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Sample records for intensidad magnet-lift mlh

  1. Localization of MLH3 at the Centrosomes

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    Lennart M. Roesner

    2014-08-01

    Full Text Available Mutations in human DNA mismatch repair (MMR genes are commonly associated with hereditary nonpolyposis colorectal cancer (HNPCC. MLH1 protein heterodimerizes with PMS2, PMS1, and MLH3 to form MutLα, MutLβ, and MutLγ, respectively. We reported recently stable expression of GFP-linked MLH3 in human cell lines. Monitoring these cell lines during the cell cycle using live cell imaging combined with confocal microscopy, we detected accumulation of MLH3 at the centrosomes. Fluorescence recovery after photobleaching (FRAP revealed high mobility and fast exchange rates at the centrosomes as it has been reported for other DNA repair proteins. MLH3 may have a role in combination with other repair proteins in the control of centrosome numbers.

  2. Biochemical characterization of MLH3 missense mutations does not reveal an apparent role of MLH3 in Lynch syndrome

    DEFF Research Database (Denmark)

    Ou, Jianghua; Rasmussen, Merete; Westers, Helga

    2009-01-01

    for eight of these MLH3 UVs identified in suspected Lynch syndrome patients, we performed several biochemical tests. We determined the protein expression and stability, protein localization and interaction of the mutant MLH3 proteins with wildtype MLH1. All eight MLH3 UVs gave protein expression levels...... comparable with wildtype MLH3. Furthermore, the UV-containing proteins, in contrast to previous studies, were all localized normally in the nucleus and they interacted normally with wildtype MLH1. Our different biochemical assays yielded no evidence that the eight MLH3 UVs tested are the cause of hereditary...

  3. Three-dimensional micro assembly of a hinged nickel micro device by magnetic lifting and micro resistance welding

    International Nuclear Information System (INIS)

    Chang, Chun-Wei; Hsu, Wensyang

    2009-01-01

    The three-dimensional micro assembly of hinged nickel micro devices by magnetic lifting and micro resistance welding is proposed here. By an electroplating-based surface machining process, the released nickel structure with the hinge mechanism can be fabricated. Lifting of the released micro structure to different tilted angles is accomplished by controlling the positions of a magnet beneath the device. An in situ electro-thermal actuator is used here to provide the pressing force in micro resistance welding for immobilizing the tilted structure. The proposed technique is shown to immobilize micro devices at controlled angles ranging from 14° to 90° with respect to the substrate. Design parameters such as the electro-thermal actuator and welding beam width are also investigated. It is found that there is a trade-off in beam width design between large contact pressure and low thermal deformation. Different dominated effects from resistivity enhancement and contact area enlargement during the welding process are also observed in the dynamic resistance curves. Finally, a lifted and immobilized electro-thermal bent-beam actuator is shown to displace upward about 27.7 µm with 0.56 W power input to demonstrate the capability of electrical transmission at welded joints by the proposed 3D micro assembly technique

  4. Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

    Science.gov (United States)

    Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason W H; Sloane, Mathew A; Ward, Robyn L

    2015-06-01

    Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

  5. Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in patients with tumor MLH1 downregulation.

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    Pinto, Diana; Pinto, Carla; Guerra, Joana; Pinheiro, Manuela; Santos, Rui; Vedeld, Hege Marie; Yohannes, Zeremariam; Peixoto, Ana; Santos, Catarina; Pinto, Pedro; Lopes, Paula; Lothe, Ragnhild; Lind, Guro Elisabeth; Henrique, Rui; Teixeira, Manuel R

    2018-02-01

    Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2, has been identified as an alternative mechanism that predisposes to the development of Lynch syndrome. In the present work, we aimed to investigate the prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients with abnormal expression of the MLH1 protein in their tumors. In a series of 38 patients who met clinical criteria for Lynch syndrome genetic testing, with loss of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we screened for constitutional methylation of the MLH1 gene promoter using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in various biological samples. We found four (4/38; 10.5%) patients with constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated decreased MLH1 expression in the cases with constitutional methylation when compared with controls. We could infer the mosaic nature of MLH1 constitutional hypermethylation in tissues originated from different embryonic germ layers, and in one family we could show that it occurred de novo. We conclude that constitutional MLH1 methylation occurs in a significant proportion of patients who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic germline mutation. Furthermore, we provide evidence that MLH1 constitutional hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome families diagnosed in our institution, especially in patients with early onset or multiple primary tumors without significant family history. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions.

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    Ranjha, Lepakshi; Anand, Roopesh; Cejka, Petr

    2014-02-28

    MutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis.

  7. The Saccharomyces cerevisiae Mlh1-Mlh3 Heterodimer Is an Endonuclease That Preferentially Binds to Holliday Junctions*

    Science.gov (United States)

    Ranjha, Lepakshi; Anand, Roopesh; Cejka, Petr

    2014-01-01

    MutLγ, a heterodimer of the MutL homologues Mlh1 and Mlh3, plays a critical role during meiotic homologous recombination. The meiotic function of Mlh3 is fully dependent on the integrity of a putative nuclease motif DQHAX2EX4E, inferring that the anticipated nuclease activity of Mlh1-Mlh3 is involved in the processing of joint molecules to generate crossover recombination products. Although a vast body of genetic and cell biological data regarding Mlh1-Mlh3 is available, mechanistic insights into its function have been lacking due to the unavailability of the recombinant protein complex. Here we expressed the yeast Mlh1-Mlh3 heterodimer and purified it into near homogeneity. We show that recombinant MutLγ is a nuclease that nicks double-stranded DNA. We demonstrate that MutLγ binds DNA with a high affinity and shows a marked preference for Holliday junctions. We also expressed the human MLH1-MLH3 complex and show that preferential binding to Holliday junctions is a conserved capacity of eukaryotic MutLγ complexes. Specific DNA recognition has never been observed with any other eukaryotic MutL homologue. MutLγ thus represents a new paradigm for the function of the eukaryotic MutL protein family. We provide insights into the mode of Holliday junction recognition and show that Mlh1-Mlh3 prefers to bind the open unstacked Holliday junction form. This further supports the model where MutLγ is part of a complex acting on joint molecules to generate crossovers in meiosis. PMID:24443562

  8. MLH1 function is context dependent in colorectal cancers.

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    Jackson, Thomas; Ahmed, Mohamed A H; Seth, Rashmi; Jackson, Darryl; Ilyas, Mohammad

    2011-02-01

    Loss of mismatch repair (MMR) function in sporadic colorectal cancer occurs most commonly because of inactivation of MLH1, and it causes an increase in mutation rate. However, it is uncertain whether loss of MMR alters any other cellular function. The aim of this study was to investigate the role of MMR in regulating cell numbers and apoptosis. MLH1 protein levels were manipulated by (a) cloning and forcibly expressing MLH1 in HCT116 (a cell line with MLH1 mutation) and RKO (a cell line with MLH1 silencing), and (b) knockdown of MLH1 in SW480 (a cell line with normal MMR function). Cell number and apoptotic bodies were measured in standard and 'high stress' (ie, after staurosporine exposure) conditions. Restoration of MLH1 function in HCT116 and RKO resulted in increased cell number (pculture conditions. However, on induction of apoptotic stress, restoration of MLH1 resulted in reduced cell numbers (pcontext dependent: in 'low stress' conditions it may act to inhibit apoptosis, while in 'high stress' conditions it may induce apoptosis. However, within the context of chromosomal instability, the effect of MLH1 on cell numbers is limited.

  9. A role for MLH3 in hereditary nonpolyposis colorectal cancer

    NARCIS (Netherlands)

    Wu, Y; Berends, MJW; Sijmons, RH; Mensink, RGJ; Verlind, E; Kooi, KA; van der Sluis, T; Kempinga, C; van der Zee, AGJ; Hollema, H; Buys, CHCM; Kleibeuker, JH; Hofstra, RMW

    2001-01-01

    We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC. We identified ten different germline MLH3 variants, one frameshift and nine missense mutations,

  10. Project JADE. Description of the MLH-method

    International Nuclear Information System (INIS)

    Sandstedt, H.; Munier, R.; Wichmann, C.; Isaksson, Therese

    2001-08-01

    This report constitutes a part of a series of reports within project JADE, comparison of deposition methods. A comparison of the deposition methods MLH (Medium Long Holes with approximately 25 copper canisters emplaced in a horizontal deposition hole about 200 metres in length bored between central and side tunnels) and KBS-3 (copper canisters are emplaced in vertical deposition holes bored in the floors of horizontal tunnels) has earlier been performed and KBS-3 was judged to be more advantageous than MLH. However, the prerequisites for the comparison have changed with time and an updated evaluation of MLH was therefore required. In this report, the current knowledge of MLH is summarized with focus on geological prerequisites, methods for boring long, horizontal deposition holes, reinforcement and sealing, deposition and cost. Comparisons with KBS-3 are performed sequentially. An MLH-repository is judged to be more sensitive to ingress of water to the deposition holes during the deposition process. This implies that a MLH repository based on today's knowledge is basically recommended for bedrock with fairly low water baring capacity. It has been demonstrated that MLH has considerable economic potential compared to KBS-3. However, the method is judged to be more technically immature than KBS-3. Particularly, methods and equipment for deposition of canisters need to be developed further. Methods and equipment for deposition can be developed, which fulfill the demands on function and safety, in the near future. MLH cannot therefore be rejected as deposition method

  11. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

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    Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Hudler, Petra [Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia); Komel, Radovan [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia)

    2009-10-28

    Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

  12. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

    Directory of Open Access Journals (Sweden)

    Hudler Petra

    2009-10-01

    Full Text Available Abstract Background Loss of DNA mismatch repair (MMR in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC. Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Methods Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. Results The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Conclusion Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

  13. Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

    International Nuclear Information System (INIS)

    Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja; Hudler, Petra; Komel, Radovan

    2009-01-01

    Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene

  14. Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christopher S Campbell

    2014-05-01

    Full Text Available In Saccharomyces cerevisiae, the essential mismatch repair (MMR endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1.

  15. Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols

    DEFF Research Database (Denmark)

    Seppälä, Toni; Pylvänäinen, Kirsi; Evans, Dafydd Gareth

    2017-01-01

    We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with colonoscopy including polypectomy.......We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with colonoscopy including polypectomy....

  16. MLH1 constitutional and somatic methylation in patients with MLH1 negative tumors fulfilling the revised Bethesda criteria.

    Science.gov (United States)

    Crucianelli, Francesca; Tricarico, Rossella; Turchetti, Daniela; Gorelli, Greta; Gensini, Francesca; Sestini, Roberta; Giunti, Laura; Pedroni, Monica; Ponz de Leon, Maurizio; Civitelli, Serenella; Genuardi, Maurizio

    2014-10-01

    Lynch syndrome (LS) is a tumor predisposing condition caused by constitutional defects in genes coding for components of the mismatch repair (MMR) apparatus. While hypermethylation of the promoter of the MMR gene MLH1 occurs in about 15% of colorectal cancer samples, it has also been observed as a constitutional alteration, in the absence of DNA sequence mutations, in a small number of LS patients. In order to obtain further insights on the phenotypic characteristics of MLH1 epimutation carriers, we investigated the somatic and constitutional MLH1 methylation status of 14 unrelated subjects with a suspicion of LS who were negative for MMR gene constitutional mutations and whose tumors did not express the MLH1 protein. A novel case of constitutional MLH1 epimutation was identified. This patient was affected with multiple primary tumors, including breast cancer, diagnosed starting from the age of 55 y. Investigation of her offspring by allele specific expression revealed that the epimutation was not stable across generations. We also found MLH1 hypermethylation in cancer samples from 4 additional patients who did not have evidence of constitutional defects. These patients had some characteristics of LS, namely early age at onset and/or positive family history, raising the possibility of genetic influences in the establishment of somatic MLH1 methylation.

  17. Cancer risks for MLH1 and MSH2 mutation carriers

    OpenAIRE

    Dowty, James G.; Win, Aung K.; Buchanan, Daniel D.; Lindor, Noralane M.; Macrae, Finlay A.; Clendenning, Mark; Antill, Yoland C.; Thibodeau, Stephen N.; Casey, Graham; Gallinger, Steve; Le Marchand, Loic; Newcomb, Polly A.; Haile, Robert W.; Young, Graeme P.; James, Paul A.

    2013-01-01

    We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation-carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer (EC) and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks to age 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, ...

  18. Mlh1-Mlh3, a Meiotic Crossover and DNA Mismatch Repair Factor, Is a Msh2-Msh3-stimulated Endonuclease*

    Science.gov (United States)

    Rogacheva, Maria V.; Manhart, Carol M.; Chen, Cheng; Guarne, Alba; Surtees, Jennifer; Alani, Eric

    2014-01-01

    Crossing over between homologous chromosomes is initiated in meiotic prophase in most sexually reproducing organisms by the appearance of programmed double strand breaks throughout the genome. In Saccharomyces cerevisiae the double-strand breaks are resected to form three prime single-strand tails that primarily invade complementary sequences in unbroken homologs. These invasion intermediates are converted into double Holliday junctions and then resolved into crossovers that facilitate homolog segregation during Meiosis I. Work in yeast suggests that Msh4-Msh5 stabilizes invasion intermediates and double Holliday junctions, which are resolved into crossovers in steps requiring Sgs1 helicase, Exo1, and a putative endonuclease activity encoded by the DNA mismatch repair factor Mlh1-Mlh3. We purified Mlh1-Mlh3 and showed that it is a metal-dependent and Msh2-Msh3-stimulated endonuclease that makes single-strand breaks in supercoiled DNA. These observations support a direct role for an Mlh1-Mlh3 endonuclease activity in resolving recombination intermediates and in DNA mismatch repair. PMID:24403070

  19. Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1.

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    Hinrichsen, Inga; Ernst, Benjamin Philipp; Nuber, Franziska; Passmann, Sandra; Schäfer, Dieter; Steinke, Verena; Friedrichs, Nicolaus; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

    2014-01-24

    Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.

  20. mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide.

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    Najla Al-Sweel

    2017-08-01

    Full Text Available Mlh1-Mlh3 is an endonuclease hypothesized to act in meiosis to resolve double Holliday junctions into crossovers. It also plays a minor role in eukaryotic DNA mismatch repair (MMR. To understand how Mlh1-Mlh3 functions in both meiosis and MMR, we analyzed in baker's yeast 60 new mlh3 alleles. Five alleles specifically disrupted MMR, whereas one (mlh3-32 specifically disrupted meiotic crossing over. Mlh1-mlh3 representatives for each class were purified and characterized. Both Mlh1-mlh3-32 (MMR+, crossover- and Mlh1-mlh3-45 (MMR-, crossover+ displayed wild-type endonuclease activities in vitro. Msh2-Msh3, an MSH complex that acts with Mlh1-Mlh3 in MMR, stimulated the endonuclease activity of Mlh1-mlh3-32 but not Mlh1-mlh3-45, suggesting that Mlh1-mlh3-45 is defective in MSH interactions. Whole genome recombination maps were constructed for wild-type and MMR+ crossover-, MMR- crossover+, endonuclease defective and null mlh3 mutants in an S288c/YJM789 hybrid background. Compared to wild-type, all of the mlh3 mutants showed increases in the number of noncrossover events, consistent with recombination intermediates being resolved through alternative recombination pathways. Our observations provide a structure-function map for Mlh3 that reveals the importance of protein-protein interactions in regulating Mlh1-Mlh3's enzymatic activity. They also illustrate how defective meiotic components can alter the fate of meiotic recombination intermediates, providing new insights for how meiotic recombination pathways are regulated.

  1. The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans.

    Science.gov (United States)

    Manhart, Carol M; Ni, Xiaodan; White, Martin A; Ortega, Joaquin; Surtees, Jennifer A; Alani, Eric

    2017-04-01

    Crossing over between homologs is initiated in meiotic prophase by the formation of DNA double-strand breaks that occur throughout the genome. In the major interference-responsive crossover pathway in baker's yeast, these breaks are resected to form 3' single-strand tails that participate in a homology search, ultimately forming double Holliday junctions (dHJs) that primarily include both homologs. These dHJs are resolved by endonuclease activity to form exclusively crossovers, which are critical for proper homolog segregation in Meiosis I. Recent genetic, biochemical, and molecular studies in yeast are consistent with the hypothesis of Mlh1-Mlh3 DNA mismatch repair complex acting as the major endonuclease activity that resolves dHJs into crossovers. However, the mechanism by which the Mlh1-Mlh3 endonuclease is activated is unknown. Here, we provide evidence that Mlh1-Mlh3 does not behave like a structure-specific endonuclease but forms polymers required to generate nicks in DNA. This conclusion is supported by DNA binding studies performed with different-sized substrates that contain or lack polymerization barriers and endonuclease assays performed with varying ratios of endonuclease-deficient and endonuclease-proficient Mlh1-Mlh3. In addition, Mlh1-Mlh3 can generate religatable double-strand breaks and form an active nucleoprotein complex that can nick DNA substrates in trans. Together these observations argue that Mlh1-Mlh3 may not act like a canonical, RuvC-like Holliday junction resolvase and support a novel model in which Mlh1-Mlh3 is loaded onto DNA to form an activated polymer that cleaves DNA.

  2. Haplotype defined by the MLH1-93G/A polymorphism is associated with MLH1 promoter hypermethylation in sporadic colorectal cancers.

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    Miyakura, Yasuyuki; Tahara, Makiko; Lefor, Alan T; Yasuda, Yoshikazu; Sugano, Kokichi

    2014-11-24

    Methylation of the MLH1 promoter region has been suggested to be a major mechanism of gene inactivation in sporadic microsatellite instability-positive (MSI-H) colorectal cancers (CRCs). Recently, single-nucleotide polymorphism (SNP) in the MLH1 promoter region (MLH1-93G/A; rs1800734) has been proposed to be associated with MLH1 promoter methylation, loss of MLH1 protein expression and MSI-H tumors. We examined the association of MLH1-93G/A and six other SNPs surrounding MLH1-93G/A with the methylation status in 210 consecutive sporadic CRCs in Japanese patients. Methylation of the MLH1 promoter region was evaluated by Na-bisulfite polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. The genotype frequencies of SNPs located in the 54-kb region surrounding the MLH1-93G/A SNP were examined by SSCP analysis. Methylation of the MLH1 promoter region was observed in 28.6% (60/210) of sporadic CRCs. The proportions of MLH1-93G/A genotypes A/A, A/G and G/G were 26% (n=54), 51% (n=108) and 23% (n=48), respectively, and they were significantly associated with the methylation status (p=0.01). There were no significant associations between genotype frequency of the six other SNPs and methylation status. The A-allele of MLH1-93G/A was more common in cases with methylation than the G-allele (p=0.0094), especially in females (p=0.0067). In logistic regression, the A/A genotype of the MLH1-93G/A SNP was shown to be the most significant risk factor for methylation of the MLH1 promoter region (odds ratio 2.82, p=0.003). Furthermore, a haplotype of the A-allele of rs2276807 located -47 kb upstream from the MLH1-93G/A SNP and the A-allele of MLH1-93G/A SNP was significantly associated with MLH1 promoter methylation. These results indicate that individuals, and particularly females, carrying the A-allele at the MLH1-93G/A SNP, especially in association with the A-allele of rs2276807, may harbor an increased risk of methylation of the MLH1 promoter

  3. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Science.gov (United States)

    Pinto, Ricardo Mouro; Dragileva, Ella; Kirby, Andrew; Lloret, Alejandro; Lopez, Edith; St Claire, Jason; Panigrahi, Gagan B; Hou, Caixia; Holloway, Kim; Gillis, Tammy; Guide, Jolene R; Cohen, Paula E; Li, Guo-Min; Pearson, Christopher E; Daly, Mark J; Wheeler, Vanessa C

    2013-10-01

    The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1

  4. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Directory of Open Access Journals (Sweden)

    Ricardo Mouro Pinto

    2013-10-01

    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  5. MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

    Science.gov (United States)

    Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

    2016-10-01

    Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (PMLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas can harbor KRAS mutations and arise from precursor polyps resembling conventional tubular/tubulovillous adenomas.

  6. DNA mismatch repair gene MLH1 induces apoptosis in prostate cancer cells.

    Science.gov (United States)

    Fukuhara, Shinichiro; Chang, Inik; Mitsui, Yozo; Chiyomaru, Takeshi; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Hirata, Hiroshi; Deng, Guoren; Gill, Ankurpreet; Wong, Darryn K; Shiina, Hiroaki; Nonomura, Norio; Dahiya, Rajvir; Tanaka, Yuichiro

    2014-11-30

    Mismatch repair (MMR) enzymes have been shown to be deficient in prostate cancer (PCa). MMR can influence the regulation of tumor development in various cancers but their role on PCa has not been investigated. The aim of the present study was to determine the functional effects of the mutL-homolog 1 (MLH1) gene on growth of PCa cells. The DU145 cell line has been established as MLH1-deficient and thus, this cell line was utilized to determine effects of MLH1 by gene expression. Lack of MLH1 protein expression was confirmed by Western blotting in DU145 cells whereas levels were high in normal PWR-1E and RWPE-1 prostatic cells. MLH1-expressing stable transfectant DU145 cells were then created to characterize the effects this MMR gene has on various growth properties. Expression of MLH1 resulted in decreased cell proliferation, migration and invasion properties. Lack of cell growth in vivo also indicated a tumor suppressive effect by MLH1. Interestingly, MLH1 caused an increase in apoptosis along with phosphorylated c-Abl, and treatment with MLH1 siRNAs countered this effect. Furthermore, inhibition of c-Abl with STI571 also abrogated the effect on apoptosis caused by MLH1. These results demonstrate MLH1 protects against PCa development by inducing c-Abl-mediated apoptosis.

  7. The MLH1 ATPase domain is needed for suppressing aberrant formation of interstitial telomeric sequences.

    Science.gov (United States)

    Jia, Pingping; Chai, Weihang

    2018-05-01

    Genome instability gives rise to cancer. MLH1, commonly known for its important role in mismatch repair (MMR), DNA damage signaling and double-strand break (DSB) repair, safeguards genome stability. Recently we have reported a novel role of MLH1 in preventing aberrant formation of interstitial telomeric sequences (ITSs) at intra-chromosomal regions. Deficiency in MLH1, in particular its N-terminus, leads to an increase of ITSs. Here, we identify that the ATPase activity in the MLH1 N-terminal domain is important for suppressing the formation of ITSs. The ATPase activity is also needed for recruiting MLH1 to DSBs. Moreover, defective ATPase activity of MLH1 causes an increase in micronuclei formation. Our results highlight the crucial role of MLH1's ATPase domain in preventing the aberrant formation of telomeric sequences at the intra-chromosomal regions and preserving genome stability. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

    Science.gov (United States)

    Yokoyama, Takanori; Takehara, Kazuhiro; Sugimoto, Nao; Kaneko, Keika; Fujimoto, Etsuko; Okazawa-Sakai, Mika; Okame, Shinichi; Shiroyama, Yuko; Yokoyama, Takashi; Teramoto, Norihiro; Ohsumi, Shozo; Saito, Shinya; Imai, Kazuho; Sugano, Kokichi

    2018-05-21

    Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

  9. High intensity Discharge lighting; Alumbrado de alta intensidad de descarga

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza E, Ernesto J [Manufacturera de Reactores, S. A., Mexico, D. F. (Mexico)

    1994-12-31

    This paper gets into contact with some fundamentals in the operation of high discharge intensity lamps. There are useful definitions, as well as the study of the operation of high pressure sodium lamps and of metallic additives operating at less than nominal power. [Espanol] Este trabajo pone al lector en contacto con algunos fundamentos de la operacion de las lamparas de alta intensidad de descarga (HID). Se encuentra con definiciones utiles, asi como el estudio de la operacion de las lamparas de sodio en alta presion y de aditivos metalicos operando a una potencia menor que la nominal.

  10. High intensity Discharge lighting; Alumbrado de alta intensidad de descarga

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza E, Ernesto J. [Manufacturera de Reactores, S. A., Mexico, D. F. (Mexico)

    1993-12-31

    This paper gets into contact with some fundamentals in the operation of high discharge intensity lamps. There are useful definitions, as well as the study of the operation of high pressure sodium lamps and of metallic additives operating at less than nominal power. [Espanol] Este trabajo pone al lector en contacto con algunos fundamentos de la operacion de las lamparas de alta intensidad de descarga (HID). Se encuentra con definiciones utiles, asi como el estudio de la operacion de las lamparas de sodio en alta presion y de aditivos metalicos operando a una potencia menor que la nominal.

  11. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations

    International Nuclear Information System (INIS)

    Flores-Rozas, H.; Kolodner, R.D.

    1998-01-01

    The Saccharomyces cerevisiae genome encodes four MutL homologs. Of these, MLH1 and PMS1 are known to act in the MSH2-dependent pathway that repairs DNA mismatches. We have investigated the role of NLH3 in mismatch repair. Mutations in MLH3 increased the rate of reversion of the hom3-10 allele by increasing the rate of deletion of a single T in a run of 7 Ts. Combination of mutations in MLH3 and MSH6 caused a synergistic increase in the hom3-10 reversion rate, whereas the hom3-10 reversion rate in an mlh3 msh3 double mutant was the same as in the respective single mutants. Similar results were observed when the accumulation of mutations at frameshift hot spots in the LYS2 gene was analyzed, although mutation of MLH3 did not cause the same extent of affect at every LYS2 frameshift hot spot. MLH3 interacted with MLH1 in a two-hybrid system. These data are consistent with the idea that a proportion of the repair of specific insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a heterodimeric MLH1-MLH3 complex in place of the MLH1-PMS1 complex

  12. Disruption of a -35kb enhancer impairs CTCF binding and MLH1 expression in colorectal cells.

    Science.gov (United States)

    Liu, Qing; Thoms, Julie A; Nunez, Andrea C; Huang, Yizhou; Knezevic, Kathy; Packham, Deborah; Poulos, Rebecca C; Williams, Rachel; Beck, Dominik; Hawkins, Nicholas J; Ward, Robyn L; Wong, Jason W H; Hesson, Luke B; Sloane, Mathew A; Pimanda, John

    2018-06-13

    MLH1 is a major tumour suppressor gene involved in the pathogenesis of Lynch syndrome and various sporadic cancers. Despite their potential pathogenic importance, genomic regions capable of regulating MLH1 expression over long distances have yet to be identified. Here we use chromosome conformation capture (3C) to screen a 650-kb region flanking the MLH1 locus to identify interactions between the MLH1 promoter and distal regions in MLH1 expressing and non-expressing cells. Putative enhancers were functionally validated using luciferase reporter assays, chromatin immunoprecipitation and CRISPR-Cas9 mediated deletion of endogenous regions. To evaluate whether germline variants in the enhancer might contribute to impaired MLH1 expression in patients with suspected Lynch syndrome, we also screened germline DNA from a cohort of 74 patients with no known coding mutations or epimutations at the MLH1 promoter. A 1.8kb DNA fragment, 35kb upstream of the MLH1 transcription start site enhances MLH1 gene expression in colorectal cells. The enhancer was bound by CTCF and CRISPR-Cas9 mediated deletion of a core binding region impairs endogenous MLH1 expression. 5.4% of suspected Lynch syndrome patients have a rare single nucleotide variant (G>A; rs143969848; 2.5% in gnomAD European, non-Finnish) within a highly conserved CTCF binding motif, which disrupts enhancer activity in SW620 colorectal carcinoma cells. A CTCF bound region within the MLH1 -35 enhancer regulates MLH1 expression in colorectal cells and is worthy of scrutiny in future genetic screening strategies for suspected Lynch syndrome associated with loss of MLH1 expression. Copyright ©2018, American Association for Cancer Research.

  13. Loss of MLH1 sensitizes colon cancer cells to DNA-PKcs inhibitor KU60648.

    Science.gov (United States)

    Hinrichsen, Inga; Ackermann, Anne; Düding, Tonja; Graband, Annika; Filmann, Natalie; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

    2017-07-01

    Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors. Therefore, we examined the expression of MLH1, MSH2, MSH6, and MSH3 in different MMR-deficient and proficient cell lines and determined their sensitivity to KU60648 by analyzing cell viability and survival. MLH1-dependent ability of double strand break (DSB) repair was monitored after irradiation via γH2AX detection. A panel of 12 colon cancer cell lines, two pairs of cells, where MLH1 knock down was compared to controls with the same genetic background, and one MLH1-deficient cell line where MLH1 was overexpressed, were included. In summary, we found that MLH1 and/or MSH3-deficient cells exhibited a significantly higher sensitivity to KU60648 than MMR-proficient cells and that overexpression of MLH1 in MLH1-deficient cells resulted in a decrease of cell sensitivity. KU60648 efficiency seems to be associated with reduced DSB repair capacity. Since the molecular testing of colon tumors for MLH1 expression is a clinical standard we believe that MLH1 is a much better marker and a greater number of patients would benefit from KU60648 treatment. © 2017 Wiley Periodicals, Inc.

  14. Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation.

    Science.gov (United States)

    Hitchins, Megan P

    2016-07-01

    Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome. MLH1 epimutations are characterized by the soma-wide distribution of methylation of a single allele of the MLH1 promoter accompanied by constitutive allelic loss of transcription. 'Primary' MLH1 epimutations, considered pure epigenetic defects, tend to arise de novo in patients without a family history or any apparent genetic mutation. These demonstrate non-Mendelian inheritance. 'Secondary' MLH1 epimutations have a genetic basis and have been linked to non-coding genetic alterations in the vicinity of MLH1. These demonstrate autosomal dominant inheritance. Despite convincing evidence of their role in causing Lynch-type cancers, routine screening for MLH1 epimutations has not been widely adopted. Complicating factors may include: the need to perform additional methylation-based testing beyond the standard genetic screening for a germline mutation; the lack of a consensus algorithm for the selection of patients warranting MLH1 epimutation testing; overlapping molecular pathology features of MLH1 methylation and loss of MLH1 expression with more prevalent sporadic MSI cancers; the rarity of MLH1 epimutation; the variable inter-generational inheritance patterns; and the cost-effectiveness of screening. Nevertheless, a positive molecular diagnosis of MLH1 epimutation is clinically important because carriers have a high personal risk of developing metachronous Lynch-type cancers, and their relatives may also be at risk of carriage. Extending existing universal and clinic-based screening algorithms for Lynch syndrome to include an additional arm of selection criteria for cases warranting MLH1 epimutation testing could provide a cost-effective means of diagnosing these cases.

  15. Development of a method for RIA of MLH

    International Nuclear Information System (INIS)

    Zhang Haoyi; Jin Lichun

    2002-01-01

    Objective: To develop a method of RIA for MLH to measure the serum level of LH in Rhesus Monkey for animal experiment in reproductive medicine. Methods: 125 I-MLH was prepared with chloramine T-Iodogen method. Rabbit anti-MLH was used as first antibody and sheep anti-rabbit IgG was used as separating agent. RIA was performed with liquid phase competitive radioassay. Results: The specific radioactivity of labelled antigen was 67 μg/mCi; antibody affinity constant was Ka = 3.44 x 10 -9 mol/L the shape of the standard curve was good. r = 0.991, intra-assay error CV = 3.49%, inter-assay error CV = 4.65%. The minimal detectable concentration was 0.42 μg/ml. Mean value of 30 normal Rhesus Monkey serum specimens was 1.17 +- 1.30 μg/ml. Conclusion: The developed method was simple reliable and sensitive. It would be of use in study of contraceptive and sex-physiology drugs

  16. Intensidades de treinamento resistido e pressão arterial de idosas hipertensas - um estudo piloto

    OpenAIRE

    Cunha,Eline Silva da; Miranda,Patrícia Angélica de; Nogueira,Silva; Costa,Eduardo Caldas; Silva,Eliane Pereira da; Ferreira,Gardênia Maria Holanda

    2012-01-01

    INTRODUÇÃO: Observa-se que a literatura apresenta uma lacuna acerca da intensidade ideal de treinamento resistido para idosos hipertensos, os poucos estudos existentes utilizam treinamentos com diferentes intensidades. OBJETIVO: Verificar o efeito de duas intensidades de treinamento resistido sobre a pressão arterial de idosas hipertensas controladas. Métodos: Dezesseis idosas hipertensas, controladas por medicação anti-hipertensiva, foram divididas em dois grupos através de sorteio. Nove pac...

  17. Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells.

    Science.gov (United States)

    Yan, Tao; Seo, Yuji; Kinsella, Timothy J

    2009-11-15

    MLH1 is a key DNA mismatch repair (MMR) protein involved in maintaining genomic stability by participating in the repair of endogenous and exogenous mispairs in the daughter strands during S phase. Exogenous mispairs can result following treatment with several classes of chemotherapeutic drugs, as well as with ionizing radiation. In this study, we investigated the role of the MLH1 protein in determining the cellular and molecular responses to prolonged low-dose rate ionizing radiation (LDR-IR), which is similar to the clinical use of cancer brachytherapy. An isogenic pair of MMR(+) (MLH1(+)) and MMR(-) (MLH1(-)) human colorectal cancer HCT116 cells was exposed to prolonged LDR-IR (1.3-17 cGy/h x 24-96 h). The clonogenic survival and gene mutation rates were examined. Cell cycle distribution was analyzed with flow cytometry. Changes in selected DNA damage repair proteins, DNA damage response proteins, and cell death marker proteins were examined with Western blotting. MLH1(+) HCT116 cells showed greater radiosensitivity with enhanced expression of apoptotic and autophagic markers, a reduced HPRT gene mutation rate, and more pronounced cell cycle alterations (increased late-S population and a G(2)/M arrest) following LDR-IR compared with MLH1(-) HCT116 cells. Importantly, a progressive increase in MLH1 protein levels was found in MLH1(+) cells during prolonged LDR-IR, which was temporally correlated with a progressive decrease in Rad51 protein (involved in homologous recombination) levels. MLH1 status significantly affects cellular responses to prolonged LDR-IR. MLH1 may enhance cell radiosensitivity to prolonged LDR-IR through inhibition of homologous recombination (through inhibition of Rad51).

  18. Clinicopathologic Risk Factor Distributions for MLH1 Promoter Region Methylation in CIMP-Positive Tumors.

    Science.gov (United States)

    Levine, A Joan; Phipps, Amanda I; Baron, John A; Buchanan, Daniel D; Ahnen, Dennis J; Cohen, Stacey A; Lindor, Noralane M; Newcomb, Polly A; Rosty, Christophe; Haile, Robert W; Laird, Peter W; Weisenberger, Daniel J

    2016-01-01

    The CpG island methylator phenotype (CIMP) is a major molecular pathway in colorectal cancer. Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic factors in CIMP-positive tumors with MLH1 DNA methylation differed from those in CIMP-positive tumors without DNA methylation of MLH1. We assessed the associations between age, sex, tumor-site, MSI status BRAF and KRAS mutations, and family colorectal cancer history with MLH1 methylation status in a large population-based sample of CIMP-positive colorectal cancers defined by a 5-marker panel using unconditional logistic regression to assess the odds of MLH1 methylation by study variables. Subjects with CIMP-positive tumors without MLH1 methylation were significantly younger, more likely to be male, and more likely to have distal colon or rectal primaries and the MSI-L phenotype. CIMP-positive MLH1-unmethylated tumors were significantly less likely than CIMP-positive MLH1-methylated tumors to harbor a BRAF V600E mutation and significantly more likely to harbor a KRAS mutation. MLH1 methylation was associated with significantly better overall survival (HR, 0.50; 95% confidence interval, 0.31-0.82). These data suggest that MLH1 methylation in CIMP-positive tumors is not a completely random event and implies that there are environmental or genetic determinants that modify the probability that MLH1 will become methylated during CIMP pathogenesis. MLH1 DNA methylation status should be taken into account in etiologic studies. ©2015 American Association for Cancer Research.

  19. Clinicopathological risk factor distributions for MLH1 promoter region methylation in CIMP positive tumors

    Science.gov (United States)

    Levine, A. Joan; Phipps, Amanda I.; Baron, John A.; Buchanan, Daniel D.; Ahnen, Dennis J.; Cohen, Stacey A.; Lindor, Noralane M.; Newcomb, Polly A.; Rosty, Christophe; Haile, Robert W.; Laird, Peter W.; Weisenberger, Daniel J.

    2015-01-01

    Background The CpG Island Methylator Phenotype (CIMP) is a major molecular pathway in colorectal cancer (CRC). Approximately 25% to 60% of CIMP tumors are microsatellite unstable (MSI-H) due to DNA hypermethylation of the MLH1 gene promoter. Our aim was to determine if the distributions of clinicopathologic factors in CIMP-positive tumors with MLH1 DNA methylation differed from those in CIMP-positive tumors without DNA methylation of MLH1. Methods We assessed the associations between age, sex, tumor-site, MSI status BRAF and KRAS mutations and family CRC history with MLH1 methylation status in a large population-based sample of CIMP-positive CRCs defined by a 5-marker panel using unconditional logistic regression to assess the odds of MLH1 methylation by study variables. Results Subjects with CIMP-positive tumors without MLH1 methylation were significantly younger, more likely to be male, more likely to have distal colon or rectal primaries and the MSI-L phenotype. CIMP-positive MLH1-unmethylated tumors were significantly less likely than CIMP-positive MLH1-methylated tumors to harbor a BRAF V600E mutation and significantly more likely to harbor a KRAS mutation. MLH1 methylation was associated with significantly better overall survival (HR=0.50; 95% Confidence Interval (0.31, 0.82)). Conclusions These data suggest that MLH1 methylation in CIMP-positive tumors is not a completely random event and implies that there are environmental or genetic determinants that modify the probability that MLH1 will become methylated during CIMP pathogenesis. Impact MLH1 DNA methylation status should be taken into account in etiologic studies. PMID:26512054

  20. Expression and promoter DNA methylation of MLH1 in colorectal cancer and lung cancer.

    Science.gov (United States)

    Ma, Yunxia; Chen, Yuan; Petersen, Iver

    2017-04-01

    Aberrant DNA methylation is a common molecular feature in human cancer. The aims of this study were to analyze the methylation status of MLH1, one of the DNA mismatch repair (MMR) genes, in human colorectal and lung cancer and to evaluate its clinical relevance. The expression of MLH1 was analyzed in 8 colorectal cancer (CRC) and 8 lung cancer cell lines by real-time RT-PCR and western blotting. The MLH1 protein expression was evaluated by immunohistochemistry on tissue microarrays including 121 primary CRC and 90 lung cancer patient samples. In cancer cell lines, the methylation status of MLH1 promoter and exon 2 was investigated by bisulfite sequencing (BS). Methylation-specific-PCR (MSP) was used to evaluate methylation status of MLH1. The expression of MLH1 mRNA was detected in 8 CRC cell lines as well as normal colonic fibroblast cells CCD-33Co. At protein levels, MLH1 was lost in one CRC cell line HCT-116 and normal cells CCD-33Co. No methylation was found in the promoter and exon 2 of MLH1 in CRC cell lines. MLH1 was expressed in 8 lung cancer cell lines at both mRNA and protein levels. Compared to cancer cells, normal bronchial epithelial cells (HBEC) had lower expression of MLH1 protein. In primary CRC, 54.5% of cases exhibited positive staining, while 47.8% of lung tumors were positive for MLH1 protein. MSP analysis showed that 58 out of 92 (63.0%) CRC and 41 out of 73 (56.2%) lung cancer exhibited MLH1 methylation. In CRC, the MLH1 methylation was significantly associated with tumor invasion in veins (P=0.012). However, no significant links were found between MLH1 expression and promoter methylation in both tumor entities. MLH1 methylation is a frequent molecular event in CRC and lung cancer patients. In CRC, methylation of MLH1 could be linked to vascular invasiveness. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Prognostic value of MLH1 promoter methylation in male patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Dongping; Chen, Xiaoying; Xu, Yan; Wang, Haiyong; Yu, Guangmao; Jiang, Luping; Hong, Qingxiao; Duan, Shiwei

    2017-04-01

    The DNA mismatch repair (MMR) gene MutL homolog 1 ( MLH1 ) is critical for the maintenance of genomic integrity. Methylation of the MLH1 gene promoter was identified as a prognostic marker for numerous types of cancer including glioblastoma, colorectal, ovarian and gastric cancer. The present study aimed to determine whether MLH1 promoter methylation was associated with survival in male patients with esophageal squamous cell carcinoma (ESCC). Formalin-fixed, paraffin-embedded ESCC tissues were collected from 87 male patients. MLH1 promoter methylation was assessed using the methylation-specific polymerase chain reaction approach. Kaplan-Meier survival curves and log-rank tests were used to evaluate the association between MLH1 promoter methylation and overall survival (OS) in patients with ESCC. Cox regression analysis was used to obtain crude and multivariate hazard ratios (HR), and 95% confidence intervals (CI). The present study revealed that MLH1 promoter methylation was observed in 53/87 (60.9%) of male patients with ESCC. Kaplan-Meier survival analysis demonstrated that MLH1 promoter hypermethylation was significantly associated with poorer prognosis in patients with ESCC (P=0.048). Multivariate survival analysis revealed that MLH1 promoter hypermethylation was an independent predictor of poor OS in male patients with ESCC (HR=1.716; 95% CI=1.008-2.921). Therefore, MLH1 promoter hypermethylation may be a predictor of prognosis in male patients with ESCC.

  2. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

    Science.gov (United States)

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-06-13

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

  3. Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer.

    Science.gov (United States)

    Funck, Alexandre; Santos, Juliana C; Silva-Fernandes, Isabelle J L; Rabenhorst, Silvia H B; Martinez, Carlos A R; Ribeiro, Marcelo L

    2014-09-01

    The DNA repair machinery plays a key role in maintaining genomic stability by preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in the MLH1 gene has been associated with an increased risk of developing colorectal cancer. Therefore, the aim of this study was to examine the expression pattern and effect of this polymorphism in normal and tumour samples from patients with colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR-RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using real-time quantitative PCR. The results indicate a significant decrease in MLH1 expression in tumour samples compared to their normal counterparts. The MLH1 gene was also significantly repressed in samples from patients who had some degree of tumour invasion into other organs. Similarly, those patients who were in a more advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1 gene expression. Finally, the mutant genotype AA of MLH1 was associated with a significant decrease in the expression of this gene. This finding suggests that this polymorphism could increase the risk of developing colorectal cancer by a defective mismatch repair system, particularly through the loss of MLH1 expression in an allele-specific manner.

  4. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    International Nuclear Information System (INIS)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Kerr, Iain D.; Min, Jinrong

    2015-01-01

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants

  5. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  6. MLH1 promoter methylation frequency in colorectal cancer patients and related clinicopathological and molecular features.

    Directory of Open Access Journals (Sweden)

    Xia Li

    Full Text Available To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC; to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis.A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR and 95% confidence intervals (95% CI were calculated.The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8-24.1%. They were 18.7% (95% CI: 14.7-23.6% and 16.4% (95% CI: 11.9-22.0% in sporadic and Lynch syndrome (LS CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215-2.215; P = 0.001, tumor location (pooled OR = 3.804, 95% CI: 2.715-5.329; P<0.001, tumor differentiation (pooled OR = 2.131, 95% CI: 1.464-3.102; P<0.001, MSI (OR: 27.096, 95% CI: 13.717-53.526; P<0.001. Significant associations were also observed between MLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427-34.631; P<0.001 and 9.419 (95% CI: 2.613-33.953; P = 0.001, respectively.The frequency of MLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation.

