    Patti, M E; McMahon, G; Mun, E C

    2005-01-01

    AIMS/HYPOTHESIS: Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive...... was assessed in all three patients. RESULTS: All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control...

  17. Central 5-HT Neurotransmission Modulates Weight Loss following Gastric Bypass Surgery in Obese Individuals

    DEFF Research Database (Denmark)

    Haahr, M. E.; Hansen, D. L.; Fisher, P. M.

    2015-01-01

    The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery....... In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m(2)] and 10 lean (three men; BMI, 24.6 ± 1.5 kg/m(2)) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First...

  18. Salvage of bilateral renal artery occlusion after endovascular aneurysm repair with open splenorenal bypass

    Directory of Open Access Journals (Sweden)

    Samuel Jessula, MDCM

    2017-09-01

    Full Text Available We report renal salvage maneuvers after accidental bilateral renal artery coverage during endovascular aneurysm repair of an infrarenal abdominal aortic aneurysm. A 79-year-old man with an infrarenal abdominal aortic aneurysm was treated with endovascular aneurysm repair. Completion angiography demonstrated coverage of the renal arteries. Several revascularization techniques were attempted, including endograft repositioning and endovascular stenting through the femoral and brachial approach. The patient eventually underwent open splenorenal bypass with a Y Gore-Tex graft (W. L. Gore & Associates, Flagstaff, Ariz. After 3 months, computed tomography showed no evidence of endoleak and patent renal arteries. Renal function was well maintained, and the patient did not require dialysis.

  19. Oil Bypass Filter Technology Performance Evaluation - January 2003 Quarterly Report

    Energy Technology Data Exchange (ETDEWEB)

    Laurence R. Zirker; James E. Francfort

    2003-01-01

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  20. Perioperative risk factors for prolonged mechanical ventilation and tracheostomy in women undergoing coronary artery bypass graft with cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Zahra S Faritous

    2011-01-01

    Full Text Available Background: Prolonged mechanical ventilation is an important recognized complication occurring during cardiovascular surgery procedures. This study was done to assess the perioperative risk factors related to postoperative pulmonary complications and tracheostomy in women undergoing coronary artery bypass graft with cardiopulmonary bypass. Methods: It was a retrospective study on 5,497 patients, including 31 patients with prolonged ventilatory support and 5,466 patients without it; from the latter group, 350 patients with normal condition (extubated in 6-8 hours without any complication were selected randomly. Possible perioperative risk factors were compared between the two groups using a binary logistic regression model. Results: Among the 5,497 women undergoing coronary artery bypass graft (CABG, 31 women needed prolonged mechanical ventilation (PMV, and 15 underwent tracheostomy. After logistic regression, 7 factors were determined as being independent perioperative risk factors for PMV. Discussion: Age ≥70 years old, left ventricular ejection fraction (LVEF ≤30%, preexisting respiratory or renal disease, emergency or re-do operation and use of preoperative inotropic agents are the main risk factors determined in this study on women undergoing CABG.

  1. EFFECT OF SIZE OF INTESTINAL DIVERSIONS IN OBESE PATIENTS WITH METABOLIC SYNDROME SUBMITTED TO GASTRIC BYPASS.

    Science.gov (United States)

    Ramos, Rafael Jacques; Mottin, Cláudio Corá; Alves, Letícia Biscaino; Benzano, Daniela; Padoin, Alexandre Vontobel

    There is no consensus on the ideal size of intestinal loops in gastric bypass of bariatric surgeries. To evaluate the metabolic outcome of patients submitted to gastric bypass with alimentary and biliopancreatic loops of different sizes. Was conducted a retrospective cohort study in diabetic obese patients (BMI≥35 kg/m2) with metabolic syndrome submitted to gastric bypass. The patients were divided into three groups according to the size of the intestinal loop: group 1, biliopancreatic limb 50 cm length and alimentary limb 100 cm length; group 2 , biliopancreatic limb 50 cm length and alimentary limb 150 cm length; and group 3, biliopancreatic limb 100 cm length and alimentary limb 150 cm length. The effect of gastric bypass with different sizes of intestinal loops in relation to the parameters that define metabolic syndrome was determined. Sixty-three patients were evaluated, and they had a mean age of 44.7±9.4 years. All were diabetics, with 62 (98.4%) being hypertensive and 51 (82.2%) dyslipidemic. The three groups were homogeneous in relation to the variables. In 24 months, there was a remission of systemic arterial hypertension in 65% of patients in group 1, 62.5% in group 2 and 68.4% in group 3. Remission of diabetes occurred in 85% of patients in group 1, 83% in group 2 and 84% in group 3. There was no statistical difference in %LEW between the groups, and waist measurements decreased in a homogeneous way in all groups. The size of loops also had no influence on the improvement in dyslipidemia. Variation in size of intestinal loops does not appear to influence improvement in metabolic syndrome in this group of patients. Não há consenso sobre o tamanho ideal das alças intestinais no bypass gástrico em Y-de-Roux em cirurgias bariátricas. Avaliar os desfechos metabólicos de pacientes submetidos ao bypass gástrico com alça intestinal alimentar e biliopancreática de tamanhos diferentes. Realizou-se coorte retrospectiva em pacientes obesos (IMC≥35 kg

  2. Optimal conditions to use Pfu exo(-) DNA polymerase for highly efficient ligation-mediated polymerase chain reaction protocols.

    Science.gov (United States)

    Angers, M; Cloutier, J F; Castonguay, A; Drouin, R

    2001-08-15

    Ligation-Mediated Polymerase Chain Reaction (LMPCR) is the most sensitive sequencing technique available to map single-stranded DNA breaks at the nucleotide level of resolution using genomic DNA. LMPCR has been adapted to map DNA damage and reveal DNA-protein interactions inside living cells. However, the sequence context (GC content), the global break frequency and the current combination of DNA polymerases used in LMPCR affect the quality of the results. In this study, we developed and optimized an LMPCR protocol adapted for Pyrococcus furiosus exo(-) DNA polymerase (Pfu exo(-)). The relative efficiency of Pfu exo(-) was compared to T7-modified DNA polymerase (Sequenase 2.0) at the primer extension step and to Thermus aquaticus DNA polymerase (Taq) at the PCR amplification step of LMPCR. At all break frequencies tested, Pfu exo(-) proved to be more efficient than Sequenase 2.0. During both primer extension and PCR amplification steps, the ratio of DNA molecules per unit of DNA polymerase was the main determinant of the efficiency of Pfu exo(-), while the efficiency of Taq was less affected by this ratio. Substitution of NaCl for KCl in the PCR reaction buffer of Taq strikingly improved the efficiency of the DNA polymerase. Pfu exo(-) was clearly more efficient than Taq to specifically amplify extremely GC-rich genomic DNA sequences. Our results show that a combination of Pfu exo(-) at the primer extension step and Taq at the PCR amplification step is ideal for in vivo DNA analysis and DNA damage mapping using LMPCR.

  3. Effective void fraction for a BWR assembly with boiling in the bypass region

    International Nuclear Information System (INIS)

    Galperin, A.; Segev, M.; Knoglinger, E.

    1991-09-01

    Average BWR assembly cross-sections for nominal conditions, namely for zero bypass void, can be utilised in the analysis of transient conditions with boiling in the bypass. A model is developed to yield an effective channel void for such conditions. The use of this void in conjunction with the 'nominal conditions' cross section library approximately preserves the assembly K-infinity corresponding to the true channel and bypass voids. The effective void is an augmentation of the actual channel void. The augment is proportional to the bypass-to-channel volume ratio, to the bypass void, and to a weight W which is introduced to quantify the fact that a water molecule in the bypass has a different assembly criticality worth than one in the channel. The formula developed is superior to the practice of choosing W=1, namely a simple, non-weighted, transfer of water from channel to bypass. The use of this approximate effective channel void reproduces actual K-infinity values of assemblies to better than 5 mk, whereas the use of a simple model sometimes misspredicts the assembly K-infinity by 40 mK. The effective void model cannot handle cases in which both channel and bypass void value are high, simply because then the effective void α ch eff becomes meaningless. A method to treat the α eff >1 domain is developed by which corrections to cross sections are provided. Such corrections are synthesised as functions of the assembly parameters. (author) figs., tabs., refs

  4. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    DEFF Research Database (Denmark)

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...

  5. Alianza Familia-Escuela: Percepciones, Creencias, Expectativas y Aspiraciones de Padres y Profesores de Enseñanza General Básica Family-School Alliance: Perceptions, Beliefs, Expectatives and Aspirations of Parents and Teachers in Primary School

    Directory of Open Access Journals (Sweden)

    Maritza Rivera

    2006-05-01

    Full Text Available Se refieren los resultados de un estudio cualitativo realizado en Santiago, cuyo propósito fue describir y comprender las percepciones, creencias, expectativas y aspiraciones de padres y profesores sobre la relación familia - escuela. El diseño metodológico se adscribió a los principios del paradigma interpretativo, según los principios de la Grounded Theory. Las técnicas de recolección fueron entrevistas semi-estructuradas y grupos focales a madres y profesores, constituyendo una muestra total de 48 sujetos. El estudio aporta información descriptiva y comprensiva sobre consensos y disensos de ambos respecto del sistema relacional familia-escuela, roles, normas, comunicación, conflictos, participación, alianza y educación. Finalmente emerge un modelo del sistema relacional familia - escuela, incluyendo barreras, facilitadores y parámetros que posibilitarían una alianza efectiva.Findings from a qualitative study made in Santiago, whose purpose was to describe and understand the parents and teachers perceptions, beliefs, expectatives, and aspirations about the family-school relationship. The methodological design adhered to the principles of the interpretative paradigm, according to the principles of the Grounded Theory. The gathering techniques were semi-organized interviews and focal groups to mothers and teachers, completing a total sample of 48 persons. This research contributes with descriptive and comprehensive information about consensus and disagreements of parents and teachers with regard to the family-school relational system, roles, rules, communication, conflicts, participation, alliance and education. Finally a model of the family-school relational system emerges, including barriers, helpers, and parameters that would make possible an effective alliance.

  6. MsDpo4—a DinB Homolog from Mycobacterium smegmatis—Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches

    Directory of Open Access Journals (Sweden)

    Amit Sharma

    2012-01-01

    Full Text Available Error-prone DNA synthesis in prokaryotes imparts plasticity to the genome to allow for evolution in unfavorable environmental conditions, and this phenomenon is termed adaptive mutagenesis. At a molecular level, adaptive mutagenesis is mediated by upregulating the expression of specialized error-prone DNA polymerases that generally belong to the Y-family, such as the polypeptide product of the dinB gene in case of E. coli. However, unlike E. coli, it has been seen that expression of the homologs of dinB in Mycobacterium tuberculosis are not upregulated under conditions of stress. These studies suggest that DinB homologs in Mycobacteria might not be able to promote mismatches and participate in adaptive mutagenesis. We show that a representative homolog from Mycobacterium smegmatis (MsDpo4 can carry out template-dependent nucleotide incorporation and therefore is a DNA polymerase. In addition, it is seen that MsDpo4 is also capable of misincorporation with a significant ability to promote G:T and T:G mismatches. The frequency of misincorporation for these two mismatches is similar to that exhibited by archaeal and prokaryotic homologs. Overall, our data show that MsDpo4 has the capacity to facilitate transition mutations and can potentially impart plasticity to the genome.

  7. Heart bypass surgery - minimally invasive

    Science.gov (United States)

    ... MIDCAB; Robot-assisted coronary artery bypass; RACAB; Keyhole heart surgery; CAD - MIDCAB; Coronary artery disease - MIDCAB ... To perform this surgery: The heart surgeon will make a 3- to 5-inch (8 to 13 centimeters) surgical cut in the left part of your chest ...

  8. Laparoscopic Roux-En-Y Gastric Bypass Improves Lipid Profile and Decreases Cardiovascular Risk: a 5-Year Longitudinal Cohort Study of 1048 Patients.

    Science.gov (United States)

    Gero, Daniel; Favre, Lucie; Allemann, Pierre; Fournier, Pierre; Demartines, Nicolas; Suter, Michel

    2018-03-01

    Dyslipidemia is a known risk factor for cardiovascular (CV) events. The aim of the study was to assess lipid profiles and their impact on CV risk changes in a large patient cohort 5 years after Roux-en-Y gastric bypass (RYGB). All patients who underwent primary RYGB for severe obesity in our two hospitals between January 1999 and December 2009 were included. The Framingham risk score was used. One thousand and forty-eight patients were included, 791 women and 257 men. Five-year complete lipid profile was available for 77% of patients. At 5 years, mean body mass index (BMI) decreased from 45.7 ± 6 to 31 ± 5.8 kg/m 2 (p profile improved more in patients with greater weight loss (%EBMIL ≥ 50 or %TWL ≥ 25%). Assuming that all patients were non-smokers and other baseline risk factors (hypertension, diabetes) remained unchanged at 5 years, the amelioration of the lipid profile itself yielded to a 27% reduction of CV risk (p profile from the first to fifth postoperative year. This improvement translates into significantly lower CV risk from the first year after surgery.

  9. Putative DNA-dependent RNA polymerase in Mitochondrial Plasmid of Paramecium caudatum Stock GT704

    Directory of Open Access Journals (Sweden)

    Trina Ekawati Tallei

    2015-10-01

    Full Text Available Mitochondria of Paramecium caudatum stock GT704 has a set of four kinds of linear plasmids with sizes of 8.2, 4.1, 2.8 and 1.4 kb. The plasmids of 8.2 and 2.8 kb exist as dimers consisting of 4.1- and 1.4-kb monomers, respectively. The plasmid 2.8 kb, designated as pGT704-2.8, contains an open reading frame encodes for putative DNA-dependent RNA polymerase (RNAP. This study reveals that this RNAP belongs to superfamily of DNA/RNA polymerase and family of T7/T3 single chain RNA polymerase and those of mitochondrial plasmid of fungi belonging to Basidiomycota and Ascomycota. It is suggested that RNAP of pGT704-2.8 can perform transcription without transcription factor as promoter recognition. Given that only two motifs were found, it could not be ascertained whether this RNAP has a full function independently or integrated with mtDNA in carrying out its function.

  10. Advancing Polymerase Ribozymes Towards Self-Replication

    Science.gov (United States)

    Tjhung, K. F.; Joyce, G. F.

    2017-07-01

    Autocatalytic replication and evolution in vitro by (i) a cross-chiral RNA polymerase catalyzing polymerization of mononucleotides of the opposite handedness; (ii) non-covalent assembly of component fragments of an existing RNA polymerase ribozyme.

  11. Temporary diabetes insipidus in 2 men after on-pump coronary artery bypass grafting.

    Science.gov (United States)

    Uyar, Ihsan Sami; Sahin, Veysel; Akpinar, Besir; Yurtman, Volkan; Abacilar, Feyzi; Okur, Faik Fevzi; Ates, Mehmet

    2013-01-01

    Many complications have been reported after cardiopulmonary bypass. A common physiologic change during the early postoperative period after cardiopulmonary bypass is increased diuresis. In patients whose urine output is increased, postoperative diabetes insipidus can develop, although reports of this are rare. We present the cases of 2 patients who underwent on-pump coronary artery bypass grafting (with cardiopulmonary bypass). Each was diagnosed with diabetes insipidus postoperatively: a 54-year-old man on the 3rd day, and a 66-year-old man on the 4th day. Each patient recovered from the condition after 6 hours of intranasal therapy with synthetic vasopressin (antidiuretic hormone). The diagnosis of diabetes insipidus should be considered in patients who produce excessive urine early after cardiac surgery in which cardiopulmonary bypass has been used.

  12. Cardiopulmonary bypass: development of John Gibbon's heart-lung machine

    OpenAIRE

    Passaroni, Andréia Cristina; Silva, Marcos Augusto de Moraes; Yoshida, Winston Bonetti

    2015-01-01

    AbstractObjective:To provide a brief review of the development of cardiopulmonary bypass.Methods:A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation.Results:The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from vari...

  13. Dacron or PTFE for above-knee femoropopliteal bypass. a multicenter randomised study

    DEFF Research Database (Denmark)

    Jensen, L P; Lepäntalo, M; Fossdal, J E

    2007-01-01

    To compare polytetrafluorethylene (PTFE) and polyester grafts (Dacron) for above knee femoropopliteal bypass.......To compare polytetrafluorethylene (PTFE) and polyester grafts (Dacron) for above knee femoropopliteal bypass....

  14. The Roles of UmuD in Regulating Mutagenesis

    Directory of Open Access Journals (Sweden)

    Jaylene N. Ollivierre

    2010-01-01

    Full Text Available All organisms are subject to DNA damage from both endogenous and environmental sources. DNA damage that is not fully repaired can lead to mutations. Mutagenesis is now understood to be an active process, in part facilitated by lower-fidelity DNA polymerases that replicate DNA in an error-prone manner. Y-family DNA polymerases, found throughout all domains of life, are characterized by their lower fidelity on undamaged DNA and their specialized ability to copy damaged DNA. Two E. coli Y-family DNA polymerases are responsible for copying damaged DNA as well as for mutagenesis. These DNA polymerases interact with different forms of UmuD, a dynamic protein that regulates mutagenesis. The UmuD gene products, regulated by the SOS response, exist in two principal forms: UmuD2, which prevents mutagenesis, and UmuD2′, which facilitates UV-induced mutagenesis. This paper focuses on the multiple conformations of the UmuD gene products and how their protein interactions regulate mutagenesis.

  15. Health and performance of calves with forestomach-bypass fed milk replacer.

    Science.gov (United States)

    McKinstry, D M; Cason, J L; Albert, T F; Sass, B

    1976-02-01

    Ten male Holstein calves were placed in groups of two calves each on similarity of age. On calf in each group was subjected to forestomach-bypass surgery at about 1 mo of age. Fortified commercial milk replacer with added minerals and vitamins was fed as the sole diet. The calves were housed indoors on slatted platforms. Weight gain was determined biweekly. Feed intake was determined daily. Necropsies were performed upon termination of the study. Recurrent ruminal bloat, fever, and anorexia of varying degrees and combinations occurred in four of the calves with forestomach bypass. Two of these calves showed slow weight gain. One of the four calves died following acute bloat while the other three calves were sacrificed following repeated episodes of bloat. The time of termination varied between 3 and 10 mo. One calf with forestomach bypass and all control calves appeared healthy throughout the experiment. Necropsies indicated that the ruminal bloat, seen in most of the forestomach-bypass calves, could be attributed to the back-flow of ingesta via the omasal-abomasal orifice. This ingesta appeared to produce gas which became trapped in the bypassed rumen.

  16. Evolution of elderly patients who underwent cardiac surgery with cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Alain Moré Duarte

    2016-01-01

    Full Text Available Introduction: There is a steady increase in the number of elderly patients with severe cardiovascular diseases who require a surgical procedure to recover some quality of life that allows them a socially meaningful existence, despite the risks.Objectives: To analyze the behavior of elderly patients who underwent cardiac surgery with cardiopulmonary bypass.Method: A descriptive, retrospective, cross-sectional study was conducted with patients over 65 years of age who underwent surgery at the Cardiocentro Ernesto Che Guevara, in Santa Clara, from January 2013 to March 2014.Results: In the study, 73.1% of patients were men; and there was a predominance of subjects between 65 and 70 years of age, accounting for 67.3%. Coronary artery bypass graft was the most prevalent type of surgery and had the longest cardiopulmonary bypass times. Hypertension was present in 98.1% of patients. The most frequent postoperative complications were renal dysfunction and severe low cardiac output, with 44.2% and 34.6% respectively.Conclusions: There was a predominance of men, the age group of 65 to 70 years, hypertension, and patients who underwent coronary artery bypass graft with prolonged cardiopulmonary bypass. Renal dysfunction was the most frequent complication.

  17. A simple technique can reduce cardiopulmonary bypass use during lung transplantation

    Directory of Open Access Journals (Sweden)

    Marcos N. Samano

    2016-04-01

    Full Text Available Cardiopulmonary bypass causes an inflammatory response and consumption of coagulation factors, increasing the risk of bleeding and neurological and renal complications. Its use during lung transplantation may be due to pulmonary hypertension or associated cardiac defects or just for better exposure of the pulmonary hilum. We describe a simple technique, or open pericardium retraction, to improve hilar exposure by lifting the heart by upward retraction of the pericardial sac. This technique permits lung transplantation without cardiopulmonary bypass when bypass use is recommended only for better exposure.

  18. Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity

    Directory of Open Access Journals (Sweden)

    Takeshi Azuma

    2011-02-01

    Full Text Available Previously, we reported that vitamin K3 (VK3, but not VK1 or VK2 (=MK-4, inhibits the activity of human DNA polymerase γ (pol γ. In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF-α induced by lipopolysaccharide (LPS. Moreover, MK-2 was found to inhibit the action of nuclear factor (NF-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates.

  19. Economic consequences of extra by-passes in district heating networks. Investment-, running- and maintenance costs

    International Nuclear Information System (INIS)

    Herbert, P.

    1995-02-01

    For various reasons, extra by-passes are installed in district heating networks to ensure a high flow temperature when the water circulation is insufficient. By 'extra by-pass' we here mean a connection between the distribution pipe and the return pipe. This study mainly deals with extra by-passes to prevent freezing. The estimation of the extra by-pass costs is based on the district heating rates. Our assumption is that an extra by-pass can be regarded as a substation in the district heating network, with regard to the demand for the water flow, heat and power. The reason is the difficulty to obtain available facts to estimate the real costs concerning extra by-passes. Therefore, the method can not claim that the information about the costs is exact but gives an indication of the size of them. The valves in an extra by-pass can be set more or less open. We assume that manual valves in extra by-passes are wide open. Thermostatic valves are, however, assumed to be adjusted in order to cause a very small water flow. 2 refs, 16 figs, 9 tabs, 6 appendices

  20. Effect of bypass on the motor activation SPECT compared to the acetazolamide SPECT

    International Nuclear Information System (INIS)

    Kawaguchi, Shoichiro; Iwahashi, Hideaki; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime

    2002-01-01

    The authors evaluated and analyzed motor activation single photon emission computed tomography (M-SPECT) in ischemic cerebrovascular disease compared to resting and acetazolamide (ACZ) activated SPECT studies. Seventeen cases with STA-MCA bypass performed for ischemic cerebrovascular disease were examined. The SPECT studies consisting of resting, ACZ activation, and motor activation stages were performed before bypass, at 1 month, and 3 months after bypass. The result of the M-SPECT was expressed as negative or positive. Before bypass: In all 17 cases, SPECT studies of the affected side showed reduction of resting cerebral blood flow (CBF) and reduction of cerebrovascular reserve capacity (CVRC). Eight cases were positive in the M-SPECT study. One week after bypass: The resting CBF increased in seven cases. Four showed preoperative positive M-SPECT. Eight cases showed improvement of the CVRC. Twelve cases were positive in M-SPECT, and two were negative in the preoperative M-SPECT. Three months after bypass: Thirteen cases showed improvement in the resting CBF, and fourteen cases showed improvement of the CVRC. Fourteen cases were positive in the M-SPECT, and among these, 6 were negative in the preoperative M-SPECT. There was a discrepancy between the improvement in CVRC and M-SPECT. M-SPECT study can provide information about the degree of hemodynamic compromise and effect of bypass surgery. (author)

  1. Direct ECC bypass phenomena in the MIDAS test facility during LBLOCA reflood phase

    International Nuclear Information System (INIS)

    Yun, B. J.; Kweon, T. S.; Ah, D. J.; Ju, I. C.; Song, C. H.; Park, J. K.

    2001-01-01

    This paper describes the experimental results of ECC Direct Bypass Phenomena in the downcomer during the late reflood phase of LBLOCA of the reactor that adopts Direct Vessel Injection as a ECC system. The experiments have been performed in MIDAS test facility using superheated steam and water. The test condition was determined, based on the preliminary analysis of TRAC code, from modified linear scaling method of 1/4.93 length scale. To measure the direct bypass fraction according to the nozzle location, separate effect tests have been performed in case of DVI-4(farthest from broken cold leg) injection, DVI-2(closest to broken cold leg) injection, and DVI-2 and 4 injection, respectively. Also the test was carried out varying the steam flow rate greatly to investigate the effect of steam flow rate on the direct bypass fraction of ECC water. Test results show that the direct bypass fraction of ECC water depends significantly on the injected steam mass flow rate. DVI-4 tests show that the direct bypass fraction increases drastically as the steam flow rate increases. However, in DVI-2 test most of the injected ECC water penetrates into lower downcomer. The direct bypass characteristic in each of DVI-2 and DVI-4 tests is reflected into the direct bypass characteristic curve of DVI-2 and 4 test. The steam condensation reaches to the theoretically allowable maximum value

  2. Effect of bypass on the motor activation SPECT compared to the acetazolamide SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Shoichiro; Iwahashi, Hideaki; Sakaki, Toshisuke; Imai, Teruhiko; Ohishi, Hajime [Nara Medical Univ., Kashihara (Japan)

    2002-03-01

    The authors evaluated and analyzed motor activation single photon emission computed tomography (M-SPECT) in ischemic cerebrovascular disease compared to resting and acetazolamide (ACZ) activated SPECT studies. Seventeen cases with STA-MCA bypass performed for ischemic cerebrovascular disease were examined. The SPECT studies consisting of resting, ACZ activation, and motor activation stages were performed before bypass, at 1 month, and 3 months after bypass. The result of the M-SPECT was expressed as negative or positive. Before bypass: In all 17 cases, SPECT studies of the affected side showed reduction of resting cerebral blood flow (CBF) and reduction of cerebrovascular reserve capacity (CVRC). Eight cases were positive in the M-SPECT study. One week after bypass: The resting CBF increased in seven cases. Four showed preoperative positive M-SPECT. Eight cases showed improvement of the CVRC. Twelve cases were positive in M-SPECT, and two were negative in the preoperative M-SPECT. Three months after bypass: Thirteen cases showed improvement in the resting CBF, and fourteen cases showed improvement of the CVRC. Fourteen cases were positive in the M-SPECT, and among these, 6 were negative in the preoperative M-SPECT. There was a discrepancy between the improvement in CVRC and M-SPECT. M-SPECT study can provide information about the degree of hemodynamic compromise and effect of bypass surgery. (author)

  3. Is Daily Low-Dose Aspirin Safe to Take Following Laparoscopic Roux-en-Y Gastric Bypass for Obesity Surgery?

    Science.gov (United States)

    Kang, Xian; Hong, Dennis; Anvari, Mehran; Tiboni, Maria; Amin, Nalin; Gmora, Scott

    2017-05-01

    Laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery is a safe and effective procedure for patients with severe obesity. One potential complication of LRYGB is the development of marginal ulcers (MUs). Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to significantly increase the likelihood of developing marginal ulcers after surgery. However, the risk associated with low-dose aspirin consumption is not well defined. We examined the impact of daily low-dose aspirin (81 mg) on the development of marginal ulcers following LRYGB. A retrospective cohort design studied patients undergoing LRYGB surgery, between January 2009 and January 2013, at a single, high-volume bariatric center in Ontario, Canada. The marginal ulcer rate of patients taking low-dose aspirin after surgery was compared to that of the control patients who did not take any NSAID. Diagnosis of MU was confirmed by upper endoscopy in patients presenting with symptoms and a history indicative of marginal ulceration. A chi-square test of independence was performed to examine the difference in marginal ulcer rates. A total of 1016 patients underwent LRYGB. Patients taking aspirin were more likely to be male, older, and have diabetes than patients not taking NSAIDs. Of the 1016 patients, 145 (14.3%) took low-dose aspirin following LRYGB and the rest did not (n = 871, 85.7%). The incidence of marginal ulceration was not significantly different between the two treatment groups (12/145, 8.3% versus 90/871, 10.3%; p = 0.45). Patients treated with LRYGB at our institution were not at increased risk of marginal ulcer formation when taking low-dose aspirin after surgery.

  4. Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Wu, Q; Li, J V; Seyfried, F; le Roux, C W; Ashrafian, H; Athanasiou, T; Fenske, W; Darzi, A; Nicholson, J K; Holmes, E; Gooderham, N J

    2015-07-01

    Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.

  5. Investigation on the Core Bypass Flow in a Very High Temperature Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Hassan, Yassin

    2013-10-22

    Uncertainties associated with the core bypass flow are some of the key issues that directly influence the coolant mass flow distribution and magnitude, and thus the operational core temperature profiles, in the very high-temperature reactor (VHTR). Designers will attempt to configure the core geometry so the core cooling flow rate magnitude and distribution conform to the design values. The objective of this project is to study the bypass flow both experimentally and computationally. Researchers will develop experimental data using state-of-the-art particle image velocimetry in a small test facility. The team will attempt to obtain full field temperature distribution using racks of thermocouples. The experimental data are intended to benchmark computational fluid dynamics (CFD) codes by providing detailed information. These experimental data are urgently needed for validation of the CFD codes. The following are the project tasks: • Construct a small-scale bench-top experiment to resemble the bypass flow between the graphite blocks, varying parameters to address their impact on bypass flow. Wall roughness of the graphite block walls, spacing between the blocks, and temperature of the blocks are some of the parameters to be tested. • Perform CFD to evaluate pre- and post-test calculations and turbulence models, including sensitivity studies to achieve high accuracy. • Develop the state-of-the art large eddy simulation (LES) using appropriate subgrid modeling. • Develop models to be used in systems thermal hydraulics codes to account and estimate the bypass flows. These computer programs include, among others, RELAP3D, MELCOR, GAMMA, and GAS-NET. Actual core bypass flow rate may vary considerably from the design value. Although the uncertainty of the bypass flow rate is not known, some sources have stated that the bypass flow rates in the Fort St. Vrain reactor were between 8 and 25 percent of the total reactor mass flow rate. If bypass flow rates are on the

  6. Indications and Outcomes of Prophylactic and Therapeutic Extracranial-to-intracranial Arterial Bypass for Cerebral Revascularization

    Directory of Open Access Journals (Sweden)

    Emre Gazyakan, MD, MSc

    2015-04-01

    Conclusions: The collaboration of neurosurgeons and plastic surgeons in performing EC-IC bypass can result in excellent outcomes with a high bypass patency rate and few complications, particularly for prophylactic EC-IC bypass.

  7. Off-pump Coronary Artery Bypass Graft in a High Risk Patient ...

    African Journals Online (AJOL)

    On-pump coronary artery bypass graft (CABG) entails the use of cardiopulmonary bypass (CPB). The procedure is safe but it's not without complications like neurocognitive deficits, cerebrovascular accidents, myocardial ischemic injury and activation of inflammatory pathways that contribute to pulmonary, renal, hematologic ...