  7. Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Rasmussen, Anders Aamann; Byriel, Lene

    2013-01-01

    In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim...... of this study was to determine in detail how DNA methylation regulates MLH1 expression and impacts clinical management....

  8. Resposta renal à maltodextrina e ao treinamento em diferentes intensidades

    Directory of Open Access Journals (Sweden)

    Cátia Fernandes Leite

    2015-03-01

    Full Text Available O objetivo foi investigar a resposta renal à ingestão de maltodextrina e à natação de padrão aeróbio ou anaeróbio de alta intensidade em ratos. Materiais e métodos O protocolo consistiu de oito semanas de natação em padrão aeróbio (sobrecarga 5% ou intermitente (sobrecarga 10%. Durante 37 dias os animais foram suplementados, por meio de gavagem, com uma dose diária de 0,48g.Kg−1 de maltodextrina dissolvida em água ou receberam água pura, antes do treinamento. Resultados O treinamento anaeróbio ocasionou aumento nas concentrações de ácido úrico, creatinina e proteínas totais e redução no glicogênio renal. A maltodextrina causou aumento no glicogênio renal. Conclusão A maltodextrina e o treinamento anaeróbio proporcionaram alterações nos parâmetros de função renal em resposta desse órgão a esses estímulos externos.

  9. Molecular analysis of MLH1 variants in Chinese sporadic colorectal cancer patients.

    Science.gov (United States)

    Peng, H X; Xu, X; Yang, R; Chu, Y M; Yang, D M; Xu, Y; Zhou, F L; Ma, W Z; Zhang, X J; Guan, M; Yang, Z H; Jin, Z D

    2016-04-26

    Single nucleotide polymorphisms (SNPs) in mismatch repair genes, especially in the MLH1 gene, are closely associated with susceptibility to hereditary nonpolyposis colorectal cancer. However, few relevant findings are available regarding the association between sporadic colorectal cancer (SCRC) and SNPs of MLH1 in Chinese patients. Therefore, the present study aimed to describe the pathogenic association between three important MLH1 polymorphisms and SCRC in the Chinese population. Peripheral blood samples from 156 SCRC patients and 311 healthy controls were collected. DNA was purified from peripheral blood, and the V384D, R217C, and I219V polymorphisms were evaluated using high-resolution melting analysis and direct sequencing. The association between the three important MLH1 polymorphisms and clinical pathological features of the SCRC patients was analyzed. In addition, PMS2-MLH1 protein interactions were determined by co-immunoprecipitation (Co-IP) to determine the protein functional alteration induced by these SNPs. Among the three polymorphisms, V384D was significantly associated with the risk of SCRC (OR = 31.36, P MLH1 R217C, V384D, and I219V variants had relative binding abilities with PMS2 of 0.59, 0.70, and 0.80, respectively, compared with the wild-type. These findings suggest that MLH1 V384D could be a promising genetic marker for susceptibility to SCRC.

  10. Role of MLH1 methylation in esophageal cancer carcinogenesis and its clinical significance.

    Science.gov (United States)

    Li, Jinyun; Ye, Dong; Wang, Lei; Peng, Yingying; Li, Qun; Deng, Hongxia; Zhou, Chongchang

    2018-01-01

    The mutL homolog-1 ( MLH1 ) is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between MLH1 methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of MLH1 methylation was significantly elevated during EC carcinogenesis. In addition, we observed that MLH1 promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20-2.66), advanced tumor grade (OR=3.7; 95% CI =2.37-5.77), lymph node metastasis (OR=2.65; 95% CI =1.81-3.88), distant metastasis (OR=7.60; 95% CI =1.23-47.19), advanced clinical stage (OR=4.46; 95% CI =2.88-6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00-2.69). The pooled sensitivity, specificity, and area under the curve of MLH1 methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that MLH1 methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated MLH1 could be a potential diagnostic and prognostic biomarker for EC.

  11. Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses.

    Science.gov (United States)

    Haraldsdottir, Sigurdis; Hampel, Heather; Wu, Christina; Weng, Daniel Y; Shields, Peter G; Frankel, Wendy L; Pan, Xueliang; de la Chapelle, Albert; Goldberg, Richard M; Bekaii-Saab, Tanios

    2016-09-01

    Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups. Patients with dMMR CRC identified by immunohistochemistry staining and treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients' charts were accessed for information on pathology, germ-line MMR mutation testing, and clinical course. A total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 74%). Patients with LS were younger, more often male, presented more often with stage III disease, and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer-specific survival (CSS) between the groups; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis. CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.Genet Med 18 9, 863-868.

  12. Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis.

    Science.gov (United States)

    Ehsani, Laleh; Osunkoya, Adeboye O

    2014-09-01

    In this study, we investigated microsatellite instability in urothelial carcinoma of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2. The study included 44 cases of urothelial carcinoma of the renal pelvis obtained from radical nephroureterectomy specimens at our institution. We evaluated the loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %) patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2 expression. Six of 8 (75 %) patients with negative MLH1 expression were male and 2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88 %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and 21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which 3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had negative MSH2 expression. Our study showed that microsatellite instability based on negative expression of MLH1 and MSH2 was more common in male patients with high-grade urothelial carcinoma. There is a strong correlation between inverted growth pattern and negative MSH2 expression. Microsatellite instability testing should be performed in patients with upper urinary tract carcinoma and may have prognostic value.

  13. High Mutation Levels are Compatible with Normal Embryonic Development in Mlh1-Deficient Mice.

    Science.gov (United States)

    Fan, Xiaoyan; Li, Yan; Zhang, Yulong; Sang, Meixiang; Cai, Jianhui; Li, Qiaoxia; Ozaki, Toshinori; Ono, Tetsuya; He, Dongwei

    2016-10-01

    To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12.5 dpc in fetuses of Mlh1 +/+ and Mlh1 -/- mice showed their own unique spectra, suggesting that deletion mutations were the main causes in the deficiency of the Mlh1 gene. Of note, fetuses of irradiated mice exhibited marked differences such as post-implantation loss and Mendelian distribution. Collectively, these results strongly suggest that high mutation ofMlh1 -/- -deficient fetuses has little effect on the fetuses during their early developmental stages, whereas Mlh1 -/- -deficient fetuses from X-ray irradiated mothers are clearly effected.

  14. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System*

    Science.gov (United States)

    Smith, Catherine E.; Bowen, Nikki; Graham, William J.; Goellner, Eva M.; Srivatsan, Anjana; Kolodner, Richard D.

    2015-01-01

    Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5′ nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3′ nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg2+ and Mn2+ for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR. PMID:26170454

  15. Concomitant mutation and epimutation of the MLH1 gene in a Lynch syndrome family.

    Science.gov (United States)

    Cini, Giulia; Carnevali, Ileana; Quaia, Michele; Chiaravalli, Anna Maria; Sala, Paola; Giacomini, Elisa; Maestro, Roberta; Tibiletti, Maria Grazia; Viel, Alessandra

    2015-04-01

    Lynch syndrome (LS) is an inherited predisposition cancer syndrome, typically caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 and PMS2. In the last years, a role for epimutations of the same genes has also been reported. MLH1 promoter methylation is a well known mechanism of somatic inactivation in tumors, and more recently, several cases of constitutional methylation have been identified. In four subjects affected by multiple tumors and belonging to a suspected LS family, we detected a novel secondary MLH1 gene epimutation. The methylation of MLH1 promoter was always linked in cis with a 997 bp-deletion (c.-168_c.116+713del), that removed exon 1 and partially involved the promoter of the same gene. Differently from cases with constitutional primary MLH1 inactivation, this secondary methylation was allele-specific and CpGs of the residual promoter region were totally methylated, leading to complete allele silencing. In the colon tumor of the proband, MLH1 and PMS2 expression was completely lost as a consequence of a pathogenic somatic point mutation (MLH1 c.199G>A, p.Gly67Arg) that also abrogated local methylation by destroying a CpG site. The evidences obtained highlight how MLH1 mutations and epimutations can reciprocally influence each other and suggest that an altered structure of the MLH1 locus results in epigenetic alteration. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Activation of Saccharomyces cerevisiae Mlh1-Pms1 Endonuclease in a Reconstituted Mismatch Repair System.

    Science.gov (United States)

    Smith, Catherine E; Bowen, Nikki; Graham, William J; Goellner, Eva M; Srivatsan, Anjana; Kolodner, Richard D

    2015-08-28

    Previous studies reported the reconstitution of an Mlh1-Pms1-independent 5' nick-directed mismatch repair (MMR) reaction using Saccharomyces cerevisiae proteins. Here we describe the reconstitution of a mispair-dependent Mlh1-Pms1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and replication factor C (RFC) and a reconstituted Mlh1-Pms1-dependent 3' nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA), RFC, PCNA, and DNA polymerase δ. Both reactions required Mg(2+) and Mn(2+) for optimal activity. The MMR reaction also required two reaction stages in which the first stage required incubation of Mlh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the substrate, followed by a second stage in which other proteins were added. Analysis of different mutant proteins demonstrated that both reactions required a functional Mlh1-Pms1 endonuclease active site, as well as mispair recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation. Mutant Mlh1-Pms1 and PCNA proteins that were defective for Exo1-independent but not Exo1-dependent MMR in vivo were partially defective in the Mlh1-Pms1 endonuclease and MMR reactions, suggesting that both reactions reflect the activation of Mlh1-Pms1 seen in Exo1-independent MMR in vivo. The availability of this reconstituted MMR reaction should now make it possible to better study both Exo1-independent and Exo1-dependent MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Protestas populares de baja intensidad en la Asturias de posguerra

    Directory of Open Access Journals (Sweden)

    Ramón García Piñeiro

    2001-01-01

    Full Text Available El régimen franquista nació y fue sostenido para imponer la identidad ideológica dentro del Movimiento y para reprimir cualquier forma de conflicto, ya fuera Isiboral o político. Hasta ahora se fia venido sosteniendo que se alcanzó plenamente tal objetivo, al menos durante la década de los cuarenta, etapa en la que, excluida la actividad guerrillera, quedaron reducidas al mínimo las manifestaciones de resistencia colectiva o individual. Esta aparente resignación social fia sido subrayada con perplejidad en más de una ocasión por los investigadores, dada la sólida ideologización y la demostrada combatividad de algunos sectores de la sociedad española. Certeramente se ha intentando relacionar la pasividad de los derrotados con la intensidad de la represión y el alarde de fuerzas del orden exhibido, aunque también se ha vinculado con las alteraciones demográficas experimentadas por la clase obrera e incluso con la política paternalista auspiciada por el ministro de Trabajo. Sin embargo, no se ha cuestionado la ya tópica concepción de la posguerra como una etapa de «paz social», imagen deliberadamente proyectada por un régimen concebido para ahogar y ocultar cualquier manifestación de disidencia. La utilización de nuevas fuentes pone al descubierto un variado repertorio de actitudes de rechazo y hostilidad política que, hasta el presente, han sido minusvalorados.

  18. Ovarian metastasis from uveal melanoma with MLH1/PMS2 protein loss in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

    Science.gov (United States)

    Lobo, João; Pinto, Carla; Freitas, Micaela; Pinheiro, Manuela; Vizcaino, Rámon; Oliva, Esther; Teixeira, Manuel R; Jerónimo, Carmen; Bartosch, Carla

    2017-03-01

    Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.

  19. Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen

    2012-01-01

    Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register...... to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks...... in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers....

  20. MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features

    Science.gov (United States)

    Li, Xia; Yao, Xiaoping; Wang, Yibaina; Hu, Fulan; Wang, Fan; Jiang, Liying; Liu, Yupeng; Wang, Da; Sun, Guizhi; Zhao, Yashuang

    2013-01-01

    Purpose To describe the frequency of MLH1 promoter methylation in colorectal cancer (CRC); to explore the associations between MLH1 promoter methylation and clinicopathological and molecular factors using a systematic review and meta-analysis. Methods A literature search of the PubMed and Embase databases was conducted to identify relevant articles published up to September 7, 2012 that described the frequency of MLH1 promoter methylation or its associations with clinicopathological and molecular factors in CRC. The pooled frequency, odds ratio (OR) and 95% confidence intervals (95% CI) were calculated. Results The pooled frequency of MLH1 promoter methylation in unselected CRC was 20.3% (95% CI: 16.8–24.1%). They were 18.7% (95% CI: 14.7–23.6%) and 16.4% (95% CI: 11.9–22.0%) in sporadic and Lynch syndrome (LS) CRC, respectively. Significant associations were observed between MLH1 promoter methylation and gender (pooled OR = 1.641, 95% CI: 1.215–2.215; P = 0.001), tumor location (pooled OR = 3.804, 95% CI: 2.715–5.329; PMLH1 promoter methylation and MLH1 protein expression, BRAF mutation (OR = 14.919 (95% CI: 6.427–34.631; PMLH1 promoter methylation in unselected CRC was 20.3%. They were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively. MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation. PMID:23555617

  1. MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults.

    Science.gov (United States)

    Alvarez, Marisa C; Santos, Juliana C; Maniezzo, Nathália; Ladeira, Marcelo S; da Silva, Artur L C; Scaletsky, Isabel C A; Pedrazzoli, José; Ribeiro, Marcelo L

    2013-05-28

    To evaluate the association between Helicobacter pylori (H. pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability (MSI). The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction (MSP-PCR) in gastric biopsy samples from uninfected or H. pylori-infected children (n = 50), from adults with chronic gastritis (n = 97) and from adults with gastric cancer (n = 92). MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene (β actin). MSI analysis was performed by screening MSI markers at 4 loci (Bat-25, Bat-26, D17S250 and D2S123) with PCR; PCR products were analysed by single strand conformation polymorphism followed by silver staining. Statistical analyses were performed with either the χ(2) test with Yates continuity correction or Fisher's exact test, and statistical significance for expression analysis was assessed using an unpaired Student's t-test. Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children, regardless of H. pylori infection status. The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H. pylori infection (P MLH1 methylation frequencies among H. pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%, respectively. We observed methylation of the MLH1 promoter (39%) and increased MSI levels (68%) in samples from gastric cancer patients in comparison to samples from H. pylori-infected adult chronic gastritis patients (P MLH1 and MGMT mRNA were significantly reduced in chronic gastritis samples that were also hypermethylated (P MLH1 methylation did not occur in earlier-stage H. pylori infections and thus might depend on the duration of infection.

  2. Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC).

    Science.gov (United States)

    Newton, K; Jorgensen, N M; Wallace, A J; Buchanan, D D; Lalloo, F; McMahon, R F T; Hill, J; Evans, D G

    2014-12-01

    Lynch syndrome (LS) patients have DNA mismatch repair deficiency and up to 80% lifetime risk of colorectal cancer (CRC). Screening of mutation carriers reduces CRC incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour-derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from LS (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations. Tumour DNA was extracted (formalin fixed, paraffin embedded, FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared. Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2% to 98.4%), specificity 87.7% (95% CI 77.9% to 94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7% to 76.5%), specificity 98.6% (95% CI 92.4% to 100.0%) for the identification of those with pathogenic MLH1 mutations. Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Autophagy influences the low-dose hyper-radiosensitivity of human lung adenocarcinoma cells by regulating MLH1.

    Science.gov (United States)

    Wang, Qiong; Xiao, Zhuya; Lin, Zhenyu; Zhou, Jie; Chen, Weihong; Jie, Wuyun; Cao, Xing; Yin, Zhongyuan; Cheng, Jing

    2017-06-01

    To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR). Conversely, the radiosensitivity of H460 cells, which express high levels of MLH1, conformed to the linear-quadratic (LQ) model. After down-regulating MLH1 expression, A549 cells showed increased HRS and inhibition of autophagy, whereas H460 cells exhibited HRS/IRR. The levels of mTOR, p-mTOR, and BNIP3 were reduced in cells harboring MLH1 shRNA, and the changes in the mTOR/p-mTOR ratio mirrored those in MLH1 expression. Low MLH1-expressing A549 cells may exhibit HRS. Both the mTOR/p-mTOR and BNIP3/Beclin-1 signaling pathways were found to be related to HRS, but only mTOR/p-mTOR is involved in the regulation of HRS via MLH1 and autophagy.

  4. Differential expression of hMLH1 in sporadic human colorectal cancer tumors and distant metastases

    DEFF Research Database (Denmark)

    Larsen, Nicolai Balle; Heiberg Engel, Peter Johan; Rasmussen, Merete

    2009-01-01

    in expression between the tumor transition zone and the invasive front. Expression of hMSH2, hMLH1, and hPMS2 was screened immunohistochemically in 92 stage IV tumors and derived liver metastases. In cases with loss of mismatch repair protein expression, lymph node metastases were also examined....... Clinicopathological parameters and Ki-67 staining indexes were evaluated and compared. Four tumors displayed a complete loss of hMLH1/hPMS2 expression at the transition zone; however, three of these expressed both proteins at the invasive front and in liver and lymph node metastases. A further four were predominantly...... hMLH1/hPMS2 negative at the transition zone, but with distinct subclones of hMLH1/hPMS2-expressing cells at the transition zone. All of these tumors expressed hMLH1/hPMS2 at the invasive front and in liver metastases, with three also expressing hMLH/hPMS2 in lymph node metastases. No significant...

  5. Constitutional MLH1 methylation presenting with colonic polyposis syndrome and not Lynch syndrome.

    Science.gov (United States)

    Kidambi, Trilokesh D; Blanco, Amie; Van Ziffle, Jessica; Terdiman, Jonathan P

    2016-04-01

    At least one-third of patients meeting clinical criteria for Lynch syndrome will have no germline mutation and constitutional epimutations leading to promoter methylation of MLH1 have been identified in a subset of these patients. We report the first case of constitutional MLH1 promoter methylation associated with a colonic polyposis syndrome in a 39 year-old man with a family history of colorectal cancer (CRC) and a personal history of 21 polyps identified over 8 years as well as the development of two synchronous CRCs over 16 months who was evaluated for a hereditary cancer syndrome. Immunohistochemistry (IHC) of multiple tumors showed absent MLH1 and PMS2 expression, though germline testing with Sanger sequencing and multiplex ligation-dependent probe amplification of these mismatch repair genes (MMR) genes was negative. A next generation sequencing panel of 29 genes also failed to identify a pathogenic mutation. Hypermethylation was identified in MLH1 intron 1 in tumor specimens along with buccal cells and peripheral white blood cells, confirming the diagnosis of constitutional MLH1 promoter methylation. This case highlights that constitutional MLH1 methylation should be considered in the differential diagnosis for a polyposis syndrome if IHC staining shows absent MMR gene expression.

  6. The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

    Science.gov (United States)

    Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

    2012-01-01

    DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

  7. Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis

    OpenAIRE

    Avdievich, Elena; Reiss, Cora; Scherer, Stefan J.; Zhang, Yongwei; Maier, Sandra M.; Jin, Bo; Hou, Harry; Rosenwald, Andreas; Riedmiller, Hubertus; Kucherlapati, Raju; Cohen, Paula E.; Edelmann, Winfried; Kneitz, Burkhard

    2008-01-01

    Mutations in the human DNA mismatch repair (MMR) gene MLH1 are associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome, HNPCC) and a significant proportion of sporadic colorectal cancer. The inactivation of MLH1 results in the accumulation of somatic mutations in the genome of tumor cells and resistance to the genotoxic effects of a variety of DNA damaging agents. To study the effect of MLH1 missense mutations on cancer susceptibility, we generated a mouse line carrying the ...

  8. Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry.

    Science.gov (United States)

    Liu, Cheng; Walker, Neal I; Leggett, Barbara A; Whitehall, Vicki Lj; Bettington, Mark L; Rosty, Christophe

    2017-12-01

    Sessile serrated adenomas are the precursor polyp of approximately 20% of colorectal carcinomas. Sessile serrated adenomas with dysplasia are rarely encountered and represent an intermediate step to malignant progression, frequently associated with loss of MLH1 expression. Accurate diagnosis of these lesions is important to facilitate appropriate surveillance, particularly because progression from dysplasia to carcinoma can be rapid. The current World Health Organization classification describes two main patterns of dysplasia occurring in sessile serrated adenomas, namely, serrated and conventional. However, this may not adequately reflect the spectrum of changes seen by pathologists in routine practice. Furthermore, subtle patterns of dysplasia that are nevertheless associated with loss of MLH1 expression are not encompassed in this classification. We performed a morphological analysis of 266 sessile serrated adenomas with dysplasia with concurrent MLH1 immunohistochemistry with the aims of better defining the spectrum of dysplasia occurring in these lesions and correlating dysplasia patterns with MLH1 expression. We found that dysplasia can be divided morphologically into four major patterns, comprising minimal deviation (19%), serrated (12%), adenomatous (8%) and not otherwise specified (79%) groups. Minimal deviation dysplasia is defined by minor architectural and cytological changes that typically requires loss of MLH1 immunohistochemical expression to support the diagnosis. Serrated dysplasia and adenomatous dysplasia have distinctive histological features and are less frequently associated with loss of MLH1 expression (13 and 5%, respectively). Finally, dysplasia not otherwise specified encompasses most cases and shows a diverse range of morphological changes that do not fall into the other subgroups and are frequently associated with loss of MLH1 expression (83%). This morphological classification of sessile serrated adenomas with dysplasia may represent an

  9. Expression of DNA mismatch repair proteins MLH1, MSH2, and MSH6 in recurrent glioblastoma.

    Science.gov (United States)

    Stark, Andreas M; Doukas, Alexander; Hugo, Heinz-Herrmann; Hedderich, Jürgen; Hattermann, Kirsten; Maximilian Mehdorn, H; Held-Feindt, Janka

    2015-02-01

    Methylated O6-methylguanin-DNA-methytransferase (MGMT) promoter methylation is associated with survival in patients with glioblastoma. Current evidence suggests that further mismatch repair genes play a pivotal role in the tumor response to treatment. Candidate genes are MLH1, MSH2, and MSH6. Formerly, we found evidence of prognostic impact of MLH1 and MSH6 immunohistochemical expression in a small series of patients with initial glioblastoma. Two hundred and eleven patients were included who underwent macroscopically total removal of primary glioblastoma and at least one re-craniotomy for recurrence. Immunohistochemical staining was performed on paraffin-embedded specimens of initial tumors with specific antibodies against MLH1, MSH2, and MSH6. RESULTS were compared to the Ki67 proliferation index and patient survival. Additionally, fresh frozen samples from 16 paired initial and recurrent specimens were examined using real-time reverse transcription polymerase chain reaction (RT-PCR) with specific primers against MLH1, MSH2, and MSH6. RESULTS were compared to MGMT status and survival. (1) Immunohistochemical expression of MSH6 was significantly associated with the Ki67 proliferation index (PMLH1, MLH2, and MSH6 over treatment combined with lacking MGMT methylation. In another two patients, decreased MLH1, MSH2, and MSH6 expression was observed in combination with MGMT promoter methylation. Our data indicate that there may be glioblastoma patient subgroups characterized by MMR-expression changes beyond MGMT promoter methylation. The immunohistochemical expression of MLH1, MSH2, and MSH6 in initial glioblastoma is not associated with patient survival.

  10. Identification of constitutional MLH1 epimutations and promoter variants in colorectal cancer patients from the Colon Cancer Family Registry

    Science.gov (United States)

    Ward, Robyn L.; Dobbins, Timothy; Lindor, Noralane M.; Rapkins, Robert W.; Hitchins, Megan P.

    2013-01-01

    Purpose: Constitutional MLH1 epimutations manifest as promoter methylation and silencing of the affected allele in normal tissues, predisposing to Lynch syndrome–associated cancers. This study investigated their frequency and inheritance. Methods: A total of 416 individuals with a colorectal cancer showing loss of MLH1 expression and without deleterious germline mutations in MLH1 were ascertained from the Colon Cancer Family Registry (C-CFR). Constitutive DNA samples were screened for MLH1 methylation in all 416 subjects and for promoter sequence changes in 357 individuals. Results: Constitutional MLH1 epimutations were identified in 16 subjects. Of these, seven (1.7%) had mono- or hemi-allelic methylation and eight had low-level methylation (2%). In one subject the epimutation was linked to the c.-27C>A promoter variant. Testing of 37 relatives from nine probands revealed paternal transmission of low-level methylation segregating with a c.+27G>A variant in one case. Five additional probands had a promoter variant without an MLH1 epimutation, with three showing diminished promoter activity in functional assays. Conclusion: Although rare, sequence changes in the regulatory region of MLH1 and aberrant methylation may alone or together predispose to the development of cancer. Screening for these changes is warranted in individuals who have a negative germline sequence screen of MLH1 and loss of MLH1 expression in their tumor. PMID:22878509

  11. Characterization of a Highly Conserved Binding Site of Mlh1 Required for Exonuclease I-Dependent Mismatch Repair

    DEFF Research Database (Denmark)

    Dherin, Claudine; Gueneau, Emeric; Francin, Mathilde

    2009-01-01

    Mlh1 is an essential factor of mismatch repair (MMR) and meiotic recombination. It interacts through its C-terminal region with MutL homologs and proteins involved in DNA repair and replication. In this study, we identified the site of yeast Mlh1 critical for the interaction with Exo1, Ntg2......, and Sgs1 proteins, designated as site S2 by reference to the Mlh1/Pms1 heterodimerization site S1. We show that site S2 is also involved in the interaction between human MLH1 and EXO1 or BLM. Binding at this site involves a common motif on Mlh1 partners that we called the MIP-box for the Mlh1 interacting...... protein box. Direct and specific interactions between yeast Mlh1 and peptides derived from Exo1, Ntg2, and Sgs1 and between human MLH1 and peptide derived from EXO1 and BLM were measured with K(d) values ranging from 8.1 to 17.4 microM. In Saccharomyces cerevisiae, a mutant of Mlh1 targeted at site S2...

  12. MLH1-93 G/a polymorphism is associated with MLH1 promoter methylation and protein loss in dysplastic sessile serrated adenomas with BRAFV600E mutation.

    Science.gov (United States)

    Fennell, Lochlan J; Jamieson, Saara; McKeone, Diane; Corish, Tracie; Rohdmann, Megan; Furner, Tori; Bettington, Mark; Liu, Cheng; Kawamata, Futoshi; Bond, Catherine; Van De Pols, Jolieke; Leggett, Barbara; Whitehall, Vicki

    2018-01-05

    Sessile serrated adenomas with BRAF mutation progress rapidly to cancer following the development of dysplasia (SSAD). Approximately 75% of SSADs methylate the mismatch repair gene MLH1, develop mismatch repair deficiency and the resultant cancers have a good prognosis. The remaining SSADs and BRAF mutant traditional serrated adenomas (TSA) develop into microsatellite stable cancers with a poor prognosis. The reason for this dichotomy is unknown. In this study, we assessed the genotypic frequency of the MLH1-93 polymorphism rs1800734 in SSADs and TSAs to determine if the uncommon variant A allele predisposes to MLH1 promoter hypermethylation. We performed genotyping for the MLH1-93 polymorphism, quantitative methylation specific PCR, and MLH1 immunohistochemistry on 124 SSAD, 128 TSA, 203 BRAF mutant CRCs and 147 control subjects with normal colonoscopy. The minor A allele was significantly associated with a dose dependent increase in methylation at the MLH1 promoter in SSADs (p = 0.022). The AA genotype was only observed in SSADs with MLH1 loss. The A allele was also overrepresented in BRAF mutant cancers with MLH1 loss. Only one of the TSAs showed loss of MLH1 and the overall genotype distribution in TSAs did not differ from controls. The MLH1-93 AA genotype is significantly associated with promoter hypermethylation and MLH1 loss in the context of SSADs. BRAF mutant microsatellite stable colorectal cancers with the AA genotype most likely arise in TSAs since the A allele does not predispose to methylation in this context.

  13. Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key.

    Science.gov (United States)

    Leong, Vivian; Lorenowicz, Jessica; Kozij, Natalie; Guarné, Alba

    2009-08-01

    DNA mismatch repair maintains genomic stability by correcting errors that have escaped polymerase proofreading. Defects on mismatch repair genes lead to an increased mutation rate, microsatellite instability and predisposition to human non-polyposis colorectal cancer (HNPCC). Human MutLalpha is a heterodimer formed by the interaction of MLH1 and PMS2 that coordinates a series of key events in mismatch repair. It has been proposed that nuclear import of MutLalpha may be the first regulatory step on the activation of the mismatch repair pathway. Using confocal microscopy and mismatch repair deficient cells, we have identified the sequence determinants that drive nuclear import of human MLH1, PMS2, and MutLalpha. Transient transfection of the individual proteins reveals that MLH1 has a bipartite and PMS2 has a single monopartite nuclear localization signal. Although dimerization is not required for nuclear localization, the MutLalpha heterodimer is imported more efficiently than the MLH1 or PMS2 monomers. Interestingly, the bipartite localization signal of MLH1 can direct import of MutLalpha even when PMS2 encompasses a mutated localization signal. Hence we conclude that the presence of redundant nuclear localization signals guarantees nuclear transport of MutLalpha and, consequently, efficient mismatch repair.

  14. Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

    Science.gov (United States)

    Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

    2016-01-01

    The mammalian DNA mismatch repair (MMR) system consists of a number of proteins that play important roles in repair of base pair mismatch mutations and in maintenance of genomic integrity. A defect in this system can cause genetic instability, which can lead to carcinogenesis. For instance, a germline mutation in one of the mismatch repair proteins, especially MLH1 or MSH2, is responsible for hereditary non-polyposis colorectal cancer. These MMR proteins also play an important role in the induction of apoptosis. Accordingly, altered expression of or a defect in MLH1 or MSH2 may confer resistance to anti-cancer drugs used in chemotherapy. We hypothesized that the ability of these two MMR proteins to regulate apoptosis are interdependent. Moreover, a defect in either one may confer resistance to chemotherapy by an inability to trigger apoptosis. To this end, we studied three cell lines-SW480, LoVo, and HTC116. These cell lines were selected based on their differential expression of MLH1 and MSH2 proteins. SW480 expresses both MLH1 and MSH2; LoVo expresses only MLH1 but not MSH2; HCT116 expresses only MSH2 but not MLH1 protein. MTT assays, a measure of cytotoxicity, showed that there were different cytotoxic effects of an anti-cancer drug, etoposide, on these cell lines, effects that were correlated with the MMR status of the cells. Cells that are deficient in MLH1 protein (HCT116 cells) were resistant to the drug. Cells that express both MLH1 and MSH2 proteins (SW480 cells) showed caspase-3 cleavage, an indicator of apoptosis. Cells that lack MLH1 (HCT116 cells) did not show any caspase-3 cleavage. Expression of full-length MLH1 protein was decreased in MMR proficient (SW480) cells during apoptosis; it remained unchanged in cells that lack MSH2 (LoVo cells). The expression of MSH2 protein remained unchanged during apoptosis both in MMR proficient (SW480) and deficient (HCT116) cells. Studies on translocation of MLH1 protein from nucleus to cytosolic fraction, an

  15. Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.

    Science.gov (United States)

    Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R

    2014-01-01

    Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

  16. Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea.

    Science.gov (United States)

    Fukushima, Takao; Katayama, Yoichi; Watanabe, Takao; Yoshino, Atsuo; Ogino, Akiyoshi; Ohta, Takashi; Komine, Chiaki

    2005-02-15

    In certain types of human cancers, transcriptional inactivation of hMLH1 by promoter hypermethylation plays a causal role in the loss of mismatch repair functions that modulate cytotoxic pathways in response to DNA-damaging agents. The aim of the present study was to investigate the role of promoter methylation of the hMLH1 gene in malignant astrocytomas. We examined the hMLH1 promoter methylation in a homogeneous cohort of patients with 41 malignant astrocytomas treated by 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea chemotherapy in combination with radiation and interferon therapy, and assessed the correlation of such methylation with clinical outcome. hMLH1 promoter methylation was found in 6 (15%) of the 41 newly diagnosed malignant astrocytomas. Hypermethylation of the hMLH1 promoter corresponded closely with a loss of immunohistochemical staining for hMLH1 protein (P = 0.0013). Patients with hMLH1-methylated tumors displayed a greater chance of responding to adjuvant therapy as compared with those with hMLH1-unmethylated tumors (P = 0.0150). The presence of hMLH1 hypermethylation was significantly associated with a longer progression-free survival on both univariate analysis (P = 0.0340) and multivariate analysis (P = 0.0161). The present study identified hMLH1 methylation status as a predictor of the clinical response of malignant astrocytomas to chloroethylnitrosourea-based adjuvant therapy. The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis.

  17. Artefactual punctate MLH1 staining can lead to erroneous reporting of isolated PMS2 loss.

    Science.gov (United States)

    Niu, Bonnie T; Hammond, Rory F L; Leen, Sarah L S; Faruqi, Asma Z; Trevisan, Giorgia; Gilks, C Blake; Singh, Naveena

    2018-05-31

    Germline mutations in the PMS2 gene are an uncommon cause of Lynch Syndrome (LS), present in PMS2 immunohistochemical expression, with retained MLH1 expression, triggers referral to genetics services due to the significant risk of LS 3 . As detection of PMS2 germline mutations is problematic 4 , this may result in patients being labeled as "Lynch-like", with implications for future surveillance 5 . A recent study suggested that some cases of isolated PMS2 loss result from MLH1 promoter methylation and are sporadic rather than likely LS 6 ; they therefore recommended MLH1 promoter methylation testing in all cases of isolated PMS2 loss 6 . This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Respostas lactacidêmicas de ratos ao treinamento intermitente de alta intensidade

    Directory of Open Access Journals (Sweden)

    Ana Carolina Panveloski-Costa

    2012-04-01

    Full Text Available Durante contrações musculares de alta intensidade intervaladas por curtos períodos de tempo há importante participação do metabolismo glicolítico e, consequentemente, aumento das concentrações de lactato sanguíneo. O objetivo do estudo foi avaliar as respostas lactacidêmicas agudas e crônicas de ratos Wistar submetidos a um treinamento intermitente de alta intensidade (salto tipo jump squat de três sessões semanais, a cada 24h, três séries de 12 repetições com intervalos de 60s entre cada uma. Houve aumento das concentrações de lactato sanguíneo durante a sessão aguda do treinamento (lactacidemia basal vs. lactacidemia após último esforço, P < 0,001. Contrariamente, após seis semanas de treinamento, ocorreu redução de 49% na resposta lactacidêmica ao exercício em relação à primeira sessão, P = 0,0002. O exercício intermitente de alta intensidade intervalado favorece a participação do sistema glicolítico; no entanto, o treinamento intermitente de alta intensidade promove redução das respostas lactacidêmicas, sugerindo melhora da capacidade de ressíntese de fosfocreatina e da biogênese mitocondrial.

  19. Cancer-Predicting Gene Expression Changes in Colonic Mucosa of Western Diet Fed Mlh1 +/- Mice

    Science.gov (United States)

    Dermadi Bebek, Denis; Valo, Satu; Reyhani, Nima; Ollila, Saara; Päivärinta, Essi; Peltomäki, Päivi; Mutanen, Marja; Nyström, Minna

    2013-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the Western world and interactions between genetic and environmental factors, including diet, are suggested to play a critical role in its etiology. We conducted a long-term feeding experiment in the mouse to address gene expression and methylation changes arising in histologically normal colonic mucosa as putative cancer-predisposing events available for early detection. The expression of 94 growth-regulatory genes previously linked to human CRC was studied at two time points (5 weeks and 12 months of age) in the heterozygote Mlh1 +/- mice, an animal model for human Lynch syndrome (LS), and wild type Mlh1 +/+ littermates, fed by either Western-style (WD) or AIN-93G control diet. In mice fed with WD, proximal colon mucosa, the predominant site of cancer formation in LS, exhibited a significant expression decrease in tumor suppressor genes, Dkk1, Hoxd1, Slc5a8, and Socs1, the latter two only in the Mlh1 +/- mice. Reduced mRNA expression was accompanied by increased promoter methylation of the respective genes. The strongest expression decrease (7.3 fold) together with a significant increase in its promoter methylation was seen in Dkk1, an antagonist of the canonical Wnt signaling pathway. Furthermore, the inactivation of Dkk1 seems to predispose to neoplasias in the proximal colon. This and the fact that Mlh1 which showed only modest methylation was still expressed in both Mlh1 +/- and Mlh1 +/+ mice indicate that the expression decreases and the inactivation of Dkk1 in particular is a prominent early marker for colon oncogenesis. PMID:24204690

  20. Cancer-predicting gene expression changes in colonic mucosa of Western diet fed Mlh1+/- mice.

    Directory of Open Access Journals (Sweden)

    Marjaana Pussila

    Full Text Available Colorectal cancer (CRC is the second most common cause of cancer-related deaths in the Western world and interactions between genetic and environmental factors, including diet, are suggested to play a critical role in its etiology. We conducted a long-term feeding experiment in the mouse to address gene expression and methylation changes arising in histologically normal colonic mucosa as putative cancer-predisposing events available for early detection. The expression of 94 growth-regulatory genes previously linked to human CRC was studied at two time points (5 weeks and 12 months of age in the heterozygote Mlh1(+/- mice, an animal model for human Lynch syndrome (LS, and wild type Mlh1(+/+ littermates, fed by either Western-style (WD or AIN-93G control diet. In mice fed with WD, proximal colon mucosa, the predominant site of cancer formation in LS, exhibited a significant expression decrease in tumor suppressor genes, Dkk1, Hoxd1, Slc5a8, and Socs1, the latter two only in the Mlh1(+/- mice. Reduced mRNA expression was accompanied by increased promoter methylation of the respective genes. The strongest expression decrease (7.3 fold together with a significant increase in its promoter methylation was seen in Dkk1, an antagonist of the canonical Wnt signaling pathway. Furthermore, the inactivation of Dkk1 seems to predispose to neoplasias in the proximal colon. This and the fact that Mlh1 which showed only modest methylation was still expressed in both Mlh1(+/- and Mlh1(+/+ mice indicate that the expression decreases and the inactivation of Dkk1 in particular is a prominent early marker for colon oncogenesis.

  1. Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in Mlh1-deficient mice.

    Science.gov (United States)

    Morioka, Takamitsu; Miyoshi-Imamura, Tomoko; Blyth, Benjamin J; Kaminishi, Mutsumi; Kokubo, Toshiaki; Nishimura, Mayumi; Kito, Seiji; Tokairin, Yutaka; Tani, Shusuke; Murakami-Murofushi, Kimiko; Yoshimi, Naoki; Shimada, Yoshiya; Kakinuma, Shizuko

    2015-03-01

    Genetic, physiological and environmental factors are implicated in colorectal carcinogenesis. Mutations in the mutL homolog 1 (MLH1) gene, one of the DNA mismatch repair genes, are a main cause of hereditary colon cancer syndromes such as Lynch syndrome. Long-term chronic inflammation is also a key risk factor, responsible for colitis-associated colorectal cancer; radiation exposure is also known to increase colorectal cancer risk. Here, we studied the effects of radiation exposure on inflammation-induced colon carcinogenesis in DNA mismatch repair-proficient and repair-deficient mice. Male and female Mlh1(-/-) and Mlh1(+/+) mice were irradiated with 2 Gy X-rays when aged 2 weeks or 7 weeks and/or were treated with 1% dextran sodium sulfate (DSS) in drinking water for 7 days at 10 weeks old to induce mild inflammatory colitis. No colon tumors developed after X-rays and/or DSS treatment in Mlh1(+/+) mice. Colon tumors developed after DSS treatment alone in Mlh1(-/-) mice, and exposure to radiation prior to DSS treatment increased the number of tumors. Histologically, colon tumors in the mice resembled the subtype of well-to-moderately differentiated adenocarcinomas with tumor-infiltrating lymphocytes of human Lynch syndrome. Immunohistochemistry revealed that expression of both p53 and β-catenin and loss of p21 and adenomatosis polyposis coli proteins were observed at the later stages of carcinogenesis, suggesting a course of molecular pathogenesis distinct from typical sporadic or colitis-associated colon cancer in humans. In conclusion, radiation exposure could further increase the risk of colorectal carcinogenesis induced by inflammation under the conditions of Mlh1 deficiency. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  2. Biallelic MLH1 SNP cDNA expression or constitutional promoter methylation can hide genomic rearrangements causing Lynch syndrome.

    Science.gov (United States)

    Morak, Monika; Koehler, Udo; Schackert, Hans Konrad; Steinke, Verena; Royer-Pokora, Brigitte; Schulmann, Karsten; Kloor, Matthias; Höchter, Wilhelm; Weingart, Josef; Keiling, Cortina; Massdorf, Trisari; Holinski-Feder, Elke

    2011-08-01

    A positive family history, germline mutations in DNA mismatch repair genes, tumours with high microsatellite instability, and loss of mismatch repair protein expression are the hallmarks of hereditary non-polyposis colorectal cancer (Lynch syndrome). However, in ~10-15% of cases of suspected Lynch syndrome, no disease-causing mechanism can be detected. Oligo array analysis was performed to search for genomic imbalances in patients with suspected mutation-negative Lynch syndrome with MLH1 deficiency in their colorectal tumours. A deletion in the LRRFIP2 (leucine-rich repeat flightless-interacting protein 2) gene flanking the MLH1 gene was detected, which turned out to be a paracentric inversion on chromosome 3p22.2 creating two new stable fusion transcripts between MLH1 and LRRFIP2. A single-nucleotide polymorphism in MLH1 exon 8 was expressed from both alleles, initially pointing to appropriate MLH1 function at least in peripheral cells. In a second case, an inherited duplication of the MLH1 gene region resulted in constitutional MLH1 promoter methylation. Constitutional MLH1 promoter methylation may therefore in rare cases be a heritable disease mechanism and should not be overlooked in seemingly sporadic patients.

  3. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1.

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; Franca, L.R.; Schulz, R.W.

    2008-01-01

    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile but

  4. Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Drost, Mark; Therkildsen, Christina

    2014-01-01

    >C missense mutation in exon 18 of the human MLH1 gene and biochemically characterization of the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch repair and, therefore, contributing to LS in the carriers....

  5. Evaluation of promoter methylation status of MLH1 gene in Iranian patients with colorectal tumors and adenoma polyps.

    Science.gov (United States)

    Zarandi, Ashkan; Irani, Shiva; Savabkar, Sanaz; Chaleshi, Vahid; Ghavideldarestani, Maryam; Mirfakhraie, Reza; Khodadoostan, Mahsa; Nazemalhosseini-Mojarad, Ehsan; Asadzadeh Aghdaei, Hamid

    2017-01-01

    The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population. Epigenetic silencing of mismatch repair genes, such as MLH1 , by methylation of CpG islands of their promoter region has been proved to be an important mechanism in colorectal carcinogenesis. Fifty colorectal cancer and polyp tissue samples including 13 Primary colorectal tumor and 37 Adenoma polyp samples were enrolled in this study. Methylation-specific polymerase chain reaction (MSP) was performed to find the frequency of MLH1 Promoter Methylation. Promoter methylation of MLH1 gene was detected in 5 out of 13 tumor tissues and 4 out of 37 adenoma polyp. The frequency of MLH1 methylation in tumor samples was significantly higher compared to that in polyp tissues (P= 0.026). No significant association was observed between MLH1 promoter methylation and clinicopathological characteristics of the patients. The frequency of  MLH1  promoter methylation in CRC and colon polyp was 18%. Our findings indicated that methylation of MLH1 promoter region alone cannot be considered as a biomarker for early detection of CRC.