  8. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

    Directory of Open Access Journals (Sweden)

    Tulika Arora

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3, which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  9. Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control

    DEFF Research Database (Denmark)

    Fernandez-Cachon, María L; Pedersen, Søren L; Rigbolt, Kristoffer T

    2018-01-01

    AIM: To determine whether intestinal expression of guanylate cyclase activator 2A (GUCA2A) and guanylate cyclase activator 2B (GUCA2B) genes is regulated in obese humans following Roux-en-Y gastric bypass (RYGB), and to evaluate the corresponding guanylin (GN) and uroguanylin (UGN) peptides...... for potentially contributing to the beneficial metabolic effects of RYGB. METHODS: Enteroendocrine cells were harvested peri- and post-RYGB, and GUCA2A/GUCA2B mRNA expression was compared. GN, UGN and their prohormones (proGN, proUGN) were administered subcutaneously in normal-weight mice to evaluate effects...... on food intake. GN and UGN, as well as their prohormones, were evaluated for effects on glucose-stimulated insulin secretion (GSIS) in rat pancreatic islets and perfused rat pancreas. RESULTS: GUCA2A and GUCA2B mRNA expression was significantly upregulated in enteroendocrine cells after RYGB. Peripheral...

  10. DNA polymerase zeta cooperates with polymerases kappa and iota in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients.

    Science.gov (United States)

    Ziv, Omer; Geacintov, Nicholas; Nakajima, Satoshi; Yasui, Akira; Livneh, Zvi

    2009-07-14

    Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase eta, the POLH gene product. A deficiency in DNA polymerase eta due to germ-line mutations in POLH causes the hereditary disease xeroderma pigmentosum variant (XPV), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer. XPV cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase zeta cooperates with DNA polymerases kappa and iota to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases zeta and kappa, but not iota, protect XPV cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load.

  11. DNA polymerase ζ cooperates with polymerases κ and ι in translesion DNA synthesis across pyrimidine photodimers in cells from XPV patients

    Science.gov (United States)

    Ziv, Omer; Geacintov, Nicholas; Nakajima, Satoshi; Yasui, Akira; Livneh, Zvi

    2009-01-01

    Human cells tolerate UV-induced cyclobutane pyrimidine dimers (CPD) by translesion DNA synthesis (TLS), carried out by DNA polymerase η, the POLH gene product. A deficiency in DNA polymerase η due to germ-line mutations in POLH causes the hereditary disease xeroderma pigmentosum variant (XPV), which is characterized by sunlight sensitivity and extreme predisposition to sunlight-induced skin cancer. XPV cells are UV hypermutable due to the activity of mutagenic TLS across CPD, which explains the cancer predisposition of the patients. However, the identity of the backup polymerase that carries out this mutagenic TLS was unclear. Here, we show that DNA polymerase ζ cooperates with DNA polymerases κ and ι to carry out error-prone TLS across a TT CPD. Moreover, DNA polymerases ζ and κ, but not ι, protect XPV cells against UV cytotoxicity, independently of nucleotide excision repair. This presents an extreme example of benefit-risk balance in the activity of TLS polymerases, which provide protection against UV cytotoxicity at the cost of increased mutagenic load. PMID:19564618

  12. Sodium/hydrogen-exchanger inhibition during cardioplegic arrest and cardiopulmonary bypass: an experimental study.

    Science.gov (United States)

    Cox, Charles S; Sauer, Henning; Allen, Steven J; Buja, L Maximilian; Laine, Glen A

    2002-05-01

    We sought to determine whether pretreatment with a sodium/hydrogen-exchange inhibitor (EMD 96 785) improves myocardial performance and reduces myocardial edema after cardioplegic arrest and cardiopulmonary bypass. Anesthetized dogs (n = 13) were instrumented with vascular catheters, myocardial ultrasonic crystals, and left ventricular micromanometers to measure preload recruitable stroke work, maximum rate of pressure rise (positive and negative), and left ventricular end-diastolic volume and pressure. Cardiac output was measured by means of thermodilution. Myocardial tissue water content was determined from sequential biopsy. After baseline measurements, hypothermic (28 degrees C) cardiopulmonary bypass was initiated. Cardioplegic arrest (4 degrees C Bretschneider crystalloid cardioplegic solution) was maintained for 2 hours, followed by reperfusion-rewarming and separation from cardiopulmonary bypass. Preload recruitable stroke work and myocardial tissue water content were measured at 30, 60, and 120 minutes after bypass. EMD 96 785 (3 mg/kg) was given 15 minutes before bypass, and 2 micromol was given in the cardioplegic solution. Control animals received the same volume of saline vehicle. Arterial-coronary sinus lactate difference was similar in both animals receiving EMD 96 785 and control animals, suggesting equivalent myocardial ischemia in each group. Myocardial tissue water content increased from baseline in both animals receiving EMD 96 785 and control animals with cardiopulmonary bypass and cardioplegic arrest but was statistically lower in animals receiving EMD 96 785 compared with control animals (range, 1.0%-1.5% lower in animals receiving EMD 96 785). Preload recruitable stroke work decreased from baseline (97 +/- 2 mm Hg) at 30 (59 +/- 6 mm Hg) and 60 (72 +/- 9 mm Hg) minutes after cardiopulmonary bypass and cardioplegic arrest in control animals; preload recruitable stroke work did not decrease from baseline (98 +/- 2 mm Hg) in animals receiving

  13. Familial X/Y Translocation Encompassing ARSE in Two Moroccan Siblings with Sensorineural Deafness.

    Science.gov (United States)

    Amasdl, Saadia; Smaili, Wiam; Natiq, Abdelhafid; Hassani, Amale; Sbiti, Aziza; Agadr, Aomar; Sanlaville, Damien; Sefiani, Abdelaziz

    2017-01-01

    Unbalanced translocations involving X and Y chromosomes are rare and associated with a contiguous gene syndrome. The clinical phenotype is heterogeneous including mainly short stature, chondrodysplasia punctata, ichthyosis, hypogonadism, and intellectual disability. Here, we report 2 brothers with peculiar gestalt, short stature, and hearing loss, who harbor an X/Y translocation. Physical examination, brainstem acoustic potential evaluation, bone age, hormonal assessment, and X-ray investigations were performed. Because of their dysmorphic features, karyotyping, FISH, and aCGH were carried out. The probands had short stature, hypertelorism, midface hypoplasia, sensorineural hearing loss, normal intelligence as well as slight radial and ulnar bowing with brachytelephalangy. R-banding identified a derivative X chromosome with an abnormally expanded short arm. The mother was detected as a carrier of the same aberrant X chromosome. aCGH disclosed a 3.1-Mb distal deletion of chromosome region Xp22.33pter. This interval encompasses several genes, especially the short stature homeobox (SHOX) and arylsulfatase (ARSE) genes. The final karyotype of the probands was: 46,Y,der(X),t(X;Y)(p22;q12).ish der(X)(DXYS129-,DXYS153-)mat.arr[hg19] Xp22.33(61091_2689408)×1mat,Xp22.33(2701273_3258404)×0mat,Yq11.222q12 (21412851_59310245)×2. Herein, we describe a Moroccan family with a maternally inherited X/Y translocation and discuss the genotype-phenotype correlations according to the deleted genes. © 2017 S. Karger AG, Basel.

  14. El estigma del suicidio vivencias de pacientes y familiares con intentos de autolisis The stigma of suicide: the experiences of patients with suicide attempts and their families

    Directory of Open Access Journals (Sweden)

    Carme Ferré-Grau

    2011-09-01

    Full Text Available El objetivo del artículo es describir y analizar las percepciones subjetivas y las experiencias vividas de las personas con uno o varios intentos de suicidio y sus familiares. Investigación cualitativa utilizando una perspectiva socio-antropológica, mediante entrevistas en profundidad a cuatro pacientes con intentos de suicidio diagnosticados de depresión mayor, según criterios diagnósticos del DSMIV y seis familiares. Resultados: El intento de suicidio conlleva la aceptación de la enfermedad depresiva tanto por parte del paciente como del familiar, produciéndose un cambio en la imagen personal, familiar y social, este cambio de identidad genera aspectos estigmatizadores. El estigma en relación a los intentos de suicidio, aumenta el sufrimiento individual y familiar, dificulta el uso oportuno de los servicios de salud, la búsqueda de ayuda y la evolución del proceso. Conclusión: Los profesionales de enfermería deben desmitificar conceptos y orientar a la familia para la recuperación de la persona con intentos de suicidio.The objective of this article is to describe and analyze the subjective perceptions and experiences of people with one or more suicide attempts and their families. Qualitative research using socio-anthropological approach through in-depth interviews to four patients with suicide attempts, diagnosed with major depression according to DSM-IV criteria and six relatives. Results: The suicide attempt leads to acceptance of depressive illness by both the patient and family by changing personal, family and social image. This change of identity generates stigmatizing aspects. The stigma related to suicide attempts, increase individual and family suffering, impedes the timely use of health services, seeking help and the evolution of the process. Conclusion: Nursing professionals should demystify some concepts and guide the family for the recovery of the person attempting suicide

  15. 21 CFR 870.4210 - Cardiopulmonary bypass vascular catheter, cannula, or tubing.

    Science.gov (United States)

    2010-04-01

    ..., or tubing. 870.4210 Section 870.4210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 870.4210 Cardiopulmonary bypass vascular catheter, cannula, or tubing. (a) Identification. A cardiopulmonary bypass vascular catheter, cannula, or tubing is a device used in cardiopulmonary surgery to...

  16. Precatheterization Use of P2Y12 Inhibitors in Non-ST-Elevation Myocardial Infarction Patients Undergoing Early Cardiac Catheterization and In-Hospital Coronary Artery Bypass Grafting: Insights From the National Cardiovascular Data Registry®.

    Science.gov (United States)

    Badri, Marwan; Abdelbaky, Amr; Li, Shuang; Chiswell, Karen; Wang, Tracy Y

    2017-09-22

    Current guidelines recommend early P2Y 12 inhibitor administration in non-ST-elevation myocardial infarction, but it is unclear if precatheterization use is associated with longer delays to coronary artery bypass grafting (CABG) or higher risk of post-CABG bleeding and transfusion. This study examines the patterns and outcomes of precatheterization P2Y 12 inhibitor use in non-ST-elevation myocardial infarction patients who undergo CABG. Retrospective analysis was done of 20 304 non-ST-elevation myocardial infarction patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry (2009-2014) who underwent catheterization within 24 hours of admission and CABG during the index hospitalization. Using inverse probability-weighted propensity adjustment, we compared time from catheterization to CABG, post-CABG bleeding, and transfusion rates between patients who did and did not receive precatheterization P2Y 12 inhibitors. Among study patients, 32.9% received a precatheterization P2Y 12 inhibitor (of these, 2.2% were given ticagrelor and 3.7% prasugrel). Time from catheterization to CABG was longer among patients who received precatheterization P2Y 12 inhibitor (median 69.9 hours [25th, 75th percentiles 28.2, 115.8] versus 43.5 hours [21.0, 71.8], P ST-elevation myocardial infarction patients who undergo early catheterization and in-hospital CABG. Despite longer delays to surgery, the majority of pretreated patients proceed to CABG <3 days postcatheterization. Precatheterization P2Y 12 inhibitor use is associated with higher risks of postoperative bleeding and transfusion. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  17. RNA binding and replication by the poliovirus RNA polymerase

    International Nuclear Information System (INIS)

    Oberste, M.S.

    1988-01-01

    RNA binding and RNA synthesis by the poliovirus RNA-dependent RNA polymerase were studied in vitro using purified polymerase. Templates for binding and RNA synthesis studies were natural RNAs, homopolymeric RNAs, or subgenomic poliovirus-specific RNAs synthesized in vitro from cDNA clones using SP6 or T7 RNA polymerases. The binding of the purified polymerase to poliovirion and other RNAs was studied using a protein-RNA nitrocellulose filter binding assay. A cellular poly(A)-binding protein was found in the viral polymerase preparations, but was easily separated from the polymerase by chromatography on poly(A) Sepharose. The binding of purified polymerase to 32 P-labeled ribohomopolymeric RNAs was examined, and the order of binding observed was poly(G) >>> poly(U) > poly(C) > poly(A). The K a for polymerase binding to poliovirion RNA and to a full-length negative strand transcript was about 1 x 10 9 M -1 . The polymerase binds to a subgenomic RNAs which contain the 3' end of the genome with a K a similar to that for virion RNA, but binds less well to 18S rRNA, globin mRNA, and subgenomic RNAs which lack portions of the 3' noncoding region

  18. Jejunal gluconeogenesis associated with insulin resistance level and its evolution after Roux-en-Y gastric bypass.

    Science.gov (United States)

    Gutierrez-Repiso, Carolina; Garcia-Serrano, Sara; Moreno-Ruiz, Francisco J; Alcain-Martinez, Guillermo; Rodriguez-Pacheco, Francisca; Garcia-Fuentes, Eduardo

    2017-04-01

    Intestinal gluconeogenesis (GNG) may play an important role in glucose homeostasis, but there is little information about the condition in humans. To study the relationship between intestinal GNG and insulin resistance, its association with the evolution of morbidly obese patients after bariatric surgery, and the effect of insulin and or leptin. Regional university hospital, Malaga (Spain). Jejunal mRNA expression of genes involved in GNG was analyzed in 3 groups of morbidly obese patients who underwent Roux-en-Y gastric bypass: with low insulin resistance (MO-low-IR), with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2D). Also, intestinal epithelial cells (IEC) from MO-low-IR were incubated with different doses of insulin and or leptin. In MO-high-IR, glutaminase, phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6 Pase), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 α), and sterol regulatory element-binding proteins 1 c (SREBP-1 c) expressions were significantly higher than in MO-low-IR. In MO-metf-T2 D, only PEPCK was significantly lower than in MO-high-IR. In IEC, an incubation with a high glucose and insulin dose produced an increase of PEPCK and SREBP-1 c, and a decrease of glutaminase, fructose 1,6-bisphosphatase (FBPase), and PGC-1 α expression. At high doses of leptin, G6 Pase and FBPase were significantly increased. The improvement of insulin resistance 3 months after bariatric surgery was positively associated with high G6 Pase and FBPase expression. mRNA expression of genes involved in GNG is increased in the jejunum of MO-high-IR, and regulated by insulin and or leptin. High mRNA expression of genes involved in GNG is associated with a better evolution of insulin resistance after bariatric surgery. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  19. A domain of the Klenow fragment of Escherichia coli DNA polymerase I has polymerase but no exonuclease activity.

    Science.gov (United States)

    Freemont, P S; Ollis, D L; Steitz, T A; Joyce, C M

    1986-09-01

    The Klenow fragment of DNA polymerase I from Escherichia coli has two enzymatic activities: DNA polymerase and 3'-5' exonuclease. The crystal structure showed that the fragment is folded into two distinct domains. The smaller domain has a binding site for deoxynucleoside monophosphate and a divalent metal ion that is thought to identify the 3'-5' exonuclease active site. The larger C-terminal domain contains a deep cleft that is believed to bind duplex DNA. Several lines of evidence suggested that the large domain also contains the polymerase active site. To test this hypothesis, we have cloned the DNA coding for the large domain into an expression system and purified the protein product. We find that the C-terminal domain has polymerase activity (albeit at a lower specific activity than the native Klenow fragment) but no measurable 3'-5' exonuclease activity. These data are consistent with the hypothesis that each of the three enzymatic activities of DNA polymerase I from E. coli resides on a separate protein structural domain.