  6. Completion of meiosis in male zebrafish (Danio rerio) despite lack of DNA mismatch repair gene mlh1

    NARCIS (Netherlands)

    Leal, M.C.; Feitsma, H.; Cuppen, E.; França, L.R.; Schulz, R.W.

    2008-01-01

    Mlh1 is a member of DNA mismatch repair (MMR) machinery and is also essential for the stabilization of crossovers during the first meiotic division. Recently, we have shown that zebrafish mlh1 mutant males are completely infertile because of a block in metaphase I, whereas females are fertile

  7. Functional characterization of MLH1 missense variants identified in Lynch Syndrome patients

    DEFF Research Database (Denmark)

    Andersen, Sofie Dabros; Liberti, Sascha Emilie; Lützen, Anne

    2012-01-01

    Germline mutations in the human DNA mismatch repair (MMR) genes MSH2 and MLH1 are associated with the inherited cancer disorder Lynch Syndrome (LS), also known as Hereditary Nonpolyposis Colorectal Cancer or HNPCC. A proportion of MSH2 and MLH1 mutations found in suspected LS patients give rise...... localization and protein-protein interaction with the dimer partner PMS2 and the MMR-associated exonuclease 1. We show that a significant proportion of examined variant proteins have functional defects in either subcellular localization or protein-protein interactions, which is suspected to lead to the cancer...

  8. The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype.

    Science.gov (United States)

    Kwok, Chau-To; Vogelaar, Ingrid P; van Zelst-Stams, Wendy A; Mensenkamp, Arjen R; Ligtenberg, Marjolijn J; Rapkins, Robert W; Ward, Robyn L; Chun, Nicolette; Ford, James M; Ladabaum, Uri; McKinnon, Wendy C; Greenblatt, Marc S; Hitchins, Megan P

    2014-05-01

    Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across ≤2.6-≤6.4 megabase regions of chromosome 3p, indicating common ancestry. A minimal ≤2.6 megabase founder haplotype common to all four families was identified, which encompassed MLH1 and additional flanking genes and segregated with the MLH1 epimutation in each family. Our findings indicate that the MLH1 c.-27C>A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.

  9. Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation.

    Science.gov (United States)

    Morak, Monika; Ibisler, Ayseguel; Keller, Gisela; Jessen, Ellen; Laner, Andreas; Gonzales-Fassrainer, Daniela; Locher, Melanie; Massdorf, Trisari; Nissen, Anke M; Benet-Pagès, Anna; Holinski-Feder, Elke

    2018-04-01

    Germline defects in MLH1 , MSH2 , MSH6 and PMS2 predisposing for Lynch syndrome (LS) are mainly based on sequence changes, whereas a constitutional epimutation of MLH1 (CEM) is exceptionally rare. This abnormal MLH1 promoter methylation is not hereditary when arising de novo, whereas a stably heritable and variant-induced CEM was described for one single allele. We searched for MLH1 promoter variants causing a germline or somatic methylation induction or transcriptional repression. We analysed the MLH1 promoter sequence in five different patient groups with colorectal cancer (CRC) (n=480) composed of patients with i) CEM (n=16), ii) unsolved loss of MLH1 expression in CRC (n=37), iii) CpG-island methylator-phenotype CRC (n=102), iv) patients with LS (n=83) and v) MLH1-proficient CRC (n=242) as controls. 1150 patients with non-LS tumours also served as controls to correctly judge the results. We detected 10 rare MLH1 promoter variants. One novel, complex MLH1 variant c.-63_-58delins18 is present in a patient with CRC with CEM and his sister, both showing a complete allele-specific promoter methylation and transcriptional silencing. The other nine promoter variants detected in 17 individuals were not associated with methylation. For four of these, a normal, biallelic MLH1 expression was found in the patients' cDNA. We report the second promoter variant stably inducing a hereditary CEM. Concerning the classification of promoter variants, we discuss contradictory results from the literature for two variants, describe classification discrepancies between existing rules for five variants, suggest the (re-)classification of five promoter variants to (likely) benign and regard four variants as functionally unclear. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Influence of MLH1 on colon cancer sensitivity to poly(ADP-ribose) polymerase inhibitor combined with irinotecan.

    Science.gov (United States)

    Tentori, Lucio; Leonetti, Carlo; Muzi, Alessia; Dorio, Annalisa Susanna; Porru, Manuela; Dolci, Susanna; Campolo, Federica; Vernole, Patrizia; Lacal, Pedro Miguel; Praz, Françoise; Graziani, Grazia

    2013-07-01

    Poly(ADP-ribose) polymerase inhibitors (PARPi) are currently evaluated in clinical trials in combination with topoisomerase I (Top1) inhibitors against a variety of cancers, including colon carcinoma. Since the mismatch repair component MLH1 is defective in 10-15% of colorectal cancers we have investigated whether MLH1 affects response to the Top1 inhibitor irinotecan, alone or in combination with PARPi. To this end, the colon cancer cell lines HCT116, carrying MLH1 mutations on chromosome 3 and HCT116 in which the wild-type MLH1 gene was replaced via chromosomal transfer (HCT116+3) or by transfection of the corresponding MLH1 cDNA (HCT116 1-2) were used. HCT116 cells or HCT116+3 cells stably silenced for PARP-1 expression were also analysed. The results of in vitro and in vivo experiments indicated that MLH1, together with low levels of Top1, contributed to colon cancer resistance to irinotecan. In the MLH1-proficient cells SN-38, the active metabolite of irinotecan, induced lower levels of DNA damage than in MLH1-deficient cells, as shown by the weaker induction of γ-H2AX and p53 phosphorylation. The presence of MLH1 contributed to induce of prompt Chk1 phosphorylation, restoring G2/M cell cycle checkpoint and repair of DNA damage. On the contrary, in the absence of MLH1, HCT116 cells showed minor Chk1 phosphorylation and underwent apoptosis. Remarkably, inhibition of PARP function by PARPi or by PARP-1 gene silencing always increased the antitumor activity of irinotecan, even in the presence of low PARP-1 expression.

  11. Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients.

    Science.gov (United States)

    Petersen, Sanne M; Dandanell, Mette; Rasmussen, Lene J; Gerdes, Anne-Marie; Krogh, Lotte N; Bernstein, Inge; Okkels, Henrik; Wikman, Friedrik; Nielsen, Finn C; Hansen, Thomas V O

    2013-10-03

    Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance. Intronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay to asses the effect on splicing. We describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732-2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T). In conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members.

  12. Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene

    NARCIS (Netherlands)

    Hu, X.; Guo, Z.; Pang, T.; Li, Q.; Afink, G.; Pontén, J.

    2000-01-01

    BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene

  13. Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.

    Science.gov (United States)

    Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P; Iacobuzio-Donahue, Christine A; Kerner, Zachary; Baylin, Stephen B; Wolfgang, Christopher L; Ahuja, Nita

    2016-12-27

    We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.

  14. Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility.

    Science.gov (United States)

    Crépin, Michel; Dieu, Marie-Claire; Lejeune, Sophie; Escande, Fabienne; Boidin, Denis; Porchet, Nicole; Morin, Gilles; Manouvrier, Sylvie; Mathieu, Michèle; Buisine, Marie-Pierre

    2012-01-01

    Constitutional epimutations of DNA mismatch repair (MMR) genes have been recently reported as a possible cause of Lynch syndrome. However, little is known about their prevalence, the risk of transmission through the germline and the risk for carriers to develop cancers. In this study, we evaluated the contribution of constitutional epimutations of MMR genes in Lynch syndrome. A cohort of 134 unrelated Lynch syndrome-suspected patients without MMR germline mutation was screened for constitutional epimutations of MLH1 and MSH2 by quantitative bisulfite pyrosequencing. Patients were also screened for the presence of EPCAM deletions, a possible cause of MSH2 methylation. Tumors from patients with constitutional epimutations were extensively analyzed. We identified a constitutional MLH1 epimutation in two proband patients. For one of them, we report for the first time evidence of transmission to two children who also developed early colonic tumors, indicating that constitutional MLH1 epimutations are associated to a real risk of transgenerational inheritance of cancer susceptibility. Moreover, a somatic BRAF mutation was detected in one affected child, indicating that tumors from patients carrying constitutional MLH1 epimutation can mimic MSI-high sporadic tumors. These findings may have important implications for future diagnostic strategies and genetic counseling. © 2011 Wiley Periodicals, Inc.

  15. Germline Hypermethylation of MLH1 and EPCAM Deletions Are a Frequent Cause of Lynch Syndrome

    NARCIS (Netherlands)

    Niessen, Renee C.; Hofstra, Robert M. W.; Westers, Helga; Ligtenberg, Marjolijn J. L.; Kooi, Krista; Jager, Paul O. J.; de Groote, Marloes L.; Dijkhuizen, Trijnie; Olderode-Berends, Maran J. W.; Hollema, Harry; Kleibeuker, Jan H.; Sijmons, Rolf H.

    It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

  16. First report of a de novo germline mutation in the MLH1 gene

    NARCIS (Netherlands)

    Stulp, Rein P; Vos, Yvonne J; Mol, Bart; Karrenbeld, Arend; de Raad, Monique; van der Mijle, Huub J C; Sijmons, Rolf H

    2006-01-01

    Hereditary non-polyposis colorectal carcinoma (HNPCC) is an autosomal dominant disorder associated with colorectal and endometrial cancer and a range of other tumor types. Germline mutations in the DNA mismatch repair (MMR) genes, particularly MLH1, MSH2, and MSH6, underlie this disorder. The vast

  17. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome.

    NARCIS (Netherlands)

    Niessen, R.C.; Hofstra, R.M.; Westers, H.; Ligtenberg, M.J.L.; Kooi, K.; Jager, P.O.; Groote, M.L. de; Dijkhuizen, T.; Olderode-Berends, M.J.; Hollema, H.; Kleibeuker, J.H.; Sijmons, R.H.

    2009-01-01

    It was shown that Lynch syndrome can be caused by germline hypermethylation of the MLH1 and MSH2 promoters. Furthermore, it has been demonstrated very recently that germline deletions of the 3' region of EPCAM cause transcriptional read-through which results in silencing of MSH2 by hypermethylation.

  18. Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis

    DEFF Research Database (Denmark)

    Hinrichsen, Inga; Brieger, Angela; Trojan, Jörg

    2013-01-01

    Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results...

  19. Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression ...

    Indian Academy of Sciences (India)

    JACEK KORDIAK

    2017-06-18

    Jun 18, 2017 ... The DLEC1, TUSC4 and MLH1 expression was analysed in lung tumour tissue samples obtained from ... among men, however, the incidence is also rising in women ... rate of lung cancer patients is still poor, mainly because .... Up to 30 PYs. 18 ..... study performed by our group, high percentage (78%).

  20. Predictive value of CHFR and MLH1 methylation in human gastric cancer.

    Science.gov (United States)

    Li, Yazhuo; Yang, Yunsheng; Lu, Youyong; Herman, James G; Brock, Malcolm V; Zhao, Po; Guo, Mingzhou

    2015-04-01

    Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan-Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3% (35/102), 21.6% (22/102), 12.7% (13/102), 9.8% (10/102), and 0% (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95% CI, 0.069-0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95% CI, 1.064-8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was

  1. MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

    Science.gov (United States)

    Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G

    2018-03-13

    Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.

  2. MLH1-Silenced and Non-Silenced Subgroups of Hypermutated Colorectal Carcinomas Have Distinct Mutational Landscapes

    Science.gov (United States)

    Donehower, Lawrence A.; Creighton, Chad J.; Schultz, Nikolaus; Shinbrot, Eve; Chang, Kyle; Gunaratne, Preethi H.; Muzny, Donna; Sander, Chris; Hamilton, Stanley R.; Gibbs, Richard A.; Wheeler, David

    2014-01-01

    Approximately 15% of colorectal carcinomas (CRC) exhibit a hypermutated genotype accompanied by high levels of microsatellite instability (MSI-H) and defects in DNA mismatch repair. These tumors, unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis. As an adjunct study to The Cancer Genome Atlas consortium that recently analyzed 224 colorectal cancers by whole exome sequencing, we compared the 35 CRC (15.6%) with a hypermutated genotype to those with a non-hypermutated genotype. We found that 22 (63%) of hypermutated CRC exhibited transcriptional silencing of the MLH1 gene, a high frequency of BRAF V600E gene mutations and infrequent APC and KRAS mutations, a mutational pattern significantly different from their non-hypermutated counterparts. However, the remaining 13 (37%) hypermutated CRC lacked MLH1 silencing, contained tumors with the highest mutation rates (“ultramutated” CRC), and exhibited higher incidences of APC and KRAS mutations, but infrequent BRAF mutations. These patterns were confirmed in an independent validation set of 250 exome-sequenced CRC. Analysis of mRNA and microRNA expression signatures revealed that hypermutated CRC with MLH1 silencing had greatly reduced levels of WNT signaling and increased BRAF signaling relative non-hypermutated CRC. Our findings suggest that hypermutated CRC include one subgroup with fundamentally different pathways to malignancy than the majority of CRC. Examination of MLH1 expression status and frequencies of APC, KRAS, and BRAF mutation in CRC may provide a useful diagnostic tool that could supplement the standard microsatellite instability assays and influence therapeutic decisions. PMID:22899370

  3. I219V polymorphism in hMLH1 gene in patients affected with ulcerative colitis.

    Science.gov (United States)

    Vietri, Maria Teresa; Riegler, Gabriele; De Paola, Marialaura; Simeone, Serena; Boggia, Maria; Improta, Alessia; Parisi, Mariarita; Molinari, Anna Maria; Cioffi, Michele

    2009-04-01

    hMLH1 gene, lying on chromosome 3p21-23, is a key factor of the mismatch repair (MMR) complex, which amends DNA replication errors. MMR alterations are involved in the development of both hereditary and sporadic forms of colorectal carcinoma related to ulcerative colitis (UC). I219V Polymorphism is located on exon 8 of hMLH1 and provides an aminoacidic substitution of isoleucine to valine, on the protein codon 219. This may affect the speed and fidelity of protein synthesis because of a tRNA paucity or changes in the mRNA secondary structure. Most of the hereditary nonpolyposis colon cancer-associated missense mutations of hMLH1 cause structural changes of the amino- or carboxy-terminal regions, involving the domains that interact with ATP and hPMS2. In this study, we analyzed the hMLH1 I219V polymorphism frequency in colectomized patients with UC. Venous blood from 100 ulcerative patients and 97 apparently healthy subjects has been collected. Out of 100 patients affected with UC, 75 noncolectomized showed an alternating course of disease, while 25 did not respond to the common drugs, and underwent colectomy. Genotyping was performed by polymerase chain reaction and following enzymatic digestion by BccI. No significant differences were found between patients with UC and controls both for genotype and allele frequencies. However, our data show a significant association when colectomized and noncolectomized patients are compared. The frequencies of G homozygosity were 28% in colectomized and 10.7% in noncolectomized patients (p < 0.05, chi(2) = 4.4, Odds ratio = 3.3). The allele frequencies of allele A were 52% in colectomized and 68% in noncolectomized patients; while those of allele G were 48% and 32%, respectively. I219V polymorphism in hMLH1 could influence the clinical course of the disease and lead to resistance to therapy.

  4. Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair.

    Science.gov (United States)

    Kosinski, Jan; Hinrichsen, Inga; Bujnicki, Janusz M; Friedhoff, Peter; Plotz, Guido

    2010-08-01

    Missense alterations of the mismatch repair gene MLH1 have been identified in a significant proportion of individuals suspected of having Lynch syndrome, a hereditary syndrome that predisposes for cancer of colon and endometrium. The pathogenicity of many of these alterations, however, is unclear. A number of MLH1 alterations are located in the C-terminal domain (CTD) of MLH1, which is responsible for constitutive dimerization with PMS2. We analyzed which alterations may result in pathogenic effects due to interference with dimerization. We used a structural model of CTD of MLH1-PMS2 heterodimer to select 19 MLH1 alterations located inside and outside two candidate dimerization interfaces in the MLH1-CTD. Three alterations (p.Gln542Leu, p.Leu749Pro, p.Tyr750X) caused decreased coexpression of PMS2, which is unstable in the absence of interaction with MLH1, suggesting that these alterations interfere with dimerization. All three alterations are located within the dimerization interface suggested by our model. They also compromised mismatch repair, suggesting that defects in dimerization abrogate repair and confirming that all three alterations are pathogenic. Additionally, we provided biochemical evidence that four alterations with uncertain pathogenicity (p.Ala586Pro, p.Leu636Pro, p.Thr662Pro, and p.Arg755Trp) are deleterious because of poor expression or poor repair efficiency, and confirm the deleterious effect of eight further alterations.

  5. Diversity of genetic events associated with MLH1 promoter methylation in Lynch syndrome families with heritable constitutional epimutation.

    Science.gov (United States)

    Leclerc, Julie; Flament, Cathy; Lovecchio, Tonio; Delattre, Lucie; Ait Yahya, Emilie; Baert-Desurmont, Stéphanie; Burnichon, Nelly; Bronner, Myriam; Cabaret, Odile; Lejeune, Sophie; Guimbaud, Rosine; Morin, Gilles; Mauillon, Jacques; Jonveaux, Philippe; Laurent-Puig, Pierre; Frébourg, Thierry; Porchet, Nicole; Buisine, Marie-Pierre

    2018-04-12

    PurposeConstitutional epimutations are an alternative to genetic mutations in the etiology of genetic diseases. Some of these epimutations, termed secondary, correspond to the epigenetic effects of cis-acting genetic defects transmitted to the offspring following a Mendelian inheritance pattern. In Lynch syndrome, a few families with such apparently heritable MLH1 epimutations have been reported so far.MethodsWe designed a long-range polymerase chain reaction next-generation sequencing strategy to screen MLH1 entire gene and applied it to 4 French families with heritable epimutations and 10 additional patients with no proven transmission of their epimutations.ResultsThis strategy successfully detected the insertion of an Alu element in MLH1 coding sequence in one family. Two previously unreported MLH1 variants were also identified in other epimutation carriers: a nucleotide substitution within intron 1 and a single-nucleotide deletion in the 5'-UTR. Detection of a partial MLH1 duplication in another family required multiplex ligation-dependent probe amplification technology. We demonstrated the segregation of these variants with MLH1 methylation and studied the functional consequences of these defects on transcription.ConclusionThis is the largest cohort of patients with MLH1 secondary epimutations associated with a broad spectrum of genetic defects. This study provides further insight into the complexity of molecular mechanisms leading to secondary epimutations.GENETICS in MEDICINE advance online publication, 12 April 2018; doi:10.1038/gim.2018.47.

  6. MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis.

    Science.gov (United States)

    Shen, Shixuan; Chen, Xiaohui; Li, Hao; Sun, Liping; Yuan, Yuan

    2018-01-01

    Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC. Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval. The Newcastle-Ottawa scale was used for quantity assessment . Subgroup and sensitivity analysis were conducted to explore sources of heterogeneity. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed for bioinformatics analysis on the correlation between MLH1 methylation and GC risk, clinicopathological behavior as well as prognosis. Results: 2365 GC and 1563 controls were included in the meta-analysis. The pooled OR of MLH1 methylation in GC was 4.895 (95% CI: 3.149-7.611, PMLH1 methylation enhanced GC risk but might not related with GC clinicopathological features and prognosis. Conclusion: MLH1 methylation is an alive biomarker for the prediction of GC and it might not affect GC behavior. Further study could be conducted to verify the impact of MLH1 methylation on GC prognosis.

  7. Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma

    International Nuclear Information System (INIS)

    Santos, Juliana Carvalho; Bastos, André Uchimura; Cerutti, Janete Maria; Ribeiro, Marcelo Lima

    2013-01-01

    Gene silencing of the repair genes MLH1 and MGMT was shown to be a mechanism underlying the development of microsatellite instability (MSI), a phenotype frequently associated with various human malignancies. Recently, aberrant methylation of MLH1, MGMT and MSI were shown to be associated with mutations in genes such as BRAF, RAS and IDH1 in colon and brain tumours. Little is known about the methylation status of MLH1 and MGMT in thyroid tumours and its association with MSI and mutational status. In a series of 96 thyroid tumours whose mutational profiles of BRAF, IDH1 and NRAS mutations and RET/PTC were previously determined, we investigated MLH1 and MGMT expression and methylation status by qPCR and methylation-specific PCR after bisulphite treatment, respectively. MSI was determined by PCR using seven standard microsatellite markers. Samples with point mutations (BRAF, IDH1 and NRAS) show a decrease in MLH1 expression when compared to negative samples. Additionally, malignant lesions show a higher MSI pattern than benign lesions. The MSI phenotype was also associated with down-regulation of MLH1. The results of this study allow us to conclude that low expression of MLH1 is associated with BRAF V600E mutations, RET/PTC rearrangements and transitions (IDH1 and NRAS) in patients with thyroid carcinoma. In addition, a significant relationship between MSI status and histological subtypes was found

  8. Repair genes expression profile of MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers.

    Science.gov (United States)

    Alves, Mônica Ghislaine Oliveira; Carta, Celina Faig Lima; de Barros, Patrícia Pimentel; Issa, Jaqueline Scholz; Nunes, Fábio Daumas; Almeida, Janete Dias

    2017-01-01

    The aim of this study was to evaluate the effect of chronic smoking on the expression profile of the repair genes MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers and never smokers. The sample consisted of thirty exfoliative cytology smears per group obtained from Smokers and Never Smokers. Total RNA was extracted and expression of the MLH1, MSH2 and ATM genes were evaluated by quantitative real-time and immunocytochemistry. The gene and protein expression data were correlated to the clinical data. Gene expression was analyzed statistically using the Student t-test and Pearson's correlation coefficient, with pMLH1, MSH2 and ATM genes were downregulated in the smoking group compared to the control with significant values for MLH1 (p=0.006), MSH2 (p=0.0001) and ATM (p=0.0001). Immunocytochemical staining for anti-MLH1, anti-MSH2 and anti-ATM was negative in Never Smokers; in Smokers it was rarely positive. No significant correlation was observed among the expression of MLH1, MSH2, ATM and age, number of cigarettes consumed per day, time of smoking during life, smoking history or levels of CO in expired air. The expression of genes and proteins related to DNA repair mechanism MLH1, MSH2 and ATM in the normal oral mucosa of chronic smokers was reduced. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Abrupt loss of MLH1 and PMS2 expression in endometrial carcinoma: molecular and morphologic analysis of 6 cases.

    Science.gov (United States)

    Pai, Rish K; Plesec, Thomas P; Abdul-Karim, Fadi W; Yang, Bin; Marquard, Jessica; Shadrach, Bonnie; Roma, Andres R

    2015-07-01

    Given that endometrial cancer (EC) is often the sentinel cancer for female Lynch syndrome patients, we have successfully implemented universal screening of ECs and have previously shown that this is the preferred method to identify these patients. However, during the course of universal screening of EC, we encountered 6 cases with an unusual pattern of mismatch-repair protein immunohistochemistry that has not been previously described in this setting. In these 6 cases, there was an abrupt loss of MLH1 and PMS2 expression in a portion of the tumor. In 3 cases, marked histologic differences were identified between the areas of the tumor with retained expression and areas with loss of expression. In 2 cases, the areas with loss of expression were of higher grade (1 demonstrated solid growth and the other demonstrated increased nuclear atypia with diffuse p53 expression). In 4 tumors, histologic features associated with microsatellite instability (MSI) were present, including increased intraepithelial lymphocytes. The areas with loss of and retained MLH1/PMS2 expression were separately microdissected and assessed for MSI and MLH1 promoter methylation. The areas with loss of MLH1 and PMS2 more commonly demonstrated MSI compared with the areas with intact expression (83% vs. 33%). MLH1 promoter methylation analysis demonstrated heterogenous hypermethylation, as all areas with loss of MLH1/PMS2 expression had more extensive methylation of MLH1 compared with those areas with retained expression. In summary, we describe the histologic and molecular features of 6 cases of EC with abrupt loss of MLH1 and PMS2 expression and demonstrate that heterogenous methylation of the MLH1 promoter results in this distinct and unusual pattern of immunohistochemical expression.

  10. A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome.

    Science.gov (United States)

    Adar, Tomer; Rodgers, Linda H; Shannon, Kristen M; Yoshida, Makoto; Ma, Tianle; Mattia, Anthony; Lauwers, Gregory Y; Iafrate, Anthony J; Chung, Daniel C

    2017-03-01

    To determine the correlation between BRAF genotype and MLH1 promoter methylation in a screening program for Lynch syndrome (LS), a universal screening program for LS was established in two medical centers. Tumors with abnormal MLH1 staining were evaluated for both BRAF V600E genotype and MLH1 promoter methylation. Tumors positive for both were considered sporadic, and genetic testing was recommended for all others. A total 1011 colorectal cancer cases were screened for Lynch syndrome, and 148 (14.6%) exhibited absent MLH1 immunostaining. Both BRAF and MLH1 methylation testing were completed in 126 cases. Concordant results (both positive or both negative) were obtained in 86 (68.3%) and 16 (12.7%) cases, respectively, with 81% concordance overall. The positive and negative predictive values for a BRAF mutation in predicting MLH1 promoter methylation were 98.9% and 41%, respectively, and the negative predictive value fell to 15% in patients ≥70 years old. Using BRAF genotyping as a sole test to evaluate cases with absent MLH1 staining would have increased referral rates for genetic testing by 2.3-fold compared with MLH1 methylation testing alone (31% vs 13.5%, respectively, PMLH1 methylation testing for BRAF wild-type cases only would significantly decrease the number of methylation assays performed and reduce the referral rate for genetic testing to 12.7%. A BRAF mutation has an excellent positive predictive value but poor negative predictive value in predicting MLH1 promoter methylation. A hybrid use of these tests may reduce the number of low-risk patients referred to genetic counseling and facilitate wider implementation of Lynch syndrome screening programs.

  11. Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer.

    Science.gov (United States)

    Castillejo, Adela; Hernández-Illán, Eva; Rodriguez-Soler, María; Pérez-Carbonell, Lucía; Egoavil, Cecilia; Barberá, Victor M; Castillejo, María-Isabel; Guarinos, Carla; Martínez-de-Dueñas, Eduardo; Juan, María-Jose; Sánchez-Heras, Ana-Beatriz; García-Casado, Zaida; Ruiz-Ponte, Clara; Brea-Fernández, Alejandro; Juárez, Miriam; Bujanda, Luis; Clofent, Juan; Llor, Xavier; Andreu, Montserrat; Castells, Antoni; Carracedo, Angel; Alenda, Cristina; Payá, Artemio; Jover, Rodrigo; Soto, José-Luis

    2015-07-01

    The prevalence of MLH1 constitutional epimutations in the general population is unknown. We sought to analyse the prevalence of MLH1 constitutional epimutations in unselected and selected series of patients with colorectal cancer (CRC). Patients with diagnoses of CRC (n=2123) were included in the unselected group. For comparison, a group of 847 selected patients with CRC who fulfilled the revised Bethesda guidelines (rBG) were also included. Somatic and constitutional MLH1 methylation was assayed via methylation-specific multiplex ligation-dependent probe amplification of cases lacking MLH1 expression. Germline alterations in mismatch-repair (MMR) genes were assessed via Sanger sequencing and methylation-specific multiplex ligation-dependent probe amplification. Loss of MLH1 expression occurred in 5.5% of the unselected series and 12.5% of the selected series (pMLH1 were detected in the unselected population (0/62); five cases from the selected series were positive for MLH1 epimutations (15.6%, 5/32; p=0.004). Our results suggest a negligible prevalence of MLH1 constitutional epimutations in unselected cases of CRC. Therefore, MLH1 constitutional epimutation analysis should be conducted only for patients who fulfil the rBG and who lack MLH1 expression with methylated MLH1. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  12. Functional characterization of rare missense mutations in MLH1 and MSH2 identified in Danish colorectal cancer patients

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Kariola, Reetta; Korhonen, Mari K

    2009-01-01

    Recently, we have performed a population based study to analyse the frequency of colorectal cancer related MLH1 and MSH2 missense mutations in the Danish population. Half of the analyzed mutations were rare and most likely only present in the families where they were identified originally. Some...... of the missense mutations were located in conserved regions in the MLH1 and MSH2 proteins indicating a relation to disease development. In the present study, we functionally characterized 10 rare missense mutations in MLH1 and MSH2 identified in 13 Danish CRC families. To elucidate the pathogenicity...

  13. Efectos del entrenamiento de fuerza con distintas intensidades relativas y nivel de rendimiento inicial sobre las respuestas neuromuscular y hormonal

    OpenAIRE

    Otero Esquina, Carlos

    2017-01-01

    Programa de Doctorado en Actividad Física, Rendimiento Deportivo y Salud El objetivo de la presente tesis doctoral fue comprobar los efectos de dos tipos de entrenamiento de fuerza distintos en intensidad e igualados en volumen en el ejercicio de sentadilla completa sobre la respuesta neuromuscular y hormonal. Para ello se realizaron 3 estudios en los que se analizaron: Estudio 1: Efectos del entrenamiento de fuerza con distintas intensidades sobre la mejora en la capacidad de salto, e...

  14. Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

    Science.gov (United States)

    Kim, Jung H; Rhee, Ye-Y; Bae, Jeong-M; Kwon, Hyeong-J; Cho, Nam-Y; Kim, Mi J; Kang, Gyeong H

    2013-07-01

    Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features

  15. Reduction of MLH1 and PMS2 confers temozolomide resistance and is associated with recurrence of glioblastoma.

    Science.gov (United States)

    Shinsato, Yoshinari; Furukawa, Tatsuhiko; Yunoue, Shunji; Yonezawa, Hajime; Minami, Kentarou; Nishizawa, Yukihiko; Ikeda, Ryuji; Kawahara, Kohichi; Yamamoto, Masatatsu; Hirano, Hirofumi; Tokimura, Hiroshi; Arita, Kazunori

    2013-12-01

    Although there is a relationship between DNA repair deficiency and temozolomide (TMZ) resistance in glioblastoma (GBM), it remains unclear which molecule is associated with GBM recurrence. We isolated three TMZ-resistant human GBM cell lines and examined the expression of O6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair (MMR) components. We used immunohistochemical analysis to compare MutL homolog 1 (MLH1), postmeiotic segregation increased 2 (PMS2) and MGMT expression in primary and recurrent GBM specimens obtained from GBM patients during TMZ treatment. We found a reduction in MLH1 expression and a subsequent reduction in PMS2 protein levels in TMZ-resistant cells. Furthermore, MLH1 or PMS2 knockdown confered TMZ resistance. In recurrent GBM tumours, the expression of MLH1 and PMS2 was reduced when compared to primary tumours.

  16. Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells

    Science.gov (United States)

    Jia, Pingping; Chastain, Megan; Zou, Ying; Her, Chengtao

    2017-01-01

    Abstract Aberrant formation of interstitial telomeric sequences (ITSs) promotes genome instabilities. However, it is unclear how aberrant ITS formation is suppressed in human cells. Here, we report that MLH1, a key protein involved in mismatch repair (MMR), suppresses telomeric sequence insertion (TSI) at intra-chromosomal regions. The frequency of TSI can be elevated by double-strand break (DSB) inducer and abolished by ATM/ATR inhibition. Suppression of TSI requires MLH1 recruitment to DSBs, indicating that MLH1's role in DSB response/repair is important for suppressing TSI. Moreover, TSI requires telomerase activity but is independent of the functional status of p53 and Rb. Lastly, we show that TSI is associated with chromosome instabilities including chromosome loss, micronuclei formation and chromosome breakage that are further elevated by replication stress. Our studies uncover a novel link between MLH1, telomerase, telomere and genome stability. PMID:28180301

  17. Tumour MLH1 promoter region methylation testing is an effective pre-screen for Lynch Syndrome (HNPCC)

    Science.gov (United States)

    Newton, K; Jorgensen, NM; Wallace, AJ; Buchanan, DD; Lalloo, F; McMahon, RFT; Hill, J; Evans, DG

    2016-01-01

    Background & Aims Lynch syndrome patients have DNA mismatch repair deficiency and up to 80% life-time risk of colorectal cancer. Screening of mutation carriers reduces colorectal cancer incidence and mortality. Selection for constitutional mutation testing relies on family history (Amsterdam and Bethesda Guidelines) and tumour derived biomarkers. Initial biomarker analysis uses mismatch repair protein immunohistochemistry and microsatellite instability. Abnormalities in either identify mismatch repair deficiency but do not differentiate sporadic epigenetic defects, due to MLH1 promoter region methylation (13% of CRCs) from Lynch Syndrome (4% of CRCs). A diagnostic biomarker capable of making this distinction would be valuable. This study compared two biomarkers in tumours with mismatch repair deficiency; quantification of methylation of the MLH1 promoter region using a novel assay and BRAF c.1799T>A, p.(Val600Glu) mutation status in the identification of constitutional mutations. Methods Tumour DNA was extracted (FFPE tissue) and pyrosequencing used to test for MLH1 promoter methylation and presence of the BRAF c.1799T>A, p.(Val600Glu) mutation 71 CRCs from individuals with pathogenic MLH1 mutations and 73 CRCs with sporadic MLH1 loss. Specificity and sensitivity was compared. Findings Unmethylated MLH1 promoter: sensitivity 94.4% (95% CI 86.2–98.4%), specificity 87.7% (95% CI 77.9–94.2%), Wild-type BRAF (codon 600): sensitivity 65.8% (95% CI 53.7–76.5%), specificity 98.6% (95% CI 92.4–100.0%) for the identification of those with pathogenic MLH1 mutations. Conclusions Quantitative MLH1 promoter region methylation using pyrosequencing is superior to BRAF codon 600 mutation status in identifying constitutional mutations in mismatch repair deficient tumours. PMID:25280751

  18. MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

    Science.gov (United States)

    Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2017-07-01

    Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (PMLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

  19. A modifier of Huntington's disease onset at the MLH1 locus.

    Science.gov (United States)

    Lee, Jong-Min; Chao, Michael J; Harold, Denise; Abu Elneel, Kawther; Gillis, Tammy; Holmans, Peter; Jones, Lesley; Orth, Michael; Myers, Richard H; Kwak, Seung; Wheeler, Vanessa C; MacDonald, Marcy E; Gusella, James F

    2017-10-01

    Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association analyses implicate a functional variant on ∼32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3'end of MLH1 and the 5'end of the neighboring LRRFIP2, and marked by an isoleucine-valine missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population.

    Science.gov (United States)

    Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui

    2017-10-03

    Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.

  1. Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer

    Science.gov (United States)

    Pussila, Marjaana; Törönen, Petri; Einarsdottir, Elisabet; Katayama, Shintaro; Krjutškov, Kaarel; Holm, Liisa; Kere, Juha; Peltomäki, Päivi; Mäkinen, Markus J; Linden, Jere; Nyström, Minna

    2018-01-01

    Abstract Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis. We conducted a long-term feeding experiment in the mouse to address expression changes arising in histologically normal colonic mucosa as putative cancer preceding events, and the effect of inherited predisposition (Mlh1+/−) and Western-style diet (WD) on those. During the 21-month experiment, carcinomas developed mainly in WD-fed mice and were evenly distributed between genotypes. Unexpectedly, the heterozygote (B6.129-Mlh1tm1Rak) mice did not show MSI in their CRCs. Instead, both wildtype and heterozygote CRC mice showed a distinct mRNA expression profile and shortage of several chromosomal segregation gene-specific transcripts (Mlh1, Bub1, Mis18a, Tpx2, Rad9a, Pms2, Cenpe, Ncapd3, Odf2 and Dclre1b) in their colon mucosa, as well as an increased mitotic activity and abundant numbers of unbalanced/atypical mitoses in tumours. Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC. PMID:29701748

  2. The Germline MLH1 K618A Variant and Susceptibility to Lynch Syndrome-Associated Tumors

    Science.gov (United States)

    Medeiros, Fabiola; Lindor, Noralane M.; Couch, Fergus J.; Highsmith, W. Edward

    2013-01-01

    Missense variants discovered during sequencing of cancer susceptibility genes can be problematic for clinical interpretation. MLH1 K618A, which results from a 2-bp alteration (AAG→GCG) leading to a substitution of lysine to alanine in codon 618, has variously been interpreted as a pathogenic mutation, a variant of unknown significance, and a benign polymorphism. We evaluated the role of MLH1 K618A in predisposition to cancer by genotyping 1512 control subjects to assess its frequency in the general population. We also reviewed the literature concerning MLH1 K618A in families with colorectal cancer. The measured allele frequency of the K618A variant was 0.40%, which is remarkably close to the 0.44% summarized from 2491 control subjects in the literature. K618A was over-represented in families with suspected Lynch syndrome. In 1366 families, the allele frequency was 0.88% (OR = 2.1, 95% CI = 1.3 to 3.5; P = 0.006). In studies of sporadic cancers of the type associated with Lynch syndrome, K618A was over-represented in 1742 cases (allele frequency of 0.83) (OR = 2.0, 95% CI = 1.2 to 3.2; P = 0.008). We conclude that MLH1 K618A is not a fully penetrant Lynch syndrome mutation, although it is not without effect, appearing to increase the risk of Lynch syndrome-associated tumors approximately twofold. Our systematic assessment approach may be useful for variants in other genes. PMID:22426235

  3. Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome

    Czech Academy of Sciences Publication Activity Database

    Švec, Jiří; Schwarzová, L.; Janošíková, B.; Štekrová, J.; Mandys, V.; Kment, M.; Vodička, Pavel

    2014-01-01

    Roč. 7, č. 8 (2014), s. 5196-5202 ISSN 1936-2625 Grant - others:GA MŠk(CZ) Prvouk-P27/LF1/1; Univerzita Karlova(CZ) CZ.2.16/3.1.00/24024 Institutional support: RVO:68378041 Keywords : germline mutation * gastric cancer * MLH1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.891, year: 2014

  4. Isolated Loss of PMS2 Immunohistochemical Expression is Frequently Caused by Heterogenous MLH1 Promoter Hypermethylation in Lynch Syndrome Screening for Endometrial Cancer Patients.

    Science.gov (United States)

    Kato, Aya; Sato, Naoki; Sugawara, Tae; Takahashi, Kazue; Kito, Masahiko; Makino, Kenichi; Sato, Toshiharu; Shimizu, Dai; Shirasawa, Hiromistu; Miura, Hiroshi; Sato, Wataru; Kumazawa, Yukiyo; Sato, Akira; Kumagai, Jin; Terada, Yukihiro

    2016-06-01

    Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2% to 6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the 4 LS-associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS identification strategy. Immunohistochemistry is recommended as a screening method for LS in EC. Isolated loss of PMS2 (IL-PMS2) expression is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing on the IL-PMS2 cases. By performing MMR-immunohistochemistry on 360 unselected ECs, we could select 8 (2.2%) cases as IL-PMS2. Heterogenous MLH1 staining and MLH1-PHM were detected in 4 of 8 (50%) IL-PMS2 tumors. Of the 5 IL-PMS2 patients who underwent genetic analysis, 1 had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM), and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases before further PMS2 genetic testing.

  5. Reduced MLH3 Expression in the Syndrome of Gan-Shen Yin Deficiency in Patients with Different Diseases.

    Science.gov (United States)

    Du, Juan; Zhong, Maofeng; Liu, Dong; Liang, Shufang; Liu, Xiaolin; Cheng, Binbin; Zhang, Yani; Yin, Zifei; Wang, Yuan; Ling, Changquan

    2017-01-01

    Traditional Chinese medicine formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the characteristic genes of gan-shen Yin deficiency constitution in different diseases. Fifty primary liver cancer (PLC) patients, 94 hypertension (HBP) patients, and 100 diabetes mellitus (DM) patients were enrolled and classified into gan-shen Yin deficiency group and non-gan-shen Yin deficiency group according to the body constitution questionnaire to assess the clinical manifestation of patients. The mRNA expressions of 17 genes in PLC patients with gan-shen Yin deficiency were different from those without gan-shen Yin deficiency. However, considering all patients with PLC, HBP, and DM, only MLH3 was significantly lower in gan-shen Yin deficiency group than that in non-gen-shen Yin deficiency. By ROC analysis, the relationship between MLH3 and gan-shen Yin deficiency constitution was confirmed. Treatment of MLH3 (-/- and -/+) mice with Liuweidihuang wan, classical prescriptions for Yin deficiency, partly ameliorates the body constitution of Yin deficiency in MLH3 (-/+) mice, but not in MLH3 (-/-) mice. MLH3 might be one of material bases of gan-shen Yin deficiency constitution.

  6. Novel Mutations in MLH1 and MSH2 Genes in Mexican Patients with Lynch Syndrome

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    Jose Miguel Moreno-Ortiz

    2016-01-01

    Full Text Available Background. Lynch Syndrome (LS is characterized by germline mutations in the DNA mismatch repair (MMR genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC, and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del and c.1852_1853delinsGC (p.K618A in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

  7. A Mononucleotide Markers Panel to Identify hMLH1/hMSH2 Germline Mutations

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    M. Pedroni

    2007-01-01

    Full Text Available Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI. MSI is present in 85–90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the “Bethesda panel”. Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germline hMLH1/hMSH2 mutations were searched for all cases showing two or more unstable microsatellites.

  8. Intensidades de treinamento resistido e pressão arterial de idosas hipertensas - um estudo piloto

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    Eline Silva da Cunha

    2012-12-01

    Full Text Available INTRODUÇÃO: Observa-se que a literatura apresenta uma lacuna acerca da intensidade ideal de treinamento resistido para idosos hipertensos, os poucos estudos existentes utilizam treinamentos com diferentes intensidades. OBJETIVO: Verificar o efeito de duas intensidades de treinamento resistido sobre a pressão arterial de idosas hipertensas controladas. Métodos: Dezesseis idosas hipertensas, controladas por medicação anti-hipertensiva, foram divididas em dois grupos através de sorteio. Nove pacientes foram submetidas a treinamento resistido moderado (G1 e sete, a treinamento resistido leve (G2. As pacientes realizaram oito semanas de treinamento resistido, com frequência de três vezes por semana em dias alternados, no período vespertino. Os exercícios realizados foram respectivamente: leg press, supino reto, extensão de joelhos, puxada frontal, flexão de joelhos, abdução de ombro, abdução unilateral de quadril com cross over e rosca direta com barra. RESULTADOS: As pacientes do G1 apresentaram redução tanto nos valores de repouso da pressão arterial diastólica (PAD p < 0,03, como da pressão arterial média (PAM p < 0,03. O G2, por sua vez, apresentou redução nos valores de repouso da PAM (p < 0,03 e uma tendência à redução na PAD (p < 0,06. A magnitude de queda em ambos os grupos foi superior aos valores apresentados na literatura. CONCLUSÂO: Tanto o treinamento resistido moderado quanto o leve, mesmo quando iniciados na terceira idade, promoveram benefícios cardiovasculares. Ambos podem ser indicados como tratamento coadjuvante para idosas hipertensas controladas por medicação.

  9. EFEITOS DO EXERCÍCIO RESISTIDO DE ALTA INTENSIDADE EM RATOS QUE RECEBERAM DEXAMETASONA

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    Rejane Walessa Pequeno Rodrigues

    Full Text Available RESUMO Introdução: A dexametasona administrada cronicamente promove alterações deletérias no metabolismo dos carboidratos. Objetivo: Avaliar os efeitos do exercício resistido de alta intensidade sobre a sensibilidade à insulina, tolerância à glicose e força muscular de ratos submetidos ao uso crônico de dexametasona. Métodos: Foram utilizados 40 ratos machos divididos randomicamente em quatro grupos: 1 Controle Sedentário (CS; 2 Controle Treinado (CT; 3 Dexametasona Sedentário (DS e 4 Dexametasona Treinado (DT. O exercício resistido foi realizado em aparelho de agachamento composto por três séries, 10 repetições, com intensidade de 75% de 1 RM durante quatro semanas. Concomitantemente, os grupos DS e DT recebiam diariamente dexametasona intraperitoneal (0,2 g/kg e os grupos CS e CT recebiam somente solução salina (0,9%. Ao final do protocolo foram realizados testes de tolerância à glicose, sensibilidade à insulina e teste de força máxima. Resultados: Nos grupos treinados (CT e DT houve aumento da força muscular de 14,78% e 36,87% respectivamente, sem ganho significativo nos grupos sedentários. No teste de tolerância à glicose, os grupos treinados (CT e DT apresentaram amplitudes atenuadas da glicose plasmática quando comparados aos grupos sedentários (CS e DS. No teste de sensibilidade à insulina, o grupo DT apresentou menor área sob a curva em relação ao grupo DS. Conclusão: O exercício resistido de alta intensidade melhora a sensibilidade à insulina, tolerância à glicose e a força muscular em ratos que receberam a dexametasona.

  10. El ritmo de intensidad en La rosa escrita de Xavier Abril

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    Óscar Coello

    2011-07-01

    Full Text Available Luego de las aventuras rítmicas practicadas por Abril en las más audaces posiciones de vanguardia, se produce una abjuración insólita –explicada luego metatextualmente– en la poiesis del artista, que lo regresa a los cauces de la elaboración versal tradicional. La rosa escrita es el poemario más emblemático de este retorno. La presente ponencia ejemplifica en un texto, a través del ritmo de intensidad, los pormenores de esta redención.Palabras claves: Xavier Abril, La rosa escrita, Vanguardia, ritmo.

  11. Creatina y entrenamiento interv??lico de alta intensidad = Creatine and hiits

    OpenAIRE

    ??lvarez S??nchez, Jos?? Luis

    2016-01-01

    El prop??sito del estudio fue determinar el efecto de la suplementaci??n con Creatina (Cr) en el entrenamiento interv??lico de alta intensidad y definir los posibles beneficios generados de dicha pr??ctica. M??todo: Se seleccionaron 12 sujetos, los cuales fueron divididos en dos grupos: Un grupo control (n=6) y un grupo experimental (n=6, Cr 20gr/d??a una semana y Cr 5gr/d??a tres semanas), todos los sujetos realizaron entrenamiento HIIT en pista dos veces por semana. Se les tomo medicione...

  12. El entrenamiento interválico de alta intensidad para el rendimiento deportivo

    OpenAIRE

    Alvarez Fernández, Iker

    2014-01-01

    El entrenamiento interválico de alta intensidad (HIIT) ha sido una parte más de los programas de entrenamiento para mejorar el rendimiento deportivo, pero su efecto puntual en los entrenamientos de deportistas altamente entrenados no se conoce en su totalidad, a pesar de ser un elemento importante de la preparación deportiva. En esta revisión veremos cómo diversas investigaciones demuestran los diferentes efectos y adaptaciones que provoca el HIIT en estos deportistas con el fin de la mejora ...

  13. RPE y velocidad como marcadores de intensidad en el press de banca

    OpenAIRE

    Bautista, I. J.; Chirosa, I. J.; Chirosa, L. J.; Martín, I.; Revilla, J.

    2016-01-01

    El propósito de esta investigación fue analizar la relación entre la evolución de la velocidad media (Velmedia) y los valores de la escala OMNI-RES, en 3 intensidades (carga Inicial [CI], máxima potencia [MP] y repetición máxima [RM]). 38 sujetos divididos en dos grupos: Entrenados (G1, n = 19) y No Entrenados (G2, n = 19) realizaron un test incremental de cargas en el ejercicio del press de banca. En la percepción subjetiva del esfuerzo (RPE) no se encontraron diferencias significativas entr...

  14. Association between MLH1 -93G>a polymorphism and risk of colorectal cancer.

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    Ting Wang

    Full Text Available The -93G>A (rs1800734 polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC risk. However, the results remain conflicting rather than conclusive.The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls was performed. Odds ratios (ORs and 95% confidence intervals (CIs were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01-1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01-1.11. This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94-3.28; AG versus GG: OR = 1.29, 95% CI = 1.10-1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24-1.68; AA versusOR = 2.29, 95% CI = 1.78-2.96. Egger's test did not show any evidence of publication bias.Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.

  15. Novel roles for MLH3 deficiency and TLE6-like amplification in DNA mismatch repair-deficient gastrointestinal tumorigenesis and progression.

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    Peng-Chieh Chen

    2008-06-01

    Full Text Available DNA mismatch repair suppresses gastrointestinal tumorgenesis. Four mammalian E. coli MutL homologues heterodimerize to form three distinct complexes: MLH1/PMS2, MLH1/MLH3, and MLH1/PMS1. To understand the mechanistic contributions of MLH3 and PMS2 in gastrointestinal tumor suppression, we generated Mlh3(-/-;Apc(1638N and Mlh3(-/-;Pms2(-/-;Apc(1638N (MPA mice. Mlh3 nullizygosity significantly increased Apc frameshift mutations and tumor multiplicity. Combined Mlh3;Pms2 nullizygosity further increased Apc base-substitution mutations. The spectrum of MPA tumor mutations was distinct from that observed in Mlh1(-/-;Apc(1638N mice, implicating the first potential role for MLH1/PMS1 in tumor suppression. Because Mlh3;Pms2 deficiency also increased gastrointestinal tumor progression, we used array-CGH to identify a recurrent tumor amplicon. This amplicon contained a previously uncharacterized Transducin enhancer of Split (Tle family gene, Tle6-like. Expression of Tle6-like, or the similar human TLE6D splice isoform in colon cancer cells increased cell proliferation, colony-formation, cell migration, and xenograft tumorgenicity. Tle6-like;TLE6D directly interact with the gastrointestinal tumor suppressor RUNX3 and antagonize RUNX3 target transactivation. TLE6D is recurrently overexpressed in human colorectal cancers and TLE6D expression correlates with RUNX3 expression. Collectively, these findings provide important insights into the molecular mechanisms of individual MutL homologue tumor suppression and demonstrate an association between TLE mediated antagonism of RUNX3 and accelerated human colorectal cancer progression.

  16. Analysis of MLH3 C2531T Polymorphism in Infertile Men with Idiopathic Azoospermia or Severe Oligozoospermia

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    MA Zaimy

    2013-04-01

    Full Text Available Introduction: Infertility is described as the inability to get pregnant after one year of unprotected intercourse. About half of infertility cases are because of male factors. Idiopathic azoospermia or severe oligozoospermia caused by genetic alterations is a significant part of male infertility. A key step of spermatogenesis is crossover events during meiotic reciprocal recombination. MLH3 protein has a crucial role in meiotic recombination and in spermatogenesis. We evaluated this function of MLH3 protein by examining the contribution of functional polymorphism in MLH3 (C2531T to the risk of male infertility. Methods: We studied this polymorphism in 110 infertile male with idiopathic azoospermia or severe oligozoospermia, and 110 fertile men with normozoospermia as a control group. MLH3 C2531T polymorphism was analyzed using the tetra-amplification refractory mutation system-PCR (4P-ARMS-PCR method. Results: Genotypes CC, CT and TT of the MLH3 gene presented frequencies of 13.6%,59.1% and 27.3%, respectively, in the men with idiopathic azoospermia or severe oligozoospermia and 37.3%,53.6% and 9.1% in the control group (p<0.001. Conclusion: The data suggest that the MLH3 C2531T polymorphism can be associated with risk of male infertility. The research data showed that presence of the polymorphic allele T leads to an increased risk of 2.35 times (OR =2.35, 95% CI =1.57-3.51; p<0.001 to develop infertility in relation to the normal control group. Therefore, the MLH3 gene polymorphism may be genetic determinant for defective spermatogenesis in the humans.

  17. GLI1 interferes with the DNA mismatch repair system in pancreatic cancer through BHLHE41-mediated suppression of MLH1.

    Science.gov (United States)

    Inaguma, Shingo; Riku, Miho; Hashimoto, Mitsuyoshi; Murakami, Hideki; Saga, Shinsuke; Ikeda, Hiroshi; Kasai, Kenji

    2013-12-15

    The mismatch repair (MMR) system is indispensable for the fidelity of DNA replication, the impairment of which predisposes to the development and progression of many types of cancers. To date, GLI1 transcription factor, a key molecule of the Hedgehog signaling pathway, has been shown to regulate the expression of several genes crucial for a variety of cancer cell properties in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), but whether GLI1 could control the MMR system was not known. Here, we showed that GLI1 and GLI2 indirectly suppressed the expression of MLH1 in PDAC cells. Through GLI1 target gene screening, we found that GLI1 and GLI2 activated the expression of a basic helix-loop-helix type suppressor BHLHE41/DEC2/SHARP1 through a GLI-binding site in the promoter. Consistent with a previous report that BHLHE41 suppresses the MLH1 promoter activity, we found that the activation of GLI1 led to the BHLHE41-dependent suppression of MLH1, and a double knockdown of GLI1 and GLI2 conversely increased the MLH1 protein in PDAC cells. Using TALEN-based modification of the MLH1 gene, we further showed that GLI1 expression was indeed associated with an increased tolerance to a methylating agent, methylnitrosourea cooperatively with a lower copy number status of MLH1. Finally, GLI1 expression was immunohistochemically related positively with BHLHE41 and inversely with MLH1 in PDAC cells and precancerous lesions of the pancreas. On the basis of these results, we propose that GLI1 depresses the MMR activity and might contribute to the development and progression of PDAC. ©2013 AACR.

  18. The mutational profile and infiltration pattern of murine MLH1-/- tumors: concurrences, disparities and cell line establishment for functional analysis.

    Science.gov (United States)

    Maletzki, Claudia; Beyrich, Franziska; Hühns, Maja; Klar, Ernst; Linnebacher, Michael

    2016-08-16

    Mice lines homozygous negative for one of the four DNA mismatch repair (MMR) genes (MLH1, MSH2, PMS2, MSH6) were generated as models for MMR deficient (MMR-D) diseases. Clinically, hereditary forms of MMR-D include Lynch syndrome (characterized by a germline MMR gene defect) and constitutional MMR-D, the biallelic form. MMR-D knockout mice may be representative for both diseases. Here, we aimed at characterizing the MLH1-/- model focusing on tumor-immune microenvironment and identification of coding microsatellite mutations in lymphomas and gastrointestinal tumors (GIT).All tumors showed microsatellite instability (MSI) in non-coding mononucleotide markers. Mutational profiling of 26 coding loci in MSI+ GIT and lymphomas revealed instability in half of the microsatellites, two of them (Rfc3 and Rasal2) shared between both entities. MLH1-/- tumors of both entities displayed a similar phenotype (high CD71, FasL, PD-L1 and CTLA-4 expression). Additional immunofluorescence verified the tumors' natural immunosuppressive character (marked CD11b/CD200R infiltration). Vice versa, CD3+ T cells as well as immune checkpoints molecules were detectable, indicative for an active immune microenvironment. For functional analysis, a permanent cell line from an MLH1-/- GIT was established. The newly developed MLH1-/- A7450 cells exhibit stable in vitro growth, strong invasive potential and heterogeneous drug response. Moreover, four additional MSI target genes (Nktr1, C8a, Taf1b, and Lig4) not recognized in the primary were identified in this cell line.Summing up, molecular and immunological mechanisms of MLH1-/- driven carcinogenesis correlate well with clinical features of MMR-D. MLH1-/- knockout mice combine characteristics of Lynch syndrome and constitutional MMR-D, making them suitable models for preclinical research aiming at MMR-D related diseases.

  19. BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.

    Science.gov (United States)

    Deihimi, Safoora; Lev, Avital; Slifker, Michael; Shagisultanova, Elena; Xu, Qifang; Jung, Kyungsuk; Vijayvergia, Namrata; Ross, Eric A; Xiu, Joanne; Swensen, Jeffrey; Gatalica, Zoran; Andrake, Mark; Dunbrack, Roland L; El-Deiry, Wafik S

    2017-06-20

    Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.

  20. MLH1 as a direct target of MiR-155 and a potential predictor of favorable prognosis in pancreatic cancer.

    Science.gov (United States)

    Liu, Wen-Jing; Zhao, Yu-Pei; Zhang, Tai-Ping; Zhou, Li; Cui, Quan-Cai; Zhou, Wei-Xun; You, Lei; Chen, Ge; Shu, Hong

    2013-08-01

    The regulation of Mut L homologue 1 (MLH1) expression by microRNA (miR)-155 and its prognostic significance in pancreatic cancer (PC) remain to be elucidated. This study aimed to address the issues. MiR-155 mimics and inhibitor were transfected to PC cell lines, Panc-1 and Capan-1. Expression of MLH1 was subsequently evaluated. Then, luciferase activity was detected after miR-155 mimics and pRL-TK plasmids containing wild-type and mutant 3'UTRs of MLH1 mRNA were co-transfected. Finally, immunohistochemical staining for MLH1 was performed in PC samples. Transfection of miR-155 mimics and inhibitor led to reversely altered protein expressions of miR-155 and MLH1, whereas the corresponding mRNA expressions were similar. A significant decrease in luciferase activity in the cells transfected with the wild-type pRL-TK plasmid was shown in contrast to those transfected with the mutant one. In addition, MLH1 was less expressed in tumor than in para-tumor tissues of PC. Extensive MLH1 expression was significantly associated with favorable differentiation and less lymph node metastasis. MLH1 expression was found to be a prognosticator in univariate analysis, and being of marginally significant impact in multivariate test. MLH1 might serve as a direct target of miR-155 and a potential prognosis predictor in PC.

  1. Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study.

    Science.gov (United States)

    Gunes, S; Agarwal, A; Henkel, R; Mahmutoglu, A M; Sharma, R; Esteves, S C; Aljowair, A; Emirzeoglu, D; Alkhani, A; Pelegrini, L; Joumah, A; Sabanegh, E

    2018-04-01

    MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation. © 2017 Blackwell Verlag GmbH.

  2. Rendimiento y calidad de forraje del pasto ovillo (Dactylis glomerata L. al variar la frecuencia e intensidad de pastoreo

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    Jorge Armando Villareal González

    2014-01-01

    Full Text Available El objetivo fue determinar el rendimiento y calidad del pasto ovillo ( Dactylis glomerata L., al variar la frecuencia e intensidad de pastoreo. Se evaluaron tres frecuencias (2, 3 y 4 semanas en primavera y verano y 4, 5 y 6 semanas durante otoño y dos intensidades de pastoreo (severa: 3 a 5 cm y ligera: 6 a 8 cm de altura de forr aje residual. Se evaluó el rendimiento de forraje, tasa de acumulación neta de forraje (TANF, composición morfoló gica y calidad del forraje. El mayor rendimiento acumulado y TANF se presentaron con pastoreo severo cada 4 y 6 sem anas y en ambas intensidades cada 3 y 5 semanas. El mayor rendimiento estacional (7,844; 7,699; 7114 kg MS ha -1 se presentó en verano en las mismas frecuencias e intensidades de pastoreo, respectivamente ( P <0.05. Durante primavera no se observaron dife rencias en rendimiento y TANF entre frecuencias de pastoreo. En otoño la frecuencia de 5 semanas superó a la de 4 ( P <0.05, pero no diferente a la de 6 semanas. En todas las estaciones del año la intensidad de pastoreo severo superó a la ligera, siendo diferentes en primavera y verano ( P <0.05. En general, el contenido de proteína total y digestibilidad in vitro de la materia seca tendieron a disminuir conforme aumentó el intervalo de pastoreo, siendo en promedio de 20 y 65 %, respectivamente. Se concluye que para obtener el mayor re ndimiento y calidad de forraje, los pastoreos deben realizarse cada 4 semanas durante primavera-verano y cada 5 semanas en otoño, a una intensidad severa.

  3. Clinical Significance of Epigenetic Inactivation of hMLH1 and BRCA1 in Tunisian Patients with Invasive Breast Carcinoma

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    Sondes Karray-Chouayekh

    2009-01-01

    Full Text Available Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli and BRCA1 (breast cancer 1, early onset in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P=.015 and 5-years disease free survival (P=.016 while hMLH1 methylation was more frequent in larger tumors (P=.002 and in presence of distant metastasis (P=.004. Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P=.006 and with overall survival (P=.015 suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer.

  4. Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation.

    Science.gov (United States)

    von Salomé, Jenny; Liu, Tao; Keihäs, Markku; Morak, Moni; Holinski-Feder, Elke; Berry, Ian R; Moilanen, Jukka S; Baert-Desurmont, Stéphanie; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    2017-12-29

    Lynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genes MLH1, MSH2, MSH6 or PMS2, with the vast majority detected in MLH1 and MSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutation MLH1 c.2059C > T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. While MLH1 c.2059C > T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution of MLH1 c.2059C > T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.

  5. Modulation of histone methylation and MLH1 gene silencing by hexavalent chromium

    International Nuclear Information System (INIS)

    Sun Hong; Zhou Xue; Chen Haobin; Li Qin; Costa, Max

    2009-01-01

    Hexavalent chromium [Cr(VI)] is a mutagen and carcinogen, and occupational exposure can lead to lung cancers and other adverse health effects. Genetic changes resulting from DNA damage have been proposed as an important mechanism that mediates chromate's carcinogenicity. Here we show that chromate exposure of human lung A549 cells increased global levels of di- and tri-methylated histone H3 lysine 9 (H3K9) and lysine 4 (H3K4) but decreased the levels of tri-methylated histone H3 lysine 27 (H3K27) and di-methylated histone H3 arginine 2 (H3R2). Most interestingly, H3K9 dimethylation was enriched in the human MLH1 gene promoter following chromate exposure and this was correlated with decreased MLH1 mRNA expression. Chromate exposure increased the protein as well as mRNA levels of G9a a histone methyltransferase that specifically methylates H3K9. This Cr(VI)-induced increase in G9a may account for the global elevation of H3K9 dimethylation. Furthermore, supplementation with ascorbate, the primary reductant of Cr(VI) and also an essential cofactor for the histone demethylase activity, partially reversed the H3K9 dimethylation induced by chromate. Thus our studies suggest that Cr(VI) may target histone methyltransferases and demethylases, which in turn affect both global and gene promoter specific histone methylation, leading to the silencing of specific tumor suppressor genes such as MLH1.

  6. Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort.

    Science.gov (United States)

    Rosty, Christophe; Clendenning, Mark; Walsh, Michael D; Eriksen, Stine V; Southey, Melissa C; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Poplawski, Nicola K; Parry, Susan; Arnold, Julie; Young, Joanne P; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A; Potter, John D; DeRycke, Melissa; Lindor, Noralane M; Thibodeau, Stephen N; Baron, John A; Win, Aung Ko; Hopper, John L; Jenkins, Mark A; Buchanan, Daniel D

    2016-02-19

    Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression. This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification). Of the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression. A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified. 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/

  7. Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Miralem Mrkonjic

    Full Text Available We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734 and microsatellite unstable (MSI-H colorectal cancers (CRCs in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability.We first tested our hypothesis in one sample from Ontario (901 cases, 1,097 controls and replicated major findings in two additional samples from Newfoundland and Labrador (479 cases, 336 controls and from Seattle (591 cases, 629 controls. Logistic regression was used to test for association between SNPs in the region of MLH1 and CRC, MSI-H CRC, MLH1 gene expression in CRC, and DNA methylation in CRC. The association between rs1800734 and MSI-H CRCs, previously reported in Ontario and Newfoundland, was replicated in the Seattle sample. Two additional SNPs, in strong linkage disequilibrium with rs1800734, showed strong associations with MLH1 promoter methylation, loss of MLH1 protein, and MSI-H CRC in all three samples. The logistic regression model of MSI-H CRC that included MLH1-promoter-methylation status and MLH1 immunohistochemistry status fit most parsimoniously in all three samples combined. When rs1800734 was added to this model, its effect was not statistically significant (P-value  = 0.72 vs. 2.3×10(-4 when the SNP was examined alone.The observed association of rs1800734 with MSI-H CRC occurs through its effect on the MLH1 promoter methylation, MLH1 IHC deficiency, or both.

  8. Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

    Science.gov (United States)

    Meunier, Katy; Ferron, Marianne; Calmel, Claire; Fléjou, Jean-François; Pocard, Marc; Praz, Françoise

    2017-09-01

    Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such. © 2017 Wiley Periodicals, Inc.

  9. Single nucleotide polymorphisms of DNA mismatch repair genes MSH2 and MLH1 confer susceptibility to esophageal cancer.

    Science.gov (United States)

    Sun, Ming-Zhong; Ju, Hui-Xiang; Zhou, Zhong-Wei; Jin, Hao; Zhu, Rong

    2014-01-01

    Defects in DNA mismatch repair genes like MSH2 and MLH1 confer increased risk of cancers. Here, single nucleotide polymorphisms (SNPs) in MSH2 and MLH1 were investigated for their potential contribution to the risk of esophageal cancer. This study recruited 614 participants from Affiliated Yancheng Hospital, School of Medicine, Southeast University, of which 289 were patients with esophageal cancer, and the remainder was healthy individuals who served as a control group. Two SNPs, MSH2 c.2063T>G and MLH1 IVS14-19A>G, were genotyped using PCR-RFLP. Statistical analysis was performed using chi-square test and logistic regression analysis. Carriers of the MSH2 c.2063G allele were at significantly higher risk for esophageal cancer compared to individuals with the TT genotype [OR = 3.36, 95% confidence interval (CI): 1.18-11.03]. The MLH1 IVS14-19A>G allele also conferred significantly increased (1.70-fold) for esophageal cancer compared to the AA genotype (OR = 1.70, 95% CI: 1.13-5.06). Further, the variant alleles interacted such that individuals with the susceptible genotypes at both MSH2 and MLH1 had a significantly exacerbated risk for esophageal cancer (OR = 12.38, 95% CI: 3.09-63.11). In brief, SNPs in the DNA mismatch repair genes MSH2 and MLH1 increase the risk of esophageal cancer. Molecular investigations are needed to uncover the mechanism behind their interaction effect.

  10. Excess of extracolonic non-endometrial multiple primary cancers in MSH2 germline mutation carriers over MLH1.

    Science.gov (United States)

    Lin-Hurtubise, Kevin M; Yheulon, Christopher G; Gagliano, Ronald A; Lynch, Henry T

    2013-12-01

    The lynch syndrome (LS) tumor spectrum involves colorectal cancer (CRC), endometrial cancer (EC), and less frequently various extracolonic non-endometrial cancers (non-EC). The organ-specific survival rates of these patients are well defined, however, the collective survival of all-cancers combined (CRC + EC + non-EC) are unclear. Fifty-two MSH2 patients and 68 MLH1 patients were followed for a median of 6.3 years after diagnosis of first cancer, regardless of type. The proportions of CRC only, EC, non-EC, and multiple primary cancers were compared between the two genotypes. Kaplan-Meier curves were developed for survival comparisons. MSH2 patients present less frequently with only CRC (37% MSH2, 62% MLH1, P = 0.0096), manifest more multiple primary cancers (38% MSH2, 18% MLH1, P = 0.013), develop more extracolonic cancers (62% MSH2, 38% MLH1, P = 0.003), non-EC only cancers (46% MSH2, 24% MLH1, P = 0.028) and carry a greater risk for urinary tract cancer (UTC) (13.4% MSH2, 1.5% MLH1, P = 0.024). There was no difference in 10-year survival between the two groups (P = 0.4). The additional propensity for UTC in MSH2 carriers argues in favor of UTC screening in MSH2 individuals. Other types of cancer screening should be tailored to the expression history of the specific LS mutation. © 2013 Wiley Periodicals, Inc.

  11. Modulation of transcription factor binding and epigenetic regulation of the MLH1 CpG island and shore by polymorphism rs1800734 in colorectal cancer.

    Science.gov (United States)

    Savio, Andrea J; Bapat, Bharati

    2017-06-03

    The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG). There was significant enrichment of transcription factor AP4 at the MLH1 promoter in GG and GA cell lines, but not the AA cell line, by chromatin immunoprecipitation studies. Preferential binding to the G allele was confirmed by sequencing in the GA cell line. The enhancer-associated histone modification H3K4me1 was enriched at the MLH1 shore; however, H3K27ac was not, indicating the shore is an inactive enhancer. These results demonstrate the role of variant rs1800734 in altering transcription factor binding as well as epigenetics at regions beyond the MLH1 CpG island in which it is located.

  12. Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols : A Prospective Lynch Syndrome Database report

    NARCIS (Netherlands)

    Seppala, Toni; Pylvanainen, Kirsi; Evans, Dafydd Gareth; Jarvinen, Heikki; Renkonen-Sinisalo, Laura; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rodland, Einar Andreas; Tharmaratnam, Kukatharmini; Cappel, Wouter H. de Vos tot Nederveen; Hill, James; Wijnen, Juul; Jenkins, Mark; Genuardi, Maurizio; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Frayling, Ian M.; Plazzer, John-Paul; Sampson, Julian R.; Capella, Gabriel; Moslein, Gabriela; Mecklin, Jukka-Pekka; Moller, Pal

    2017-01-01

    BACKGROUND: We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenicMLH1variants(path_MLH1) despite follow-up with colonoscopy including polypectomy. METHODS: The cohort included Finnish carriers enrolled in 3-yearly colonoscopy (n = 505; 4625 observation

  13. Common mutations identified in the MLH1 gene in familial Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Jisha Elias

    2017-12-01

    In this study we identified three families with Lynch syndrome from a rural cancer center in western India (KCHRC, Goraj, Gujarat, where 70-75 CRC patients are seen annually. DNA isolated from the blood of consented family members of all three families (8-10 members/family was subjected to NGS sequencing methods on an Illumina HiSeq 4000 platform. We identified unique mutations in the MLH1 gene in all three HNPCC family members. Two of the three unrelated families shared a common mutation (154delA and 156delA. Total 8 members of a family were identified as carriers for 156delA mutation of which 5 members were unaffected while 3 were affected (age of onset: 1 member <30yrs & 2 were>40yr. The family with 154delA mutation showed 2 affected members (>40yr carrying the mutations.LYS618DEL mutation found in 8 members of the third family showed that both affected and unaffected carried the mutation. Thus the common mutations identified in the MLH1 gene in two unrelated families had a high risk for lynch syndrome especially above the age of 40.

  14. Influência da altura do selim e intensidade do exercício sobre assimetrias na pedalada de ciclistas

    Directory of Open Access Journals (Sweden)

    Fernando Diefenthaeler

    2016-09-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n4p411   Assimetrias na pedalada quantificadas durante o ciclismo estacionário, em que a postura do ciclista e a intensidade não mudam significativamente, podem não reproduzir situações de treino e competições em que os ciclistas experimentam diferentes intensidades e optam por mudar a postura no selim para otimização da potência. Estudos prévios mostraram assimetrias no torque e potência de ciclistas. Não é claro se mudanças na posição do selim e intensidade afetam essas assimetrias. O objetivo do presente estudo foi determinar as assimetrias na pedalada durante o ciclismo em diferentes alturas de selim e diferentes intensidades de esforço. Doze ciclistas competitivos realizaram um teste incremental máximo, um teste de carga constante (domínio severo e um teste de Wingate. Os testes de carga constante e Wingate foram repetidos usando três alturas de selim (referência e 2,5% abaixo ou acima da referência, que foi medida pela distância da sínfise púbica até o solo. O torque gerado no pedivela foi medido durante todo o ciclo de pedalada. Assimetrias (maior torque na perna preferida foram encontradas em todas as alturas de selim (p<0,001 em ambas as intensidades. O índice de assimetria foi similar em todas as alturas de selim (p<0,05 em ambas as intensidades. Os resultados sugerem que ciclistas assimétricos apresentam um padrão consistente independente de pequenas mudanças na posição do selim ou intensidade do exercício. Como implicação prática, ciclistas produzindo torque assimétrico podem estar adaptados a esta condição e sendo continuamente expostos a esforços e sobrecargas assimétricas nos membros inferiores.

  15. Epigenetic silencing of the DNA mismatch repair gene, MLH1, induced by hypoxic stress in a pathway dependent on the histone demethylase, LSD1

    Science.gov (United States)

    Lu, Yuhong; Wajapeyee, Narendra; Turker, Mitchell S.; Glazer, Peter M.

    2014-01-01

    SUMMARY Silencing of the MLH1 gene is frequently seen in sporadic cancers. We report that hypoxia causes decreased H3K4 methylation at the MLH1 promoter via the H3K4 demethylases, LSD1 and PLU-1, and promotes long-term silencing of the promoter in a pathway that requires LSD1. Knockdown of LSD1 or its co-repressor, CoREST, also prevents the re-silencing (and cytosine DNA methylation) of the endogenous MLH1 promoter in RKO colon cancer cells following transient reactivation by the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC). The results demonstrate that hypoxia is a critical driving force for silencing of MLH1 through chromatin modification and indicate that the LSD1/CoREST complex is essential for MLH1 silencing. PMID:25043185

  16. Distinct features between MLH1-methylated and unmethylated colorectal carcinomas with the CpG island methylator phenotype: implications in the serrated neoplasia pathway.

    Science.gov (United States)

    Kim, Jung Ho; Bae, Jeong Mo; Cho, Nam-Yun; Kang, Gyeong Hoon

    2016-03-22

    The presence or absence of MLH1 methylation may critically affect the heterogeneity of colorectal carcinoma (CRC) with the CpG island methylator phenotype (CIMP). Here, we investigated the differential characteristics of CIMP-high (CIMP-H) CRCs according to MLH1 methylation status. To further confirm the MLH1-dependent features in CIMP-H CRC, an independent analysis was performed using data from The Cancer Genome Atlas (TCGA). In our CIMP-H CRC samples, MLH1-methylated tumors were characterized by older patient age, proximal colonic location, mucinous histology, intense lymphoid reactions, RUNX3/SOCS1 promoter methylation, BRAF mutations, and microsatellite instability-high (MSI-H) status. By contrast, MLH1-unmethylated tumors were associated with earlier age of onset, increased distal colorectal localization, adverse pathologic features, and KRAS mutations. In the TCGA dataset, the MLH1-silenced CIMP-H CRC demonstrated proximal location, MSI-H status, hypermutated phenotype, and frequent BRAF mutations, but the MLH1-non-silenced CIMP-H CRC was significantly associated with high frequencies of KRAS and APC mutations. In conclusion, the differential nature of CIMP-H CRCs depends primarily on the MLH1 methylation status. Based on the current knowledge, the sessile serrated adenoma/polyp may be the major precursor of MLH1-methylated CIMP-H CRCs, whereas MLH1-unmethylated CIMP-H CRCs may develop predominantly from KRAS-mutated traditional serrated adenomas and less commonly from BRAF-mutated traditional serrated adenomas and/or sessile serrated adenomas/polyps.

  17. The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype

    NARCIS (Netherlands)

    Kwok, C.T.; Vogelaar, I.P.; Zelst-Stams, W.A.G. van; Mensenkamp, A.R.; Ligtenberg, M.J.L.; Rapkins, R.W.; Ward, R.L.; Chun, N.; Ford, J.M.; Ladabaum, U.; McKinnon, W.C.; Greenblatt, M.S.; Hitchins, M.P.

    2014-01-01

    Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional

  18. Fruits, vegetables and hMLH1 protein-deficient and-proficient colon cancer: the Netherlands Cohort Study

    NARCIS (Netherlands)

    Wark, P.A.; Weijenberg, M.P.; Veer, van 't P.; Wijhe, van G.; Luchtenborg, M.; Muijen, van G.N.P.; Goeij, de A.F.P.M.; Goldbohm, R.A.; Brandt, van den P.A.

    2005-01-01

    Clinical and pathologic differences exist between colon carcinomas deficient and proficient in the mismatch repair protein hMLH1. Animal and in vitro studies suggest that fruits, vegetables, folate, and antioxidants are associated with colonic expression of mismatch repair genes.METHODS:

  19. Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients

    DEFF Research Database (Denmark)

    Petersen, Sanne M; Dandanell, Mette; Rasmussen, Lene J

    2013-01-01

    Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomi...

  20. Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Bongaerts, B.W.C.; Wouters, K.A.D.; Kester, A.D.M.; Schouten, L.J.; Goeij, A.F.P.M. de; Bruïne, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den; Engeland, M. van; Weijenberg, M.P.

    2008-01-01

    Intake of dietary factors that serve as methyl group donors may influence promoter hypermethylation in colorectal carcinogenesis. We investigated whether dietary folate, vitamin B2 and vitamin B6, methionine and alcohol were associated with mutL homologue 1 (MLH1) hypermethylation and the related

  1. First description of mutational analysis of MLH1, MSH2 and MSH6 in Algerian families with suspected Lynch syndrome.

    Science.gov (United States)

    Ziada-Bouchaar, H; Sifi, K; Filali, T; Hammada, T; Satta, D; Abadi, N

    2017-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer (CRC) linked to germline defects in Mismatch Repair (MMR) genes. We present here, the first molecular study of the correlation between CRC and mutations occurring in these genes performed in twenty-one unrelated Algerian families. The presence of germline mutations in MMR genes, MLH1, MSH2 and MSH6 genes was tested by sequencing all exons plus adjacent intronic sequences and Multiplex ligand-dependent probe amplification (MLPA) for testing large genomic rearrangements. Pathogenic mutations were identified in 20 % of families with clinical suspicion on HNPCC. Two novel variants described for the first time in Algerian families were identified in MLH1, c.881_884delTCAGinsCATTCCT and a large deletion in MSH6 gene from a young onset of CRC. Moreover, the variants of MSH2 gene: c.942+3A>T, c.1030C>T, the most described ones, were also detected in Algerian families. Furthermore, the families HNPCC caused by MSH6 germline mutation may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations. In this study, we confirmed that MSH2, MLH1, and MSH6 contribute to CRC susceptibility. This work represents the implementation of a diagnostic algorithm for the identification of Lynch syndrome patients in Algerian families.

  2. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

    NARCIS (Netherlands)

    Weijenberg, M.P.; Luchtenborg, M.; Goeij, A.F. de; Brink, M.; Muijen, G.N.P. van; Bruine, A.P. de; Goldbohm, R.A.; Brandt, P.A. van den

    2007-01-01

    OBJECTIVE: To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat

  3. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

    Science.gov (United States)

    Weijenberg, Matty P; Lüchtenborg, Margreet; de Goeij, Anton F P M; Brink, Mirian; van Muijen, Goos N P; de Bruïne, Adriaan P; Goldbohm, R Alexandra; van den Brandt, Piet A

    2007-10-01

    To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene. After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients. Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC. Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.

  4. Efecto de la intensidad del contramovimiento sobre el rendimiento del salto vertical

    Directory of Open Access Journals (Sweden)

    Marcos Gutiérrez-Dávila

    2015-03-01

    Full Text Available El propósito de esta investigación ha sido comprobar el efecto de la intensidad del contramovimiento sobre el rendimiento del salto vertical. Para el control de la intensidad se han utilizado tres protocolos de saltos verticales con participación de brazos: a saltos verticales partiendo desde la posición de erguidos (CMJ + S; b partiendo de un salto previo donde la altura de caída estaba regulada por el participante (DJ-AR, y c partiendo de un salto previo máximo (DJ-M. Han participado 28 deportistas practicantes de modalidades deportivas donde el salto vertical constituye una habilidad básica. Se ha utilizado una plataforma de fuerza, operando a 500 Hz, sincronizada temporalmente a una cámara de vídeo, que registraba a 210 Hz el plano sagital de los saltos realizados sobre la plataforma. La aceleración vertical del CM se determinó a partir de la fuerza neta vertical y la masa del saltador. A continuación, los sucesivos registros de la velocidad vertical y las posiciones de componente vertical adoptadas por el CM se determinaron mediante integración de las componentes verticales de las funciones de aceleración-tiempo y velocidad-tiempo, respectivamente. Las constantes de integración se determinaron mediante imágenes de vídeo (2D. Los resultados han puesto de manifiesto que, cuando se realizan saltos con alturas de caída superiores a 0,39 ± 0,05 m, el pico de potencia durante la fase propulsiva (PP(propulsiva, el impulso vertical de propulsión (Iv(propulsión., y la altura de salto (Ycm vuelo, se reducen de forma significativa (p < 0,001, lo que nos permite afirmar que se reduce el rendimiento durante la fase propulsiva.

  5. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    Energy Technology Data Exchange (ETDEWEB)

    Zavodna, Katarina; Krivulcik, Tomas; Bujalkova, Maria Gerykova [Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia); Slamka, Tomas; Martinicky, David; Ilencikova, Denisa [National Cancer Institute, Department of Oncologic Genetics, Klenova 1, 833 01 Bratislava (Slovakia); Bartosova, Zdena [Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava (Slovakia)

    2009-11-20

    Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. We found six rearrangements in the MSH2 gene (five deletions and dup5-6), and one aberration in the MLH1 gene (del5-6). The MSH2 deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1 or MSH2 gene (heterozygous LGR region, SNP, or

  6. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

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    Ilencikova Denisa

    2009-11-01

    Full Text Available Abstract Background Depending on the population studied, large genomic rearrangements (LGRs of the mismatch repair (MMR genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC. It has been reported that loss of heterozygosity (LOH at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. Methods The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. Results We found six rearrangements in the MSH2 gene (five deletions and dup5-6, and one aberration in the MLH1 gene (del5-6. The MSH2 deletions were of three types (del1, del1-3, del1-7. We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. Conclusion LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1

  7. Partial loss of heterozygosity events at the mutated gene in tumors from MLH1/MSH2 large genomic rearrangement carriers

    International Nuclear Information System (INIS)

    Zavodna, Katarina; Krivulcik, Tomas; Bujalkova, Maria Gerykova; Slamka, Tomas; Martinicky, David; Ilencikova, Denisa; Bartosova, Zdena

    2009-01-01

    Depending on the population studied, large genomic rearrangements (LGRs) of the mismatch repair (MMR) genes constitute various proportions of the germline mutations that predispose to hereditary non-polyposis colorectal cancer (HNPCC). It has been reported that loss of heterozygosity (LOH) at the LGR region occurs through a gene conversion mechanism in tumors from MLH1/MSH2 deletion carriers; however, the converted tracts were delineated only by extragenic microsatellite markers. We sought to determine the frequency of LGRs in Slovak HNPCC patients and to study LOH in tumors from LGR carriers at the LGR region, as well as at other heterozygous markers within the gene to more precisely define conversion tracts. The main MMR genes responsible for HNPCC, MLH1, MSH2, MSH6, and PMS2, were analyzed by MLPA (multiplex ligation-dependent probe amplification) in a total of 37 unrelated HNPCC-suspected patients whose MLH1/MSH2 genes gave negative results in previous sequencing experiments. An LOH study was performed on six tumors from LGR carriers by combining MLPA to assess LOH at LGR regions and sequencing to examine LOH at 28 SNP markers from the MLH1 and MSH2 genes. We found six rearrangements in the MSH2 gene (five deletions and dup5-6), and one aberration in the MLH1 gene (del5-6). The MSH2 deletions were of three types (del1, del1-3, del1-7). We detected LOH at the LGR region in the single MLH1 case, which was determined in a previous study to be LOH-negative in the intragenic D3S1611 marker. Three tumors displayed LOH of at least one SNP marker, including two cases that were LOH-negative at the LGR region. LGRs accounted for 25% of germline MMR mutations identified in 28 Slovakian HNPCC families. A high frequency of LGRs among the MSH2 mutations provides a rationale for a MLPA screening of the Slovakian HNPCC families prior scanning by DNA sequencing. LOH at part of the informative loci confined to the MLH1 or MSH2 gene (heterozygous LGR region, SNP, or

  8. Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?

    International Nuclear Information System (INIS)

    Roon, Eddy HJ van; Hes, Frederik J; Tops, Carli MJ; Wezel, Tom van; Boer, Judith M; Morreau, Hans; Puijenbroek, Marjo van; Middeldorp, Anneke; Eijk, Ronald van; Meijer, Emile J de; Erasmus, Dianhdra; Wouters, Kim AD; Engeland, Manon van; Oosting, Jan

    2010-01-01

    To investigate the etiology of MLH1 promoter methylation in mismatch repair (MMR) mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer. We studied a set of 46 MSI-H colon tumors cases with MLH1 promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13). Tumors were tested for CIMP marker methylation and mutations linked to methylation: BRAF, KRAS, GADD45A and the MLH1 -93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for GADD45A mutations and germline MLH1 methylation. SNP array analysis was performed on a subset of tumors. We identified two cases (33 and 60 years) with MLH1 germline promoter methylation. BRAF mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044). CIMP-high was infrequent and related to BRAF mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. GADD45A sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity. Somatic or germline GADD45A mutations did not explain sporadic MSI-H colon cancer. Although germline MLH1 methylation was found in two individuals, locus-specific somatic MLH1 hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through somatic mutation of BRAF

  9. Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?

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    Hes Frederik J

    2010-05-01

    Full Text Available Abstract Background To investigate the etiology of MLH1 promoter methylation in mismatch repair (MMR mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer. Methods We studied a set of 46 MSI-H colon tumors cases with MLH1 promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13. Tumors were tested for CIMP marker methylation and mutations linked to methylation: BRAF, KRAS, GADD45A and the MLH1 -93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for GADD45A mutations and germline MLH1 methylation. SNP array analysis was performed on a subset of tumors. Results We identified two cases (33 and 60 years with MLH1 germline promoter methylation. BRAF mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044. CIMP-high was infrequent and related to BRAF mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. GADD45A sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity. Conclusion Somatic or germline GADD45A mutations did not explain sporadic MSI-H colon cancer. Although germline MLH1 methylation was found in two individuals, locus-specific somatic MLH1 hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through

  10. Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma.

    Science.gov (United States)

    Pećina-Šlaus, Nives; Kafka, Anja; Bukovac, Anja; Vladušić, Tomislav; Tomas, Davor; Hrašćan, Reno

    2017-07-01

    Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1 (D16S3399), and CDH1 (D16S752) were also investigated for microsatellite instability. Our study revealed constant presence of microsatellite instability in meningioma patients when compared to their autologous blood DNA. Altogether 38% of meningiomas showed microsatellite instability at one microsatellite locus, 16% on two, and 13.3% on three loci. The percent of detected microsatellite instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (p = 0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were observed when MLH1 or MSH2 was tested against specific histopathological meningioma subtype or World Health Organization grade. However, genetic changes in DVL3 were strongly associated with anaplastic histology of meningioma (χ 2  = 9.14; p = 0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.

  11. Performance of Lynch syndrome predictive models in quantifying the likelihood of germline mutations in patients with abnormal MLH1 immunoexpression.