  20. Rural Bypass of Critical Access Hospitals in Iowa: Do Visiting Surgical Specialists Make a Difference?

    Science.gov (United States)

    Weigel, Paula A M; Ullrich, Fred; Ward, Marcia M

    2018-02-01

    Rural bypass for elective surgical procedures is a challenge for critical access hospitals, yet there are opportunities for rural hospitals to improve local retention of surgical candidates through alternative approaches to developing surgery lines of business. In this study we examine the effect of visiting surgical specialists on the odds of rural bypass. Discharge data from the 2011 State Inpatient Databases and State Ambulatory Surgery Databases for Iowa were linked to outreach data from the Office of Statewide Clinical Education Programs and Iowa Physician Information System to model the effect of surgeon specialist supply on rural patients' decision to bypass rural critical access hospitals. Patients in rural communities with a local general surgeon were more likely to be retained in a community than to bypass. Those in communities with visiting general surgeons were more likely to bypass, as were those in communities with visiting urologists and obstetricians. Patients in communities with visiting ophthalmologists and orthopedic surgeons were at higher odds of being retained for their elective surgeries. In addition to known patient and local hospital factors that have an influence on bypass behavior among rural patients seeking elective surgery, availability of surgeon specialists also plays an important role in whether patients bypass or not. Visiting ophthalmologists and orthopedic surgeons were associated with less bypass, as was having local general surgeons. Visiting general surgeons, urologists, and obstetricians were associated with greater odds of bypass. © 2016 National Rural Health Association.

  1. Effects of graphite surface roughness on bypass flow computations for an HTGR

    Energy Technology Data Exchange (ETDEWEB)

    Tung, Yu-Hsin, E-mail: touushin@gmail.com [Idaho National Laboratory, P.O. Box 1625, M.S. 3855, Idaho Falls, ID (United States); Johnson, Richard W., E-mail: Rich.Johnson@inl.gov [Idaho National Laboratory, P.O. Box 1625, M.S. 3855, Idaho Falls, ID (United States); Sato, Hiroyuki, E-mail: sato.hiroyuki09@jaea.go.jp [Idaho National Laboratory, P.O. Box 1625, M.S. 3855, Idaho Falls, ID (United States)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer CFD calculations are made of bypass flow between graphite blocks in HTGR. Black-Right-Pointing-Pointer Several turbulence models are employed to compare to friction and heat transfer correlations. Black-Right-Pointing-Pointer Parameters varied include bypass gap width and surface roughness. Black-Right-Pointing-Pointer Surface roughness causes increases in max fuel and coolant temperatures. Black-Right-Pointing-Pointer Surface roughness does not cause increase in outlet coolant temperature variation. - Abstract: Bypass flow in a prismatic high temperature gas reactor (HTGR) occurs between graphite blocks as they sit side by side in the core. Bypass flow is not intentionally designed to occur in the reactor, but is present because of tolerances in manufacture, imperfect installation and expansion and shrinkage of the blocks from heating and irradiation. It is desired to increase the knowledge of the effects of such flow; it has been suggested that it may be as much as 20% of the total helium coolant flow [INL Report 2007, INL/EXT-07-13289]. Computational fluid dynamic (CFD) simulations can provide estimates of the scale and impacts of bypass flow. Previous CFD calculations have examined the effects of bypass gap width, level and distribution of heat generation and effects of shrinkage. The present contribution examines the effects of graphite surface roughness on the bypass flow for different relative roughness factors for three gap widths. Such calculations should be validated using specific bypass flow measurements. While such experiments are currently underway for the specific reference prismatic HTGR design for the next generation nuclear plant (NGNP) program of the U.S. Dept. of Energy, the data are not yet available. To enhance confidence in the present calculations, wall shear stress and heat transfer results for several turbulence models and their associated wall treatments are first compared for steady flow in a

  2. Arterial pressure during cardiopulmonary bypass is not associated with acute kidney injury

    DEFF Research Database (Denmark)

    Kandler, K; Jensen, M E; Nilsson, J C

    2015-01-01

    BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is common and is associated with increased mortality. We wanted to investigate if the arterial pressure or the use of norepinephrine during cardiopulmonary bypass were associated with AKI. METHODS: A retrospective analysis of patients who...... underwent coronary artery bypass grafting with or without concomitant procedures was conducted. AKI was defined using the RIFLE criteria. Data on arterial pressure and use of norepinephrine during cardiopulmonary bypass were entered in a binary logistic regression model to control for possible perioperative...... and in higher amounts, during cardiopulmonary bypass, in patients who developed AKI. These differences in arterial pressures and use of norepinephrine between the groups were not found to be significant when entered in the binary logistic regression model. CONCLUSION: No independent relationship between...

  3. Rankine cycle load limiting through use of a recuperator bypass

    Science.gov (United States)

    Ernst, Timothy C.

    2011-08-16

    A system for converting heat from an engine into work includes a boiler coupled to a heat source for transferring heat to a working fluid, a turbine that transforms the heat into work, a condenser that transforms the working fluid into liquid, a recuperator with one flow path that routes working fluid from the turbine to the condenser, and another flow path that routes liquid working fluid from the condenser to the boiler, the recuperator being configured to transfer heat to the liquid working fluid, and a bypass valve in parallel with the second flow path. The bypass valve is movable between a closed position, permitting flow through the second flow path and an opened position, under high engine load conditions, bypassing the second flow path.

  4. Numerical simulation of an alternative to prevent hydrates formation in a bypass section

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Lucilla Coelho; Oliveira Junior, Joao Americo Aguirre; Fonte, Clarissa Bergman [Engineering Simulation and Scientific Software Ltda. (ESSS), Florianopolis, SC (Brazil); Silva, Fabricio Soares da; Moraes, Carlos Alberto Capela [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil)

    2012-07-01

    This work presents the use of Computational Fluid Dynamics to evaluate the feasibility of MEG (monoethylene glycol) injection as an alternative to prevent hydrate formation in a bypass section, present in an inlet module of a separation device of a subsea separation system. As the bypass section is open to the main pipeline, MEG will probably be dragged due to secondary flows generated by the main flow stream. The MEG removal rate is estimated, as well as the internal heat transfer between the currents and the heat loss to the external environment in order to estimate the temperature in the equipment. In a first step, the MEG removal was evaluated considering the heat transfer between the liquid phase (composed of water, oil and MEG) and the gas phase as well as the heat transfer by forced convection to the external environment. In a second step, the influence of a thermal insulation layer around the bypass line, reducing the heat loss to the external environment, was studied. Both simulations (with or without thermal insulation) showed the establishment of secondary flows in the open connection between the main line and bypass line, promoting the removal of MEG from the bypass section and enabling other components of the liquid phase and/or gas to enter in the bypass line. This MEG removal is faster when thermal isolation was considered, due to the fact that higher temperatures are established in the bypass, maintaining the liquid phase with lower densities and viscosities. With regard to temperature, the insulation was able to keep higher temperatures at the bypass line than those obtained without insulation, indicating that the combination of MEG injection and thermal insulation may be able to avoid the critical condition for hydrate formation. (author)

  5. 21 CFR 870.4270 - Cardiopulmonary bypass cardiotomy suction line blood filter.

    Science.gov (United States)

    2010-04-01

    ... blood filter. 870.4270 Section 870.4270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Devices § 870.4270 Cardiopulmonary bypass cardiotomy suction line blood filter. (a) Identification. A cardiopulmonary bypass cardiotomy suction line blood filter is a device used as part of a gas exchange (oxygenator...

  6. Two distinct modes of RecA action are required for DNA polymerase V-catalyzed translesion synthesis.

    Science.gov (United States)

    Pham, Phuong; Seitz, Erica M; Saveliev, Sergei; Shen, Xuan; Woodgate, Roger; Cox, Michael M; Goodman, Myron F

    2002-08-20

    SOS mutagenesis in Escherichia coli requires DNA polymerase V (pol V) and RecA protein to copy damaged DNA templates. Here we show that two distinct biochemical modes for RecA protein are necessary for pol V-catalyzed translesion synthesis. One RecA mode is characterized by a strong stimulation in nucleotide incorporation either directly opposite a lesion or at undamaged template sites, but by the absence of lesion bypass. A separate RecA mode is necessary for translesion synthesis. The RecA1730 mutant protein, which was identified on the basis of its inability to promote pol V (UmuD'(2)C)-dependent UV-mutagenesis, appears proficient for the first mode of RecA action but is deficient in the second mode. Data are presented suggesting that the two RecA modes are "nonfilamentous". That is, contrary to current models for SOS mutagenesis, formation of a RecA nucleoprotein filament may not be required for copying damaged DNA templates. Instead, SOS mutagenesis occurs when pol V interacts with two RecA molecules, first at a 3' primer end, upstream of a template lesion, where RecA mode 1 stimulates pol V activity, and subsequently at a site immediately downstream of the lesion, where RecA mode 2 cocatalyzes lesion bypass. We posit that in vivo assembly of a RecA nucleoprotein filament may be required principally to target pol V to a site of DNA damage and to stabilize the pol V-RecA interaction at the lesion. However, it is only a RecA molecule located at the 3' filament tip, proximal to a damaged template base, that is directly responsible for translesion synthesis.

  7. Duodenum inclusion in alimentary transit for preventing or correcting nutritional deficiencies resulting from Roux-en-y gastric bypass in obesity treatment.

    Science.gov (United States)

    Ceneviva, Reginaldo

    2016-01-01

    Nutritional and metabolic complications can develop after Roux-en-Y gastric bypass (RYGB) when there is an exaggerated response to the anatomical and functional changes or when there is inadequate nutritional supplementation. Severe malnutrition is rare, but deficiencies of vitamin B12, iron, calcium and thiamin, metabolic bone disease and gallstones are common after RYGB. Shortage of vitamin B12, iron, calcium and also cholelithiasis are caused at least partially by excluding the duodenum and proximal jejunum from food transit. We designed a new procedure, with the maintenance of the duodenum and proximal jejunum in the gastrointestinal transit through interposition of jejunal loop, as a primary operation to prevent such deficiencies or as corrective surgery for severe malnutrition after RYGB with failure in responding to conservative treatment. Complicações nutricionais e metabólicas podem se desenvolver após a derivação gástrica em Y de Roux (DGYR) quando há uma resposta exagerada às mudanças anatômicas e funcionais ou quando há suplementação nutricional inadequada. A desnutrição grave é rara, mas deficiências de vitamina B12, ferro, cálcio e tiamina, doença óssea metabólica e cálculos biliares são comuns após a DGYR. Dessas deficiências mencionadas, a de vitamina B12, de ferro, de cálcio e também a colelitíase, são causadas, ao menos parcialmente, pela exclusão do duodeno e jejuno proximal. Um novo procedimento com a manutenção do duodeno e do jejuno proximal no trânsito gastrointestinal, mediante interposição de alça jejunal, foi idealizado como operação primária para prevenir essas deficiências ou como cirurgia corretiva de desnutrição grave após DGYR com falha na resposta a exaustivas tentativas de tratamento conservador.

  8. Polymerase study: Improved detection of Salmonella and Campylobacter through the optimized use of DNA polymerases in diagnostic real-time PCR

    DEFF Research Database (Denmark)

    Søndergaard, Mette Sofie Rousing; Löfström, Charlotta; Al-Habib, Zahra Fares Sayer

    DNA extractions and intermediate or bad with the crude extractions, while TaKaRa ExTaq HS only performed well with the purest extractions of fecal samples and intermediate with semi-automated magnetic beads based extracted fecal samples. In conclusion, our data shows that exchanging the DNA polymerase......Diagnostic analyses of foodborne pathogens are increasingly based on molecular methods such as PCR, which can improve the sensitivity and reduce the analysis time. The core of PCR is the enzyme performing the reaction: the DNA polymerase. Changing the polymerase can influence the sensitivity...... commercially available polymerases and four master mixes in two validated PCR assays, for Campylobacter and Salmonella, respectively, to develop more sensitive, robust and cost effective assays. The polymerases were screened on purified DNA and the five best performing, for each PCR assay, were then applied...

  9. As relações familiares do adolescente ofensor sexual Adolescente ofensor sexual y família Family relations of the sexual offender adolescent

    Directory of Open Access Journals (Sweden)

    Liana Fortunato Costa

    2013-04-01

    de distanciamiento y autoritarismo. Una mejor comprensión de la violencia presente en las relaciones familiares de ese adolescente es fundamental, porque una característica de eses sujetos es la falta de habilidad social, y ese aspecto proviene de un proceso pobre de vinculación con sus padres.This text deals with a qualitative research about family relations of the sexual offender adolescent, with emphasis on the paternal figures, and is based on the interviews that precede the offer of a group intervention with the adolescents and their families. The interviews were conducted with seven adolescents and their mothers. Three nuclei results were interpreted: the family interaction of this adolescent is organized to guarantee the survival of the family; this adolescent presents an intense and paradoxical relation with his mother; there is an extremely poor living relation and affective link with the father. We conclude that the intra-family sexual violence made by the adolescents is linked with the family affective dynamics of distance and authoritarianism. A better comprehension of the violence present in the family relations of this adolescent is of fundamental importance because one of their characteristics is the lack of social ability, which originates from a poor process of linking with their parents.

  10. Target vessel detection by epicardial ultrasound in off-pump coronary bypass surgery.

    Science.gov (United States)

    Hayakawa, Masato; Asai, Tohru; Kinoshita, Takeshi; Suzuki, Tomoaki; Shiraishi, Shoichiro

    2013-01-01

    The detection of embedded coronary arteries is difficult especially in off-pump coronary bypass surgery. From June 2010, we introduced high-frequency epicardial ultrasound (ECUS) to assess and evaluate embedded arteries during off-pump coronary bypass surgery. Between June 2010 and June 2011, a total of 89 consecutive patients underwent isolated coronary bypass surgery at our institution. The patients consisted of 72 men and 17 women with a mean age of 67.9 years. We routinely use the VeriQC system (MediStim, Oslo, Norway) to detect the target vessels in the operation. The patients were assigned to one of two groups, depending on whether ECUS was used in the operation (n = 10, ECUS group) or not (n = 79, non-ECUS group). We analyzed the impact of introducing the ECUS in terms of operative outcome. All patients underwent revascularization using the off-pump technique without emergent conversion to cardiopulmonary bypass during surgery. The total number of distal anastomoses was 299, and 12 target vessels could not be identified either visually or on palpation. Thus, the frequency of the embedded coronary arteries was 4.01% (12/299 cases). The preoperative profiles of the two groups were not significantly different. Operation time was significantly longer in the ECUS group (P = 0.02). There were no significant differences in postoperative outcome between the two groups. In the present study, in which the target coronary arteries could not be detected either visually or on palpation in 12 (4.01%) of 299 cases, the use of high-frequency ECUS allowed all patients to undergo off-pump coronary bypass surgery without conversion to cardiopulmonary bypass during the operation. High-frequency ECUS is therefore useful in off-pump coronary bypass surgery.

  11. 78. Coronary bypass using bilateral internal mammary arteries in an achondroplast

    Directory of Open Access Journals (Sweden)

    Mohamed Abdulwahab Alassal

    2015-10-01

    Full Text Available Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is very rare. Shortage of veins and sometimes, inadequate vein quality can cause difficulties during surgery. Only two achondroplastic cases were reported in literature that underwent coronary bypass surgery, in which the left internal mammary artery and vein grafts were used. To the best of our knowledge using bilateral internal mammary arteries in such patients was not reported. We report here a 55 years old male achondroplastic dwarf who had triple vessels coronary disease that underwent successful coronary bypass surgery using bilateral mammary arteries. Anatomic and surgical challenges in achondroplasia are highlighted

  12. Assessment of extracranial-intracranial bypass patency with 64-slice multidetector computerized tomography angiography

    Energy Technology Data Exchange (ETDEWEB)

    Thines, Laurent [Lille University Hospital, Department of Neurosurgery, Lille (France); Toronto Western Hospital, Division of Neurosurgery and Department of Surgery, Toronto, ON (Canada); Toronto Western Hospital, University of Toronto Brain Vascular Malformation Study Group, Toronto, ON (Canada); Agid, Ronit; Da Costa, Leodante; Terbrugge, Karel G. [Toronto Western Hospital, Division of Neuroradiology, Department of Medical Imaging, Toronto, ON (Canada); Toronto Western Hospital, University of Toronto Brain Vascular Malformation Study Group, Toronto, ON (Canada); Dehdashti, Amir R.; Wallace, M.C.; Tymianski, Michael [Toronto Western Hospital, Division of Neurosurgery and Department of Surgery, Toronto, ON (Canada); Toronto Western Hospital, University of Toronto Brain Vascular Malformation Study Group, Toronto, ON (Canada)

    2009-08-15

    Extracranial-intracranial (EC/IC) bypass is a useful procedure for the treatment of cerebral vascular insufficiency or complex aneurysms. We explored the role of multidetector computed tomography angiography (MDCTA), instead of digital subtraction angiography (DSA), for the postoperative assessment of EC/IC bypass patency. We retrospectively analyzed a consecutive series of 21 MDCTAs from 17 patients that underwent 25 direct or indirect EC/IC bypass procedures between April 2003 and November 2007. Conventional DSA was available for comparison in 13 cases. MDCTA used a 64-slice MDCT scanner (Aquilion 64, Toshiba). The proximal and distal patencies were analyzed independently on MDCTA and DSA by a neuroradiologist and a neurosurgeon. The bypass was considered patent when the entire donor vessel was opacified without discontinuity from proximal to distal ends and was visibly in contact with the recipient vessel. MDCTA depicted the patency status in every patient. Bypasses were patent in 22 cases, stenosed in one, and occluded in two. DSA always confirmed the results of the MDCTA (sensitivity = 100%, 95% CI = 0.655-1.0; specificity 100%, 95% CI = 0.05-1.0). MDCTA is a non-invasive and accurate exam to assess the postoperative EC/IC bypass patency and is a promising technique in routine follow-up. (orig.)

  13. The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N

    2013-01-01

    β-cell function is improved in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to an exaggerated glucagon-like peptide 1 (GLP-1) secretion, but causality has not been established. The aim of this study...... consisted of two experimental days, allowing a meal test with infusion of saline or Ex-9 in random order. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased and glucagon secretion was augmented. GLP-1R blockade did not affect β......-cell function and meal-induced glucagon release before the operation, but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance...

  14. DNA repair synthesis in human fibroblasts requires DNA polymerase delta

    International Nuclear Information System (INIS)

    Nishida, C.; Reinhard, P.; Linn, S.

    1988-01-01

    When UV-irradiated cultured diploid human fibroblasts were permeabilized with Brij-58 then separated from soluble material by centrifugation, conservative DNA repair synthesis could be restored by a soluble factor obtained from the supernatant of similarly treated HeLa cells. Extensive purification of this factor yielded a 10.2 S, 220,000-dalton polypeptide with the DNA polymerase and 3'- to 5'-exonuclease activities reported for DNA polymerase delta II. Monoclonal antibody to KB cell DNA polymerase alpha, while binding to HeLa DNA polymerase alpha, did not bind to the HeLa DNA polymerase delta. Moreover, at micromolar concentrations N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate (BuPdGTP) and 2-(p-n-butylanilino)-2'-deoxyadenosine 5'-triphosphate (BuAdATP) were potent inhibitors of DNA polymerase alpha, but did not inhibit the DNA polymerase delta. Neither purified DNA polymerase alpha nor beta could promote repair DNA synthesis in the permeabilized cells. Furthermore, under conditions which inhibited purified DNA polymerase alpha by greater than 90%, neither monoclonal antibodies to DNA polymerase alpha, BuPdGTP, nor BuAdATP was able to inhibit significantly the DNA repair synthesis mediated by the DNA polymerase delta. Thus, it appears that a major portion of DNA repair synthesis induced by UV irradiation might be catalyzed by DNA polymerase delta. When xeroderma pigmentosum human diploid fibroblasts were utilized, DNA repair synthesis dependent upon ultraviolet light could be restored by addition of both T4 endonuclease V and DNA polymerase delta, but not by addition of either one alone

  15. The Application of Advanced Technique of Fan Frame Unit on High Bypass Ratio Aero Engine

    Directory of Open Access Journals (Sweden)

    Hou Peng

    2017-01-01

    Full Text Available High bypass ratio aero-engine was widely used on military and civil aviation domain, as the power of larger aircraft. Fan frame unit was the main bearing frame of high bypass ratio aero-engine, which composed of strut, HUB MID BOX and external bypass parts. Resin/composite was used on external bypass parts(acoustic liner, containment ring, fan outlet guide vane and fan case skin fillets, which not only reduced the weight and manufacturing cost, but also improved the noise absorption, containment and anti-fatigue ability of engine. The design of composite was becoming a key technique for high bypass ratio aero-engine. In special test of the core engine, nitrogen cooling system was designed to cool the cavity of spool. The nitrogen pipeline passed through the inner cavity of fan frame, then inserted into NO. 3 bearing seal, so nitrogen gas was sent into the cavity of core engine spool. On high bypass ratio aero-engine, the external bypass and fan frame inner cavity were the design platform for advanced technique, such as composite and pipeline system, and also provided guarantee for reliable operation of engine.

  16. Cost-utility analysis comparing laparoscopic vs open aortobifemoral bypass surgery

    Directory of Open Access Journals (Sweden)

    Krog AH

    2017-06-01

    Full Text Available Anne Helene Krog,1,2 Mehdi Sahba,3 Erik M Pettersen,4 Torbjørn Wisløff,5,6 Jon O Sundhagen,2 Syed SH Kazmi2 1Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 2Department of Vascular Surgery, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Oslo, 3Department of Vascular Surgery, Østfold Central Hospital, Kalnes, 4Department of Vascular Surgery, Sørlandet Hospital HF, Kristiansand, 5Department of Health Management and Health Economics, University of Oslo, 6Norwegian Institute of Public Health, Oslo, Norway Objectives: Laparoscopic aortobifemoral bypass has become an established treatment option for symptomatic aortoiliac obstructive disease at dedicated centers. Minimally invasive surgical techniques like laparoscopic surgery have often been shown to reduce expenses and increase patients’ health-related quality of life. The main objective of our study was to measure quality-adjusted life years (QALYs and costs after totally laparoscopic and open aortobifemoral bypass. Patients and methods: This was a within trial analysis in a larger ongoing randomized controlled prospective multicenter trial, Norwegian Laparoscopic Aortic Surgery Trial. Fifty consecutive patients suffering from symptomatic aortoiliac occlusive disease suitable for aortobifemoral bypass surgery were randomized to either totally laparoscopic (n=25 or open surgical procedure (n=25. One patient dropped out of the study before surgery. We measured health-related quality of life using the EuroQol (EQ-5D-5L questionnaire at 4 different time points, before surgery and for 6 months during follow-up. We calculated the QALYs gained by using the area under the curve for both groups. Costs were calculated based on prices for surgical equipment, vascular prosthesis and hospital stay. Results: We found a significantly higher increase in QALYs after laparoscopic vs open aortobifemoral bypass surgery, with a difference of 0.07 QALYs, (p=0

  17. COMPARISON OF SIX COMMERCIALLY-AVAILABLE DNA POLYMERASES FOR DIRECT PCR

    Directory of Open Access Journals (Sweden)

    Masashi Miura

    2013-12-01

    Full Text Available SUMMARY The use of a “direct PCR” DNA polymerase enables PCR amplification without any prior DNA purification from blood samples due to the enzyme's resistance to inhibitors present in blood components. Such DNA polymerases are now commercially available. We compared the PCR performance of six direct PCR-type DNA polymerases (KOD FX, Mighty Amp, Hemo KlenTaq, Phusion Blood II, KAPA Blood, and BIOTAQ in dried blood eluted from a filter paper with TE buffer. GoTaq Flexi was used as a standard DNA polymerase. PCR performance was evaluated by a nested PCR technique for detecting Plasmodium falciparum genomic DNA in the presence of the blood components. Although all six DNA polymerases showed resistance to blood components compared to the standard Taq polymerase, the KOD FX and BIOTAQ DNA polymerases were resistant to inhibitory blood components at concentrations of 40%, and their PCR performance was superior to that of other DNA polymerases. When the reaction mixture contained a mild detergent, only KOD FX DNA polymerase retained the original amount of amplified product. These results indicate that KOD FX DNA polymerase is the most resistant to inhibitory blood components and/or detergents. Thus, KOD FX DNA polymerase could be useful in serological studies to simultaneously detect antibodies and DNA in eluents for antibodies. KOD FX DNA polymerase is thus not limited to use in detecting malaria parasites, but could also be employed to detect other blood-borne pathogens.

  18. NMOS-Based Integrated Modular Bypass for Use in Solar Systems (NIMBUS: Intelligent Bypass for Reducing Partial Shading Power Loss in Solar Panel Applications

    Directory of Open Access Journals (Sweden)

    Pieter Bauwens

    2016-06-01

    Full Text Available NMOS-based Integrated Modular Bypass for Use in Solar systems (NIMBUS is designed as a replacement for the traditional bypass diode, used in common solar panels. Because of the series connection between the individual solar cells, the power output of a photovoltaic (PV panel will drop disproportionally under partial shading. Currently, this is solved by dividing the PV panel into substrings, each with a diode bypass placed in parallel. This allows an alternative current path. However, the diodes still have a significant voltage drop (about 350 mV, and due to the fairly large currents in a panel, the diodes are dissipating power that we would rather see at the output of the panel. The NIMBUS chip, being a low-voltage-drop switch, aims to replace these diodes and, thus, reduce that power loss. NIMBUS is a smart bypass: a completely stand-alone system that detects the failing of one or more cells and activates when necessary. It is designed for a 100-mV voltage drop under a 5-A load current. When two or more NIMBUS chips are placed in parallel, an internal synchronization circuit ensures proper operation to provide for larger load currents. This paper will elaborate on the operation, design and implementation of the NIMBUS chip, as well as on the first measurements.

  19. A Time Interval of More Than 18 Months Between a Pregnancy and a Roux-en-Y Gastric Bypass Increases the Risk of Iron Deficiency and Anaemia in Pregnancy.

    Science.gov (United States)

    Crusell, Mie; Nilas, Lisbeth; Svare, Jens; Lauenborg, Jeannet

    2016-10-01

    The aim of the study is to explore the impact of time between Roux-en-Y gastric bypass (RYGB) and pregnancy on obstetrical outcome and nutritional derangements. In a retrospective cross-sectional study of pregnant women admitted for antenatal care at two tertiary hospitals, we examined 153 women with RYGB and a singleton pregnancy of at least 24 weeks. The women were stratified according to a pregnancy pregnancy, gestational hypertension, length of pregnancy, mode of delivery and foetal birth weight. The two groups were comparable regarding age, parity and prepregnancy body mass index. The frequency of iron deficiency anaemia (ferritin pregnancy outcome or birth weight between the two groups. A long surgery-to-pregnancy time interval after a RYGB increases the risk of iron deficiency anaemia but not of other nutritional deficits. Time interval does not seem to have an adverse effect on the obstetrical outcome, including intrauterine growth restriction. Specific attention is needed on iron deficit with increasing surgery-to-pregnancy time interval.

  20. Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding

    Directory of Open Access Journals (Sweden)

    Corbo Laura

    2001-11-01

    Full Text Available Abstract Background The yeast yCCR4 factor belongs to the CCR4-NOT transcriptional regulatory complex, in which it interacts, through its leucine-rich repeat (LRR motif with yPOP2. Recently, yCCR4 was shown to be a component of the major cytoplasmic mRNA deadenylase complex, and to contain a fold related to the Mg2+-dependent endonuclease core. Results Here, we report the identification of nineteen yCCR4-related proteins in eukaryotes (including yeast, plants and animals, which all contain the yCCR4 endonuclease-like fold, with highly conserved CCR4-specific residues. Phylogenetic and genomic analyses show that they form four distinct families, one of which contains the yCCR4 orthologs. The orthologs in animals possess a leucine-rich repeat domain. We show, using two-hybrid and far-Western assays, that the human member binds to the human yPOP2 homologs, i.e. hCAF1 and hPOP2, in a LRR-dependent manner. Conclusions We have identified the mammalian orthologs of yCCR4 and have shown that the human member binds to the human yPOP2 homologs, thus strongly suggesting conservation of the CCR4-NOT complex from yeast to human. All members of the four identified yCCR4-related protein families show stricking conservation of the endonuclease-like catalytic motifs of the yCCR4 C-terminal domain and therefore constitute a new family of potential deadenylases in mammals.

  1. Numerical and experimental investigation on labyrinth seal mechanism for bypass flow reduction in prismatic VHTR core

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Su-Jong, E-mail: paper80@snu.ac.r [Department of Nuclear Engineering, Seoul National University, San 56-1, Daehak-Dong, Kwanak-Gu, Seoul 151-742 (Korea, Republic of); Lee, Jeong-Hun [Department of Nuclear Engineering, Seoul National University, San 56-1, Daehak-Dong, Kwanak-Gu, Seoul 151-742 (Korea, Republic of); Lee, Sang-Moon [Department of Mechanical Engineering, Inha University, 253 Yonghyun-Dong, Nam-Gu, Incheon 402-751 (Korea, Republic of); Tak, Nam-il; Kim, Min-Hwan [Korea Atomic Energy Research Institute, 150-1 Deokjin-Dong, 1045 Daedeokdaero, Yuseong, Daejeon 305-353 (Korea, Republic of); Kim, Kwang-Yong [Department of Mechanical Engineering, Inha University, 253 Yonghyun-Dong, Nam-Gu, Incheon 402-751 (Korea, Republic of); Park, Goon-Cherl [Department of Nuclear Engineering, Seoul National University, San 56-1, Daehak-Dong, Kwanak-Gu, Seoul 151-742 (Korea, Republic of)

    2013-09-15

    Highlights: • Bypass flow reduction method was developed by applying labyrinth seal mechanism. • Grooves on side walls of replaceable reflector block were made. • Design of the grooved wall of the reflector block was optimized by the RSA method. • The flow resistance of the bypass gap rose from 18.04 to 26.24 by the optimization. • The bypass ratios at the inlet and outlet were reduced by 36.19% and 14.66%, respectively. -- Abstract: Core bypass flow in block type very high temperature reactor (VHTR) occurs due to the inevitable gaps between the hexagonal core blocks for the block installation and refueling. Since the core bypass flow affects the reactor safety and efficiency, it should be minimized to enhance the core thermal margin. In this regard, the core bypass flow reduction method applying the labyrinth seal mechanism was developed and optimized by using the single-objective shape optimization method. Response surface approximation (RSA) method was adopted as the optimization method. Side wall of the replaceable reflector block was redesigned and response surface approximate model was adopted to optimize the shape of the reflector wall. Computational fluid dynamics (CFD) analyses were carried out not only to assess the limitation of existing method of bypass flow reduction, but also to optimize the design of a newly developed reduction method. The experiment with Seoul National University (SNU) multi-block experimental facility was performed to demonstrate the performance of the reduction method. It was found that the effect of the existing bypass flow reduction method by sealing the bypass gap exit was restricted nearby the lower region of the core. However, the flow resistance factor of the bypass gap increased from 18.04 to 26.24 by the optimized reduction method. The results of the performance test showed that the bypass flow distribution was reduced throughout the entire core regions. The bypass flow ratios at the inlet and the outlet were

  2. "Candy cane syndrome:" an underappreciated cause of abdominal pain and nausea after Roux-en-Y gastric bypass surgery.