    Science.gov (United States)

    Cabreira, Verónica; Pinto, Carla; Pinheiro, Manuela; Lopes, Paula; Peixoto, Ana; Santos, Catarina; Veiga, Isabel; Rocha, Patrícia; Pinto, Pedro; Henrique, Rui; Teixeira, Manuel R

    2017-01-01

    Lynch syndrome (LS) accounts for up to 4 % of all colorectal cancers (CRC). Detection of a pathogenic germline mutation in one of the mismatch repair genes is the definitive criterion for LS diagnosis, but it is time-consuming and expensive. Immunohistochemistry is the most sensitive prescreening test and its predictive value is very high for loss of expression of MSH2, MSH6, and (isolated) PMS2, but not for MLH1. We evaluated if LS predictive models have a role to improve the molecular testing algorithm in this specific setting by studying 38 individuals referred for molecular testing and who were subsequently shown to have loss of MLH1 immunoexpression in their tumors. For each proband we calculated a risk score, which represents the probability that the patient with CRC carries a pathogenic MLH1 germline mutation, using the PREMM 1,2,6 and MMRpro predictive models. Of the 38 individuals, 18.4 % had a pathogenic MLH1 germline mutation. MMRpro performed better for the purpose of this study, presenting a AUC of 0.83 (95 % CI 0.67-0.9; P < 0.001) compared with a AUC of 0.68 (95 % CI 0.51-0.82, P = 0.09) for PREMM 1,2,6 . Considering a threshold of 5 %, MMRpro would eliminate unnecessary germline mutation analysis in a significant proportion of cases while keeping very high sensitivity. We conclude that MMRpro is useful to correctly predict who should be screened for a germline MLH1 gene mutation and propose an algorithm to improve the cost-effectiveness of LS diagnosis.

  12. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management

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    Ramsoekh Dewkoemar

    2009-12-01

    Full Text Available Abstract Background Lynch syndrome (LS is associated with a high risk for colorectal cancer (CRC and extracolonic malignancies, such as endometrial carcinoma (EC. The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers. Methods The studypopulation consisted out of 67 proven LS families. Clinical information including mutation status and tumour diagnosis was collected. Cumulative risks were calculated and compared using Kaplan Meier survival analysis. Results MSH6 mutation carriers, both males and females had the lowest risk for developing CRC at age 70 years, 54% and 30% respectively and the age of onset was delayed by 3-5 years in males. With respect to endometrial carcinoma, female MSH6 mutation carriers had the highest risk at age 70 years (61% compared to MLH1 (25% and MSH2 (49%. Also, the age of EC onset was delayed by 5-10 years in comparison with MLH1 and MSH2. Conclusions Although the cumulative lifetime risk of LS related cancer is similar, MLH1, MSH2 and MSH6 mutations seem to cause distinguishable cancer risk profiles. Female MSH6 mutation carriers have a lower CRC risk and a higher risk for developing endometrial carcinoma. As a consequence, surveillance colonoscopy starting at age 30 years instead of 20-25 years is more suitable. Also, prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers.

  13. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

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    Catherine E Smith

    2013-10-01

    Full Text Available Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  14. Dominant mutations in S. cerevisiae PMS1 identify the Mlh1-Pms1 endonuclease active site and an exonuclease 1-independent mismatch repair pathway.

    Science.gov (United States)

    Smith, Catherine E; Mendillo, Marc L; Bowen, Nikki; Hombauer, Hans; Campbell, Christopher S; Desai, Arshad; Putnam, Christopher D; Kolodner, Richard D

    2013-10-01

    Lynch syndrome (hereditary nonpolypsis colorectal cancer or HNPCC) is a common cancer predisposition syndrome. Predisposition to cancer in this syndrome results from increased accumulation of mutations due to defective mismatch repair (MMR) caused by a mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2/scPMS1. To better understand the function of Mlh1-Pms1 in MMR, we used Saccharomyces cerevisiae to identify six pms1 mutations (pms1-G683E, pms1-C817R, pms1-C848S, pms1-H850R, pms1-H703A and pms1-E707A) that were weakly dominant in wild-type cells, which surprisingly caused a strong MMR defect when present on low copy plasmids in an exo1Δ mutant. Molecular modeling showed these mutations caused amino acid substitutions in the metal coordination pocket of the Pms1 endonuclease active site and biochemical studies showed that they inactivated the endonuclease activity. This model of Mlh1-Pms1 suggested that the Mlh1-FERC motif contributes to the endonuclease active site. Consistent with this, the mlh1-E767stp mutation caused both MMR and endonuclease defects similar to those caused by the dominant pms1 mutations whereas mutations affecting the predicted metal coordinating residue Mlh1-C769 had no effect. These studies establish that the Mlh1-Pms1 endonuclease is required for MMR in a previously uncharacterized Exo1-independent MMR pathway.

  15. The mRNA level of MLH1 in peripheral blood is a biomarker for the diagnosis of hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Yu, Hong; Li, Hui; Cui, Yongan; Xiao, Wei; Dai, Guihong; Huang, Junxing; Wang, Chaofu

    2016-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by functional defects in mismatch repair (MMR) genes, including mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2). This study aimed to assess whether the mRNA expression of MLH1 in peripheral blood could be used as a biomarkers for the diagnosis of HNPCC. The mRNA level of MLH1 was determined in 19 HNPCC families (46 members) using real-time quantitative polymerase chain reaction (qPCR). The mRNA levels of MLH1 in HNPCC were significantly lower than controls (P MLH1 for the diagnosis of HNPCC with the area under curve of 0.858. At an optimal cut-off value (0.511), the mRNA level of MLH1 had a sensitivity of 81.3% and a specificity of 86.7% for distinguishing HNPCC from controls. In conclusion, the mRNA expression of MLH1 in peripheral blood may serve as a biomarker for the diagnosis of HNPCC.

  16. DNA mismatch repair proteins MLH1 and PMS2 can be imported to the nucleus by a classical nuclear import pathway.

    Science.gov (United States)

    de Barros, Andrea C; Takeda, Agnes A S; Dreyer, Thiago R; Velazquez-Campoy, Adrian; Kobe, Boštjan; Fontes, Marcos R M

    2018-03-01

    MLH1 and PMS2 proteins form the MutLα heterodimer, which plays a major role in DNA mismatch repair (MMR) in humans. Mutations in MMR-related proteins are associated with cancer, especially with colon cancer. The N-terminal region of MutLα comprises the N-termini of PMS2 and MLH1 and, similarly, the C-terminal region of MutLα is composed by the C-termini of PMS2 and MLH1, and the two are connected by linker region. The nuclear localization sequences (NLSs) necessary for the nuclear transport of the two proteins are found in this linker region. However, the exact NLS sequences have been controversial, with different sequences reported, particularly for MLH1. The individual components are not imported efficiently, presumably due to their C-termini masking their NLSs. In order to gain insights into the nuclear transport of these proteins, we solved the crystal structures of importin-α bound to peptides corresponding to the supposed NLSs of MLH1 and PMS2 and performed isothermal titration calorimetry to study their binding affinities. Both putative MLH1 and PMS2 NLSs can bind to importin-α as monopartite NLSs, which is in agreement with some previous studies. However, MLH1-NLS has the highest affinity measured by a natural NLS peptide, suggesting a major role of MLH1 protein in nuclear import compared to PMS2. Finally, the role of MLH1 and PMS2 in the nuclear transport of the MutLα heterodimer is discussed. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  17. Germline MLH1 Mutations Are Frequently Identified in Lynch Syndrome Patients With Colorectal and Endometrial Carcinoma Demonstrating Isolated Loss of PMS2 Immunohistochemical Expression.

    Science.gov (United States)

    Dudley, Beth; Brand, Randall E; Thull, Darcy; Bahary, Nathan; Nikiforova, Marina N; Pai, Reetesh K

    2015-08-01

    Current guidelines on germline mutation testing for patients suspected of having Lynch syndrome are not entirely clear in patients with tumors demonstrating isolated loss of PMS2 immunohistochemical expression. We analyzed the clinical and pathologic features of patients with tumors demonstrating isolated loss of PMS2 expression in an attempt to (1) determine the frequency of germline MLH1 and PMS2 mutations and (2) correlate mismatch-repair protein immunohistochemistry and tumor histology with germline mutation results. A total of 3213 consecutive colorectal carcinomas and 215 consecutive endometrial carcinomas were prospectively analyzed for DNA mismatch-repair protein expression by immunohistochemistry. In total, 32 tumors from 31 patients demonstrated isolated loss of PMS2 immunohistochemical expression, including 16 colorectal carcinomas and 16 endometrial carcinomas. Microsatellite instability (MSI) polymerase chain reaction was performed in 29 tumors from 28 patients with the following results: 28 tumors demonstrated high-level MSI, and 1 tumor demonstrated low-level MSI. Twenty of 31 (65%) patients in the study group had tumors demonstrating histopathology associated with high-level MSI. Seventeen patients underwent germline mutation analysis with the following results: 24% with MLH1 mutations, 35% with PMS2 mutations, 12% with PMS2 variants of undetermined significance, and 29% with no mutations in either MLH1 or PMS2. Three of the 4 patients with MLH1 germline mutations had a mutation that results in decreased stability and quantity of the MLH1 protein that compromises the MLH1-PMS2 protein complex, helping to explain the presence of immunogenic but functionally inactive MLH1 protein within the tumor. The high frequency of MLH1 germline mutations identified in our study has important implications for testing strategies in patients suspected of having Lynch syndrome and indicates that patients with tumors demonstrating isolated loss of PMS2 expression

  18. Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704.

    Science.gov (United States)

    Lawrence, Yaacov R; Moughan, Jennifer; Magliocco, Anthony M; Klimowicz, Alexander C; Regine, William F; Mowat, Rex B; DiPetrillo, Thomas A; Small, William; Simko, Jeffry P; Golan, Talia; Winter, Kathryn A; Guha, Chandan; Crane, Christopher H; Dicker, Adam P

    2018-02-01

    The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

  19. Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

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    Metcalf, Alexander M; Spurdle, Amanda B

    2014-03-01

    Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

  20. CpG Island Methylator Phenotype Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis

    Science.gov (United States)

    Fu, Tao; Pappou, Emmanouil P.; Guzzetta, Angela A.; Jeschke, Jana; Kwak, Ruby; Dave, Pujan; Hooker, Craig M.; Morgan, Richard; Baylin, Stephen B.; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Ahuja, Nita

    2012-01-01

    Purpose Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis. Experimental Design Demographics, tumor characteristics and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation and CpG island methylator phenotype (CIMP) status was performed. A Cox proportional hazard model was built to predict survival. Results CIMP+ was detected in 27 of 99 (27.3%) duodenal adenocarcinomas, and was associated with MSI (P = 0.011) and MLH1 methylation (P CIMP− tumors. No BRAF V600E mutation was detected. Among the CIMP+ tumors, 15 (55.6%) were CIMP+/MLH1-unmethylated (MLH1-U). Kaplan-Meier analysis showed tumors classified by CIMP, CIMP/MLH1 methylation status or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), while CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value regarding both OS (P CIMP+/MLH1-U tumors had the worst OS and TTR. Conclusions Our results demonstrate existence of CIMP in duodenal adenocarcinomas. The combination of CIMP+/MLH1-U appears to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI or CIMP development. PMID:22825585

  1. EFECTOS ENTRENAMIENTO INTERVÁLICO DE MÁXIMA INTENSIDAD EN HIPOXIA (EIMIH SOBRE LA COMPOSICIÓN CORPORAL

    Directory of Open Access Journals (Sweden)

    M. Camacho-Cardenosa

    2015-04-01

    Full Text Available Tradicionalmente, el entrenamiento en altura ha sido utilizado para mejorar el rendimiento de los deportistas. Con el desarrollo de nuevas tecnologías que permiten simular situaciones de altitud en cualquier parte del mundo, se han empezado a estudiar los efectos de la exposición a la misma en combinación con otros métodos de entrenamiento, por ejemplo, el entrenamiento interválico de máxima intensidad (Czuba et al. 2013 Por otra parte, recientemente se han llevado a cabo otros estudios que analizaron los efectos del estímulo hipóxico sobre los cambios en la composición corporal (Kaiser & Verges, 2013.Objetivo: Combinar entrenamiento en altitud simulada y entrenamiento de máxima intensidad para analizar los efectos sobre la composición corporal en sujetos activos.

  2. Comportamientos abusivos de baja intensidad en las organizaciones: una revisión de la literatura y de sus implicancias

    Directory of Open Access Journals (Sweden)

    Lidia Moroni

    2014-01-01

    Full Text Available Los comportamientos abusivos en el trabajo afectan el clima organizacional y deterioran el compromiso de los empleados. Entre ellos los comportamientos abusivos de baja intensidad son los más difíciles de detectar, pues se manifiestan de modo sutil y subjetivo, a través de sucesivas interacciones entre los actores involucrados. La literatura organizacional ofrece múltiples constructos cuyas definiciones y alcances se superponen entre sí y dificultan su adecuado tratamiento. Basado en una revisión de la literatura empírica, este trabajo analiza 14 constructos diferentes referidos como comportamientos abusivos de baja intensidad, con el objetivo de identificar aquellas dimensiones comunes que los caracterizan y examinar los factores del contexto organizacional que facilitan su ocurrencia y propagación. Esta revisión concluye presentando sus implicancias prácticas.

  3. Comportamientos abusivos de baja intensidad en las organizaciones: una revisión de la literatura y de sus implicancias

    Directory of Open Access Journals (Sweden)

    Lidia Moroni

    2014-10-01

    Full Text Available Los comportamientos abusivos en el trabajo afectan el clima organizacional y deterioran el compromiso de los empleados. Entre ellos los comportamientos abusivos de baja intensidad son los más difíciles de detectar, pues se manifiestan de modo sutil y subjetivo, a través de sucesivas interacciones entre los actores involucrados. La literatura organizacional ofrece múltiples constructos cuyas definiciones y alcances se superponen entre sí y dificultan su adecuado tratamiento. Basado en una revisión de la literatura empírica, este trabajo analiza 14 constructos diferentes referidos como comportamientos abusivos de baja intensidad, con el objetivo de identificar aquellas dimensiones comunes que los caracterizan y examinar los factores del contexto organizacional que facilitan su ocurrencia y propagación. Esta revisión concluye presentando sus implicancias prácticas.

  4. Respuestas y adaptaciones de la funci??n y estructura musculares al entrenamiento oclusivo con resistencias de baja intensidad

    OpenAIRE

    Mart??n Hern??ndez, Juan

    2013-01-01

    137 p. Los objetivos de esta tesis doctoral, que se presenta como compendio de publicaciones, fueron: (1) Estudiar las respuestas de la arquitectura muscular a una sola sesi??n de entrenamiento oclusivo y comparar ??stas con las observadas tras una sesi??n de entrenamiento tradicional con resistencias de alta intensidad; (2) Estudiar las adaptaciones de la fuerza din??mica y el grosor muscular a dos vol??menes diferentes de entrenamiento oclusivo; (3) Comparar estos resultados con los obte...

  5. Intensidad y dirección de la ansiedad competitiva y expectativas de resultados en atletas y nadadores

    Directory of Open Access Journals (Sweden)

    Amparo Pozo Calvo

    2007-01-01

    Full Text Available El presente estudio describe el estado de ansiedad cognitiva y somática precompetitiva y la autoconfianza en sus dimensiones de "intensidad" y de "dirección", y las relaciona con las expectativas de resultados. Una muestra de 59 nadadores y deportistas de atlétismo cumplimentó la versión modificada (Jones y Swain, 1992 del CSAI-2 antes de competir, y registró el puesto que esperaba obtener en la prueba. Comparado el puesto esperado con el puesto real se formaron tres grupos de sujetos con distintas expectativas de resultados. Los resultados descriptivos del estudio ofrecen valores medios en la intensidad de la ansiedad más bajos que anteriores estudios con otras modalidades deportivas, la correlación entre las subescalas de intensidad y dirección es más elevada. Los sujetos que obtienen un puesto en la competición superior al puesto que esperaban son los que presentan menor ansiedad cognitiva, menor ansiedad somática y mayor autoconfianza. Este grupo es el que valora como más facilitadora la ansiedad y la autoconfianza.

  6. Identification and verification of a pathogenic MLH1 mutation c.1145dupA in a Lynch syndrome family

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    Huang Feifei

    2017-06-01

    Full Text Available Lynch syndrome (LS, an autosomal-dominant disorder with an increased risk of predominantly colorectal and endometrial cancers, is caused by germ-line mutations in mismatch repair genes. The identification of germ-line mutations that predispose to cancer is important to further our understanding of tumorigenesis, guide patient management and inform the best practice for healthcare. A 45-year-old woman with atypical endometrial hyperplasia who suffered colon cancer at the age of 30 years underwent hysterectomy and genetic counseling. Pedigree analysis revealed her family fulfilling the Amsterdam I criteria. Next-generation sequencing was offered to the patient. A mutation in the MLH1 gene, c.1145dupA, was identified and verified by Sanger sequencing. In addition, her nine family members were tested for the mutation. Two were affected (colon cancer at the age of 43 years and 45 years and one healthy relative carried the same mutation in the MLH1 gene. The mutation resulted in a frame-shift (p.Met383Aspfs*12 located in exon12, as well as a polypeptide truncation of 393 amino acids by the formation of a premature stop codon. An immunohistochemistry analysis of endometrial hyperplasia tissues revealed defects in MLH1 and PMS2 protein expression in the patient. Based on the 2015 American College of Medical Genetics and Genomics (ACMG guideline, we report this MLH1 c.1145dupA variation to be a pathogenic mutation that contributes to a strongly increased cancer risk in this LS family. Proper screening suggestions were offered to the three affected patients and the healthy carrier. To the best of our knowledge, this germ-line mutation of MLH1 was previously submitted to the Leiden Open Variation Database (LOVD database, but no comprehensive evidence or supporting observations were reported previously in the literature. The present report found a single nucleotide insertion in exon12 of the MLH1 gene, which can be considered causative of Lynch phenotype

  7. EFEITO DA ACUPUNTURA SISTÊMICA NA INTENSIDADE DA DOR DE PACIENTES COM CERVICALGIA

    Directory of Open Access Journals (Sweden)

    Aryanna Kelly Carneiro Rios Passos Alves

    2013-09-01

    Full Text Available Dor é uma qualidade sensorial complexa, puramente subjetiva, difícil de ser definida, descrita ou interpretada. É um mecanismo de proteção do corpo, ocorre sempre que qualquer tecido estiver sendo lesado. As dores cervicais afetam 30% de homens e 43% de mulheres em algum momento de suas vidas. Para o alívio da cervicalgia existem evidências de que a acupuntura é efetiva através de sua técnica em estimular pontos reflexos que tenham a propriedade de restabelecer o equilíbrio, alcançando, assim, resultados na diminuição do quadro álgico. O objetivo deste estudo foi avaliar a influência de um protocolo de acupuntura sistêmica para tratamento de cervicalgia na intensidade de dor, pressão arterial e frequência cardíaca. Realizou-se um estudo clínico com 11 sujeitos, de ambos os sexos, com idade média de 32,0 ± 13,2 anos. O tratamento foi composto por 4 sessões de atendimento segmentadas em uma sessão semanal e a avaliação da dor foi realizada antes e após cada sessão através da escala visual analogica (EVA. Os resultados encontrados sugerem que a acupuntura reduziu a dor em pacientes portadores de cervicalgia após 4 semanas de tratamento.

  8. O equilíbrio do capital e a sua intensidade: pontos da filosofia neopatrimonialista

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    Rodrigo Antônio Chaves da Silva

    2007-11-01

    Full Text Available O equilíbrio do capital é um estado funcional, ou de movimento das partes patrimoniais em prol dos lucros ou de alcance dos objetivos empresariais. A relatividade das funções sistemáticas do patrimônio aponta a razão da intensidade do equilíbrio, o grau em que o mesmo consegue se manter, isto é, a sua vitalidade no tempo de sua existência na continuidade aziendal. O objetivo do presente estudo, em caráter intervencionista, é mostrar os efeitos desta relação, de modo que uma análise avançada garanta profícua e zelosa consultoria contábil para uma administração patrimonial segura e coerente. O artigo discute este problema, que traduz uma das partes da teoria do Neopatrimonialismo Filosófico e que agrega valor à proposta do Neopatrimonialismo. The equilibrium of the capital is a state by function, or of movement fromthe parts of patrimonies with objective us profits, or reach by undertakerintection. The relativity of the function sistematicys by patrimonydesmontrate the reason by equilibrium intensity, of dimension to maintainhimself, of vitality by time patrimony of social existence. The objective thisstudy by character of intervetion is to desmontrate that efects this relations,of the analysis advance guarantee a useful and zealous orientationaccountants of the a management patrimony coherent and security. Thearticle discuss this problem that translate a by parts from the teory by Neopatrimonial philosophic by aggregate value by proposal of doctrine Neopatrimonial.

  9. The silent mutation MLH1 c.543C>T resulting in aberrant splicing can cause Lynch syndrome: a case report.

    Science.gov (United States)

    Yamaguchi, Tatsuro; Wakatsuki, Tomokazu; Kikuchi, Mari; Horiguchi, Shin-Ichiro; Akagi, Kiwamu

    2017-06-01

    The proband was a 67-year-old man with transverse and sigmoid colon cancer. Microsatellite instability analysis revealed a high frequency of microsatellite instability, and immunohistochemical staining showed the absence of both MLH1 and PMS2 proteins in the sigmoid colon cancer tissue specimens from the patient. DNA sequencing revealed a nucleotide substitution c.543C>T in MLH1, but this variant did not substitute an amino acid. The MLH1 c.543C>T variant was located 3 bases upstream from the end of exon 6 and created a new splice donor site 4 bases upstream from the end of exon 6. Consequently, the last 4 bases of exon 6 were deleted and frameshift occurred. Thus, the MLH1 c.543C>T silent mutation is considered 'pathogenic'. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors.

    Science.gov (United States)

    Pineda, M; González-Acosta, M; Thompson, B A; Sánchez, R; Gómez, C; Martínez-López, J; Perea, J; Caldés, T; Rodríguez, Y; Landolfi, S; Balmaña, J; Lázaro, C; Robles, L; Capellá, G; Rueda, D

    2015-06-01

    Lynch syndrome (LS) is an autosomal dominant cancer-susceptibility disease caused by inactivating germline mutations in mismatch repair (MMR) genes. Variants of unknown significance (VUS) are often detected in mutational analysis of MMR genes. Here we describe a large family fulfilling Amsterdam I criteria carrying two rare VUS in the MLH1 gene: c.121G > C (p.D41H) and c.2128A > G (p.N710D). Collection of clinico-pathological data, multifactorial analysis, in silico predictions, and functional analyses were used to elucidate the clinical significance of the identified MLH1 VUS. Only the c.121G > C variant cosegregated with LS-associated tumors in the family. Diagnosed colorectal tumors were microsatellite unstable although immunohistochemical staining revealed no loss of MMR proteins expression. Multifactorial likelihood analysis classified c.2128A > G as a non-pathogenic variant and c.121G > C as pathogenic. In vitro functional tests revealed impaired MMR activity and diminished expression of c.121G > C. Accordingly, the N710 residue is located in the unconserved MLH1 C-terminal domain, whereas D41 is highly conserved and located in the ATPase domain. The obtained results will enable adequate genetic counseling of c.121G > C and c.2128A > G variant carriers and their families. Furthermore, they exemplify how cumulative data and comprehensive analyses are mandatory to refine the classification of MMR variants. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for Lynch syndrome.

    Science.gov (United States)

    Zighelboim, Israel; Powell, Matthew A; Babb, Sheri A; Whelan, Alison J; Schmidt, Amy P; Clendenning, Mark; Senter, Leigha; Thibodeau, Stephen N; de la Chapelle, Albert; Goodfellow, Paul J

    2009-01-01

    We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister's colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified.

  12. Mlh1 is required for female fertility in Drosophila melanogaster: An outcome of effects on meiotic crossing over, ovarian follicles and egg activation.

    Science.gov (United States)

    Vimal, Divya; Kumar, Saurabh; Pandey, Ashutosh; Sharma, Divya; Saini, Sanjay; Gupta, Snigdha; Ravi Ram, Kristipati; Chowdhuri, Debapratim Kar

    2018-03-01

    Mismatch repair (MMR) system, a conserved DNA repair pathway, plays crucial role in DNA recombination and is involved in gametogenesis. The impact of alterations in MMR family of proteins (bacterial MutS and MutL homologues) on mammalian fertility is well documented. However, an insight to the role of MMR in reproduction of non-mammalian organisms is limited. Hence, in the present study, we analysed the impact of mlh1 (a MutL homologue) on meiotic crossing over/recombination and fertility in a genetically tractable model, Drosophila melanogaster. Using mlh1 e00130 hypomorphic allele, we report female specific adverse reproductive outcome for reduced mlh1 in Drosophila: mlh1 e00130 homozygous females had severely reduced fertility while males were fertile. Further, mlh1 e00130 females contained small ovaries with large number of early stages as well as significantly reduced mature oocytes, and laid fewer eggs, indicating discrepancies in egg production and ovulation. These observations contrast the sex independent and/or male specific sterility and normal follicular development as well as ovulation reported so far for MMR family proteins in mammals. However, analogous to the role(s) of mlh1 in meiotic crossing over and DNA repair processes underlying mammalian fertility, ovarian follicles from mlh1 e00130 females contained significantly increased DNA double strand breaks (DSBs) and reduced synaptonemal complex foci. In addition, large proportion of fertilized eggs display discrepancies in egg activation and fail to proceed beyond stage 5 of embryogenesis. Hence, reduction of the Mlh1 protein level leads to defective oocytes that fail to complete embryogenesis after fertilization thereby reducing female fertility. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Four novel germline mutations in the MLH1 and PMS2 mismatch repair genes in patients with hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Montazer Haghighi, Mahdi; Radpour, Ramin; Aghajani, Katayoun; Zali, Narges; Molaei, Mahsa; Zali, Mohammad Reza

    2009-08-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common cause of early onset hereditary colorectal cancer. In the majority of HNPCC families, microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found. The entire coding sequence of MMR genes (MLH1, MLH2, MLH6, and PMS2) was analyzed using direct sequencing. Also, tumor tests were done as MSI and immunohistochemistry testing. We were able to find three novel MLH1 and one novel PMS2 germline mutations in three Iranian HNPCC patients. The first was a transversion mutation c.346A>C (T116P) and happened in the highly conserved HATPase-c region of MLH1 protein. The second was a transversion mutation c.736A>T (I246L), which caused an amino acid change of isoleucine to leucine. The third mutation (c.2145,6 delTG) was frameshift and resulted in an immature stop codon in five codons downstream. All of these three mutations were detected in the MLH1 gene. The other mutation was a transition mutation, c.676G>A (G207E), which has been found in exon six of the PMS2 gene and caused an amino acid change of glycine to glutamic acid. MSI assay revealed high instability in microsatellite for two patients and microsatellite stable for one patient. In all patients, an abnormal expression of the MMR proteins in HNPCC was related to the above novel mutations.

  14. MLH1 V384D polymorphism associates with poor response to EGFR tyrosine kinase inhibitors in patients with EGFR L858R-positive lung adenocarcinoma.

    Science.gov (United States)

    Chiu, Chao-Hua; Ho, Hsiang-Ling; Doong, Howard; Yeh, Yi-Chen; Chen, Mei-Yu; Chou, Teh-Ying; Tsai, Chun-Ming

    2015-04-10

    A significant fraction of patients with lung adenocarcinomas harboring activating epidermal growth factor receptor (EGFR) mutations do not experience clinical benefits from EGFR tyrosine kinase inhibitor (TKI) therapy. Using next-generation sequencing, we screened 739 mutation hotspots in 46 cancer-related genes in EGFR L858R-mutant lung adenocarcinomas from 29 patients who received EGFR-TKI therapy; 13 had short ( 1 year) progression-free survival (PFS). We discovered MLH1 V384D as a genetic variant enriched in the group of patients with short PFS. Next, we investigated this genetic variation in 158 lung adenocarcinomas with the EGFR L858R mutation and found 14 (8.9%) patients had MLH1 V384D; available blood or non-tumor tissues from patients were also tested positive for MLH1 V384D. Patients with MLH1 V384D had a significantly shorter median PFS than those without (5.1 vs. 10.6 months; P= 0.001). Multivariate analysis showed that MLH1 V384D polymorphism was an independent predictor for a reduced PFS time (hazard ratio, 3.5; 95% confidence interval, 1.7 to 7.2; P= 0.001). In conclusion, MLH1 V384D polymorphism is associated with primary resistance to EGFR-TKIs in patients with EGFR L858R-positive lung adenocarcinoma and may potentially be a novel biomarker to guide treatment decisions.

  15. Chronic exposure to arsenic, estrogen, and their combination causes increased growth and transformation in human prostate epithelial cells potentially by hypermethylation-mediated silencing of MLH1.

    Science.gov (United States)

    Treas, Justin; Tyagi, Tulika; Singh, Kamaleshwar P

    2013-11-01

    Chronic exposure to arsenic and estrogen is associated with risk of prostate cancer, but their mechanism is not fully understood. Additionally, the carcinogenic effects of their co-exposure are not known. Therefore, the objective of this study was to evaluate the effects of chronic exposure to arsenic, estrogen, and their combination, on cell growth and transformation, and identify the mechanism behind these effects. RWPE-1 human prostate epithelial cells were chronically exposed to arsenic and estrogen alone and in combination. Cell growth was measured by cell count and cell cycle, whereas cell transformation was evaluated by colony formation assay. Gene expression was measured by quantitative real-time PCR and confirmed at protein level by Western blot analysis. MLH1 promoter methylation was determined by pyrosequencing method. Exposure to arsenic, estrogen, and their combinations increases cell growth and transformation in RWPE-1 cells. Increased expression of Cyclin D1 and Bcl2, whereas decreased expression of mismatch repair genes MSH4, MSH6, and MLH1 was also observed. Hypermethylation of MLH1 promoter further suggested the epigenetic inactivation of MLH1 expression in arsenic and estrogen treated cells. Arsenic and estrogen combination caused greater changes than their individual treatments. Findings of this study for the first time suggest that arsenic and estrogen exposures cause increased cell growth and survival potentially through epigenetic inactivation of MLH1 resulting in decreased MLH1-mediated apoptotic response, and consequently increased cellular transformation. © 2013 Wiley Periodicals, Inc.

  16. Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells

    Science.gov (United States)

    Yoneshima, Yasuto; Abolhassani, Nona; Iyama, Teruaki; Sakumi, Kunihiko; Shiomi, Naoko; Mori, Masahiko; Shiomi, Tadahiro; Noda, Tetsuo; Tsuchimoto, Daisuke; Nakabeppu, Yusaku

    2016-01-01

    Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results in cell growth suppression and DNA instability. To explore the mechanisms of these phenotypes, we analysed ITPA-deficient human and mouse cells. We found that both growth suppression and accumulation of single-strand breaks in nuclear DNA of ITPA-deficient cells depended on MLH1/PMS2. The cell growth suppression of ITPA-deficient cells also depended on p53, but not on MPG, ENDOV or MSH2. ITPA deficiency significantly increased the levels of p53 protein and p21 mRNA/protein, a well-known target of p53, in an MLH1-dependent manner. Furthermore, MLH1 may also contribute to cell growth arrest by increasing the basal level of p53 activity. PMID:27618981

  17. Age-Dependent Cancer Risk Is not Different in between MSH2 and MLH1 Mutation Carriers

    International Nuclear Information System (INIS)

    Olschwang, S.; Olschwang, S.; Yu, K.

    2009-01-01

    Lynch syndrome is mostly characterized by early-onset colorectal and endometrial adenocarcinomas. Over 90% of the causal mutations occur in two mismatch repair genes, MSH2 and MLH1. The aim of this study was to evaluate the age-dependent cancer risk in MSH2 or MLH1 mutation carriers from data of DNA diagnostic laboratories. To avoid overestimation, evaluation was based on the age-dependent proportion of mutation carriers in asymptomatic first-degree relatives of identified mutation carriers. Data from 859 such eligible relatives were collected from 8 centers; 387 were found to have inherited the mutation from their relatives. Age-dependent risks were calculated either using a nonparametric approach for four discrete age groups or assuming a modified Weibull distribution for the dependence of risk on age. Cancer risk was estimated starting at 28 (25-32 0.68 confidence interval) and to reach near 0.70 at 70 years. The risks were very similar for MSH2 and MLH1 mutation carriers. Although not statistically significant, the risk in males appeared to precede that for females by ten years. This difference needs to be investigated on a larger dataset. If confirmed, this would indicate that the onset of the colonoscopic surveillance may be different in male and female mutation carriers.

  18. High frequency induction of mitotic recombination by ionizing radiation in Mlh1 null mouse cells

    International Nuclear Information System (INIS)

    Wang Qi; Ponomareva, Olga N.; Lasarev, Michael; Turker, Mitchell S.

    2006-01-01

    Mitotic recombination in somatic cells involves crossover events between homologous autosomal chromosomes. This process can convert a cell with a heterozygous deficiency to one with a homozygous deficiency if a mutant allele is present on one of the two homologous autosomes. Thus mitotic recombination often represents the second mutational step in tumor suppressor gene inactivation. In this study we examined the frequency and spectrum of ionizing radiation (IR)-induced autosomal mutations affecting Aprt expression in a mouse kidney cell line null for the Mlh1 mismatch repair (MMR) gene. The mutant frequency results demonstrated high frequency induction of mutations by IR exposure and the spectral analysis revealed that most of this response was due to the induction of mitotic recombinational events. High frequency induction of mitotic recombination was not observed in a DNA repair-proficient cell line or in a cell line with an MMR-independent mutator phenotype. These results demonstrate that IR exposure can initiate a process leading to mitotic recombinational events and that MMR function suppresses these events from occurring

  19. Intensidade de ataque de tripes, de alternaria e da queima-das-pontas em cultivares de cebola

    OpenAIRE

    Leite,Germano L.D.; Santos,Marília Cristina dos; Rocha,Silma L.; Costa,Cândido A. da; Almeida,Chrystian I. Maia e

    2004-01-01

    Avaliou-se a intensidade de ataque de Thrips tabaci Lind., a incidência de Alternaria porri (Ellis) e Botrytis squamosa J.C. Walker em nove cultivares de cebola [Aurora, Primavera, CNPH 6400, Crioula Alto-Vale, Vale-Ouro (IPA 11), Franciscana (IPA-16), Piraouro, Conquista e Serrana], num experimento no delineamento em blocos casualizados com cinco repetições. Foram feitas avaliações semanais, do transplantio até a colheita, em dez plantas/parcela do número de T. tabaci presente na bainha das ...

  20. Ejercicio Intermitente de Alta Intensidad (HIIT) y pérdida de grasa corporal: una revisión

    OpenAIRE

    Parodi Feye, Andrés Santiago

    2015-01-01

    Este trabajo corresponde al Trabajo Final Integrador del curso de Especialización en Programación y Evaluación del Ejercicio. En el mismo se realiza una revisión de la literatura científica, sobre los diferentes protocolos de Entrenamiento Intermitente de Alta Intensidad (HIIT), entendiendo éste último como un tipo de esfuerzo compuesto de períodos frecuentes de trabajo intenso seguidos por períodos de recuperación menos intensos, en lo que atañe a la pérdida de masa adiposa en sujetos obesos...

  1. Intensidad exportadora y percepción de barreras a la exportación: Un estudio de casos

    OpenAIRE

    García Pérez, F.; Avella Camarero, L.

    2007-01-01

    Mediante un estudio de casos analizamos la experiencia exportadora de 11 PYMEs asturianas y alicantinas. Nuestro objetivo es comprobar si la percepción de barreras a la exportación difiere entre aquellas PYMEs más comprometidas (o exitosas) con la exportación y aquellas otras cuyos ingresos por ventas provienen mayoritariamente del mercado español. Observamos que existe una relación directa entre la intensidad exportadora y la percepción de impedimentos a la exportación. Además, la importanci...

  2. EFECTO DE UN PROTOCOLO DE ENTRENAMIENTO INTERVÁLICO DE ALTA INTENSIDAD SOBRE MASA GRASA CORPORAL EN ADOLESCENTES

    Directory of Open Access Journals (Sweden)

    Alba Camacho-Cardenosa

    2016-01-01

    Full Text Available Fundamentos: La infancia y la adolescencia son etapas claves para el desarrollo de enfermedades crónicas, siendo la distribución de grasa un importante factor en este sentido. El objetivo del estudio fue evaluar los efectos sobre parámetros de grasa de un programa de alta intensidad desarrollado en adolescentes durante las clases de educación física. Métodos: Durante el año 2013, 35 escolares cacereños participaron en el estudio divididos en dos grupos. El grupo de alta intensidad realizó durante 8 semanas de 4 a 6 series de sprints de 20 segundos a máxima intensidad con una relación esfuerzo/recuperación de 1:3 a 1:1. El otro grupo desarrolló ejercicio aeróbico continuo durante el mismo tiempo. Se llevó a cabo una evaluación de la masa grasa antes y tras el programa de entrenamiento. El test ANOVA de medidas repetidas se usó para analizar si existían diferencias estadísticamente significativas entre ambos grupos. Resultados: El grupo de entrenamiento aeróbico continuo mostró diferencias estadísticamente significativas en el análisis intra-grupo en el porcentaje de masa grasa del tronco (Pre:15,66±4,16 vs Post:16,95±4,03; +1,29%; p=0,04 y el porcentaje de grasa total (Pre:21,58±3,93/ Post:22,34±3,70; p=0,05. Conclusiones: El programa de entrenamiento de actividad física de alta intensidad en la escuela llevado a cabo durante las clases de Educación Física no mejoró los parámetros de masa grasa evaluados. Sin embargo, el mantenimiento de estos parámetros podría ser un buen resultado durante el desarrollo de esta etapa, donde se produce un incremento.

  3. Comportamientos abusivos de baja intensidad en las organizaciones : una revisión de la literatura y de sus implicacias

    OpenAIRE

    Moroni, Lidia; Guillermo E., Dabos

    2014-01-01

    Los comportamientos abusivos en el trabajo afectan el clima organizacional y deterioran el compromiso de los empleados. Entre ellos los comportamientos abusivos de baja intensidad son los más difíciles de detectar, pues se manifiestan de modo sutil y subjetivo, a través de sucesivas interacciones entre los acto- res involucrados. La literatura organizacional ofrece múltiples constructos cuyas definiciones y alcances se superponen entre sí y dificultan su adecuado tratamiento. Basado en una re...

  4. Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer.

    Science.gov (United States)

    Saadallah-Kallel, Amana; Abdelmaksoud-Dammak, Rania; Triki, Mouna; Charfi, Slim; Khabir, Abdelmajid; Sallemi-Boudawara, Tahia; Mokdad-Gargouri, Raja

    2017-08-01

    Aberrant DNA methylation of CpG islands occurred frequently in CRC and associated with transcriptional silencing of key genes. In this study, the CIMP combined with MLH1 or p16 INK4a methylation status was determined in CRC patients and correlated with clinicopathological parameters and overall survival. Our data showed that CIMP+ CRCs were identified in 32.9% of cases and that CACNAG1 is the most frequently methylated promoter. When we combined the CIMP with the MLH1 or the p16 INK4a methylation status, we found that CIMP-/MLH1-U (37.8%) and CIMP-/p16 INK4a -U (35.4%) tumors were the most frequent among the four subtypes. Statistical analysis showed that tumor location, lymphovascular invasion, TNM stage, and MSI differed among the group of patients. Kaplan-Meier analyses revealed differences in overall survival according to the CIMP combined with MLH1 or p16 INK4a methylation status. In a multivariate analysis, CIMP/MLH1 and CIMP/p16 INK4a methylation statuses were predictive of prognosis, and the OS was longer for patients with tumors CIMP-/MLH1-M, as well as CIMP-/p16 INK4a -M. Furthermore, DNMT1 is significantly overexpressed in tumors than in normal tissues as well as in CIMP+ than CIMP- tumors. Our results suggest that tumor classification based on the CIMP status combined with MLH1 or p16 INK4a methylation is useful to predict prognosis in CRC patients.

  5. Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.

    Science.gov (United States)

    Li, Xia; Wang, Yibaina; Zhang, Zuoming; Yao, Xiaoping; Ge, Jie; Zhao, Yashuang

    2013-11-01

    CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 ( MLH1 ) and DNA repair gene O 6 -methylguanine-DNA methyltransferase ( MGMT ) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

  6. Epigenetic Loss of MLH1 Expression in Normal Human Hematopoietic Stem Cell Clones is Defined by the Promoter CpG Methylation Pattern Observed by High-Throughput Methylation Specific Sequencing.

    Science.gov (United States)

    Kenyon, Jonathan; Nickel-Meester, Gabrielle; Qing, Yulan; Santos-Guasch, Gabriela; Drake, Ellen; PingfuFu; Sun, Shuying; Bai, Xiaodong; Wald, David; Arts, Eric; Gerson, Stanton L

    Normal human hematopoietic stem and progenitor cells (HPC) lose expression of MLH1 , an important mismatch repair (MMR) pathway gene, with age. Loss of MMR leads to replication dependent mutational events and microsatellite instability observed in secondary acute myelogenous leukemia and other hematologic malignancies. Epigenetic CpG methylation upstream of the MLH1 promoter is a contributing factor to acquired loss of MLH1 expression in tumors of the epithelia and proximal mucosa. Using single molecule high-throughput bisulfite sequencing we have characterized the CpG methylation landscape from -938 to -337 bp upstream of the MLH1 transcriptional start site (position +0), from 30 hematopoietic colony forming cell clones (CFC) either expressing or not expressing MLH1 . We identify a correlation between MLH1 promoter methylation and loss of MLH1 expression. Additionally, using the CpG site methylation frequencies obtained in this study we were able to generate a classification algorithm capable of sorting the expressing and non-expressing CFC. Thus, as has been previously described for many tumor cell types, we report for the first time a correlation between the loss of MLH1 expression and increased MLH1 promoter methylation in CFC derived from CD34 + selected hematopoietic stem and progenitor cells.

  7. Promoter hypermethylation of DNA repair genes MLH1 and MSH2 in adenocarcinomas and squamous cell carcinomas of the lung

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    A. Gomes

    2014-01-01

    Full Text Available Five years survival of lung cancer is 16%, significantly lower than in prostate (99.9%, breast (88.5% and colon (64.1% carcinomas. When diagnosed in the surgical stage it increases to 50% but this group only comprises 14–16% of the cases. DNA methylation has emerged as a potential cancer-specific biomarker. Hypermethylation of CpG islands located in the promoter regions of tumour suppressor genes is now firmly established as an important mechanism for gene inactivation.This retrospective study included 40 squamous cell carcinomas and 40 adenocarcinomas in various surgical TNM stages to define methylation profile and possible silencing of DNA repair genes – MLH1 and MSH2 – using Methylation-Specific PCR and protein expression by immunohistochemistry in tumoural tissue, preneoplastic lesions and respiratory epithelium with normal histological features.The protein expression of MLH1 and MSH2 genes, in the available preneoplastic lesions and in normal cylindrical respiratory epithelium appeared reduced. The frequency of promoter hypermethylation found on these DNA repair genes was elevated, with a higher prevalence of methylation of MLH1 gene in 72% of squamous cell carcinoma. The differences are not so obvious for MSH2 promoter hypermethylation. No correlation was found among the status of methylation, the protein expression and the clinicopathological characteristics.With a larger study, a better characterization of the hypermethylation status of neoplastic and preneoplastic lesions in small biopsies would be achieved, inherent to tumour histology, heterogeneity and preservation, and finally differences in the study population to elucidate other possible mechanisms of altered expression of the hMLH1 and hMSH. Resumo: A sobrevivência aos cinco anos no cancro do pulmão é de 16%, significativamente inferior que nos carcinomas na próstata (99,9%, mama (88,5% e cólon (64,1%. Quando diagnosticado na fase cir

  8. EL CONTROL DE LA INTENSIDAD DEL ESFUERZO Y SU INCIDENCIA SOBRE LA ACTIVIDAD FÍSICA EN EDAD ESCOLAR

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    Borja Sañudo Corrales

    2007-01-01

    Full Text Available El objetivo del presente estudio fue dotar a los alumnos de una herramienta que les permitiese controlar la intensidad de su actividad física utilizando para ello la valoración subjetiva del esfuerzo. 32 sujetos (n1=12 niños y n2=20 niñas de 11,5 ± 0,5 años participaron en un programa de entrenamiento en circuito integrado por seis postas. Se registró la frecuencia cardiaca con pulsómetros y la percepción subjetiva del esfuerzo mediante la escala OMNI. Tras las siete sesiones del programa se observaron correlaciones muy altas entre ambos parámetros (r=0,54-0,76. Una vez finalizado el estudio los alumnos fueron capaces de regular su esfuerzo dentro de un rango de frecuencia cardiaca establecido en un 53,13% respecto a la frecuencia cardiaca percibida y 56,25% respecto a la frecuencia cardiaca medida, facilitándoles así un procedimiento práctico para el control de la intensidad durante la actividad física.

  9. Parasitismo intestinal e intensidad de las helmintiasis adquiridas del suelo en dos comunidades de la costa norte colombiana

    Directory of Open Access Journals (Sweden)

    Alberto García Laverde

    1966-01-01

    Full Text Available Una encuesta basada en el examen cualitativo y cuantitativo de una sola muestra de materias fecales de 247 indígenas de la Guajira, demostró parásitos intestinales en el 93 por ciento de las personas estudiadas. La prevalencia de E. bistolytica fue del 61 por ciento, y las cifras para las otras especies de amibas fue igualmente alta, lo cual viene a confirmar que estos indígenas viven en condiciones ambientales y de higiene personal que favorecen ampliamente la transmisión de ciertos parásitos. Por otra parte, el clima desértico de la península explica que la prevalencia de helmintiasis adquiridas del suelo haya sido relativamente baja en esta encuesta y su intensidad leve en la gran mayoría de los casos. En 12 personas se hizo el hallazgo de huevos de tricbostrongylus sp., parásito no registrado anteriormente en la literatura médica Colombiana. Como comparación se dan los datos de las helmintiasis adquiridas del suelo en otra comunidad de la Costa Atlántica, en el barrio Santa María, de la ciudad de Cartagena, en donde tanto la prevalencia como la intensidad de estos parasitismos son muy altas. Se sugieren puntos para futura investigación parasitológica en la Guajira Colombiana

  10. Promoter hypermethylation of CDKN2A, MGMT, MLH1, and DAPK genes in laryngeal squamous cell carcinoma and their associations with clinical profiles of the patients.

    Science.gov (United States)

    Pierini, Stefano; Jordanov, Stanislav H; Mitkova, Atanaska V; Chalakov, Ivan J; Melnicharov, Mincho B; Kunev, Kuncho V; Mitev, Vanio I; Kaneva, Radka P; Goranova, Teodora E

    2014-08-01

    Laryngeal squamous cell carcinoma (laryngeal SCC) is a frequently occurring cancer of the head and neck area. Epigenetic changes of tumor-related genes contribute to its genesis and progression. We assessed promoter methylation status of the selected genes (CDKN2A, MGMT, MLH1, and DAPK) using methylation-sensitive high resolution melting (MS-HRM) in 100 patients with laryngeal SCC and studied the correlations with clinical characteristics. The prevalence of promoter methylation in MGMT, CDKN2A, MLH1, and DAPK was 59 of 97 (60.8%), 46 of 97 (47.4%), 45 of 97 (46.4%), and 41 of 97 patients (42.3%), respectively. Significantly increased methylation of CDKN2A was observed in heavy smokers. Epigenetic inactivation of CDKN2A and MLH1 were found to be associated with lymph node involvement. An inverse correlation was present between MLH1 methylation and alcohol consumption. Our results strongly suggest that deregulation of p16-associated, and MLH1-associated pathways, because of promoter hypermethylation, is associated with increased cancer cell migration, tumor invasiveness, and, thus, aggressive phenotype. Copyright © 2013 Wiley Periodicals, Inc.

  11. A novel deletion in the splice donor site of MLH1 exon 6 in a Japanese colon cancer patient with Lynch syndrome.

    Science.gov (United States)

    Yamaguchi, Junya; Sato, Yuri; Kita, Mizuho; Nomura, Sachio; Yamamoto, Noriko; Kato, Yo; Ishikawa, Yuichi; Arai, Masami

    2015-10-01

    Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4_545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Perfilhamento em pastagens de azevém em sucessão a soja ou milho, sob diferentes métodos e intensidades de pastejo

    Directory of Open Access Journals (Sweden)

    Armindo Barth Neto

    2013-03-01

    Full Text Available O objetivo deste trabalho foi avaliar a densidade populacional de perfilhos, a massa de forragem, o padrão populacional de perfilhamento e o índice de estabilidade de pastagens de azevém anual (Lolium multiflorum estabelecidas após os cultivos de soja ou milho, submetidas a diferentes métodos e intensidades de pastejo por cordeiros. Foram avaliados os métodos de pastejo rotativo e contínuo, sob as intensidades moderada (oferta de forragem correspondente a 2,5 vezes o potencial de consumo de cordeiros e baixa (correspondente a 5,0 vezes. Utilizou-se o delineamento experimental de blocos ao acaso, em arranjo fatorial 2x2x2, com quatro repetições. As avaliações foram feitas mensalmente, entre agosto e outubro de 2010, durante a fase de pastejo. A densidade populacional de perfilhos apresentou diferenças significativas para métodos e intensidades de pastejo, e foi maior na área previamente cultivada com soja. As maiores massas de forragem foram observadas em pastagens subsequentes à soja e com baixa intensidade de pastejo, enquanto as menores, nas pastagens subsequentes ao milho e com moderada intensidade de pastejo. No período de florescimento, a densidade de perfilhos reduziu-se e suas massas individuais aumentaram. A intensidade de pastejo moderada reduz o percentual de perfilhos florescidos. A redução da densidade de perfilhos durante o florescimento não compromete o índice de estabilidade do pasto.

  13. IMPORTÂNCIA E INTERACÇÕES DA INTENSIDADE DA DISTRIBUIÇÃO COM A PERFORMANCE: ESTUDO EXPLORATÓRIO DE ÁGUA ENGARRAFADA

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    Joana Cabeçadas

    2006-04-01

    Full Text Available Este estudo pretende abordar a importância da variável intensidade da distribuição como estratégia de marketing, bem como as interações com outras variáveis relevantes para as empresas. Tal análise revela-se extremamente importante, já que, para produtos para os quais não faz sentido adotar estratégias de diferenciação, as empresas devem compreender bem as implicações e determinantes da intensidade da distribuição. Procura-se avaliar a importância da competitividade da força de vendas, enquanto força interna. O estudo demonstra e justifica a relação positiva que existe entre a competitividade da força de vendas e as variáveis intensidade da distribuição e performance da força de vendas. Como o mercado em estudo é extremamente competitivo, evidencia-se a relevância da intensidade da competição. Verifica-se que um aumento dessa variável tem um impacto positivo na intensidade da distribuição e na performance da força de vendas. Na maioria dos casos confirma-se que a quota de mercado, enquanto medida de performance do ano anterior, influencia positivamente a nossa variável estratégica. Por sua vez, o aumento da intensidade da distribuição melhora a performance da força de vendas e, conseqüentemente, o desempenho da empresa.

  14. Monitorización de la intensidad del entrenamiento de la fuerza mediante la percepción subjetiva de la velocidad

    OpenAIRE

    Herrera Diaz, Miguel

    2013-01-01

    La monitorización y cuantificación de la intensidad en ejercicios con resistencias externas es una máxima en el alto rendimiento deportivo. Diferentes propuestas metodológicas y dispositivos se utilizan para su valoración. Las escalas subjetivas del esfuerzo tratan de abordar esta temática. Tradicionalmente, las escalas subjetivas del esfuerzo para monitorizar y cuantificar la intensidad en los ejercicios con resistencias externas son la escala de Borg y la escala OMNI-RES. Recien...

  15. Curva de intensidad frecuencia y duración de inundaciones (IFD) para el municipio Venezuela, provincia Ciego de Ávila, Cuba

    OpenAIRE

    Brown Manrique, Oscar; Gallardo Ballat, Yurisbel; Valdés, José E.

    2013-01-01

    La investigación se desarrolló en el municipio de Venezuela de la provincia de Ciego de Ávila, con el propósito de construir las curvas de intensidad frecuencia duración de las inundaciones sobre la base de las precipitaciones efectivas de esa localidad y su ajuste a las funciones de Talbot y Aparicio. Se determinaron igualmente el índice de precipitación efectiva normal (IPN) de gran utilidad para la determinación de la intensidad de este fenómeno. Los resultados demuestran que las precipita...

  16. Curva de intensidad frecuencia y duración de inundaciones (IFD) para el municipio Venezuela, provincia Ciego de Ávila, Cuba

    OpenAIRE

    Oscar Brown Manrique; Yurisbel Gallardo Ballat; José E. Valdés

    2013-01-01

    La investigacion se desarrolló en el minicipio de Venezuela de la provincia de Ciego de Ávila, con el proposito de construir las curvas de intensidad frecuencia duracion de las inundaciones sobre la base de las precipitaciones efectivas de esa localidad y su ajuste a las funciones de Talbot y Aparicio. Se determinaron igualmente el índice de precipitación efectiva normal (IPN) de gran utilidad para la determinacion de la intensidad de este fenómeno. Los resultados demuestran que las precipita...

  17. Intensidade de fluorescência em resina composta: influência do polimento superficial e dos meios de armazenagem

    Directory of Open Access Journals (Sweden)

    Ângela Dalla Nora

    Full Text Available INTRODUÇÃO: A resina composta é um material versátil em Odontologia Estética, principalmente por suas propriedades ópticas, dentre as quais a fluorescência. Poucos são os estudos que avaliaram esta propriedade e a comparação dos resultados encontrados torna-se difícil em função da inexistência de padronização nas metodologias na confecção e na armazenagem dos corpos de prova. OBJETIVO: Verificar a influência do polimento superficial e do meio de armazenagem, em estudos in vitro, em que se avalia a propriedade óptica de fluorescência em resinas compostas. MATERIAL E MÉTODO: Foram preparados 70 corpos de prova circulares (10 mm × 2 mm com resina composta microhíbrida (Opallis,- A2E - FGM. Os meios de armazenagem foram: água deionizada, água da torneira e saliva artificial. Os protocolos de polimento superficial, realizados em politriz após a obtenção dos corpos de prova, utilizaram lixas de granulações 600, 1200 e 2500. Os valores de intensidade de fluorescência foram avaliados através do espectrofotômetro Cary Eclipse, após 1, 7 e 21 dias. RESULTADO: Não houve diferença estatisticamente significativa na Intensidade de Fluorescência entre os grupos submetidos aos diferentes protocolos de polimento. Quanto aos meios de armazenagem, a partir do sétimo dia, a variação de fluorescência foi significativamente maior em água da torneira e deionizada, quando comparada à variação observada em saliva artificial, resultado que se manteve após 21 dias. CONCLUSÃO: O protocolo de polimento superficial não promoveu alterações significativas na fluorescência da resina composta avaliada. Quanto ao meio de armazenagem, a intensidade de fluorescência foi menos afetada quando em saliva artificial.

  18. INTENSIDAD DE LA MUSICA: EFECTO SOBRE LA FRECUENCIA CARDIACA Y EL ESFUERZO PERCIBIDO DURANTE LA ACTIVIDAD FISICA

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    Jorge Marín Hernández

    2001-12-01

    Full Text Available La música ha sido ampliamente utilizada en la práctica de ejercicios aeróbicos en la industria deportiva. El propósito de este estudio fue comparar el efecto de diferentes intensidades de la música sobre la frecuencia cardiaca (FC y el esfuerzo percibido (EP durante ejercicio estandarizado en un cicloergómetro. 13 hombres y 5 mujeres voluntarios, físicamente activos (edad 20.6 ± 2.2 años realizaron una prueba bajo tres condiciones en diferentes días, asignadas en un diseño contrabalanceado de medidas repetidas: no música (NM, música a 70 dB, (M70 y música a 85 dB (M85. Ellos se ejercitaron por 20 min. con una carga de trabajo constante predeterminada y equivalente al 80% de su FCMax (kp = 1.47 ± 0.4, 90 rev/min. La música utilizada fue del tipo 'Merengue House' en español con un tempo de 131 ± 4.30 bpm, las diferentes intensidades fueron calibradas con un sonómetro. La FC y el EP fueron registrados a los 10 y 20 min. con un monitor de FC Polar y la escala EP-15 de Borg. Prueba FC 10 min. FC 20 min. EP 10 min. EP 20 min. NM 164.78 ± 8.37 172.11 ± 8.54 12.06 ±1.92 13.78 ±2.58 M70 165.11 ±11.16 173.00 ±12.05 12.00 ±2.11 13.56 ±2.89 M85 163.00 ± 7.58 170.17 ± 7.87 11.50 ±1.55 12.94 ±2.07 Tanto para FC como para EP un ANOVA 3 x 2 con medidas repetidas indicó que los promedios a los 20 min. fueron significativamente mayores que a los 10 min. (p<0.05. Las diferencias en FC y EP entre las tres condiciones no fueron significativas (p >0.05. Los resultados indican que los rangos de intensidades de música estudiados M70 y M85 no produjeron un efecto sobre el EP y la FC cuando se realizó ejercicio estandarizado en un cicloergómetro comparado con una condición sin música NM.

  19. Leyes de atenuación de la intensidad macrosísmica en Colombia

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    Gómez Capera Augusto Antonio

    2002-08-01

    ";,";sans-serif";; font-size: 12pt; mso-ansi-language: EN-US;" lang="EN-US">For superficial earthquakes, the geometrical spreading coefficient its more important than the coefficient of physical absorption.

    Con el fin de establecer los patrones de atenuaci6n de la intensidad macrosísmica con la distancia en el territorio colombiano, en el presente artículo se han analizado los mapas de isosistas de 34 terremotos fuertes. Usando modelos teóricos preestablecidos y los valores de profundidad focal macrosísmica, se establecen tres rangos diferentes de profundidad (h  20 km, h < 60 km y h > 60 km, para los cuales se obtienen tres diferentes relaciones de atenuación:

     

    [Fórmula]

    [Fórmula]

    [Fórmula]

     

    Para sismos superficiales el coeficiente de atenuación geométrica adquiere mayor importancia que el coeficiente de atenuación física.

  20. Expression of DNA repair proteins MSH2, MLH1 and MGMT in human benign and malignant thyroid lesions: An immunohistochemical study

    Science.gov (United States)

    Giaginis, Constantinos; Michailidi, Christina; Stolakis, Vasileios; Alexandrou, Paraskevi; Tsourouflis, Gerasimos; Klijanienko, Jerzy; Delladetsima, Ioanna; Theocharis, Stamatios

    2011-01-01

    Summary Background DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, and minimizes cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations in the expression levels of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins MSH2, MLH1 and MGMT in benign and malignant thyroid lesions. Material/Methods MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 90 patients with benign and malignant lesions. Results The expression levels of MLH1 was significantly upregulated in cases with malignant compared to those with benign thyroid lesions (p=0.038). The expression levels of MGMT was significantly downregulated in malignant compared to benign thyroid lesions (p=0.001). Similar associations for both MLH1 and MGMT between cases with papillary carcinoma and hyperplastic nodules were also noted (p=0.014 and p=0.026, respectively). In the subgroup of malignant thyroid lesions, MSH2 downregulation was significantly associated with larger tumor size (p=0.031), while MLH1 upregulation was significantly associated with the presence of lymphatic and vascular invasion (p=0.006 and p=0.002, respectively). Conclusions Alterations in the mismatch repair proteins MSH2 and MLH1 and the direct repair protein MGMT may result from tumor development and/or progression. Further studies are recommended to draw definite conclusions on the clinical significance of DNA repair proteins in thyroid neoplasia. PMID:21358597

  1. Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

    Science.gov (United States)

    Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

    2009-06-01

    It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

  2. Atenuação da intensidade de luz e profundidade de polimerização de resinas compostas

    OpenAIRE

    Werlang, Jean Felipe Garlet; Dalfovo, Ricardo João; Neiva, Ivana Froede; Obici, Andresa Carla

    2016-01-01

    Objetivo: Avaliar a atenuação da luz através de diferentes espessuras de resina composta e a profundidade de polimerização. Materiais e Métodos: Foram utilizadas as resinas Opallis e Llis de esmalte (E) e de dentina (D), na cor A3. Para atenuação da luz foram empregadas matrizes metálicas (6,0mm de diâmetro e espessuras de 0,5, 1,0, 1,5 e 2,0mm), as quais foram posicionadas na janela de leitura do radiômetro e a intensidade de luz medida antes e após a interposição do material. A profundidade...

  3. Genotyping of BRCA1, BRCA2, p53, CDKN2A, MLH1 and MSH2 genes in a male patient with secondary breast cancer

    International Nuclear Information System (INIS)

    Vodusek, Ana Lina; Novakovic, Srdjan; Stegel, Vida; Jereb, Berta

    2011-01-01

    Some tumour suppressor genes (BRCA2) and mismatch repair genes (MSH2, MLH1) are correlated with an increased risk for male breast cancer. Our patient developed secondary breast cancer after the treatment for Hodgkin’s disease in childhood. DNA was isolated from the patients’ blood and screened for mutations, polymorphisms and variants in BRCA1, BRCA2, p53, CDKN2A, MLH1 and MSH2 genes. We found no mutations but common polymorphisms, and three variants in mismatch repair genes. Nucleotide variants c.2006-6T>C and p.G322D in MSH2 might be correlated with male breast cancer

  4. IMMUNOHISTOCHEMICAL STUDY OF MSH2, MSH6, PMS2, MLH1 IN EVALUATION OF DIFFERENTIATION GRADE OF COLON ADENOCARCINOMA

    Directory of Open Access Journals (Sweden)

    G. A. Raskin

    2015-01-01

    Full Text Available Microsatellite instability is associated with dysfunction of the MSH2, MLH1, PMS2 and MSH6 genes, which participate in the repair of unpaired nucleotides of DNA. It is known that microsatellite instability is an independent prognostic factor in determining the differentiation grade of colon cancer. The use of immunohistochemistry to study the repair system of unpaired nucleotides has its own characteristics and limitations. Materials and methods. The study included 39 patients with colon adenocarcinoma. Moderately-differentiated colon adenocarcinoma was the most common histological type (72 %. There were 8 % of well-differentiated and 12 % poorly-differentiated carcinomas. Immunohistochemical analysis of SH2, MSH6, PMS2 and MLH1 proteins was done according to the standard protocol. Results. Out of 39 cases, 6 (15 % had loss of expression of at least one of the studied proteins. Out of these 6 cases with indirect signs of MSI-H, 3 were poorlydifferentiated, 1 was mucinous and 2 were moderately differentiated adenocarcinomas. Conclusion. Thus, immunohistochemical analysis of DNA repair genes can be used to determine the histological differentiation of colon adenocarcinoma.

  5. Intensidad de las clases de Educación Física: Deportes de equipo vs. deportes individuales

    Directory of Open Access Journals (Sweden)

    Juan L. Yuste

    2013-01-01

    Full Text Available Debido al incremento de obesidad infantil y adoles- cente, se recomienda realizar 60 minutos de actividad físico-deportiva a una intensidad de moderada a vigoro- sa ( MVPA la mayoría de días a la semana. Sin embargo, las clases de Educación Física (EF son el único momento en el que los alumnos realizan actividad físico-deportiva obligatoria. Se pretende comprobar el efecto que tie- nen sesiones de EF de deportes de equipo ( DE y de- portes individuales ( DI sobre el nivel de intensidad de estas en un estudio con diseño no experimental, de tipo descriptivo-comparativo. Se registró la frecuencia car- diaca media ( FCM de 107 estudiantes de la Región de Murcia (60 chicos y 47 chicas de entre 12 y 18 años edad durante 9 sesiones de EF. Los valores de FCM y % de cla- se en MVPA son significativamente mayores ( p = 0.000; p = 0.004 en DE (141.77 ± 14.75ppm; 45,13 ± 18,01% frente a DI (119.06 ± 19.20ppm; 23,81 ± 25,85%. Res- pecto al tamaño del efecto ( TE del tipo de sesión ( DE vs DI sobre la FCM , % MVPA y Tiempo MVPA , los resul- tados señalan un TE por debajo del mínimo ( TE 0.05. Aunque los resultados muestran que la inten- sidad y duración de las sesiones de nuestro estudio no cumplen con las recomendaciones para la mejora car- diovascular, las sesiones de EF donde se trabajaron DE como contenido se han asociado con mayores valores de frecuencia cardiaca.

  6. EFEITOS DA TERAPIA LASER DE BAIXA INTENSIDADE EM MODELO EXPERIMENTAL DE TENDINOPATIA EM RATOS: REVISÃO DE LITERATURA

    Directory of Open Access Journals (Sweden)

    Diego Rodrigues Pessoa

    2017-12-01

    Full Text Available Tendinopatia é o termo utilizado para descrever lesões que afetam os tendões (tendinites e tendinoses, caracterizada pela presença de inflamação e degeneração tecidual, associada à sobrecarga mecânica e a movimentos repetitivos. Diversas modalidades terapêuticas têm sido estudadas no tratamento das tendinopatias, entre elas, destaca-se a terapia a laser de baixa intensidade (TLBI que visa acelerar o processo regenerativo, diminuir a inflamação e reduzir a dor.  Diante do exposto, este trabalho teve como objetivo realizar revisão de literatura, de artigos científicos com foco nos efeitos da terapia a laser de baixa intensidade (TLBI, em modelo experimental de tendinopatia em ratos. O estudo baseou-se na investigação de publicações entre janeiro de 2011 a outubro de 2016, em bases de dados eletrônicas com o emprego dos descritores “tendinopatia”, “laserterapia”, “ratos”, “tendão” e “terapia a laser de baixa intensidade”, combinados aos descritores booleanos. Foram selecionados sete artigos que apontam que a TLBI possibilitou a redução de importantes marcadores pró-inflamatórios, tais como IL-6 e TNF-α, bem como a proliferação aumentada de tenócitos, independentemente da dosagem aplicada. Os estudos científicos selecionados nesta revisão sistemática sinalizaram efeitos positivos da TLBI, principalmente na modulação da resposta inflamatória aguda ou crônica após a indução da tendinopatia.

  7. Efecto agudo de dos intensidades de ejercicio aeróbico sobre la presión arterial en reposo de personas normotensas

    Directory of Open Access Journals (Sweden)

    M. Gamboa Granados

    2014-09-01

    Conclusión: Se comprueba la existencia del efecto hipotensor en la presión arterial sistólica después de realizar 2 sesiones de ejercicio en banda sin fin, sin embargo los mejores resultados se obtuvieron al realizar ejercicio a una intensidad del 70% de la frecuencia cardiaca reserva.

  8. Tumor mismatch repair immunohistochemistry and DNA MLH1 methylation testing of patients with endometrial cancer diagnosed at age younger than 60 years optimizes triage for population-level germline mismatch repair gene mutation testing.

    Science.gov (United States)

    Buchanan, Daniel D; Tan, Yen Y; Walsh, Michael D; Clendenning, Mark; Metcalf, Alexander M; Ferguson, Kaltin; Arnold, Sven T; Thompson, Bryony A; Lose, Felicity A; Parsons, Michael T; Walters, Rhiannon J; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K; Blomfield, Penelope B; Quinn, Michael A; Kirk, Judy A; Stewart, Colin J; Obermair, Andreas; Young, Joanne P; Webb, Penelope M; Spurdle, Amanda B

    2014-01-10

    Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

  9. Meat and fish consumption, APC gene mutations and hMLH1 expression in colon and rectal cancer: a prospective cohort study (the Netherlands)

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Goeij, de A.F.P.M.; Wark, P.A.; Brink, M.; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Bruine, de A.P.; Goldbohm, R.A.; Veer, van 't P.; Brandt, van den P.A.

    2005-01-01

    Objective:The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods:The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer

  10. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva

    2008-01-01

    deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...

  11. RRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes

    NARCIS (Netherlands)

    Domingo, E; Niessen, RC; Oliveira, C; Alhopuro, P; Moutinho, C; Espin, E; Armengol, M; Sijmons, RH; Kleibeuker, JH; Seruca, R; Aaltonen, LA; Imai, K; Yamamoto, H; Schwartz, S; Hofstra, RMW

    2005-01-01

    Recently, it was shown that the oncogenic activation of BRAF, a member of the RAS/RAF family of kinases, by the V600E mutation is characteristic for sporadic colon tumors with microsatellite instability. Further, it was shown to associate with the silencing of the mismatch repair (MMR) gene MLH1 by

  12. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers : A study of hereditary nonpolyposis colorectal cancer families

    NARCIS (Netherlands)

    Vasen, HFA; Stormorken, A; Menko, FH; Nagengast, FM; Kleibeuker, JH; Griffioen, G; Taal, BG; Moller, P; Wijnen, JT

    2001-01-01

    Purpose: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and

  13. Phenotype comparison of MLH1 and MSH2 mutation carriers in a cohort of 1,914 individuals undergoing clinical genetic testing in the United States

    NARCIS (Netherlands)

    F. Kastrinos (Fay); E.M. Stoffel (Elena); J. Balmana (Judith); E.W. Steyerberg (Ewout); R. Mercado (Rowena); S. Syngal (Sapna)

    2008-01-01

    textabstractBackground and Aims: Lynch syndrome is caused by germ-line mismatch repair gene mutations. We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic expression. Methods: This is a

  14. Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

    Science.gov (United States)

    Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

    2015-01-01

    Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593

  15. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families.

    NARCIS (Netherlands)

    Vasen, H.F.; Stormorken, A.; Menko, F.H.; Nagengast, F.M.; Kleibeuker, J.H.; Griffioen, G.; Taal, B.G.; Moller, P.; Wijnen, J.T.

    2001-01-01

    PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease characterized by the clustering of colorectal cancer, endometrial cancer, and various other cancers. The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and

  16. Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds.

    NARCIS (Netherlands)

    Scheenstra, R; Rijcken, FE; Koornstra, JJ; Hollema, H; Fodde, R; Menko, F.H.; Sijmons, RH; Bijleveld, CM; Kleibeuker, J.H.

    2003-01-01

    The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an APC gene mutation and a mismatch repair gene (for example, MLH1) mutation has never been described. In the present case

  17. Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Kunitoshi Shigeyasu

    Full Text Available To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP and microsatellite instability (MSI have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown.This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox's proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS.By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088, better tumor differentiation (P = 0.0267 and CIMP-high and MLH1 3' methylated status (P = 0.0312. Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis.CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer.

  18. Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome.

    Science.gov (United States)

    Schneider, Nayê Balzan; Pastor, Tatiane; Paula, André Escremim de; Achatz, Maria Isabel; Santos, Ândrea Ribeiro Dos; Vianna, Fernanda Sales Luiz; Rosset, Clévia; Pinheiro, Manuela; Ashton-Prolla, Patricia; Moreira, Miguel Ângelo Martins; Palmero, Edenir Inêz

    2018-05-01

    Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome, caused by germline mutations in one of the major genes involved in mismatch repair (MMR): MLH1, MSH2, MSH6 and more rarely, PMS2. Recently, germline deletions in EPCAM have been also associated to the syndrome. Most of the pathogenic MMR mutations found in LS families occur in MLH1 or MSH2. Gene variants include missense, nonsense, frameshift mutations, large genomic rearrangements and splice-site variants and most of the studies reporting the molecular characterization of LS families have been conducted outside South America. In this study, we analyzed 60 unrelated probands diagnosed with colorectal cancer and LS criteria. Testing for germline mutations and/or rearrangements in the most commonly affected MMR genes (MLH1, MSH2, EPCAM and MSH6) was done by Sanger sequencing and MLPA. Pathogenic or likely pathogenic variants were identified in MLH1 or MSH2 in 21 probands (35.0%). Of these, approximately one-third were gene rearrangements. In addition, nine variants of uncertain significance (VUS) were identified in 10 (16.6%) of the sixty probands analyzed. Other four novel variants were identified, only in MLH1. Our results suggest that MSH6 pathogenic variants are not common among Brazilian LS probands diagnosed with CRC and that MMR gene rearrangements account for a significant proportion of the germline variants in this population underscoring the need to include rearrangement analysis in the molecular testing of Brazilian individuals with suspected Lynch syndrome. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Prevalencia e intensidad parasitaria en Mugil cephalus (Pisces: Mugilidae, del Río Colorado, Baja California, México

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    Martha E Valles-Ríos

    2000-06-01

    Full Text Available La prevalencia e intensidad parasitaria de la lisa cabezona, Mugil cephalus Linnaeus, 1758, fue cuantificada durante un ciclo anual (febrero 1994 a febrero 1995 en la confluencia de los ríos Colorado y Hardy, Baja California, México. Dos especies de parásitos fueron reconocidas: Contracaecum multipapillatum (von Drasche, 1882 (Ascaridida: Anisakidae y Ergasilus versicolor Wilson, 1911 (Poecilostomatoida: Ergasilidae. Las larvas del nematodo C. multipapillatum, representadas por dos estadíos (A y B, exhibieron prevalencias de 30% y 14.5%, respectivamente; mientras que el copépodo E. versicolor, mostró una prevalencia de 72.7%. La intensidad media de C. multipapillatum fue 6.18 y 2.37 parásitos/huésped para los estadíos A y B, respectivamente, y en E. versicolor, ésta fue de 4.01. El número de parásitos (táxones combinados incrementó con la talla del pez (r= 0.22, p= 0.02, pero fue independiente del factor de condición (K LP del huésped.The parasitic prevalence and mean intensity in the striped mullet, Mugil cephalus, was seasonally determined during an annual cycle (February 1994 to February 1995 in the confluence of the Colorado and Hardy rivers, Baja California, México. Two species of parasites were identified, a nematode, Contracaecum multipapillatum (von Drasche, 1882 (Ascaridida: Anisakidae, and a copepod, Ergasilus versicolor Wilson, 1911 (Poecilostomatoida: Ergasilidae. The larvae of C. multipapillatum, which were represented by two size classes (A and B stages, had prevalences of 30% and 14.5%, respectively; while A. versicolor had a prevalence of 72.7%. The mean intensity of C. multipapillatum was 6.18 and 2.37 individuals per infected fish for A and B stages, respectively; and for A. versicolor, it was of 4.01. The number of parasites (taxa combined increased with the size of fish (r= 0.22, p= 0.02, but it was independent of the host’s condition factor (K SL.

  20. ESTIMACIÓN MENSUAL DE INTENSIDAD DE LA LLUVIA EN 30 MINUTOS A PARTIR DE DATOS PLUVIOMÉTRICOS

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    Hilario Ramírez Cruz

    2015-04-01

    Full Text Available Algunos modelos de simulación hidrológica para el estudio de erosión hídrica, como el Soil and Water Assessment Tool (SWAT, requieren como dato de entrada la intensidad de lluvia máxima mensual en 30 min (I30, a obtenerse de preferencia a partir de pluviógrafo o de una estación meteorológica automática (EMA. En ausencia de pluviógrafo o de una EMA, el objetivo de este trabajo fue obtener el I30 mensual a partir de información pluviométrica. Se aplicaron las ecuaciones de lluvia intensa generalizada, propuestas por Bell (1969, Chen (1983 y la Organización Meteorológica Mundial (OMM (WMO, 2009, para obtener el I30 a partir de precipitaciones máximas en 24 h de cuatro estaciones climatológicas ubicadas en la cuenca del río Copalita, Oaxaca: Pluma Hidalgo, San Francisco Ozolotepec, San Miguel Suchixtepec y La Hamaca. Como parte de la metodología se obtuvieron las alturas de precipitaciones máximas mensuales con duración de 30 min, para periodos de retorno T de 10, 20, 25, 50 y 100 años. Los resultados se validaron con las isoyetas de intensidad de la Secretaría de Comunicaciones y Transporte (SCT, obtenidas a partir de pluviógrafo (SCT, 2000, (SCT, 2014 para diferentes duraciones y periodos de retorno. El análisis de varianza y comparación de medias para T de 10 años (Tukey, P > 0.05 indicó que los datos de la SCT no exhiben diferencia significativa en comparación con aquellos obtenidos por los métodos de Chen y OMM, pero no así en contraste con el método de Bell. Finalmente se dejaron factores recomendados para obtener el I30 de 10 años de periodo de retorno a partir de lluvia en 24 h y 10 años de periodo de retorno para cada una de las estaciones bajo estudio.

  1. Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs.

    Science.gov (United States)

    Hinrichsen, Inga; Kemp, Matthias; Peveling-Oberhag, Jan; Passmann, Sandra; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

    2014-01-01

    Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC) specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV). However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR) genes and thereby enhanced progression of hepatocarcinogenesis has been the subject of controversial discussion. We investigated promoter methylation pattern of the MMR genes MLH1, MSH2 and PMS2 as well as the cyclin-dependent kinase inhibitor 2A gene (p16) in 61 well characterized patients with HCCs associated with HCV, Hepatitis B virus infection or alcoholic liver disease. DNA was isolated from formalin-fixed, paraffin-embedded tumour and non-tumour adjacent tissue and analysed by methylation-specific PCR. Moreover, microsatellite analysis was performed in tissues showing methylation in MMR gene promoters. Our data demonstrated that promoter methylation of MLH1, MSH2, PMS2 and p16 is present among all considered HCCs. Hereby, promoter silencing was detectable more frequently in advanced-stage HCCs than in low-stage ones. However, there was no significant correlation between aberrant DNA methylation of MMR genes or p16 and HCV infection in related HCC specimens. In summary, we show that promoter methylation of essential MMR genes and p16 is detectable in HCCs most dominantly in pT3 stage tumour cases. Since loss of MMR proteins was previously described to be not only responsible for tumour development but also for chemotherapy resistance, the knowledge of mechanisms jointly responsible for HCC progression might enable significant improvement of individual HCC therapy in the future.

  2. Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs.

    Directory of Open Access Journals (Sweden)

    Inga Hinrichsen

    Full Text Available Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV. However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR genes and thereby enhanced progression of hepatocarcinogenesis has been the subject of controversial discussion. We investigated promoter methylation pattern of the MMR genes MLH1, MSH2 and PMS2 as well as the cyclin-dependent kinase inhibitor 2A gene (p16 in 61 well characterized patients with HCCs associated with HCV, Hepatitis B virus infection or alcoholic liver disease. DNA was isolated from formalin-fixed, paraffin-embedded tumour and non-tumour adjacent tissue and analysed by methylation-specific PCR. Moreover, microsatellite analysis was performed in tissues showing methylation in MMR gene promoters. Our data demonstrated that promoter methylation of MLH1, MSH2, PMS2 and p16 is present among all considered HCCs. Hereby, promoter silencing was detectable more frequently in advanced-stage HCCs than in low-stage ones. However, there was no significant correlation between aberrant DNA methylation of MMR genes or p16 and HCV infection in related HCC specimens. In summary, we show that promoter methylation of essential MMR genes and p16 is detectable in HCCs most dominantly in pT3 stage tumour cases. Since loss of MMR proteins was previously described to be not only responsible for tumour development but also for chemotherapy resistance, the knowledge of mechanisms jointly responsible for HCC progression might enable significant improvement of individual HCC therapy in the future.

  3. Association between hMLH1 hypermethylation and JC virus (JCV) infection in human colorectal cancer (CRC).

    Science.gov (United States)

    Vilkin, Alex; Niv, Yaron

    2011-04-01

    Incorporation of viral DNA may interfere with the normal sequence of human DNA bases on the genetic level or cause secondary epigenetic changes such as gene promoter methylation or histone acetylation. Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA. Chromosomal instability (CIN) was established as the key mechanism in cancer development. Later, it was found that CRC results not only from the progressive accumulation of genetic alterations but also from epigenetic changes. JC virus (JCV) is a candidate etiologic factor in sporadic CRC. It may act by stabilizing β-catenin, facilitating its entrance to the cell nucleus, initialing proliferation and cancer development. Diploid CRC cell lines transfected with JCV-containing plasmids developed CIN. This result provides direct experimental evidence for the ability of JCV T-Ag to induce CIN in the genome of colonic epithelial cells. The association of CRC hMLH1 methylation and tumor positivity for JCV was recently documented. JC virus T-Ag DNA sequences were found in 77% of CRCs and are associated with promoter methylation of multiple genes. hMLH1 was methylated in 25 out of 80 CRC patients positive for T-Ag (31%) in comparison with only one out of 11 T-Ag negative cases (9%). Thus, JCV can mediate both CIN and aberrant methylation in CRC. Like other viruses, chronic infection with JCV may induce CRC by different mechanisms which should be further investigated. Thus, gene promoter methylation induced by JCV may be an important process in CRC and the polyp-carcinoma sequence.

  4. Epigenetic Silencing of the MLH1 Promoter in Relation to the Development of Gastric Cancer and its use as a Biomarker for Patients with Microsatellite Instability: a Systematic Analysis.

    Science.gov (United States)

    Hu, Guimei; Qin, Lijun; Zhang, Xinjun; Ye, Guoliang; Huang, Tao

    2018-01-01

    Human mutL homolog 1 (MLH1) promoter methylation was reported in gastric cancer (GC). This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. The combined odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area under the curve (AUC) were analyzed. A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis. MLH1 promoter methylation was significantly higher in GC samples than in gastric adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age and microsatellite instability (MSI), but it was not associated with gender, H. pylori infection, smoking, drinking behaviors, pathological histology, tumor differentiation, clinical stage, lymph node status, distant metastasis, or overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity value (MLH1 promoter methylation in GC with MSI vs. GC with microsatellite stability (MSS) samples were 0.64, 0.96, and 0.90, respectively. Our results suggest that the detection of MLH1 promoter methylation may be a potential prognostic biomarker for GC patients with MSI. © 2018 The Author(s). Published by S. Karger AG, Basel.

  5. Análise do efeito de diferentes intensidades e intervalos de recuperação na percepção subjetiva de atletas

    Directory of Open Access Journals (Sweden)

    Michel Santos Silva

    2011-03-01

    Full Text Available A pesquisa analisou os efeitos de diferentes intensidades e diferentes intervalos de recuperação do treinamento resistido na percepção subjetiva de esforço (PSE em atletas jovens. Foram selecionados 23 adolescentes, homens, com 17.06 ± .73 anos de idade, 68.01 ± 8.09 kg massa corporal e 173.65 ± 5.61 cm de estatura. Submetidos à adequação de cargas (5 RM, 10 RM ou 15 RM e intervalo de recuperação (30, 60 ou 120 s, onde ao final de cada série foi pedido para apontar o esforço percebido na escala OMNI-RES. A estatística utilizada foi a two-way ANOVA. As diferenças significativas foram analisadas pelo post-hoc de Bonferroni. Na PSE não foram encontradas diferenças significativas entre as intensidades nos intervalos de recuperação avaliados. Com relação aos intervalos com a mesma intensidade, verificou-se diferença entre 15 RM e intervalo de 120 e 60 s com 15 RM e intervalo de 30 s. Para as intensidades de 10 e 5 RM, apenas o intervalo de 120 s apresentou diferença em relação a 5 e 10 RM com intervalo de 30 s demonstrou que entre as intensidades e intervalos de recuperação ocorreram diferenças significativas. Conclui-se que quanto menor o intervalo de recuperação maior serão os níveis de fadiga, independente do número de repetições executadas em todas as intensidades, podendo inferir que a PSE mostrou-se sensível a diminuição do intervalo de recuperação.

  6. Hipotensão pós-exercício em hipertensos submetidos ao exercício aeróbio de intensidades variadas e exercício de intensidade constante Hipotensión pós ejercicio en hipertensos sometidos a ejercicio aerobio de intensidades variadas y ejercicio de intensidad constante Post-exercise hypotension in hypertensive individuals submitted to aerobic exercises of alternated intensities and constant intensity-exercise

    Directory of Open Access Journals (Sweden)

    Gisela Arsa da Cunha

    2006-12-01

    Full Text Available O exercício agudo pode resultar em hipotensão pós-exercício (HPE, que tem sido observada em normotensos e hipertensos, especialmente após exercícios contínuos (intensidade baixa a moderada. O objetivo foi comparar os efeitos hipotensores de exercícios de intensidade variada (EIV e constante (EIC e verificar se EIV potencializa a HPE. Onze hipertensos (56,8 ± 2,6 anos; IMC = 26,5 ± 0,3kg/m² foram submetidos a teste ergométrico (TE e a duas sessões de exercícios submáximos em esteira (45 min, em dias distintos e com intervalo de 48h, sendo uma sessão de EIV alternando-se 2 min a 55,9 ± 2,6% e 1 min a 74,5 ± 4,0% da reserva de freqüência cardíaca (RFC e uma sessão de EIC a 60 ± 2,5% da RFC. Em ambas as sessões os participantes permaneciam em repouso por 10 min (rep para aferição da pressão arterial (PA e freqüência cardíaca (FC, e então executaram 5 min de aquecimento seguidos de 45 min de EIV ou EIC. A PA e a FC foram monitoradas a cada 5 min de exercício e aos 5, 10, 15, 30, 60, 90 e 120 min de recuperação pós-exercício (rec. ANOVA e teste t de Student evidenciaram HPE de pressão arterial sistólica (PAS após ambas as sessões (p El ejercicio agudo puede resultar en hipotensión pos ejercicio (HPE, que ha sido observada en normotensos e hipertensos, especialmente después de ejercicios continuos (intensidad baja a moderada. El objetivo ha sido comparar los efectos hipotensores de Ejercicios de Intensidad Variada (EIV y Constante (EIC y verificar si EIV potencia la HPE. Once hipertensos (56,8 ± 2,6 años; IMC 26,5 ± 0,3kg/m² fueron sometidos a test ergométrico (TE y a dos sesiones de ejercicios submáximos en cinta ergométrica (45 min, en días distintos y con intervalo de 48h, con una sesión de EIV alternándose 2 min a 55,9 ± 2,6% e 1 min a 74,5 ± 4,0% de la reserva de frecuencia cardíaca (RFC y una sesión de EIC a 60 ± 2,5% de RFC. En ambas sesiones, los participantes permanecían en reposo por

  7. Análises macro e microscópicas de enxertos cutâneos por semeadura após laserterapia de baixa intensidade

    Directory of Open Access Journals (Sweden)

    Elisângela Barboza da Silva

    Full Text Available OBJETIVO: observar se a laserterapia de baixa intensidade acelera o processo inflamatório, a cicatrização e epitelização de enxertos cutâneos por semeadura. MÉTODOS: vinte ratos foram submetidos a esta técnica de enxertia e divididos em dois grupos iguais, um tratado com laser e outro controle. RESULTADOS: houve menor tempo de reação inflamatória, maior velocidade de cicatrização, epitelização e queratinização nos animais tratados com laser em relação aos não tratados. CONCLUSÃO: a laserterapia de baixa intensidade é efetiva no auxílio ao tratamento de enxertos por semeadura.