    Science.gov (United States)

    Aryaie, Amir H; Fayezizadeh, Mojtaba; Wen, Yuxiang; Alshehri, Mohammed; Abbas, Mujjahid; Khaitan, Leena

    2017-09-01

    "Candy cane" syndrome (a blind afferent Roux limb at the gastrojejunostomy) has been implicated as a cause of abdominal pain, nausea, and emesis after Roux-n-Y gastric bypass (RYGB) but remains poorly described. To report that "candy cane" syndrome is real and can be treated effectively with revisional bariatric surgery SETTING: All patients underwent "candy cane" resection at University Hospitals of Cleveland. All patients who underwent resection of the "candy cane" between January 2011 and July 2015 were included. All had preoperative workup to identify "candy cane" syndrome. Demographic data; pre-, peri-, and postoperative symptoms; data regarding hospitalization; and postoperative weight loss were assessed through retrospective chart review. Data were analyzed using Student's t test and χ 2 analysis where appropriate. Nineteen patients had resection of the "candy cane" (94% female, mean age 50±11 yr), within 3 to 11 years after initial RYGB. Primary presenting symptoms were epigastric abdominal pain (68%) and nausea/vomiting (32%), particularly with fibrous foods and meats. On upper gastrointestinal study and endoscopy, the afferent blind limb was the most direct outlet from the gastrojejunostomy. Only patients with these preoperative findings were deemed to have "candy cane" syndrome. Eighteen (94%) cases were completed laparoscopically. Length of the "candy cane" ranged from 3 to 22 cm. Median length of stay was 1 day. After resection, 18 (94%) patients had complete resolution of their symptoms (Psyndrome is a real phenomenon that can be managed safely with excellent outcomes with resection of the blind afferent limb. A thorough diagnostic workup is paramount to proper identification of this syndrome. Surgeons should minimize the size of the blind afferent loop left at the time of initial RYGB. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  3. The mechanism of action of poly (ADP-ribose) polymerases inhibitors and its application perspective

    International Nuclear Information System (INIS)

    Huang Xiaofei; Cao Jianping

    2008-01-01

    Poly (ADP-ribose) polymerases (PARP) constitute a family of enzymes involved in the regulation of many cellular processes. It plays a vital role in many physical and physiopathological processes,, In the past ten years scientists have conducted extensive research on PARP and its inhibitors, among which the role of PARP inhihitors in radiosensitization, chemopotentiation and neuroprotection have been placed close attention. There have been several PARP inhibitors entering the clinical trials, which predicts its sound application perspectives. (authors)

  4. Polymerase Gamma Disease through the Ages

    Science.gov (United States)

    Saneto, Russell P.; Naviaux, Robert K.

    2010-01-01

    The most common group of mitochondrial disease is due to mutations within the mitochondrial DNA polymerase, polymerase gamma 1 ("POLG"). This gene product is responsible for replication and repair of the small mitochondrial DNA genome. The structure-function relationship of this gene product produces a wide variety of diseases that at times, seems…

  5. High sensitive RNA detection by one-step RT-PCR using the genetically engineered variant of DNA polymerase with reverse transcriptase activity from hyperthermophilies.

    Science.gov (United States)

    Okano, Hiroyuki; Baba, Misato; Kawato, Katsuhiro; Hidese, Ryota; Yanagihara, Itaru; Kojima, Kenji; Takita, Teisuke; Fujiwara, Shinsuke; Yasukawa, Kiyoshi

    2018-03-01

    One-step RT-PCR has not been widely used even though some thermostable DNA polymerases with reverse transcriptase (RT) activity were developed from bacterial and archaeal polymerases, which is owing to low cDNA synthesis activity from RNA. In the present study, we developed highly-sensitive one-step RT-PCR using the single variant of family A DNA polymerase with RT activity, K4pol L329A (L329A), from the hyperthermophilic bacterium Thermotoga petrophila K4 or the 16-tuple variant of family B DNA polymerase with RT activity, RTX, from the hyperthermophilic archaeon Thermococcus kodakarensis. Optimization of reaction condition revealed that the activities for cDNA synthesis and PCR of K4pol L329A and RTX were highly affected by the concentrations of MgCl 2 and Mn(OCOCH 3 ) 2 as well as those of K4pol L329A or RTX. Under the optimized condition, 300 copies/μl of target RNA in 10 μl reaction volumes were successfully detected by the one-step RT-PCR with K4pol L329A or RTX, which was almost equally sensitive enough compared with the current RT-PCR condition using retroviral RT and thermostable DNA polymerase. Considering that K4pol L329A and RTX are stable even at 90-100°C, our results suggest that the one-step RT-PCR with K4pol L329A or RTX is more advantageous than the current one. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. [Coronary artery bypass grafting without use of cardiopulmonary bypass].

    Science.gov (United States)

    Mujanović, Emir; Bergsland, Jacob; Hadziselimović, Mehdin; Softić, Muniba; Azabagic, Azur; Stanimirović-Mujanović, Sanja; Kabil, Emir

    2002-01-01

    Although it is possible to find a number of comparative studies in the world literature discussing the results of coronary artery bypass surgery (CABG) with and without cardiopulmonary bypass (CPB), until now such analysis has not been made in Bosnia and Herzegovina. The main aim of this scientific work was to compare morbidity and mortality, need for blood transfusions, length of stay in the intensive care unit and total length of hospitalisation in two groups of patients operated with these methods. One hundred and four patients with coronary artery disease operated in Cardiovascular Clinic Tuzla, from September, 1998 to September 2002 divided in two groups, were included in this study. There were 52 patients in the first group operated with CPB and 52 patients in the second group operated without CPB. The groups were matched for gender, age, ejection fraction and preoperative risk factors. The incidence of postoperative complications was lower in patients operated without CPB (5.77% vs. 21.15%). The mortality rate was reduced in patients operated without CPB (0.00% vs. 5.76%). There were reduced need for transfusion in patients operated without CPB (0.28 vs. 1.11 units of blood). The average time spent on respirators was shorter in patients operated without CPB (1.50 vs. 4.76 hours). The average time of total hospitalisation was also shorter in patients operated withouth CPB (6.53 vs. 8.13 days). In conclusion CABG without CPB has many advantages compared to the conventional method. Mortality and morbidity are reduced and there is less need for transfusion. The time spent on mechanical ventilation is reduced and less time is spent in intensive care and the total hospitalisation time is also less.

  7. Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a Randomized Clinical Trial.

    Science.gov (United States)

    Kalinowski, Piotr; Paluszkiewicz, Rafał; Ziarkiewicz-Wróblewska, Bogna; Wróblewski, Tadeusz; Remiszewski, Piotr; Grodzicki, Mariusz; Krawczyk, Marek

    2017-11-01

    The aim of the study was to compare the influence of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized clinical trial (NCT01806506). Rapid weight loss and malabsorption after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may impair liver function. Sixty-six morbidly obese patients randomized to SG or RYGB were included in a secondary outcome analysis. Intraoperative liver biopsies were categorized with NAFLD Activity Score (NAS) and liver function tests were done before surgery and after 1, 6 and 12 months. NASH was present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess weight loss was 68.7 ± 19.7% after SG and 62.8 ± 18.5% after RYGB (P > 0.05). At 1 month international normalized ratio (INR) increased after RYGB (0.98 ± 0.05 vs 1.14 ± 0.11; P liver function than after SG.

  8. CHANGES IN QUALITY OF LIFE AFTER SHORT AND LONG TERM FOLLOW-UP OF ROUX-EN-Y GASTRIC BYPASS FOR MORBID OBESITY

    Directory of Open Access Journals (Sweden)

    Rafael M. LAURINO NETO

    2013-09-01

    Full Text Available Context It is unclear whether health-related quality of life (HRQL is sustained in a long-term follow-up of morbidly obese patients who underwent Roux-en-Y gastric bypass (RYGB. Objective This study aims to analyze the HRQL changes following RYGB in short and long-term follow-up. Methods We compared the health-related quality of life among three separate patient groups, using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36. Group A - 50 preoperative morbidly obese patients; Group B - 50 RYGB patients 1-2 years post-surgery; Group C - 50 RYGB patients more than 7 years post-surgery. Results The groups were similar for gender, age and body mass index before surgery. We observed that physical functioning, social function, emotional role functioning and mental health scales did not vary between the three groups. The physical role functioning scale was unchanged in the short-term and decreased compared to the preoperative scale in the long-term follow-up. Bodily pain improved after the operation but returned to the initial level after 7 years. The vitality and general health perceptions improved after the operation and maintained these results after 7 years compared with the preoperative perceptions. Conclusions RYGB improved health-related quality of life in three SF-36 domains (bodily pain, general health perceptions and vitality in the short-term and two SF-36 domains (general health perceptions and vitality in the long-term.

  9. Autologous blood sequestration using a double venous reservoir bypass circuit and polymerized hemoglobin prime.

    Science.gov (United States)

    Neragi-Miandoab, Siyamek; Guerrero, J Luis; Vlahakes, Gus J

    2002-01-01

    Cardiac surgery often necessitates transfusion of homologous blood. Hemoglobin based oxygen carrying solutions (HBOCs) transport oxygen, suggesting use in cardiopulmonary bypass. HBOC was used in a novel oxygenator double-reservoir circuit that permits acute sequestration of a portion of the autologous blood volume during bypass. Two groups of seven mongrel dogs each were studied in an experimental bypass model using global myocardial ischemia and cardioplegia protection: HBOC group, initial venous return drained to a separate reservoir and hypothermic bypass was conducted with HBOC containing perfusate in a second bypass reservoir; Control group, crystalloid prime in a conventional circuit. Hemodynamics and metabolic and hematologic parameters were measured before and 60 min after aortic clamp removal and reinfusion of sequestered autologous blood. Blood gases, base excess, hematocrit, total hemoglobin, and platelet counts were measured. In the HBOC group, metabolic acidosis did not occur, and ventricular function was preserved. Net conservation of platelets was noted at study conclusion: control 33+/-13 x 10(3) per mm3 versus HBOC 48+/-13 x 10(3), p conservation of the platelet mass occurs, a portion of which is not exposed to the deleterious effects of hypothermia and cardiopulmonary bypass.

  10. Inhibition of Vascular c-Jun N-Terminal Kinase 2 Improves Obesity-Induced Endothelial Dysfunction After Roux-en-Y Gastric Bypass.

    Science.gov (United States)

    Doytcheva, Petia; Bächler, Thomas; Tarasco, Erika; Marzolla, Vincenzo; Engeli, Michael; Pellegrini, Giovanni; Stivala, Simona; Rohrer, Lucia; Tona, Francesco; Camici, Giovanni G; Vanhoutte, Paul M; Matter, Christian M; Lutz, Thomas A; Lüscher, Thomas F; Osto, Elena

    2017-11-14

    Roux-en-Y gastric bypass (RYGB) reduces obesity-associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c-Jun N-terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity-induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. After 7 weeks of a high-fat high-cholesterol diet, obese rats underwent RYGB or sham surgery; sham-operated ad libitum-fed rats received, for 8 days, either the control peptide D-TAT or the JNK peptide inhibitor D-JNKi-1 (20 mg/kg per day subcutaneous). JNK peptide inhibitor D-JNKi-1 treatment improved endothelial vasorelaxation in response to insulin and glucagon-like peptide-1, as observed after RYGB. Obesity increased aortic phosphorylation of JNK2, but not of JNK1. RYGB and JNK peptide inhibitor D-JNKi-1 treatment blunted aortic JNK2 phosphorylation via activation of glucagon-like peptide-1-mediated signaling. The inhibitory phosphorylation of insulin receptor substrate-1 was reduced, whereas the protein kinase B/endothelial NO synthase pathway was increased and oxidative stress was decreased, resulting in improved vascular NO bioavailability. Decreased aortic JNK2 phosphorylation after RYGB rapidly improves obesity-induced endothelial dysfunction. Pharmacological JNK inhibition mimics the endothelial protective effects of RYGB. These findings highlight the therapeutic potential of novel strategies targeting vascular JNK2 against the severe cardiovascular disease associated with obesity. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  11. Quantitation of RHD by real-time polymerase chain reaction for determination of RHD zygosity and RHD mosaicism/chimerism

    DEFF Research Database (Denmark)

    Krog, Grethe Risum; Clausen, Frederik Banch; Dziegiel, Morten Hanefeld

    2007-01-01

    Determination of RHD zygosity of the spouse is crucial in preconception counseling of families with history of hemolytic disease of the fetus and newborn caused by anti-D. RHD zygosity can be determined by quantitative real-time polymerase chain reaction (PCR) basically by determining RHD dosage,......, and this feature is relevant in investigating RHD mosaicism and chimerism....

  12. Using the Hepatitis C Virus RNA-Dependent RNA Polymerase as a Model to Understand Viral Polymerase Structure, Function and Dynamics

    Directory of Open Access Journals (Sweden)

    Ester Sesmero

    2015-07-01

    Full Text Available Viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as Hepatitis C virus (HCV, human immunodeficiency virus (HIV and Ebola virus. For this reason they are key targets for therapies to treat viral infections. Although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. These features allow their functional properties to be compared, with the goal of broadly applying the knowledge acquired from studying specific viral polymerases to other viral polymerases about which less is known. Here we review the structural and functional properties of the HCV RNA-dependent RNA polymerase (NS5B in order to understand the fundamental processes underlying the replication of viral genomes. We discuss recent insights into the process by which RNA replication occurs in NS5B as well as the role that conformational changes play in this process.

  13. Biliary reconstruction options for bile duct stricture in patients with prior Roux-en-Y reconstruction.

    Science.gov (United States)

    Shah, Mihir M; Martin, Benjamin M; Stetler, Jamil L; Patel, Ankit D; Davis, S Scott; Lin, Edward; Sarmiento, Juan M

    2017-09-01

    Comprehensive description with illustrations of the 4 biliary reconstruction options for bile duct injury in patients with history of Roux-en-Y gastric bypass. Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  14. Plastic surgery improves long-term weight control after bariatric surgery.