  8. Efeitos de diferentes intensidades de exercício sobre a concentração sérica de interleucinas

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    Pedro Rogério da Silva Neves

    2014-12-01

    Full Text Available O presente estudo teve como objetivo analisar os efeitos agudos e de curta duração de duas intensidades de exercício aeróbio sobre a concentração circulante de IL-6 e IL-10. Quinze homens jovens fisicamente ativos (21,0 ± 1,9 anos foram submetidos a duas sessões de exercício (“crossover”: alta intensidade de exercício (AIE- (80% VO2pico, e baixa intensidade de exercício (BIE- (40% VO2pico, com intervalo de sete dias (“Wash out”. Amostras de sangue foram coletadas em tubos com EDTA, antes do exercício (basal, imediatamente após o exercício (agudo e após 2 h de recuperação passiva. As concentrações séricas de IL-6 e IL-10 foram determinadas com a utilização de kits comerciais de ELISA. Os resultados demonstraram elevação aguda da IL- 6, em resposta ao AIE em relação ao BIE (p < 0,05, enquanto que a IL-10 apresentou maior redução sistêmica aguda para BIE em comparação a AIE (p < 0,05. Não houve diferença na variação das citocinas após 2 h do término do exercício. Conclui-se que ambas as sessões agudas de exercício são capazes de modular a concentração circulante destas citocinas, e que a magnitude das alterações são dependentes da intensidade do esforço.

  9. Fatores de risco associados à intensidade de dor nas costas em escolares do município de Teutônia (RS

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    Matias Noll

    2016-06-01

    Full Text Available Resumo Este estudo teve como objetivo verificar a prevalência e intensidade de dor nas costas (DC e os fatores de risco associados a um nível de elevada intensidade de dor em escolares do Ensino Fundamental de Teutônia, RS. Participaram deste estudo epidemiológico 1.597 escolares de 5ª a 8ª séries. Os dados foram coletados por meio de um questionário autoaplicável e analisados a partir de uma análise multivariável e do cálculo das razões de prevalência (RP (α=0,05. Verificou-se que a prevalência de DC nos últimos três meses foi de 55,7% (n = 802 e que a elevada intensidade de DC está associada com as variáveis: frequência de dor (RP = 1,37; p = 0,001, impedimento ao fazer atividades do dia a dia (RP = 1,25; p = 0,001 e meio de transporte do material escolar (RP = 1,10; p = 0,026. Estes resultados podem auxiliar os professores de educação física a planejar suas atividades curriculares.

  10. Intensidades da poda seca e do desbaste de cacho na composição da uva Cabernet Sauvignon

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    Alberto Miele

    2013-12-01

    Full Text Available A pesquisa foi realizada durante quatro anos, num vinhedo de Cabernet Sauvignon (Vitis vinifera L., em Bento Gonçalves-RS. O objetivo foi determinar o efeito das intensidades da poda seca e do desbaste de cacho em variáveis relacionadas aos componentes de produção da videira e à composição do mosto de uva. Os tratamentos consistiram em dois níveis de poda seca - curta e longa - e quatro de desbaste de cacho (% - 0; 25; 50 e 75 -; com cinco repetições. O delineamento experimental foi o em blocos casualizados, com os tratamentos em parcelas subdivididas. Os resultados mostram que a poda seca e o desbaste de cacho tiveram efeito altamente significativo na produtividade do vinhedo que, na média dos quatro anos, variou de 10.971 kg/ha − poda curta, 75% de desbaste − a 32.819 kg/ha − poda longa, 0% de desbaste. Houve, também, efeito significativo na produtividade por gema, peso de ramos podados por gema e por hectare, área foliar/peso fresco do fruto e produtividade/peso de ramos podados. Entretanto, o efeito nas variáveis relacionadas a açúcar e acidez do mosto da uva foi pouco expressivo. O componente 1 da análise de componentes principais discriminou o tratamento poda curta a 75% de desbaste de cacho dos tratamentos poda longa-0% de desbaste e poda longa-25% de desbaste.

  11. EFEITOS DA LASERTERAPIA DE BAIXA INTENSIDADE E EXTRATOS VEGETAIS NO PROCESSO DE REPARO TECIDUAL: REVISÃO INTEGRATIVA

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    Ana Paula Pinto

    2017-05-01

    Full Text Available Na prática clínica a Laserterapia de Baixa Intensidade (LBI tem sido usada para promover o alívio da dor, a ação anti-inflamatória, e para acelerar o processo de cicatrização em casos de lesão por queimaduras, feridas cirúrgicas e úlceras crônicas. Além da LBI, diversos tipos de extratos vegetais na forma hidroalcoólica ou óleo essencial, também são usadas para estimular a nutrição de células, a regeneração de tecidos e promover a velocidade de cicatrização de feridas. Neste estudo buscou-se evidências que comparasse ou associasse os efeito da LBI à óleos ou extratos vegetais no processo de cicatrização de feridas. Utilizou-se como metodologia a revisão integrativa. Na análise dos artigos, foram identificados 36 artigos, entretanto após adotar os critérios de inclusão descritos na metodologia, restaram apenas três artigos, sendo duas pesquisas que compararam os efeitos da LBI com o extrato hidroalcoólico uma que analisou a atividade das duas terapias, utilizando o extrato das folhas da Solidago chilensis e a irradiação com laser. Conclui-se que utilização a da LBI e os extratos vegetais, isoladamente, mostram-se efetivas durante o processo de reparo tecidual.

  12. De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one.

    Science.gov (United States)

    Goel, Ajay; Nguyen, Thuy-Phuong; Leung, Hon-Chiu E; Nagasaka, Takeshi; Rhees, Jennifer; Hotchkiss, Erin; Arnold, Mildred; Banerji, Pia; Koi, Minoru; Kwok, Chau-To; Packham, Deborah; Lipton, Lara; Boland, C Richard; Ward, Robyn L; Hitchins, Megan P

    2011-02-15

    Lynch syndrome is an autosomal dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2. Constitutional epimutations of the MLH1 gene, characterized by soma-wide methylation of a single allele of the promoter and allelic transcriptional silencing, have been identified in a subset of Lynch syndrome cases lacking a sequence mutation in MLH1. We report two individuals with no family history of colorectal cancer who developed that disease at age 18 and 20 years. In both cases, cancer had arisen because of the de novo occurrence of a constitutional MLH1 epimutation and somatic loss-of-heterozygosity of the functional allele in the tumors. We show for the first time that the epimutation in one case arose on the paternally inherited allele. Analysis of 13 tumors from seven individuals with constitutional MLH1 epimutations showed eight tumors had lost the second MLH1 allele, two tumors had a novel pathogenic missense mutation and three had retained heterozygosity. Only 1 of 12 tumors demonstrated the BRAF V600E mutation and 3 of 11 tumors harbored a mutation in KRAS. The finding that epimutations can originate on the paternal allele provides important new insights into the mechanism of origin of epimutations. It is clear that the second hit in MLH1 epimutation-associated tumors typically has a genetic not epigenetic basis. Individuals with mismatch repair-deficient cancers without the BRAF V600E mutation are candidates for germline screening for sequence or methylation changes in MLH1. Copyright © 2010 UICC.

  13. The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer.

    Science.gov (United States)

    Savio, Andrea J; Mrkonjic, Miralem; Lemire, Mathieu; Gallinger, Steven; Knight, Julia A; Bapat, Bharat

    2017-01-01

    Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 ( MLH1 ), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 ( MLH1 -93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours. Further, in peripheral blood mononuclear cell (PBMC) DNA of both CRC cases and non-cancer controls, the variant allele of rs1800734 is associated with hypomethylation at the MLH1 shore, a region upstream of its CpG island that is less dense in CpG sites . To determine whether this genotype-epigenotype association is present in other tissue types, including colorectal tumours, we assessed DNA methylation in matched normal colorectal tissue, tumour, and PBMC DNA from 349 population-based CRC cases recruited from the Ontario Familial Colorectal Cancer Registry. Using the semi-quantitative real-time PCR-based MethyLight assay, MLH1 shore methylation was significantly higher in tumour tissue than normal colon or PBMCs ( P  MLH1 was not associated with MSI status or promoter CpG island hypermethylation, regardless of genotype. To confirm these results, bisulfite sequencing was performed in matched tumour and normal colorectal specimens from six CRC cases, including two cases per genotype (wildtype, heterozygous, and homozygous variant). Bisulfite sequencing results corroborated the methylation patterns found by MethyLight, with significant hypomethylation in normal colorectal tissue of variant SNP allele carriers. These results indicate that the normal tissue types tested (colorectum and PBMC) experience dynamic genotype-associated epigenetic alterations at the MLH1 shore, whereas tumour DNA incurs aberrant hypermethylation compared to normal DNA.

  14. Isolated loss of PMS2 immunohistochemical expression is frequently caused by heterogeneous MLH1 promoter hypermethylation in Lynch syndrome screening for endometrial cancer patients

    OpenAIRE

    Kato, Aya; Sato, Naoki; Sugawara, Tae; Takahashi, Kazue; Kito, Masahiko; Makino, Kenichi; Sato, Toshiharu; Shimizu, Dai; Shirasawa, Hiromitu; Miura, Hiroshi; Sato, Wataru; Kumazawa, Yukiyo; Sato, Akira; Kumagai, Jin; Terada, Yukihiro

    2016-01-01

    Lynch syndrome (LS) is an autosomal dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) and is associated with increased risk of various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2–6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation ...

  15. Loss of mutL homolog-1 (MLH1) expression promotes acquisition of oncogenic and inhibitor-resistant point mutations in tyrosine kinases.

    Science.gov (United States)

    Springuel, Lorraine; Losdyck, Elisabeth; Saussoy, Pascale; Turcq, Béatrice; Mahon, François-Xavier; Knoops, Laurent; Renauld, Jean-Christophe

    2016-12-01

    Genomic instability drives cancer progression by promoting genetic abnormalities that allow for the multi-step clonal selection of cells with growth advantages. We previously reported that the IL-9-dependent TS1 cell line sequentially acquired activating substitutions in JAK1 and JAK3 upon successive selections for growth factor independent and JAK inhibitor-resistant cells, suggestive of a defect in mutation avoidance mechanisms. In the first part of this paper, we discovered that the gene encoding mutL homolog-1 (MLH1), a key component of the DNA mismatch repair system, is silenced by promoter methylation in TS1 cells. By means of stable ectopic expression and RNA interference methods, we showed that the high frequencies of growth factor-independent and inhibitor-resistant cells with activating JAK mutations can be attributed to the absence of MLH1 expression. In the second part of this paper, we confirm the clinical relevance of our findings by showing that chronic myeloid leukemia relapses upon ABL-targeted therapy correlated with a lower expression of MLH1 messenger RNA. Interestingly, the mutational profile observed in our TS1 model, characterized by a strong predominance of T:A>C:G transitions, was identical to the one described in the literature for primitive cells derived from chronic myeloid leukemia patients. Taken together, our observations demonstrate for the first time a causal relationship between MLH1-deficiency and incidence of oncogenic point mutations in tyrosine kinases driving cell transformation and acquired resistance to kinase-targeted cancer therapies.

  16. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival.

    Science.gov (United States)

    Cosgrove, Casey M; Cohn, David E; Hampel, Heather; Frankel, Wendy L; Jones, Dan; McElroy, Joseph P; Suarez, Adrian A; Zhao, Weiqiang; Chen, Wei; Salani, Ritu; Copeland, Larry J; O'Malley, David M; Fowler, Jeffrey M; Yilmaz, Ahmet; Chassen, Alexis S; Pearlman, Rachel; Goodfellow, Paul J; Backes, Floor J

    2017-09-01

    To determine the relationship between mismatch repair (MMR) classification and clinicopathologic features including tumor volume, and explore outcomes by MMR class in a contemporary cohort. Single institution cohort evaluating MMR classification for endometrial cancers (EC). MMR immunohistochemistry (IHC)±microsatellite instability (MSI) testing and reflex MLH1 methylation testing was performed. Tumors with MMR abnormalities by IHC or MSI and MLH1 methylation were classified as epigenetic MMR deficiency while those without MLH1 methylation were classified as probable MMR mutations. Clinicopathologic characteristics were analyzed. 466 endometrial cancers were classified; 75% as MMR proficient, 20% epigenetic MMR defects, and 5% as probable MMR mutations. Epigenetic MMR defects were associated with advanced stage, higher grade, presence of lymphovascular space invasion, and older age. MMR class was significantly associated with tumor volume, an association not previously reported. The epigenetic MMR defect tumors median volume was 10,220mm 3 compared to 3321mm 3 and 2,846mm 3 , for MMR proficient and probable MMR mutations respectively (PMLH1 methylation analysis defines a subset of tumors that have worse prognostic features and reduced RFS. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations.

    Science.gov (United States)

    Wang, Tao; Stadler, Zsofia K; Zhang, Liying; Weiser, Martin R; Basturk, Olca; Hechtman, Jaclyn F; Vakiani, Efsevia; Saltz, Lenard B; Klimstra, David S; Shia, Jinru

    2018-04-01

    Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). This led to subsequent MLH1 methylation testing and next generation sequencing which demonstrated that the loss of all MMR proteins was associated with concurrent promoter hypermethylation of MLH1 and double somatic truncating mutations in MSH2. These molecular findings, in conjunction with the patient's age being 80 years and the fact that the patient had no personal or family cancer history, indicated that the MMR deficiency was highly likely sporadic in nature. Thus, the stringent Lynch syndrome type surveillance programs were not recommended to the patient and her family members. This case illustrates a rare but important scenario where a null IHC phenotype signifies complex underlying molecular alternations that bear clinical management implications, highlighting the need for recognition and awareness of such unusual IHC staining patterns.

  18. INTENSIDAD DE VIDA INTERIOR

    Directory of Open Access Journals (Sweden)

    HÉCTOR OCAMPO MARÍN

    2014-11-01

    Full Text Available El alfarero que no cree en su trabajo, el pintor apático e indolente; el profesor resignado; el artista envanecido con su primer triunfo; el intelectual amargado; el científico incurioso, son personas condenadas a un nivel subyacente, a la mediocracia sombría. Una falla, no de fondo, corregible desde luego, en la estructura de la personalidad, ha malogrado al alfarero que no pudo llegar a ser ceramista; al comerciante que no ascendió a gran empresario; al profesor que no alcanzó a ser ideólogo; al artista incapaz de conquistar una fama; al científico que no abrió nuevas ventanas de luz a la humanidad.

  19. Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols: a Prospective Lynch Syndrome Database report.

    Science.gov (United States)

    Seppälä, Toni; Pylvänäinen, Kirsi; Evans, Dafydd Gareth; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rødland, Einar Andreas; Tharmaratnam, Kukatharmini; de Vos Tot Nederveen Cappel, Wouter H; Hill, James; Wijnen, Juul; Jenkins, Mark; Genuardi, Maurizio; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Frayling, Ian M; Plazzer, John-Paul; Sampson, Julian R; Capella, Gabriel; Möslein, Gabriela; Mecklin, Jukka-Pekka; Møller, Pål

    2017-01-01

    We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1 ) despite follow-up with colonoscopy including polypectomy. The cohort included Finnish carriers enrolled in 3-yearly colonoscopy ( n  = 505; 4625 observation years) and carriers from other countries enrolled in colonoscopy 2-yearly or more frequently ( n  = 439; 3299 observation years). We examined whether the longer interval between colonoscopies in Finland could explain the high incidence of CRC and whether disease expression correlated with differences in population CRC incidence. Cumulative CRC incidences in carriers of path_MLH1 at 70-years of age were 41% for males and 36% for females in the Finnish series and 58% and 55% in the non-Finnish series, respectively ( p  > 0.05). Mean time from last colonoscopy to CRC was 32.7 months in the Finnish compared to 31.0 months in the non-Finnish (p > 0.05) and was therefore unaffected by the recommended colonoscopy interval. Differences in population incidence of CRC could not explain the lower point estimates for CRC in the Finnish series. Ten-year overall survival after CRC was similar for the Finnish and non-Finnish series (88% and 91%, respectively; p > 0.05). The hypothesis that the high incidence of CRC in path_MLH1 carriers was caused by a higher incidence in the Finnish series was not valid. We discuss whether the results were influenced by methodological shortcomings in our study or whether the assumption that a shorter interval between colonoscopies leads to a lower CRC incidence may be wrong. This second possibility is intriguing, because it suggests the dogma that CRC in path_MLH1 carriers develops from polyps that can be detected at colonoscopy and removed to prevent CRC may be erroneous. In view of the excellent 10-year overall survival in the Finnish and non-Finnish series we remain strong advocates of current surveillance practices for those with LS pending

  20. EFEITO DA INTENSIDADE DE DESRAMA NA PRODUÇÃO DE Pinus elliottii Engelm., IMPLANTADO EM SOLO POBRE, NO ESTADO DO RIO GRANDE DO SUL

    Directory of Open Access Journals (Sweden)

    Juarez Martins Hoppe

    1999-06-01

    Full Text Available No presente trabalho estudou-se a influência da intensidade de desrama sobre a produção de madeira de Pinus elliottii Engelm. em um experimento em blocos casualizados com três repetições e 5 tratamentos, definidos por: T1 - testemunha, sem desrama; T2 - desrama dos ramos seco; T3 - desrama de 40 % da altura total; T4 - desrama de 50 % da altura total; e T5 - desrama de 60 % da altura total das árvores. Observou-se que o diâmetro e a produção de madeira foram fortemente influenciados pela intensidade da desrama, aos 11 anos de idade. A testemunha com 263,5 m3/ha não diferiu do tratamento com desrama de ramos secos com 245,1 m3/ha, mas ambos diferiram dos tratamentos com desrama de 40 % da altura total com 231,5 m3/ha, da desrama de 50 % da altura total com 225,5 m3/ha, da desrama com 60 % da altura total com 211,6 m3/ha. A menor perda de produção foi de 12,1 % obtida no tratamento com desrama de 40 % da altura total, e a maior de 19,7 % ocorreu no tratamento de desrama com 60 % da altura total. Estes resultados permitem concluir pela recomendação da utilização de desrama com intensidade inferior a 40 % da altura total das árvores, pois permitem menores perdas de produção, ganhos em incremento diamétrico e na qualidade da madeira.

  1. Efeito da intensidade de desrama na produção de Pinus elliottii Engelm., implantado em solo pobre, no estado do Rio Grande do Sul.

    Directory of Open Access Journals (Sweden)

    Paulo Renato Schneider

    2009-09-01

    Full Text Available Normal 0 21 false false false MicrosoftInternetExplorer4 No presente trabalho estudou-se a influência da intensidade de desrama sobre a produção de madeira de Pinus elliottii Engelm. em um experimento em blocos  casualizados com três repetições e 5 tratamentos, definidos por: T1 - testemunha, sem desrama; T2 - desrama dos ramos seco; T3 - desrama de 40 % da altura total; T4 - desrama de 50 % da altura total; e T5 - desrama de 60 % da altura total das árvores. Observou-se que o diâmetro e a produção de madeira foram fortemente influenciados pela intensidade da desrama, aos 11 anos de idade. A testemunha com 263,5 m3/ha não diferiu do tratamento com desrama de ramos secos com 245,1 m3/ha, mas ambos diferiram dos tratamentos com desrama de 40 % da altura total com 231,5 m3/ha, da desrama de 50 % da altura total com 225,5 m3/ha, da desrama com 60 % da altura total com 211,6 m3/ha. A menor perda de produção foi de 12,1 % obtida no tratamento com desrama de 40 % da altura total, e a maior de 19,7 % ocorreu no tratamento de desrama com 60 % da altura total. Estes resultados permitem concluir pela recomendação da utilização de desrama com intensidade inferior a 40 % da altura total das árvores, pois permitem menores perdas de produção, ganhos em incremento diamétrico e na qualidade da madeira.

  2. Respostas fisiológicas, perceptuais e afetivas de seis protocolos de treinamento intervalado de alta intensidade em universitários

    OpenAIRE

    Follador, Lucio

    2016-01-01

    Orientador : Prof. Dr. Sergio Gregorio da Silva Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Educação Física. Defesa: Curitiba, 26/02/2016 Inclui referências : f. 50-59 Área de concentração: Exercício e esporte Resumo: Objetivo: comparar as respostas fisiológicas, perceptuais e afetivas de seis protocolos de treinamento intervalado de alta intensidade (HIIT, do inglês High Intensity Interval Training) em univer...

  3. Efecto del fotoperiodo y la intensidad lumínica sobre la esporulación de peronospora sparsa berkeley, bajo condiciones controladas

    OpenAIRE

    Soto S., Johana Carolina; Filgueira D., Juan José

    2009-01-01

    El mildeo velloso de la rosa, producido por Peronospora sparsa, es una de las enfermedades más limitantes y costosas en los cultivos comerciales de rosa en Colombia. La estrecha relación de la enfermedad con las condiciones climáticas ha llevado a realizar estudios del parásito en condiciones microclimáticas controladas. Esta investigación buscó ahondar en el conocimiento de la biología del mildeo velloso de la rosa, evaluando para ello el efecto del fotoperiodo y la intensidad lumínica sobre...

  4. Respostas ecofisiológicas de Cybistax antisyphilitica Mart. (Ipê verde) em função das alterações na intensidade de luz

    OpenAIRE

    Freitas, Fernanda Monteiro de

    2016-01-01

    Luz apresenta uma ampla variação em ambientes florestais do Bioma Cerrado. Cybistax antisyphilitica (ipê-verde), ocupa fisionomias de cerrado sentido restrito, cerradões, além de áreas alteradas. Objetivou-se nesse trabalho compreender como plantas jovens de C. antisyphilitica, responde morfológica e fisiologicamente às alterações na intensidade de luz. Aos cinco meses de idade, 90 mudas de C. antisyphilitica foram levadas para um fragmento de floresta estacional semidecidual, ...

  5. Efeitos da atividade física de intensidades variadas em ratos com hipertensão renovascular 2R1CL

    OpenAIRE

    Soares, Everton Rocha

    2008-01-01

    VII Na hipertensão arterial (HA) ocorre uma inabilidade dos neurônios do bulbo ventrolateral caudal (CVLM) em contrabalancear o aparente aumento da atividade dos neurônios do bulbo ventrolateral rostral (RVLM). Além disso, o aumento da atividade do sistema renina angiotensina (SRA) representa uma importante alteração hormonal que leva à hipertensão, por aumentar o tônus vasomotor simpático e prejudicar a função barorreflexa. A atividade física (AF) de baixa e moderada intensidade tem sido usa...

  6. Evaluación fisiológica del lactato como marcador bioquímico utilizado para indicar la intensidad del ejercicio

    OpenAIRE

    Álvarez Romero, Javier Alejandro

    2014-01-01

    Pretende esta revisión contribuir en la posibilidad de utilización del lactato como marcador cuantitativo de la intensidad del ejercicio. Además, es conocido que esta sustancia tiene una estrecha relación con la liberación de hidrogeniones pero ha sido catalogada erróneamente como una relación causa efecto en lo referente a la acidosis láctica. Se muestran en esta revisión otras funciones del lactato recientemente descubiertas y las aplicaciones de dichas funciones en la Fisiología del Ejerci...

  7. Valoración de la intensidad del entrenamiento de fuerza a través de la velocidad en el aula

    OpenAIRE

    Sarabia, José Manuel; Hernández-Davó, Jose Luis; Javaloyes Torres, Alejandro; López-Grueso, Raúl; Sabido, Rafael

    2017-01-01

    El entrenamiento de fuerza ha recabado gran interés por la literatura científica en los últimos años, dada su importancia en campos tan dispares como el rendimiento deportivo, la calidad de vida en la tercera edad, o la mejora de patologías que se reflejan en la incapacidad funcional de los pacientes. Desde el punto de vista de la valoración y la planificación del entrenamiento de fuerza son distintas las variables claves que lo definen, ocupando especial relevancia la intensidad de dicho ent...

  8. Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression analysis as potential prognostic or differentiating markers for NSCLC patients in the Polish population.

    Science.gov (United States)

    Kordiak, Jacek; Czarnecka, Karolina H; Pastuszak-Lewandoska, Dorota; Antczak, Adam; Migdalska-Sęk, Monika; Nawrot, Ewa; Domańska-Senderowska, Daria; Kiszałkiewicz, Justyna; Brzeziańska-Lasota, Ewa

    2017-06-01

    According to the latest data, lung cancer is one of the most common cancer worldwide, men contributing nearly 21.2% and women 8.6% of all diagnosed cancers. Late detection of tumour drastically reduces the chance for a cure. Thus, it is important to search for candidate biomarkers for screening of early stage nonsmall cell lung carcinoma (NSCLC). Tumour suppressor genes, DLEC1, TUSC4 and MLH1, localized on 3p21 are recognized to play a role in NSCLC carcinogenesis. The aim of this study was to assess the relationship between the DLEC1, TUSC4 and MLH1 mRNA expression, and clinical features of NSCLC patients, tobacco addiction, and tumour histopathological characteristics. The DLEC1, TUSC4 and MLH1 expression was analysed in lung tumour tissue samples obtained from 69 patients diagnosed with NSCLC: squamous cell carcinoma (n = 34), adenocarcinoma (n = 24), large cell carcinoma (n = 5), carcinoma adenosquamosum (n = 5). A decreased gene expression (RQ MLH1 in 50.7% and for TUSC4 in 26% of NSCLC samples. DLEC1 was decreased in more aggressive subtypes: large cell carcinoma and adenocarcinoma-squamous cell carcinoma. The simultaneous downregulation of two of the studied genes, DLEC1 andMLH1,was observed in 30.4% of NSCLCsamples, highlighting the importance of these two genes in lung carcinogenesis. We found no correlation between the DLEC1, TUSC4 and MLH1 gene expression and NSCLC patient characteristics (gender, age and smoking) or cancer histopathology. No significant differences in the gene expression among NSCLC subtypes indicate the weakness of DLEC1, TUSC4 and MLH1 expression analysis as potential differentiating markers of NSCLC subtypes in the Polish population.

  9. Epigenetic Silencing of the MLH1 Promoter in Relation to the Development of Gastric Cancer and its use as a Biomarker for Patients with Microsatellite Instability: a Systematic Analysis

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    Guimei Hu

    2018-01-01

    Full Text Available Background/Aims: Human mutL homolog 1 (MLH1 promoter methylation was reported in gastric cancer (GC. This study determined the clinicopathological, prognostic, and diagnostic effects of MLH1 promoter methylation in GC. Methods: The combined odds ratio (OR or hazard ratio (HR and their corresponding 95% confidence intervals (95% CI were calculated. The pooled sensitivity, specificity, and area under the curve (AUC were analyzed. Results: A total of 4654 GC patients and 3669 non-malignant controls were identified in this systematic analysis. MLH1 promoter methylation was significantly higher in GC samples than in gastric adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age and microsatellite instability (MSI, but it was not associated with gender, H. pylori infection, smoking, drinking behaviors, pathological histology, tumor differentiation, clinical stage, lymph node status, distant metastasis, or overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity value (< 0.5 in patients with GC compared with adjacent tissues, gastric adenomas, chronic gastritis, normal gastric mucosa, and normal healthy blood samples. The pooled sensitivity, specificity, and AUC of MLH1 promoter methylation in GC with MSI vs. GC with microsatellite stability (MSS samples were 0.64, 0.96, and 0.90, respectively. Conclusions: Our results suggest that the detection of MLH1 promoter methylation may be a potential prognostic biomarker for GC patients with MSI.

  10. Parâmetros de intensidade e sudorese de jogadores de futsal por posição de jogo

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    Luis Felipe Tubagi Polito

    2015-10-01

    Full Text Available RESUMOIntrodução:O número de participantes em programas de treinamento de futsal tem crescido como alter-nativa de prática esportiva entre adolescentes. A aptidão física e o perfil hídrico de adolescentes praticantes de futsal são escassos na literatura científica.Objetivo:Determinar a composição corporal e as característi-cas metabólicas de adolescentes do sexo masculino participantes de programa de treinamento de futsal e relacioná-los com a posição tática.Métodos:Foram avaliados 10 adolescentes do sexo masculino com idades entre 12 e 13 anos e nível de maturação sexual de 3,7 ± 0,7 para pilosidade e 3,6 ± 1,0 no desenvolvimento do genital externo. Os adolescentes foram submetidos à avaliação antropométrica (peso corporal, estatura e composição corporal, neuromotora (teste de impulsão vertical e horizontal e shuttle run e de demanda metabólica (distância percorrida, gasto calórico, número de passos e variação hídrica.Resultados:Os resul-tados dos atletas foram analisados pelas 4 posições de jogo (goleiros, fixos, alas e pivôs utilizando análise de variância Anovaone-way e post-hoc Scheffé com uma margem de erro de 5%, demonstrando que os goleiros apresentaram maior porcentagem de gordura que as demais posições de jogo, não havendo diferenças entre elas. A massa magra apresentou tendência inversa, com menor valor de muscularidade nos goleiros que nas posições de linha, onde os alas e pivôs apresentaram valores superiores aos fixos. Os goleiros apresentaram demanda metabólica menor em função da intensidade analisada durante os jogos comparado com as demais posições, corroborando com outros estudos similares. Para todos os grupos, a ingestão de água ad libitum foi suficiente para manter o estado de hidratação.Conclusão:Assim pudemos concluir que existem diferenças na demanda metabólica entre as posições de jogo, o que sugere prescrição especifica do treinamento buscando evitar o

  11. Aferição dos equipamentos de laser de baixa intensidade Calibration of low-level laser therapy equipment

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    Thiago Y. Fukuda

    2010-08-01

    Full Text Available CONTEXTUALIZAÇÃO: A laserterapia de baixa intensidade (LBI vem sendo cada vez mais utilizada, porém ainda não há consenso na literatura quanto ao tempo em que os equipamentos devem ser submetidos à aferição ou calibragem. OBJETIVO: Analisar a potência média real (PmR dos equipamentos de LBI na região da Grande São Paulo. MÉTODOS: Para análise dos equipamentos, utilizou-se um potenciômetro (Lasercheck, próprio para aferição de equipamentos contínuos, o qual foi programado com dados referentes ao comprimento de onda do laser a ser avaliado, obtendo-se assim a PmR emitida. Os equipamentos foram analisados de duas formas: uma, com o LBI desaquecido, e outra, após 10 minutos de uso (aquecido, sendo que três análises foram feitas para cada condição. A caneta emissora foi acoplada ao potenciômetro, o qual fornecia a PmR emitida pelo LBI. Todos os dados e informações referentes à aplicação do laser foram coletados por um questionário respondido pelos responsáveis. RESULTADOS: Os 60 equipamentos avaliados mostraram déficit na PmR com os equipamentos desaquecidos e aquecidos. A análise estatística (ANOVA mostrou diminuição significativa (PBACKGROUND: Despite the increase in the use of low-level laser therapy (LLLT, there is still a lack of consensus in the literature regarding how often the equipment must be calibrated. OBJECTIVE: To evaluate the real average power of LLLT devices in the Greater São Paulo area. METHODS: For the evaluation, a LaserCheck power meter designed to calibrate continuous equipment was used. The power meter was programmed with data related to the laser's wavelength to gauge the real average power being emitted. The LLLT devices were evaluated in two ways: first with the device cooled down and then with the device warmed up for 10 minutes. For each condition, three tests were performed. The laser probe was aligned with the power meter, which provided the real average power being emitted by the

  12. CARACTERIZACIÓN DE LA RECEPCIÓN EN VOLEIBOL EN CATEGORIA JUVENIL, EN FUNCIÓN DE LA INTENSIDAD DEL SET

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    Sebastián Carrero Pajares

    2015-05-01

    Full Text Available La recepción en voleibol es una de las acciones más importante dentro del K1. La importancia de ésta, estriba en la construcción de un ataque con éxito, puesto que si la recepción es defectuosa, el balón no llegará al colocador en las condiciones idóneas para organizar un ataque eficaz. Sin una buena recepción no se consiguen ataques rápidos o múltiples, con lo que estamos facilitando el juego de defensa del equipo contrario (Fiedler, 1982; González, Ureña, Santos, Llop & Navarro, 2001. Debido a su importancia, son diversos los estudios que han analizado dicha acción, pero pocos los que han tenido en cuenta variables situacionales como el número de set, el lugar del partido (Campos,  Stanganélli, Campos, Pasquarelli & Gómez, 2014 o la intensidad del set (Drikos, & Vagenas, 2011. Poniendo de manifiesto la importancia de tener en cuenta las variables situacionales en los estudios de analisis de juego Objetivo: El objetivo de nuestra investigación es analizar las características de la recepción en voleibol, en función de la intensidad del partido.

  13. Avaliação da intensidade de dor e sinais vitais no pós-operatório de cirurgia cardíaca

    Directory of Open Access Journals (Sweden)

    Adriana de Fátima Alencar Miranda

    2011-04-01

    Full Text Available O objetivo do estudo é analisar as alterações nos sinais vitais de pacientes em pós-operatório de cirurgias cardíacas, mediante intensidade de dor referida. Trata-se de estudo descritivo-exploratório, que utilizou o método de análise quantitativa na investigação de 38 pacientes submetidos à primeira renovação de curativos. A análise dos dados, mensurados antes e após a realização do procedimento de enfermagem, indicaram que a manifestação da dor ocorreu em diferentes classificações. As principais alterações nos sinais vitais ocorreram na pressão arterial. Concluiu-se que a intensidade dolorosa mantém relações com os resultados dos sinais vitais e o cuidado prestado é imprescindível ao restabelecimento do estado de saúde do paciente no pós-operatório.

  14. Impacto da Congruência entre Autoconceito e Personalidade de Marca na Intensidade da Qualidade de Relacionamento e Lealdade do Consumidor

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    Andréa de Albuquerque de Lima

    2013-03-01

    Full Text Available O estudo investigou o impacto da congruência com marca (sendo essa expressa pela similaridade entre o autoconceito e a percepção de personalidade de marca sob o ponto de vista do consumidor na intensidade da qualidade de relacionamento e lealdade do consumidor à marca. Os principais construtos mensurados para posteriormente compor o modelo estrutural foram: autoconceito e personalidade de marca, ambos mensurados pela escala proposta por Muniz (2005 composto por cinco dimensões (credibilidade, diversão, audácia, sofisticação e sensibilidade. Já os construtos integrantes da qualidade de relacionamento (comprometimento afetivo, satisfação e confiança e pós-venda (lealdade foram mensurados através das escalas propostas por Baptista (2005. Realizou-se um e-survey com 626 casos. O objeto de estudo foram consumidores de tênis das marcas Adidas e Nike. Os resultados revelam que a congruência com marca impacta diretamente na intensidade do comprometimento afetivo, da confiança e da satisfação do consumidor e possui um efeito indireto sobre lealdade, sendo esse intermediado pelos componentes da qualidade de relacionamento.DOI:10.5585/remark.v12i1.2508

  15. Intensidade Moral nas Decisões de Marketing Turístico: proposta de uma escala de mensuração

    Directory of Open Access Journals (Sweden)

    Taís Alexandre Antunes Paes

    2012-12-01

    Full Text Available ResumoA atividade turística vêm ganhando ênfase nas ultimas décadas por ser uma atividade que tem contribuído para o desenvolvimento social e econômico de várias regiões. Tal atividade apresenta importância, na medida em que, a tomada de decisão de um gestor pode gerar benefícios ou malefícios sobre a sociedade no qual o turismo está inserido. Desta forma, este trabalho apresenta como objetivo desenvolver uma escala de mensuração do construto intensidade moral considerando o contexto da tomada de decisão ética dos gestores da atividade turística. A revisão da literatura indicou que o construto intensidade moral não possuía uma escala validada para este contexto. O construto intensidade moral foi proposto por Jones (1991 que tomou como base a análise do tópico moral em si, considerando que cada indivíduo reagirá de maneira diferente em varias intensidades diante de situações éticas. Este considera que o construto intensidade moral é constituído de seis características: magnitude das consequências, consenso social, probabilidade de efeito, imediatismo temporal, proximidade e concentração do efeito. Tendo em vista as considerações apresentadas foram desenvolvidos três cenários com diferentes contextos (social, econômico e ambiental associados a dilemas éticos da atividade turística, mais seis itens referentes as seis características da intensidade moral. Para o desenvolvimento e validação da escala foram utilizadas três amostras, duas com estudantes e uma com gestores. Os testes empíricos indicaram a consistência dos itens e dos cenários desenvolvidos, com  variações de percepções segundo os tipos de cenários. Ao final são propostas idéias de aplicações da escalas e

  16. Comportamento ingestivo de cordeiras em pastagem consorciada de inverno sob diferentes intensidades de desfolha Ingestive behavior of lambs on mixed winter pasture under different grazing intensities

    Directory of Open Access Journals (Sweden)

    Carine Lisete Glienke

    2008-11-01

    Full Text Available Avaliou-se a relação entre a estrutura do pasto, as variáveis ambientais e o comportamento ingestivo de cordeiras Ile de France × Texel em pastagem consorciada de aveia-preta (Avena strigosa Schreb., azevém (Lolium multiflorum Lam. e trevo-vermelho (Trifolium pratense L. sob quatro intensidades de desfolha (muito alta, alta, média e baixa. Utilizaram-se pastejos intermitentes considerando a soma térmica de 300 graus-dia como critério para determinar os intervalos de pastejo. As avaliações do comportamento ingestivo foram feitas por meio de observação visual em quatro períodos contínuos de 24 horas realizados no período de maio a outubro de 2006. O maior tempo de pastejo ocorreu na intensidade baixa. Altas intensidades de desfolha ocasionaram aumento da densidade populacional de perfilhos de azevém e não alteraram o peso desses perfilhos. A massa de bocados e a qualidade da dieta selecionada pelas cordeiras foram semelhantes entre as intensidades testadas. Em pastagem de aveia+azevém+trevo-vermelho, quando o intervalo de pastejo é determinado pela soma térmica de 300 graus-dia, a utilização de intensidades de desfolha que variam de baixa a muito alta não altera o comportamento ingestivo de cordeiras. O comportamento ingestivo é afetado pelo ciclo do pasto e pelo fotoperíodo e a seletividade dos animais reduz ao final do período de utilização da pastagem, quando ocorre aumento no tempo de pastejo e na distância percorrida em busca de locais de alimentação.The relationship between the pasture structure, environmental variables and the ingestive behavior of crossbred Ile de France-Texel lambs on a mixed winter pasture of oats (Avena strigosa Schreb., Italian ryegrass (Lolium multiflorum Lam., and red clover (Trifolium pratense L. under four grazing intensities ('very high', 'high', 'average', and 'low' was evaluated. Intermittent grazing was used, considering the thermal sum of 300 degree-days to determine the grazing

  17. A influência do controle subjetivo de intensidade sobre fadiga percebida e lactato capilar em duas formas de treinamento resistido

    Directory of Open Access Journals (Sweden)

    Cauê Vazquez La Scala Teixeira

    2015-05-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2015v17n3p309   A percepção subjetiva de esforço (PSE é um método utilizado para controlar a intensidade no treinamento resistido (TR. Porém há escassez de estudos que comparam respostas fisiológicas e perceptivas agudas entre formas distintas de TR. O estudo teve como objetivo comparar as respostas agudas de lactato (LAC e fadiga percebida (FAD entre treinamento resistido manual (TRM e TR com pesos livres (TRPL com intensidades controladas por PSE, bem como observar a correlação entre LAC e FAD nas duas intervenções. Participaram 14 homens (40,29+8,63 anos, IMC = 26,53+5,24 Kg/m² previamente não treinados que foram submetidos a sessões únicas de TRM e TRPL, com intensidade controlada por PSE (entre 5 e 7. LAC e FAD foram analisados nos momentos pré-teste e pós-teste. Para análise dos dados, utilizou-se análise de variância com medidas repetidas e post-hoc de Bonferroni. Adotou-se nível de significância de 5% (P ≤ 0,05. O tamanho do efeito (ES foi calculado para analisar a magnitude das respostas e o coeficiente de correlação linear de Pearson para verificar associação entre LAC e FAD. Ambas as intervenções aumentaram LAC no período pós-teste em relação ao pré-teste, porém o aumento foi maior no TRM. A FAD aumentou no período pós-teste em relação ao pré-teste, em ambos os protocolos, sem diferença entre eles. No entanto, o ES foi maior para o TRM. A correlação entre FAD e LAC foi moderada em três das quatro avaliações. Foi possível concluir que na mesma zona de intensidade na PSE pode representar respostas fisiológicas diferentes entre duas formas distintas de TR, portanto, a utilização da PSE para controle de intensidade, nessas condições, deve ser vista com cautela.

  18. INTENSIDAD DE LOS SABORES BÁSICOS DEL TOMATE (Lycopersicon esculentum EN SEIS ESTADOS DE MADUREZ INTENSITY OF BASIC TASTES OF TOMATO (Lycopersicon esculentum IN SIX MATURITY STAGES

    Directory of Open Access Journals (Sweden)

    KATHERIN CASTRO

    2009-06-01

    Full Text Available El tomate (Lycopersicon esculentum, la hortaliza más sembrada en Colombia, es considerada una de las más importantes por su volumen de producción y demanda. La exigencia del consumidor en sus características organolépticas hace necesario un estudio detallado acerca de sus propiedades fisicoquímicas y sensoriales. El análisis sensorial se realizó con un panel entrenado de cinco jueces y las muestras de tomate fueron escogidas de acuerdo con parámetros físicos de color (Cuadro 1 y calidad en los seis estados de madurez del fruto. Se empleó el método de perfil descriptivo, con una escala de respuesta de 0 a 10 puntos, con el fin de cuantificar la intensidad de los sabores básicos (dulce, ácido, amargo, salado y umami. Se realizó un diseño aleatorizado en bloques con seis réplicas por cada tratamiento y un nivel de significancia del 5%. Este indicó la inexistencia de diferencias significativas en las intensidades para cada estado de madurez (p≤ 0,05, y la existencia de diferencias significativas en las intensidades para cada sabor básico evaluado (p>0,05. Mediante el perfil sensorial, se logró establecer que en los estados de madurez 1 y 2, el atributo de mayor intensidad fue el ácido, en los estados de madurez 3, 4 y 5, el atributo que sobresalió fue el dulce y en el estado 6, el atributo percibido en mayor grado fue el umami. Los sabores amargo y salado, se percibieron en una baja intensidad, en los diferentes estados de madurez.The tomato (Lycopersicon esculentum, the vegetable more seeding in the country, is considered one of most important by its volume of production and demand. The exigency of the consumer in sensory characteristics makes necessary a detailed study about its physicochemistry and sensory properties. The sensory analysis was made with a trained panel of five judges and the tomato samples were chosen according to parameters of color and quality in the six ripeness stages of the fruit. Was made using the

  19. Influencia del tipo e intensidad de luz en la formación y multiplicación de embriones somáticos de soya

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    Jorge Liusvert Pérez Pérez

    2012-07-01

    Full Text Available Título en ingles: Influence of light type and intensity on induction and proliferation of somatic embryos in soybean Resumen: La embriogénesis somática representa una alternativa para la regeneración de plantas, sobre la cual influyen diversos factores durante el cultivo in vitro. Entre estos, las condiciones de iluminación durante la formación de embriones somáticos es determinante. Sin embargo, no existen trabajos que refieran el efecto de la luz solar en la formación de embriones somáticos de soya. Este trabajo tuvo como objetivo evaluar el efecto del tipo e intensidad de luz en la formación y multiplicación de embriones somáticos de soya cultivar INCASoy-27. Para ello, cotiledones inmaduros de 3,0-4,0 mm de longitud fueron colocados en medio de cultivo con 40 mg.l-1 de ácido 2,4-diclorofenoxiacético, sacarosa 3% y pH 7,0 en cámaras de crecimiento con luz artificial e intensidades luminosas de 5-10 µmol.m-2.s-1 y 68-73 µmol.m-2.s-1, y en cámaras de crecimiento con luz solar con 50-65µmol.m-2.s-1. El mayor número de cotiledones embriogénicos (95,31 se obtuvo en condiciones de luz artificial con alta intensidad luminosa. La mayor formación de embriones somáticos se obtuvo en luz artificial (9,65 y luz solar (8,45 respectivamente con alta intensidad luminosa. No se encontraron diferencias significativas en la multiplicación de los embriones somáticos, al emplear ambas fuente de luz con alta intensidad luminosa. Esta es la primera referencia sobre formación y multiplicación de embriones somáticos de soya con empleo de luz solar. Palabras clave: Cultivo de tejido; embriogénesis somática; fotoperíodo; Glycine max. Abstract: The somatic embryogenesis represents an alternative for the regeneration of plants, in which influence diverse factors during the cultivation. Among these factors, the conditions of illumination during the induction of somatic embryos are determinant. However, works not exist that refer the effect

  20. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    International Nuclear Information System (INIS)

    Lüchtenborg, Margreet; Weijenberg, Matty P; Wark, Petra A; Saritas, A Merdan; Roemen, Guido MJM; Muijen, Goos NP van; Bruïne, Adriaan P de; Brandt, Piet A van den; Goeij, Anton FPM de

    2005-01-01

    The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Mutations at the phosphorylation sites (codons 31, 33, 37, and 45) in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656) and 36% (235/656), respectively). Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656). Nine percent of all tumours (58/656) lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency

  1. Secondary mutation in a coding mononucleotide tract in MSH6 causes loss of immunoexpression of MSH6 in colorectal carcinomas with MLH1/PMS2 deficiency.