    Science.gov (United States)

    Balagué, Nicolas; Combescure, Christophe; Huber, Olivier; Pittet-Cuénod, Brigitte; Modarressi, Ali

    2013-10-01

    The positive impact of Roux-en-Y gastric bypass on weight, comorbidities, and health-related quality of life is well documented. However, 50 percent of patients regain some of the lost weight after 2 years with Roux-en-Y gastric bypass and present a mean weight regain of 10 to 15 percent after several years, partially losing the previously obtained benefits. The authors hypothesize that body contouring could decrease weight regain, leading to better long-term weight control after Roux-en-Y gastric bypass. In a matched control study, variations in weight for 98 patients with body contouring after Roux-en-Y gastric bypass were compared with those of 102 matched control patients with Roux-en-Y gastric bypass alone. Data were collected prospectively at 1, 3, 6, 9, 12, and 18 months after Roux-en-Y gastric bypass and then yearly until 7 years. After a massive mean weight loss of 45.2 kg during the first 2 years after Roux-en-Y gastric bypass, patients with Roux-en-Y gastric bypass alone presented a higher continuous mean weight regain than those with Roux-en-Y gastric bypass and body contouring (1.78 kg/year versus 0.51 kg/year of weight regain, respectively; p = 0.001). After 7 years, patients with Roux-en-Y gastric bypass presented significantly higher mean weight regain than patients with Roux-en-Y gastric bypass and body contouring (i.e., 10.8 percent versus 3.6 percent mean weight gain, respectively; p weight of 2.04 kg by body contouring, the weight regain was 22.9 kg for patients with Roux-en-Y gastric bypass alone and only 6.2 kg for those with Roux-en-Y gastric bypass and body contouring. The authors demonstrated that patients with body contouring present better long-term weight control after Roux-en-Y gastric bypass. Therefore, body contouring must be considered as a reconstructive operation in the treatment of morbid obesity. Therapeutic, III.

  15. Sodium flow measurement in large pipelines of sodium cooled fast breeder reactors with bypass type flow meters

    International Nuclear Information System (INIS)

    Rajan, K.K.; Jayakumar, T.; Aggarwal, P.K.; Vinod, V.

    2016-01-01

    Highlights: • Bypass type permanent magnet flow meters are more suitable for sodium flow measurement. • A higher sodium velocity through the PMFM sensor will increase its sensitivity and resolution. • By modifying the geometry of bypass line, higher sodium velocity through sensor is achieved. • With optimized geometry the sensitivity of bypass flow meter system was increased by 70%. - Abstract: Liquid sodium flow through the pipelines of sodium cooled fast breeder reactor circuits are measured using electromagnetic flow meters. Bypass type flow meter with a permanent magnet flow meter as sensor in the bypass line is selected for the flow measurement in the 800 NB main secondary pipe line of 500 MWe Prototype Fast Breeder Reactor (PFBR), which is at the advanced stage of construction at Kalpakkam. For increasing the sensitivity of bypass flow meters in future SFRs, alternative bypass geometry was considered. The performance enhancement of the proposed geometry was evaluated by experimental and numerical methods using scaled down models. From the studies it is observed that the new configuration increases the sensitivity of bypass flow meter system by around 70%. Using experimentally validated numerical tools the volumetric flow ratio for the bypass configurations is established for the operating range of Reynolds numbers.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  17. Morphologic and Biochemical Changes in Dogs After Portacaval Shunt Plus Bile Fistula or Ileal Bypass: Failure of Bile Fistula or Ileal Bypass to Prevent Hepatocyte Atrophy

    Science.gov (United States)

    Thompson, Jon S.; Porter, Kendrick A.; Hayashida, Nobuo; McNamara, Donald J.; Parker, Thomas S.; Russell, William J. I.; Francavilla, Antonio; Starzl, Thomas E.

    2010-01-01

    External biliary fistula (BF) or ileal bypass (IB) was performed in dogs at the time of or 2 weeks after portacaval shunt (PCS). The pathologic changes in the dog livers 2 to 4 weeks later were compared to those caused by PCS alone. Histopathologic differences between PCS alone vs. PCS plus BF or IB could not be found. Thus, the experiments did not confirm recent observations by others in rats that BF prevents or reverses the hepatic injury of PCS. As estimated by plasma mevalonic acid determinations, the increase in hepatic cholesterol synthesis that is characteristic after BF or IB was suppressed in animals with PCS. BF and IB reduced but did not eliminate the postprandial elevation in serum bile acid that occurs after PCS. The findings have possible relevance in planning the treatment of patients with familial hypercholesterolemia with the combined use of PCS and IB. PMID:6862371

  18. Endovascular Placement of an Extraluminal Femoropopliteal Bypass Graft in Human Cadavers

    International Nuclear Information System (INIS)

    Maynar, Manuel; Llorens, Rafael; Lopez-Sanchez, Carmen; Garcia-Martinez, Virginio; Qian Zhong; Lopera, Jorge; Castaneda, Wilfrido R.

    2005-01-01

    Purpose. A method to create an extraluminal femoropopliteal bypass graft using endovascular techniques was evaluated in situ on cadaver extremities in an attempt to develop a minimally invasive alternative technique for the management of infrainguinal occlusive arterial disease. Methods. The endovascular placement of an extraluminal femoropopliteal bypass graft was undertaken in 5 cadaver legs. Following percutaneous access to the popliteal artery (PA) or common femoral artery (CFA), a Rosch-Uchida needle was used to perforate the vascular wall, followed by the creation of an extraluminal tract using a looped wire and catheter. Once the desired level was reached the needle was again used to perforate the vascular wall of the proximal superficial femoral artery (SFA) or PA depending on the access used. Self-expanding expanded polytetrafluoroethylene (ePTFE) stent-grafts were then deployed to establish the extraluminal femoropopliteal bypass connecting the two arterial puncture sites. Following dilatation of the stent-graft, angiography was performed to assess the endoprostheses and to look for contrast leaks. Results. Technical success was achieved in all 5 legs. Procedure time varied from 15 to 30 min. The angiographic studies performed immediately after completion of the bypass procedure showed patency of the grafts with no evidence of kinking or leakage in any of the cases. Conclusion. This study has proved that the endovascular placement of an extraluminal femoropopliteal bypass graft in human cadaver legs using endovascular techniques under fluoroscopic control is technically feasible

  19. Accurate Digital Polymerase Chain Reaction Quantification of Challenging Samples Applying Inhibitor-Tolerant DNA Polymerases.

    Science.gov (United States)

    Sidstedt, Maja; Romsos, Erica L; Hedell, Ronny; Ansell, Ricky; Steffen, Carolyn R; Vallone, Peter M; Rådström, Peter; Hedman, Johannes

    2017-02-07

    Digital PCR (dPCR) enables absolute quantification of nucleic acids by partitioning of the sample into hundreds or thousands of minute reactions. By assuming a Poisson distribution for the number of DNA fragments present in each chamber, the DNA concentration is determined without the need for a standard curve. However, when analyzing nucleic acids from complex matrixes such as soil and blood, the dPCR quantification can be biased due to the presence of inhibitory compounds. In this study, we evaluated the impact of varying the DNA polymerase in chamber-based dPCR for both pure and impure samples using the common PCR inhibitor humic acid (HA) as a model. We compared the TaqMan Universal PCR Master Mix with two alternative DNA polymerases: ExTaq HS and Immolase. By using Bayesian modeling, we show that there is no difference among the tested DNA polymerases in terms of accuracy of absolute quantification for pure template samples, i.e., without HA present. For samples containing HA, there were great differences in performance: the TaqMan Universal PCR Master Mix failed to correctly quantify DNA with more than 13 pg/nL HA, whereas Immolase (1 U) could handle up to 375 pg/nL HA. Furthermore, we found that BSA had a moderate positive effect for the TaqMan Universal PCR Master Mix, enabling accurate quantification for 25 pg/nL HA. Increasing the amount of DNA polymerase from 1 to 5 U had a strong effect for ExTaq HS, elevating HA-tolerance four times. We also show that the average Cq values of positive reactions may be used as a measure of inhibition effects, e.g., to determine whether or not a dPCR quantification result is reliable. The statistical models developed to objectively analyze the data may also be applied in quality control. We conclude that the choice of DNA polymerase in dPCR is crucial for the accuracy of quantification when analyzing challenging samples.

  20. Familias con deficiencia mental educable: riesgo y salud familiar Familias com deficiências mentais educáveis: riscos e saúde familiar Families with educable mental deficiencies: Risks and family health

    Directory of Open Access Journals (Sweden)

    Gloria S Urbano Franco

    2011-12-01

    Full Text Available El conocimiento de la familia es esencial para su cuidado, máxime si algunos de sus miembros requieren de protección permanente porque sufren Deficiencia Mental Educable (DME. Objetivo: Determinar el Riesgo Familiar Total (RFT y el Grado de Salud Familiar (GSF de las familias con uno o más miembros con DME, de un Centro Educativo Distrital de Bogotá, 2007-2009. Esta investigación se apoya en las teorías de Riesgo Familiar Total de Amaya y Organización Sistémica de Friedemann. Metodología: Estudio descriptivo, cuantitativo, con n = 129 familias evaluadas con los instrumentos: "Riesgo Familiar Total: RFT: 6-69" y "Grado de Salud Familiar ISF: GEN-25" de Amaya. Resultados: Se encontraron 77% de familias nucleares (nucleares o nucleares modificadas en proporciones parecidas, con 66 % de sus miembros dependientes por edad o DME. El RFT calificó a las familias amenazadas en un 22% de la muestra y riesgo alto de 2%. El ISF: GEN-25 mostró que el 21% fueron clasificadas como familias organizadas, 34% como poco organizadas y 28% como poco satisfechas, aunque 43% mostraban que eran altamente organizadas, solo 27% estaban satisfechas. Conclusión: Por los riesgos descritos, la baja organización o la poca satisfacción, las familias requieren apoyo inmediato para mitigar los riesgos y asesoría de Enfermería en Salud Mental para mejorar la organización y satisfacción. Paralelamente, todas las familias, por su particularidad asociada con la presencia de DME, requieren de cuidado permanente y asesoría para cubrir las demandas de protección contra amenaza de crisis.Oconhecimento da família é essencial para seu cuidado, principalmente quando algum dos membros dela requer proteção permanente por causa de uma Deficiência Mental Educável (DME. Objetivo: Determinar o Risco Familiar Total (RTF e o Grau de Saúde Familiar (GSF das famílias que têm dois ou mais membros com DME, de um Centro Educacional Distrital de Bogotá, 2007-2009. Esta

  1. Quantum dots for a high-throughput Pfu polymerase based multi-round polymerase chain reaction (PCR).

    Science.gov (United States)

    Sang, Fuming; Zhang, Zhizhou; Yuan, Lin; Liu, Deli

    2018-02-26

    Multi-round PCR is an important technique for obtaining enough target DNA from rare DNA resources, and is commonly used in many fields including forensic science, ancient DNA analysis and cancer research. However, multi-round PCR is often aborted, largely due to the accumulation of non-specific amplification during repeated amplifications. Here, we developed a Pfu polymerase based multi-round PCR technique assisted by quantum dots (QDs). Different PCR assays, DNA polymerases (Pfu and Taq), DNA sizes and GC amounts were compared in this study. In the presence of QDs, PCR specificity could be retained even in the ninth-round amplification. Moreover, the longer and more complex the targets were, the earlier the abortion happened in multi-round PCR. However, no obvious enhancement of specificity was found in multi-round PCR using Taq DNA polymerase. Significantly, the fidelity of Pfu polymerase based multi-round PCR was not sacrificed in the presence of QDs. Besides, pre-incubation at 50 °C for an hour had no impact on multi-round PCR performance, which further authenticated the hot start effect of QDs modulated in multi-round PCR. The findings of this study demonstrated that a cost-effective and promising multi-round PCR technique for large-scale and high-throughput sample analysis could be established with high specificity, sensibility and accuracy.

  2. Preliminary Calculations of Bypass Flow Distribution in a Multi-Block Air Test

    International Nuclear Information System (INIS)

    Kim, Min Hwan; Tak, Nam Il

    2011-01-01

    The development of a methodology for the bypass flow assessment in a prismatic VHTR (Very High Temperature Reactor) core has been conducted at KAERI. A preliminary estimation of variation of local bypass flow gap size between graphite blocks in the NHDD core were carried out. With the predicted gap sizes, their influence on the bypass flow distribution and the core hot spot was assessed. Due to the complexity of gap distributions, a system thermo-fluid analysis code is suggested as a tool for the core thermo-fluid analysis, the model and correlations of which should be validated. In order to generate data for validating the bypass flow analysis model, an experimental facility for a multi-block air test was constructed at Seoul National University (SNU). This study is focused on the preliminary evaluation of flow distribution in the test section to understand how the flow is distributed and to help the selection of experimental case. A commercial CFD code, ANSYS CFX is used for the analyses

  3. Active bypass flow control for a seal in a gas turbine engine

    Science.gov (United States)

    Ebert, Todd A.; Kimmel, Keith D.

    2017-03-14

    An active bypass flow control system for controlling bypass compressed air based upon leakage flow of compressed air flowing past an outer balance seal between a stator and rotor of a first stage of a gas turbine in a gas turbine engine is disclosed. The active bypass flow control system is an adjustable system in which one or more metering devices may be used to control the flow of bypass compressed air as the flow of compressed air past the outer balance seal changes over time as the outer balance seal between the rim cavity and the cooling cavity wears In at least one embodiment, the metering device may include an annular ring having at least one metering orifice extending therethrough, whereby alignment of the metering orifice with the outlet may be adjustable to change a cross-sectional area of an opening of aligned portions of the outlet and the metering orifice.

  4. [Prevention of side effects and complications after operation for partial ileal bypass].

    Science.gov (United States)

    Mirchuk, K K; Sedletskiĭ, Iu I

    2014-01-01

    Side effects and complications of the application of partial ileal bypass used for dislipidemia were analyzed in 162 patients with atherosclerosis. It was shown, that the partial ileal bypass operation could lead to the development of series of undesirable side effects such as diarrhea, hypovitaminosis B12, off-state intestine enteritis. The application of modification of partial ileal bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve with the maintenance of its functions disposed the diarrhea and minimized the risk of the development of hypovitaminosis B12 after operation. It is possible to prevent the development of enteritis of off-state loop of the small intestine by using microanastomosis between off-state and functioning iliac intestine. The partial ileal bypass operation didn't influence on body weight, wouldn't increase the risk of stone formation in the gallbladder and kidneys. The risk of the development of hypovitaminosis B12 is minimal after operation.

  5. Exercise thallium-201 scintigraphy in evaluating aortocoronary bypass surgery

    International Nuclear Information System (INIS)

    Iskandrian, A.S.; Haaz, W.; Segal, B.L.; Kane, S.A.

    1981-01-01

    Thirty patients with recurrent symptoms after aortocoronary bypass graft surgery underwent angiography as well as exercise thallium 201 imaging. Exercise imaging has been shown to be highly specific (100 percent in our study) in evaluating patients after bypass surgery. Patients with complete revascularization have normal thallium 201 images. Similarly, exercise-induced defects are seen only in the presence of incomplete revascularization. There are patients, however, with incomplete revascularization with normal exercise images, but these generally limited to the right coronary artery or the diagonal vessels or their grafts

  6. Construct exploit constraint in crash analysis by bypassing canary

    Science.gov (United States)

    Huang, Ning; Huang, Shuguang; Huang, Hui; Chang, Chao

    2017-08-01

    Selective symbolic execution is a common program testing technology. Developed on the basis of it, some crash analysis systems are often used to test the fragility of the program by constructing exploit constraints, such as CRAX. From the study of crash analysis based on symbolic execution, this paper find that this technology cannot bypass the canary stack protection mechanisms. This paper makes the improvement uses the API hook in Linux. Experimental results show that the use of API hook can effectively solve the problem that crash analysis cannot bypass the canary protection.

  7. Cardiopulmonary bypass in pregnancy

    OpenAIRE

    Mukul Chandra Kapoor

    2014-01-01

    Cardiac surgery carried out on cardiopulmonary bypass (CPB) in a pregnant woman is associated with poor neonatal outcomes although maternal outcomes are similar to cardiac surgery in non-pregnant women. Most adverse maternal and fetal outcomes from cardiac surgery during pregnancy are attributed to effects of CPB. The CPB is associated with utero-placental hypoperfusion due to a number of factors, which may translate into low fetal cardiac output, hypoxia and even death. Better maternal and f...

  8. Basics of cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Manjula Sarkar

    2017-01-01

    Full Text Available Cardiopulmonary bypass (CPB provides a bloodless field for cardiac surgery. It incorporates an extracorporeal circuit to provide physiological support in which venous blood is drained to a reservoir, oxygenated and sent back to the body using a pump. Team effort between surgeon, perfusionist and anaesthesiologist is paramount for the successful use of CPB. However, it also has its share of complications and strategies to reduce these complications are the area of the current research.

  9. Sequential Vein Bypass Grafting is Not Associated with an Increase of Either In-hospital or Mid-term Adverse Events in Off-pump Coronary Artery Bypass Grafting

    Directory of Open Access Journals (Sweden)

    Fucheng Xiao

    2015-01-01

    Full Text Available Background: The impact of sequential vein bypass grafting on clinical outcomes is less known in off-pump coronary artery bypass grafting (CABG. We aimed to evaluate the effects of sequential vein bypass grafting on clinical outcomes in off-pump CABG. Methods: From October 2009 to September 2013 at the Fuwai Hospital, 127 patients with at least one sequential venous graft were matched with 127 patients of individual venous grafts only, using propensity score matching method to obtain risk-adjusted outcome comparison. In-hospital measurement was composite outcome of in-hospital death, myocardial infarction (MI, stroke, requirement for intra-aortic ballon pump (IABP assistance and prolonged ventilation. Major adverse cardiac events (MACEs: Death, MI or repeat revascularization and angina recurrence were considered as mid-term endpoints. Results: No significant difference was observed among the groups in baseline characteristics. Intraoperative mean blood flow per vein graft was 40.4 ml in individual venous grafts groups versus 59.5 ml in sequential venous grafts groups (P < 0.001. There were no differences between individual and sequential venous grafts groups with regard to composite outcome of in-hospital mortality, MI, stroke, IABP assistance and prolonged ventilation (11.0% vs. 14.2%, P = 0.45. Individual in-hospital measurement also did not differ significantly between the two groups. At about four years follow-up, the survival estimates free from MACEs (92.5% vs. 97.3%, P = 0.36 and survival rates free of angina recurrence (80.9% vs. 85.5%, P = 0.48 were similar among individual and sequential venous grafts groups with a mean follow-up of 22.5 months. In the Cox regression analysis, sequential vein bypass grafting was not identified as an independent predictor of both MACEs and angina recurrence. Conclusions: Compared to individual vein bypass grafting, sequential vein bypass grafting was not associated with an increase of either in

  10. GTP-dependent binding and nuclear transport of RNA polymerase II by Npa3 protein

    DEFF Research Database (Denmark)

    Staresincic, Lidija; Walker, Jane; Dirac-Svejstrup, A Barbara

    2011-01-01

    in yeast extracts. Indeed, Npa3 depletion in vivo affects nuclear localization of RNAPII; the polymerase accumulates in the cytoplasm. Npa3 is a member of the GPN-LOOP family of GTPases. Npa3 mutants that either cannot bind GTP or that bind but cannot hydrolyze it are inviable and unable to support nuclear...... transport of RNAPII. Surprisingly, we were unable to detect interactions between Npa3 and proteins in the classical importin a/ß pathway for nuclear import. Interestingly, Npa3-RNAPII binding is significantly increased by the addition of GTP or its slowly hydrolyzable analogue guanosine 5'-3-O......-(thio)triphosphate (GTP¿S). Moreover, the Npa3 mutant that binds GTP, but cannot hydrolyze it, binds RNAPII even in the absence of added GTP, whereas the mutant that cannot bind GTP is unable to bind the polymerase. Together, our data suggest that Npa3 defines an unconventional pathway for nuclear import of RNAPII, which...

  11. Bypassing BDD Construction for Reliability Analysis

    DEFF Research Database (Denmark)

    Williams, Poul Frederick; Nikolskaia, Macha; Rauzy, Antoine

    2000-01-01

    In this note, we propose a Boolean Expression Diagram (BED)-based algorithm to compute the minimal p-cuts of boolean reliability models such as fault trees. BEDs make it possible to bypass the Binary Decision Diagram (BDD) construction, which is the main cost of fault tree assessment....

  12. Video-assisted minimally invasive coronary operations without cardiopulmonary bypass : A multicenter study

    NARCIS (Netherlands)

    Benetti, F; Mariani, MA; Sani, G; Boonstra, PW; Grandjean, JG; Giomarelli, P; Toscano, M

    1996-01-01

    Objective: The need to avoid the risks associated with cardiopulmonary bypass has led to the interest in coronary operations without cardiopulmonary bypass, Patients and methods: From April 1994 to September 1995, 44 patients (mean age 63.3 +/- 10.0 years, range 43 to 83 years) were selected for

  13. Progress in Management of Sediment Bypassing at Coastal Inlets: Natural Bypassing, Weir Jetties, Jetty Spurs, and Engineering Aids in Design

    National Research Council Canada - National Science Library

    Seabergh, William C; Kraus, Nicholas C

    2003-01-01

    .... Artificial bypassing mimics or preserves the pathways of sediment in the littoral zone and harmonizes the requirement for deepening navigation channels within the context of the natural sediment...

  14. An active site aromatic triad in Escherichia coli DNA Pol IV coordinates cell survival and mutagenesis in different DNA damaging agents.

    Directory of Open Access Journals (Sweden)

    Ryan W Benson

    Full Text Available DinB (DNA Pol IV is a translesion (TLS DNA polymerase, which inserts a nucleotide opposite an otherwise replication-stalling N(2-dG lesion in vitro, and confers resistance to nitrofurazone (NFZ, a compound that forms these lesions in vivo. DinB is also known to be part of the cellular response to alkylation DNA damage. Yet it is not known if DinB active site residues, in addition to aminoacids involved in DNA synthesis, are critical in alkylation lesion bypass. It is also unclear which active site aminoacids, if any, might modulate DinB's bypass fidelity of distinct lesions. Here we report that along with the classical catalytic residues, an active site "aromatic triad", namely residues F12, F13, and Y79, is critical for cell survival in the presence of the alkylating agent methyl methanesulfonate (MMS. Strains expressing dinB alleles with single point mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in addition to its role in TLS, modulates DinB's accuracy in bypassing distinct lesions. The high bypass fidelity of prevalent alkylation lesions is evident even when the DinB active site performs error-prone NFZ-induced lesion bypass. The analyses carried out with the active site aromatic triad suggest that the DinB active site residues are poised to proficiently bypass distinctive DNA lesions, yet they are also malleable so that the accuracy of the bypass is lesion-dependent.

  15. Cognitive outcomes in elderly high-risk patients after off-pump versus conventional coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Jensen, Birte Ostergaard; Hughes, Pia; Rasmussen, Lars S

    2006-01-01

    It has been suggested that the risk of cerebral dysfunction is less with off-pump coronary artery bypass grafting (OPCAB) than with conventional coronary artery bypass grafting (CCAB). However, evidence for this statement is preliminary, and additional insight is needed.......It has been suggested that the risk of cerebral dysfunction is less with off-pump coronary artery bypass grafting (OPCAB) than with conventional coronary artery bypass grafting (CCAB). However, evidence for this statement is preliminary, and additional insight is needed....

  16. Pattern and predictors of dual antiplatelet use after coronary artery bypass graft surgery.

    Science.gov (United States)

    Mori, Makoto; Shioda, Kayoko; Yun, James J; Mangi, Abeel A; Darr, Umer; Geirsson, Arnar

    2018-02-01

    Resumption of dual antiplatelet therapy after coronary artery bypass grafting in patients presenting with acute coronary syndrome is recommended, but the current practice pattern in the United States remains unknown. We aimed to investigate the current pattern of dual antiplatelet therapy use after coronary artery bypass grafting at the Yale-New Haven Hospital. We conducted a single-center retrospective review of patients who presented with acute coronary syndrome and underwent coronary artery bypass grafting between 2014 and 2016. The primary outcome was hospital discharge with dual antiplatelet therapy. Mixed-effect multivariate logistic regression was used to evaluate predictors of dual antiplatelet therapy use or nonuse, accounting for surgeon-specific preference. The discriminatory ability of the model was evaluated with receiver operating characteristics analysis. Of 572 patients included, only 29% were discharged with dual antiplatelet therapy. In the mixed-effect multivariate model isolating surgeon preferences, increase in age (odds ratio, 0.95; 95% confidence interval, 0.92-0.98; P dual antiplatelet therapy use. Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting was associated with increased odds of dual antiplatelet therapy use (odds ratio, 31.5; 95% confidence interval, 12.8-77.2; P dual antiplatelet therapy use in patients with acute coronary syndrome who underwent coronary artery bypass grafting was low and variable among surgeons. The use or nonuse was guided by previously established risk factors of recurrent ischemia and bleeding, along with surgeon preference. Published by Elsevier Inc.

  17. La invención de la familia: supervivencia, anacronismo y ficción en la fotografía familiar del primer franquismo = Invention of family: survival, anachronism and fiction in family photography during Francoism

    Directory of Open Access Journals (Sweden)

    Mónica Alonso Riveiro

    2015-01-01

    Full Text Available A mediados del siglo XX la fotografía familiar se había popularizado en Europa. Ello produjo una modernización en los códigos de representación; se fotografía con más espontaneidad, los retratos pierden su carácter idealizado y solemne y, paulatinamente, desparece también el carácter ritual del acto fotográfico. En cambio, en la España del primer franquismo la fotografía familiar muestra una pervivencia de antiguos usos, técnicas y estéticas. Se mantienen valores anacrónicos (carácter ritual, confianza en su carácter probatorio y consideración como objeto de culto que remiten a la concepción decimonónica del medio.El presente estudio pretende, a partir de fotografías familiares españolas de esta época, identificar y describir estos anacronismos. También explicar cómo estos valores llevaron a los españoles a considerar la fotografía como el medio ideal para representar y (reconstruir la unidad de la familia, quebrada tras la guerra por el exilio o la muerte. In the middle of the 20th, family photography has been popular in Europe. This popularization led to a change in the codes of representation; the photos become more spontaneous, portraits lose their idealization and the act of shooting, gradually, lose their cult conception. In contrast, in Spain during the first years of Franco regime, family photography shows the survival of ancient practices, techniques  and aesthetics. Some anachronistic values that refer to the nineteenth-century conception of the medium, (ritual character, confidence in his probative value and the consideration as an cult item survives in photography.This paper demonstrates these anachronisms with a collection of family photographs from this period. Also explain how these values led the Spaniards to consider photography as the ideal for representing and (rebuild the unity of the family, broken after the war by exile or death.

  18. Preliminary Estimation of Local Bypass Flow Gap Sizes for a Prismatic VHTR Core

    International Nuclear Information System (INIS)

    Kim, Min Hwan; Jo, Chang Keun; Lee, Won Jae

    2009-01-01

    The Very High Temperature Reactor (VHTR) has been selected for the Nuclear Hydrogen Development and Demonstration (NHDD) project. In the VHTR design, core bypass flow has been one of key issues for core thermal margins and target temperature of the core outlet. The core bypass flow in the prismatic VHTR varies with the core life due to the irradiation shrinkage/ swelling and thermal expansion of the graphite blocks, which could be a significant proportion of the total core flow. Thus, accurate prediction of the bypass flow is of major importance in assuring the core thermal margin. To predict the bypass flow, first of all, local gap sizes between graphite blocks in the core should be determined. The objectives of this work are to develop a methodology for determining the gap sizes and to perform a preliminary evaluation for a reference reactor

  19. The Translesion Polymerase Pol η Is Required for Efficient Epstein-Barr Virus Infectivity and Is Regulated by the Viral Deubiquitinating Enzyme BPLF1.

    Science.gov (United States)

    Dyson, Ossie F; Pagano, Joseph S; Whitehurst, Christopher B

    2017-10-01

    Epstein-Barr virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. We previously showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis (TLS) pathway, a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument, indicating that BPLF1 may function both early and late during infection. The BPLF1 protein expresses deubiquitinating activity that is strictly conserved across the Herpesviridae ; mutation of the active site cysteine results in a loss of enzymatic activity. Infection with an EBV BPLF1 knockout virus results in decreased EBV infectivity. Polymerase eta (Pol η), a specialized DNA repair polymerase, functions in TLS and allows for DNA replication complexes to bypass lesions in DNA. Here we report that BPLF1 interacts with Pol η and that Pol η protein levels are increased in the presence of functional BPLF1. BPLF1 promotes a nuclear relocalization of Pol η molecules which are focus-like in appearance, consistent with the localization observed when Pol η is recruited to sites of DNA damage. Knockdown of Pol η resulted in decreased production of infectious virus, and further, Pol η was found to bind to EBV DNA, suggesting that it may allow for bypass of damaged viral DNA during its replication. The results suggest a mechanism by which EBV recruits cellular repair factors, such as Pol η, to sites of viral DNA damage via BPLF1, thereby allowing for efficient viral DNA replication. IMPORTANCE Epstein-Barr virus is the causative agent of infectious mononucleosis and infects approximately 90% of the world's population. It causes lymphomas in individuals with acquired and innate immune disorders and is strongly associated with Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphomas, nasopharyngeal carcinoma (NPC), and

  20. Noninvasive detection of coronary artery bypass graft patency by intravenous electron beam computed tomographic angiography.

    Science.gov (United States)

    Yamakami, Shoji; Toyama, Junji; Okamoto, Mitsuhiro; Matsushita, Toyoaki; Murakami, Yoshimasa; Ogata, Masaki; Ito, Shigenori; Fukutomi, Tatsuya; Okayama, Naotsuka; Itoh, Makoto

    2003-11-01

    This study evaluates the usefullness of intravenous electron beam computed tomographic angiography (EBA) for the detection of coronary artery bypass graft patency in 43 patients (33 men and 10 women, mean age, 65 years) who had coronary artery bypass graft surgery. EBA was performed a few days before selective bypass graft angiography (SGA). Forty axial cross-sections of angiographic images of the heart were acquired consecutively by an electrocardiographic trigger signal at 40% of the RR interval, which corresponds to the end-systolic phase. EBA data were reconstructed as a three-dimensional shaded surface display of the heart and bypass grafts. Detectability of the patency of bypass gratis was evaluated, taking selective angiographic images of the bypass grafts as a gold standard. One hundred and nine grafts (96%) out of 114 grafts were subjected to evaluation: 37 grafts were left internal mammary artery grafts (LIMA), 7 were right internal mammary artery grafts (RIMA), 6 were gastroepiploic artery grafts (GEA), 7 were free gastroepiploic artery grafts with venous drainage (free-GEA), 7 were radial artery grafts (RAG), and 45 were saphenous vein gratis (SVG). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBA were 98%, 100%, 100%, 91%, and 98%, respectively. EBA sampled at the end-systolic period was determined to be useful for the detection of coronary artery bypass graft patency and occlusion.