    Science.gov (United States)

    Shia, Jinru; Zhang, Liying; Shike, Moshe; Guo, Min; Stadler, Zsofia; Xiong, Xiaoling; Tang, Laura H; Vakiani, Efsevia; Katabi, Nora; Wang, Hangjun; Bacares, Ruben; Ruggeri, Jeanine; Boland, C Richard; Ladanyi, Marc; Klimstra, David S

    2013-01-01

    Immunohistochemical staining for DNA mismatch repair proteins may be affected by various biological and technical factors. Staining variations that could potentially lead to erroneous interpretations have been recognized. A recently recognized staining variation is the significant reduction of staining for MSH6 in some colorectal carcinomas. The frequency and specific characteristics of this aberrant MSH6 staining pattern, however, have not been well analyzed. In this study of 420 colorectal carcinoma samples obtained from patients fulfilling the Revised Bethesda Guidelines, we detected 9 tumors (2%) showing extremely limited staining for MSH6 with positive staining present in PMS2 protein-deficient carcinomas (n=5, including 1 with a pathogenic mutation in PMS2); and (2) MLH1, PMS2 and MSH2 normal but with chemotherapy or chemoradiation therapy before surgery (n=4). To test our hypothesis that somatic mutation in the coding region microsatellite of the MSH6 gene might be a potential underlying mechanism for such limited MSH6 staining, we evaluated frameshift mutation in a (C)(8) tract in exon 5 of the MSH6 gene in seven tumors that had sufficient DNA for analysis, and detected mutation in four; all four tumors belonged to the MLH1/PMS2-deficient group. In conclusion, our data outline the main scenarios where significant reduction of MSH6 staining is more likely to occur in colorectal carcinoma, and suggest that somatic mutations of the coding region microsatellites of the MSH6 gene is an underlying mechanism for this staining phenomenon in MLH1/PMS2-deficient carcinomas.

  2. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    Directory of Open Access Journals (Sweden)

    de Bruïne Adriaan P

    2005-12-01

    Full Text Available Abstract Background The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1 and Ras (K-ras pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. Methods In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Results Mutations at the phosphorylation sites (codons 31, 33, 37, and 45 in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656 and 36% (235/656, respectively. Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656. Nine percent of all tumours (58/656 lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. Conclusion CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.

  3. Screening of the DNA mismatch repair genes MLH1, MSH2 and MSH6 in a Greek cohort of Lynch syndrome suspected families

    International Nuclear Information System (INIS)

    Thodi, Georgia; Fountzilas, George; Yannoukakos, Drakoulis; Fostira, Florentia; Sandaltzopoulos, Raphael; Nasioulas, George; Grivas, Anastasios; Boukovinas, Ioannis; Mylonaki, Maria; Panopoulos, Christos; Magic, Mirjana Brankovic

    2010-01-01

    Germline mutations in the DNA mismatch repair genes predispose to Lynch syndrome, thus conferring a high relative risk of colorectal and endometrial cancer. The MLH1, MSH2 and MSH6 mutational spectrum reported so far involves minor alterations scattered throughout their coding regions as well as large genomic rearrangements. Therefore, a combination of complete sequencing and a specialized technique for the detection of genomic rearrangements should be conducted during a proper DNA-testing procedure. Our main goal was to successfully identify Lynch syndrome families and determine the spectrum of MLH1, MSH2 and MSH6 mutations in Greek Lynch families in order to develop an efficient screening protocol for the Greek colorectal cancer patients' cohort. Forty-two samples from twenty-four families, out of which twenty two of Greek, one of Cypriot and one of Serbian origin, were screened for the presence of germline mutations in the major mismatch repair genes through direct sequencing and MLPA. Families were selected upon Amsterdam criteria or revised Bethesda guidelines. Ten deleterious alterations were detected in twelve out of the twenty-four families subjected to genetic testing, thus our detection rate is 50%. Four of the pathogenic point mutations, namely two nonsense, one missense and one splice site change, are novel, whereas the detected genomic deletion encompassing exon 6 of the MLH1 gene has been described repeatedly in the LOVD database. The average age of onset for the development of both colorectal and endometrial cancer among mutation positive families is 43.2 years. The mutational spectrum of the MMR genes investigated as it has been shaped by our analysis is quite heterogeneous without any strong indication for the presence of a founder effect

  4. Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

    Science.gov (United States)

    Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

    2018-04-01

    The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

  5. Hsp27, Hsp70 and mismatch repair proteins hMLH1 and hMSH2 expression in peripheral blood lymphocytes from healthy subjects and cancer patients.

    Science.gov (United States)

    Nadin, Silvina Beatriz; Vargas-Roig, Laura M; Drago, Gisela; Ibarra, Jorge; Ciocca, Daniel R

    2007-07-08

    Mismatch repair (MMR) deficiency and higher expression levels of heat shock proteins (Hsps) have been implicated with drug resistance to topoisomerase II poisons (doxorubicin) and to platinum compounds (cisplatin). This study was designed to determine individual influences of doxorubicin and cisplatin treatment on the expression of Hsp27, Hsp70, hMLH1 and hMSH2 proteins and in the DNA damage status in peripheral blood lymphocytes (PBLs). In addition, we studied whether these proteins and the DNA damage correlated with the survival of cancer patients. PBLs from 10 healthy donors and 25 cancer patients (before and after three cycles of chemotherapy) were exposed to in vitro treatments: C (control), HS (heat shock at 42 degrees C), Do or Pt (doxorubicin or cisplatin alone), and HS+Do or HS+Pt (heat shock+doxorubicin or heat shock+cisplatin). PBLs were collected at time 0 (T0: immediately after drug treatment) and after 24h of repair (T24). Hsp27, Hsp70, hMLH1 and hMSH2 were studied by immunocytochemistry and the DNA damage by alkaline comet assay. Immunofluorescence studies and confocal microscopy revealed that hMLH1 and hMSH2 colocalized with Hsp27 and Hsp72 (inducible form of Hsp70). hMLH1 and hMSH2 were significantly induced by Pt and HS+Pt at T24 in cancer patients, but only modestly influenced by Do. Cancer patients presented higher basal expression of total and nuclear Hsp27 and Hsp70 than controls, and these proteins were also increased by HS, Do and HS+Do. The Hsp70 induction by Pt and HS+Pt was noted in cancer patients, especially nuclear Hsp70. In cancer patients, basal DNA damage was slightly higher than in healthy persons; and after Pt and HS+Pt treatments, DNA migration and number of apoptotic cells were higher than controls. Hsps accomplished a cytoprotective function in pre-chemotherapy PBLs (HS before Do or Pt), but not in post-chemotherapy samples. In Pt-treated patients the ratio N/C (nuclear/cytoplasmic) of Hsp27 was related to disease free survival

  6. PARÂMETROS DE CURVAS TEMPO-INTENSIDADE DOS ESTÍMULOS DOCE E AMARGO DE EDULCORANTES: SELEÇÃO POR ANÁLISE DISCRIMINANTE POR PASSO E ANÁLISE DE CORRELAÇÃO

    Directory of Open Access Journals (Sweden)

    Helena Maria André Bolini CARDELLO

    2009-07-01

    Full Text Available

    A análise tempo-intensidade é uma técnica que permite estudar as variações de intensidade de estímulos sensoriais com o decorrer do tempo. Para este estudo, são coletados os valores de parâmetros das curvas obtidas, os quais são submetidos a análises estatísticas, que fornecem informações sobre o estimulo sensorial gerado pela amostra avaliada. Esse processo é trabalhoso, uma vez que são analisadas várias curvas, em razão do número de amostras, provadores e repetições. O objetivo do presente trabalho foi verificar a possibilidade de diminuir o número de parâmetros que devem ser obtidos de cada curva. Para isso, foram realizadas análises de correlação entre os parâmetros e análise discriminante por passos. Os edulcorantes estudados foram: aspartame, extrato de folhas de estévia e ciclamato/sacarina 2:1, em doçura equivalente à sacarose em solução a 3%, 10%,20% e 30%. Os parâmetros obtidos foram: tempo para atingir a intensidade máxima (TImáx, tempo onde a intensidade máxima começa a declinar (Td, tempo de duração da intensidade máxima (Platô, área total sob a curva (Área, tempo total de duração do estímulo (Ttot e intensidade máxima percebida (Imáx Concluiu-se que, para os gostos doce e amargo, para os edulcorantes estudados, o parâmetro Área poderia ser eliminado .

  7. Perfil sensorial da bebida café (Coffea arabica L. determinado por análise tempo-intensidade Sensorial profile of beverage coffee (Coffea arabica L. determined by analysis time-intensity

    Directory of Open Access Journals (Sweden)

    Marlene A. M. Monteiro

    2005-12-01

    Full Text Available O presente trabalho teve como objetivo avaliar o gosto amargo, sabor fermentado e sabor queimado de nove amostras (mole/clara, dura/clara, rio/clara, mole/expresso, dura/expresso, rio/expresso, mole/escura, dura/escura e rio/escura da bebida café (Coffea arabica L. por meio da análise Tempo-Intensidade (TI. Foram avaliados seis parâmetros da curva: tempo para atingir a intensidade máxima (TImáx, intensidade máxima do estímulo (Imáx, tempo correspondente ao ponto onde a intensidade máxima começa a declinar (Td, tempo de duração da intensidade máxima (Platô, área sob a curva (Área e tempo total de duração do estímulo (Ttot. A análise demonstrou que as amostras de torra escura tiveram maior intensidade máxima (Imáx e tempo de duração do estímulo (Ttot para gosto amargo e sabor queimado, sendo que as amostras de torra clara apresentaram menor intensidade destes estímulos. Em relação ao sabor fermentado, a amostra rio/expresso foi a que apresentou maior intensidade.The present work had as objective to evaluate the bitter taste, fermented flavor and burned flavor of nine samples (soft/light, hard/light, rio/light, soft/express, hard/express, rio/express, soft/dark, hard/dark and rio/dark of the drink coffee (Coffea arabica L. through the analysis Time-Intensity (TI. Six parameters of the curve were evaluated: time to reach the maximum intensity (TImáx, maximum intensity of the incentive (Imáx, time corresponding to the point where the maximum intensity begins to refuse (Td, time of duration of the maximum intensity (Plateau, area under the curve (Área and total time of duration of the incentive (Ttot. The analysis demonstrated that the samples of dark toast had larger maximum intensity (Imáx and time of duration of the incentive (Ttot for bitter taste and burned flavor, while the samples of light toast presented smaller intensity of these stimulus. For the fermented flavor, the sample rio/express was the one that

  8. The importance of proper bioinformatics analysis and clinical interpretation of tumor genomic profiling: a case study of undifferentiated sarcoma and a constitutional pathogenic BRCA2 mutation and an MLH1 variant of uncertain significance.

    Science.gov (United States)

    Varga, Elizabeth; Chao, Elizabeth C; Yeager, Nicholas D

    2015-09-01

    Next-generation sequencing (NGS) technology is increasingly utilized to identify therapeutic targets for patients with malignancy. This technology also has the capability to reveal the presence of constitutional genetic alterations, which may have significant implications for patients and their family members. Here we present the case of a 23 year old Caucasian patient with recurrent undifferentiated sarcoma who had NGS-based tumor analysis using an assay which simultaneously analyzed the entire coding sequence of 236 cancer-related genes (3769 exons) plus 47 introns from 19 genes often rearranged or altered in cancer. Pathogenic alterations were reported in tumor as the predicted protein alterations, BRCA2 "R645fs*15″ and MLH1 "E694*". Because constitutional BRCA2 and MLH1 gene mutations are associated with Hereditary Breast Ovarian Cancer Syndrome (HBOCS) and Lynch syndrome respectively, sequence analysis of DNA isolated from peripheral blood was performed. The presence of the alterations, BRCA2 c.1929delG and MLH1 c.2080G>T, corresponding to the previously reported predicted protein alterations, were confirmed by Sanger sequencing in the constitutional DNA. An additional DNA finding was reported in this analysis, MLH1 c.2081A>C at the neighboring nucleotide. Further evaluation of the family revealed that all alterations were paternally inherited and the two MLH1 substitutions were in cis, more appropriately referred to as MLH1 c.2080_2081delGAinsTC, which is classified as a variant of uncertain significance. This case illustrates important considerations related to appropriate interpretation of NGS tumor results and follow-up of patients with potentially deleterious constitutional alterations.

  9. The MLH1 c.1852_1853delinsGC (p.K618A variant in colorectal cancer: genetic association study in 18,723 individuals.

    Directory of Open Access Journals (Sweden)

    Anna Abulí

    Full Text Available Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

  10. Project on Alternative Systems Study - PASS. Comparison of technology of KBS-3, MLH, VLH and VDH concepts by using an expert group

    International Nuclear Information System (INIS)

    Olsson, Lars; Sandstedt, H.

    1992-09-01

    This report constitutes a technical comparison and ranking of four repository concepts for final disposal of spent nuclear fuel, that have been studied by SKB: KBS-3, Medium Long Holes (MLH), Very Long Holes (VLH) and Very Deep Holes (VDH). The technical comparison is part of the project 'Project on Alternative Systems Study, PASS', which was initiated by SKB. With the objective of presenting a ranking of the four concepts. Besides this comparison of Technology the ranking is separately made for Long-term Performance and Safety, and Costs before the merging into one verdict. The ranking regarding Technology was carried out in accordance with the method Analytical Hierarchy Process, AHP, and by the aid of expert judgement in the form of a group consisting of six experts. The AHP method implies that the criteria for comparison are ordered in a hierarchy and that the ranking is carried out by pairwise comparison of the criteria. In the evaluation process a measure of the relative importance of each criterion is obtained. The result of the expert judgement exercise was that each expert individually ranked the four concepts in the following order with the top ranked alternative first: KBS-3, MLH, VLH and VDH. The common opinion among the experts was that the top ranking of KBS-3 is significant and the the major criteria used in the study could change substantially without changing the top ranking of KBS-3

  11. Efectos de la ingesta ad libitum de bebidas hidratantes sobre el peso corporal, la frecuencia cardíaca y el volumen plasmático durante una actividad física de alta intensidad y larga duración -Informe preliminar- Body weight, the heart rate, and the plasma volume during a high-intesity, long-duration run

    Directory of Open Access Journals (Sweden)

    Rubiela Flórez Manrique

    2004-02-01

    Full Text Available Objetivo: determinar la magnitud de la ingesta ad libitum de tres bebidas hidratantes de diferente osmolaridad y establecer sus efectos sobre el porcentaje de pérdida del peso corporal (PC, el aumento de la frecuencia cardíaca (FC y la reducción porcentual del volumen plasmático (VP en nueve deportistas con entrenamiento aeróbico, sometidos, bajo condiciones ambientales neutras, a una actividad física de alta intensidad 80% de la FC de reserva (FCR80 y larga duración 88 minutos. Metodología: el protocolo experimental se realizó en banda rodante, luego de nueve minutos de calentamiento, a una velocidad equivalente al 50% de la FCR y con una pendiente del 1%; siguieron 88 minutos de carrera, en tres intervalos, los dos iniciales de 29 minutos y el último de 30; la pendiente se mantuvo y la velocidad se incrementó al 80% de la FCR; finalmente, 90 minutos de recuperación, en tres intervalos de 30 minutos cada uno. No se hizo reposición hídrica durante el tratamiento deshidratado (DH; durante los tratamientos con hidratación se empleó un volumen similar de tres bebidas de diferente osmolaridad (H-I, H-II, H-III, el cual fue ingerido ad libitum. Resultados: durante la etapa de ejercicio la pérdida hídrica fue de 1.440 ml/h mientras que el volumen ingerido fue de 407 ml/h. Se observó, en cada uno de los tratamientos, una pérdida porcentual del PC (p<0,001; un incremento de la FC (p<0,05, y excepto con H-II y H-III una reducción porcentual del VP (p<0,05. No hubo diferencias intertratamientos en el porcentaje de la pérdida del PC, en el aumento de la FC ni en la reducción porcentual del VP. Conclusiones: la ingesta ad libitum fue menor que la cantidad recomendada internacionalmente por lo que, probablemente, no se pudieron establecer los efectos de la osmolaridad de las bebidas hidratantes sobre las variables estudiadas. Estos hallazgos nos obligan a revisar las prácticas de hidratación de nuestros deportistas ya que, al parecer

  12. Avaliação da intensidade de raleio na qualidade de frutos de nespereira Evaluation of thinning intensity on loquat fruit quality

    Directory of Open Access Journals (Sweden)

    Aexandre Manzoni Grassi

    2010-01-01

    Full Text Available A nespereira é uma frutífera de origem subtropical, porém com ampla adaptação a regiões de clima temperado com temperaturas baixas pouco rigorosas. Possui inflorescência que origina uma quantidade de frutos superior ao que pode suportar a árvore, produzindo elevada quantidade de frutos de baixo calibre, sendo necessário o raleio de frutos para a melhoria da qualidade. Assim, objetivou-se avaliar o efeito da intensidade de raleio na qualidade de frutos de nespereira. Avaliaram-se as respostas de cinco cultivares e uma seleção de nespereira a quatro intensidades de raleio de frutos (4, 6, 8 e 10 frutos por panícula. As panículas foram selecionadas em relação ao tamanho (aproximadamente 1,5 cm de diâmetro e ensacadas utilizando-se papel jornal. Todas as panículas foram raleadas e ensacadas no mesmo dia. A colheita foi realizada quando os frutos estavam maduros, no ponto de consumo. Foram avaliados comprimento e diâmetro do fruto, massa do fruto e da semente, pH, acidez titulável e teor de sólidos solúveis. Conclui-se que a melhor qualidade de frutos pode ser obtida quando as panículas são raleadas com intensidades de 4 frutos, os quais resultam em maior comprimento, diâmetro e massa. As variáveis massa da semente, pH, acidez titulável e sólidos solúveis não foram afetadas pela intensidade de raleio.Loquat is a fruit of subtropical origin, but with wide adaptation in temperate regions with low, fairly rigorous temperatures. It presents an inflorescence that leads to higher quantity of fruit than the tree can support, resulting in a high quantity of low caliber fruit. To increase the fruit size is necessary to realize the thinning. Thus, the objective of this work was to evaluate the effects of thinning intensities on the loquat fruit quality. It was studied five cultivars and one loquat selection and four thinning intensities (4, 6, 8, and 10 fruit per panicle. Panicles were selected according to equivalent sizes (1.5 cm

  13. ASMATHOUR (1971 – PARA CORO E PERCUSSÃO – DE GILBERTO MENDES: UMA ABORDAGEM ANALÍTICA DO USO DE CONTRASTES DE DENSIDADE E DE INTENSIDADE

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    Adriana Francato

    2005-12-01

    Full Text Available O presente artigo aborda a obra Asthmatour, para coro e percussão, composta em 1971 pelo compositor brasileiro Gilberto Mendes e propõe uma análise musical enfocando o uso de contrastes de densidade e de intensidade pelo compositor no decorrer da obra. Na análise, foram usadas como referências manuscritos que retratam seu processo composicional e que foram compilados pela pesquisadora Rosemara Staub de Barros Zago (ZAGO:2000 e obras teóricas de autores que analisam os movimentos surgidos no século XX, como David Cope (COPE:1993 e Michael Nyman (NYMAN:2000. O compositor cria uma estrutura delimitada e definida e, a partir dela, utiliza o recurso da montagem na organização dos materiais, num processo aberto à criação do intérprete.

  14. Distribución geográfica, prevalencia e intensidad de las infecciones de Gregarina ronderosi (Eugregarinorida: Gregarinidae en Dichroplus elongatus (Orthoptera: Acrididae

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    Christian Bardi

    2016-01-01

    Full Text Available regarina ronderosi es un parásito obligado del tracto digestivo del acrídido plaga Dichroplus elongatus y una de las únicas dos eugregarinas de acrídidos argentinos descriptas con su ciclo de vida completo. Dada la falta de conocimiento acerca de aspectos epizootiológicos fundamentales de las infecci- ones causadas por eugregarinas en acrídidos de Argentina, el objetivo de esta contribución es iniciar el registro de la distribución geográfica de G. ronderosi en la región Pampeana, su prevalencia natural y la intensidad de las infecciones en condiciones naturales. Para ello, se colectaron ejemplares de D. elongatus (2008 – 2012 en distintos puntos de la región Pampeana. Se obtuvieron y analizaron un total de 4084 ejemplares provenientes de cuarenta y dos localidades. La prevalen- cia promedio de G. ronderosi para el total de localidades con presencia (diecisiete localidades fue de 29,7 ± EE 6,6% (n = 1071. El total de individuos infectados (n = 396 fue categorizado respecto de la intensidad de las infecciones: tres (0,8% presentaron infecciones muy fuertes, ochenta (20% fuerte, doscientos diez (53% moderadas y ciento tres (26% infecciones leves. Se ha ampliado la distribución ge- ográfica conocida, se han registrado prevalencias elevadas que sugieren la ocur - rencia de epizootias y se han registrado por primera vez en condiciones naturales infecciones de G. ronderosi categorizadas como Fuertes y Muy Fuertes.

  15. Efecto del fotoperiodo y la intensidad lumínica sobre la esporulación de Peronospora sparsa Berkeley, bajo condiciones controladas

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    Soto S. Johana Carolina

    2009-08-01

    Full Text Available

    El mildeo velloso de la rosa, producido por Peronospora sparsa, es una de las enfermedades más limitantes y costosas en los cultivos comerciales de rosa en Colombia. La estrecha relación de la enfermedad con las condiciones climáticas ha llevado a realizar estudios del parásito en condiciones microclimáticas controladas. Esta investigación buscó ahondar en el conocimiento de la biología del mildeo velloso de la rosa, evaluando para ello el efecto del fotoperiodo y la intensidad lumínica sobre la esporulación del parásito cultivado en folíolos de rosa en cámara húmeda bajo condiciones ambientales controladas. Se evaluaron los siguientes fotoperiodos: 24 horas bajo una intensidad lumínica de 1.000 lux; 8, 12 y 24 horas luz a 790 lux; 8, 16 y 24 horas a 560 lux; 12 horas a 120 lux, y finalmente 0 horas luz (oscuridad total. La esporulación se vio favorecida por fotoperiodos de 8 a 16 horas a 560 lux, y presentó un alto desempeño con periodos de 12 horas a 790 lux. La exposición continua a la luz demostró tener un efecto inhibidor sobre la esporulación de P. sparsa. Así mismo, determinó la producción de esporangios con características atípicas, como bajo contenido citoplasmático y menor tamaño.

  16. Influencia de la intensidad de uso sobre algunas propiedades físicas en un suelo del Valle del Cauca, Colombia

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    Alveiro Salamanca Jiménez

    2015-03-01

    Full Text Available La intensidad de uso y manejo del suelo generalmente altera el comportamiento de sus propiedades físicas y acelera su degradación. Con el fin de medir el impacto de dicha intensidad, se llevó a cabo un muestreo en la estación experimental del CIAT-Palmira, Valle del Cauca, Colombia. Se escogieron seis lotes con diferentes historiales, desde uso semestral muy intensivo hasta uso reducido con descanso por más de 10 años, y se tomaron muestras de suelo a inco profundidades del perfil para evaluar las siguientes propiedades:conductividad hidráulica, permeabilidad al aire, porosidad total, porosidad drenable, compactabilidad, porosidad residual, materia orgánica y resistenciamecánica a la penetración. Se encontró que el uso de maquinaria y las labores de fangueo mejoraron las propiedades físicas sólo en los 15 cm superficiales, pero han causado graves problemas de compactación en las profundidadesinferiores. El pisoteo del ganado también ha compactado el perfil, limitando las condiciones físicas para ser explorado por las raíces de los pastos.Los períodos de descanso han favorecido la estabilidad estructural del suelo y con ello la calidad del mismo. Se recomienda implementar prácticastendientes a reducir los riesgos por compactación, que ayuden a frenar la degradación y a recuperar la capacidad productiva de estos suelos.

  17. Participação nos lucros ou resultados e banco de horas: intensidade do trabalho e desgaste operário

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    José Augusto Pina

    Full Text Available INTRODUÇÃO: As transformações operadas no processo de trabalho na indústria automobilística no Brasil desde os anos 1990 apontam para o fortalecimento da gestão da força de trabalho como um dos determinantes do processo saúde-doença dos trabalhadores. OBJETIVOS: Discutem-se dois elementos da gestão: a participação nos lucros ou resultados (PLR e o banco de horas (BH e assinala-se a relação de ambos com a intensidade do trabalho e o desgaste operário. Métodos: Apóia-se em revisão bibliográfica e em análise dos acordos coletivos dos metalúrgicos do ABC-SP, entre 2001 e 2008. RESULTADOS: A análise realizada mostrou que a reorganização do tempo de trabalho, o prolongamento da jornada e a manutenção do elevado grau de intensidade do trabalho ocasionados pelo BH e as metas vinculadas à PLR exercem pressão sobre o trabalhador para o aumento quantitativo e qualitativo do trabalho, evidenciando que esses instrumentos gerenciais propiciam a intensificação do trabalho e o desgaste operário. Também afetam drasticamente o tempo de não trabalho fora da jornada, inclusive prejudicando a reposição e o desenvolvimento da capacidade biopsíquica do trabalhador. CONCLUSÃO: A PLR e o BH podem ser caracterizados como uma forma de administração por estresse que eleva e potencializa as cargas de trabalho e o desgaste operário.

  18. Fibromyalgia patients' quality of life and pain intensity variation Variação da intensidade da dor e da qualidade de vida de pacientes com fibromialgia

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    José Eduardo Martinez

    2008-12-01

    Full Text Available INTRODUCTION: One of the most reported issues on the Fibromyalgia syndrome is the pain intensity variation and its impact on patients' life quality. OBJECTIVES: 1 to establish the correlation among pain, anxiety and depression intensity perception; 2 to determine whether there is a correlation between pain intensity variation and the impact of fibromyalgia on patients' quality of life. MATERIAL AND METHODS: A study was carried out with 21 patients, who received a diary to register their perceptions on pain, anxiety and depression intensity. The patients have made this procedure three times a day, for a fifteen-day period. The impact on life quality was measured by the the Fibromyalgia Impact Questionaire (FIQ. RESULTS: It was observed a significant variation on pain intensity during the day periods. There was not a significant variation for anxiety and depression through the day periods. It was not observed any significant correlation between pain and depression or pain and anxiety intensity perception at any time of the day, during the study period. When considering the whole study period, it was observed that there was a correlation between pain and anxiety and pain and depression in the morning. CONCLUSION: It is concluded that there is a significant pain variation through the day periods and there is a correlation between pain and anxiety and pain and depression in the morning. There is a significant correlation of life quality with pain in the morning, anxiety in the afternoon and evening; and depression in all periods of the day.INTRODUÇÃO: Uma das questões mais relatadas é a variação da intensidade da dor no decorrer do dia e seu impacto na qualidade de vida. OBJETIVOS: Estabelecer a correlação entre a percepção da intensidade da dor, da ansiedade e da depressão e determinar a correlação entre a variação da intensidade da dor e o impacto na qualidade de vida. MATERIAL E MÉTODOS: Estudou-se 21 pacientes com fibromialgia. As

  19. Avaliação da expressão tecidual do gene de reparo MLH1 e dos níveis de dano oxidativo ao DNA em doentes com câncer colorretal Evaluation of expression of mismatch repair gene MLH1 and levels of oxidative DNA damage in normal and neoplastic tissues of patients with colorectal cancer

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    Carlos Augusto Real Martinez

    2009-09-01

    Full Text Available O dano oxidativo ao DNA provocado por radicais livres de oxigênio representa um dos principais mecanismos responsáveis pelas etapas iniciais da carcinogênese colorretal. O estresse oxidativo ocasiona erros de pareamento de bases possibilitando o aparecimento de mutações em genes controladores do ciclo celular. As células possuem um sistema de defesa representado pelos genes de reparo do DNA que corrigindo os erros de pareamento impedem o desenvolvimento de mutações. Poucos estudos avaliaram a relação entre dano oxidativo ao DNA e a expressão tecidual do gene de reparo MLH1. OBJETIVO: O objetivo do presente estudo foi avaliar os níveis de estresse oxidativo ao DNA e a expressão tecidual do gene de reparo MLH1 nas células da mucosa cólica normal e neoplásica de doentes com câncer colorretal. MATERIAL E MÉTODO: Foram estudados 44 doentes com diagnóstico de adenocarcinoma colorretal. Foram excluídos os doentes com câncer colorretal hereditário, portadores de câncer relacionado às doenças inflamatórias intestinais e os submetidos à radioquimioterapia neoadjuvante. Para a avaliação dos níveis de dano oxidativo ao DNA utilizou-se a técnica da eletroforese alcalina em gel de célula isolada (ensaio do cometa avaliando 100 células obtidas dos tecidos normal e neoplásico. Para a avaliação da expressão do gene MLH1 utilizou-se a técnica de reação de polimerase em cadeia em tempo real (RT-PCR com primer especificamente desenhados para amplificação do gene. A comparação dos resultados encontrados para os níveis de estresse oxidativo ao DNA, e expressão do gene MLH1 nos tecidos normais e neoplásicos foi feito pelo teste t de Student, adotando-se nível de significância de 5% (pThe oxidative DNA damage caused by oxygen free radicals is one of the most important mechanisms responsible for the initial steps of colorectal carcinogenesis. The oxidative stress can cause errors in the pairing of nitrogenous bases that

  20. Intensity of musculoskeletal pain and (in ability to work in nursing Intensidad del dolor musculo-esquelético y la (incapacidad para el trabajo en la enfermería Intensidade da dor musculoesquelética e a (incapacidade para o trabalho na enfermagem

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    Tânia Solange Bosi de Souza Magnago

    2012-12-01

    Full Text Available OBJECTIVE: the aim was to evaluate the association between the intensity of musculoskeletal pain and reduction in work ability among nursing workers. METHOD: a cross-sectional study, involving 592 nursing staff in a public university hospital in Rio Grande do Sul, Brazil. The Brazilian version of the Finnish questionnaire for calculating Work Ability Index was used, whose score varies from 7 to 49 points. The score was dichotomized as reduced work ability (7 to 36 points and good/excellent ability (37 to 49 points. The intensity of musculoskeletal pain over the previous week was evaluated, using a numerical pain scale. RESULT: 43.3% of the participants had reduced work ability and 48.8% reported strong to unbearable pain. Even after adjusting for potentially confounding factors (function and length of service in the function, the workers who mentioned strong to unbearable pain were four times more likely to be classified in the group with reduced work ability. CONCLUSION: A positive association was determined between intensity of musculoskeletal pain and reduction in work ability. It is necessary to adopt intervention measures in the organizational structure, so as to promote/restore work ability.OBJETIVO: se objetivó evaluar la asociación entre intensidad del dolor musculo-esquelético y reducción de la capacidad para el trabajo en trabajadores de enfermería. MÉTODO: Estudio transversal, envolviendo 592 trabajadores de enfermería de un hospital universitario público de Rio Grande do Sul, Brasil. Se utilizó la versión brasileña del cuestionario Finlandés para el cálculo del Índice de Capacidad para el Trabajo, cuyo score de los puntos varia de 7 a 49. La puntuación fue dicotómica como reducida capacidad para el trabajo (7 a 36 puntos y buena/óptima capacidad (37 a 49 puntos. Se evaluó la intensidad de dolor musculo-esquelético en la última semana, utilizándose escala numérica de dolor. RESULTADO: De los participantes, 43

  1. Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.

    Science.gov (United States)

    Berginc, Gasper; Bracko, Matej; Ravnik-Glavac, Metka; Glavac, Damjan

    2009-01-01

    Microsatellite instability (MSI) is present in more than 90% of colorectal cancers of patients with Lynch syndrome, and is therefore a feasible marker for the disease. Mutations in MLH1, MSH2, MSH6 and PMS2, which are one of the main causes of deficient mismatch repair and subsequent MSI, have been linked to the disease. In order to establish the role of each of the 4 genes in Slovenian Lynch syndrome patients, we performed MSI analysis on 593 unselected CRC patients and subsequently searched for the presence of point mutations, larger genomic rearrangements and MLH1 promoter hypermethylation in patients with MSI-high tumours. We detected 43 (7.3%) patients with MSI-H tumours, of which 7 patients (1.3%) harboured germline defects: 2 in MLH1, 4 in MSH2, 1 in PMS2 and none in MSH6. Twenty-nine germline sequence variations of unknown significance and 17 deleterious somatic mutations were found. MLH1 promoter methylation was detected in 56% of patients without detected germline defects and in 1 (14%) suspected Lynch syndrome. Due to the minor role of germline MSH6 mutations, we adapted the Lynch syndrome detection strategy for the Slovenian population of CRC patients, whereby germline alterations should be first sought in MLH1 and MSH2 followed by a search for larger genomic rearrangements in these two genes. When no germline mutations are found tumors should be further tested for the presence of germline defects in PMS2 and MSH6. The choice about which gene should be tested first can be guided more accurately by the immunohistochemical analysis. Our study demonstrates that the incidence of MMR mutations in a population should be known prior to the application of one of several suggested strategies for detection of Lynch syndrome.

  2. [Immunohistochemical examination of MSH2, PMS2, MLH1, MSH6 compared with the analysis of microsatellite instability in colon adenocarcinoma].

    Science.gov (United States)

    Raskin, G A; Ianus, G A; Kornilov, A V; Orlova, R V; Petrov, S V; Protasova, A É; Pozharisskiĭ, K M; Imianitov, E N

    2014-01-01

    Adenocarcinoma of the colon in 10-20% is associated with microsatellite instability, which can occur both in sporadic cancers and in hereditary nonpolyposis colon cancer. Our analysis of 195 cases of adenocarcinoma of the colon showed that microsatellite instability (MSI-H) was found only in 1.5% of patients. Subsequent choice of patients with suspected hereditary Lynch syndrome led to the identification of additional 17 patients with microsatellite instability. They passed an analysis of genes of repair system of unpaired nucleotides of DNA. The study showed that immunohistochemical staining of MSH2, MSH6, MLH1, PMS2 could effectively conduct a preliminary screening of the Lynch syndrome but was unable to divide cases of sporadic and hereditary MSI-H colon cancer.

  3. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva

    2008-01-01

    Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridizat......Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic...... deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...... from several 100 kb, including large flanking regions, to rearrangements, allowing convenient design...

  4. Análisis de la máxima intensidad de la isla de calor urbana nocturna de la ciudad de Rancagua (Chile y sus factores explicativos.

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    Pablo Sarricolea

    2008-12-01

    Full Text Available Las ciudades constituyen el hábitat por excelencia de los seres humanos, y pese a su diversidad presentan características ambientales (clima urbano comunes en muchas partes del mundo, como por ejemplo la presencia de la Isla de Calor Urbana (ICU, que corresponde a un aumento de origen antrópico de las temperaturas de la ciudad en comparación con su entorno inmediato de carácter natural y rural, siendo más intensa dicha diferencia en las noches. Por ello, el propósito de esta investigación es analizar la Máxima Intensidad de la Isla de Calor Urbana (MIICU de Rancagua a partir de mediciones de las temperaturas con transectos móviles y estaciones meteorológicas fijas. Se ha determinado que la máxima intensidad de la isla de calor urbana de Rancagua bordea los 6°C en verano y primavera, y 3°C para invierno y otoño. Los factores que explican las distribuciones de las temperaturas urbanas de Rancagua corresponden a las distancias a fuentes húmedas (río Cachapoal y las densidades poblacionales; y en menor medida las características topográficas del emplazamiento de la ciudad y las áreas verdes urbanas medidas a partir del índice normalizado de diferencias vegetales (NDVI. La principal conclusión de esta investigación indica que la ausencia de parques urbanos en Rancagua explica la distribución de las temperaturas y la elevada intensidad de la isla de calor, y también la no significativa relación entre temperaturas y NDVI. De no revertirse esta situación, la sostenibilidad ambiental futura de la ciudad de Rancagua se verá muy amenazada por el crecimiento urbano.Cities are the environment for excellence in human beings, and despite their diversity, environmental features (urban climate are common in many parts of the world, such as the presence of the Urban Heat Island (UHI. This corresponds to a temperature increase due to human activities in the city compared with its immediate natural and rural surroundings, the difference

  5. Efecto de la intensidad de diodos electroluminosos y fotoperiodo en la optimización de la producción de biomasa de Spirulina ( Arthrospira

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    V. Vásquez - Villalobos

    2017-01-01

    Full Text Available Se optimizó la producción de biomasa ( ф de cultivos batch d e Spirulina sp. en fotobiorreactores a escala de laboratorio (FBL de 0,2 L, por efecto de X 1 : intensidad de diodos electroluminosos (LED’s entre 1,25 a 41,7 klux y X 2 : fotoperiodo de12/12 a 24/0, h de luz/h de oscuridad (L/O utilizando un diseño compuesto central rotacional (DCCR y metodología de superficie de respuesta (MSR. Asimismo, se eval uaron las características hidráulicas y el valor ф de un cultivo batch de Spirulina en un fotobiorreactor de canal bucle cerrado abierto a la atmósfera (FB - BCAA por efecto de la iluminación LED de 8,3±1,9 klux y fotoperiodos de 12/12 y 24/0 h L/O. En los FBL se encontró dos zonas óptimas de ф , ambas con una intensidad LED de 21,5 klux y fotoperiodos 12/12 y 24/0 h L/O, siendo los valores ф de 1,65 y 1,62 respectivamente. El modelo matemático que indicó estas zonas fue de segundo orden (p = 0,000396 < 0,05 con una consistencia de predicción de R² = 0,92. En el FB - BCAA, el cultivo de Spirulina sp. con fotoperiodo de 12/12 h L/O, mostr ó un valor ф de 0,72, una adaptación más rápida de λ = 4,62 h, una mayor velocidad específica de crecimiento de μ max = 0,033 h - 1 y menor tiempo de consumo de energía de 74,05 h ; comparado con el cultivo desarrollado con fotoperiodo 24/0 h L/O. Los parámetros hidráulicos del FB - BCAA fueron: volumen de operación 2,5 L, velocidad de flujo 0,26 m/s, números de Reynolds ( Re 15488, Froude ( Fr 0,60 y Vedernikov ( V ed 0,90.

  6. Análise tempo-intensidade dos estímulos doce e amargo de extrato de folhas de estévia [Stevia rebaudiana (Bert. Bertoni] em doçura equivalente a sacarose

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    CARDELLO Helena Maria André Bolini

    1999-01-01

    Full Text Available O extrato de folhas de estévia (Stevia rebaudiana Bertoni é o único edulcorante utilizado na substituição da sacarose, que pode ser produzido totalmente no Brasil. O objetivo deste estudo foi determinar os comportamentos de características temporais dos estímulos doce e amargo da estevia em doçuras equivalentes a soluções de sacarose (DESS a 3 e 10%. As curvas tempo-intensidade (T-I para cada substância foram coletadas utilizando-se o programa "Sistema de Coleta de Dados Tempo-Intensidade - SCDTI" para Windows, onde os provadores registravam com auxílio do "mouse" a percepção de cada estímulo solicitado em função do tempo, para cada amostra. Os parâmetros das curvas T-I coletados foram: tempo de intensidade máxima (TImax, intensidade máxima (Imax, tempo onde a intensidade máxima começa a declinar (Td, tempo de platô (Platô, área sob a curva (Área e tempo total de duração do estímulo (Ttot. Os parâmetros Td, Ttot, Área e Platô das curvas T-I para o estímulo doce nos dois níveis de doçura foram significativamente superiores para estévia, enquanto TImax e Imax foram significativamente menores (p£0,05, sendo que as diferenças entre os valores para as duas substâncias foram muito maiores a DESS a 10%. A sacarose não apresentou nenhum registro para o estímulo amargo tanto a 3 como a 10%, enquanto a estévia apresentou curvas T-I características, com intensidade e o tempo total de duração dependente da concentração.

  7. Associação entre intensidade de uso de mídias sociais, credibilidade e decisão de compra

    Directory of Open Access Journals (Sweden)

    Maria Laura Ferranty MacLennan

    2014-07-01

    Full Text Available O objetivo desta pesquisa é analisar o uso de mídias sociais, credibilidade das informações on-line com as decisões de compra de consumidores. Com base em referencial teórico sobre redes sociais, mídias sociais e comportamento de compra on-line, realizou-se esta pesquisa. Os dados foram levantados por meio de survey eletrônico e analisados com o uso de análise fatorial e regressão linear múltipla. Os resultados indicam a associação entre a decisão de compra do cliente e a intensidade de acesso na internet. Também se relacionam a decisão de compra e a importância das informações consultadas na internet, de modo que, quanto maior o tempo e a exposição a conteúdos on-line, maior a influência da exposição no ambiente on-line nas decisões de compra dos usuários. Diferentemente de estudos anteriores, não se observa significância entre as variáveis gênero e idade dos respondentes nas decisões de compra da amostra investigada. 

  8. Influencia de la intensidad de la precipitación en las medidas de los pluviómetros de balancín en las Islas Baleares.

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    José A. Guijarro

    2002-12-01

    Full Text Available Se han comparado las medidas de los pluviómetros de balancín de ocho estaciones meteorológicas automáticas de las Islas Baleares con las de sendos pluviómetros convencionales (tipo Hellmann ubicados en las mismas. La influencia de la precipitación en los errores de los primeros se ha contrastado mediante ajustes de regresión lineal simple y polinómica, haciendo intervenir diferentes potencias en las cantidades de precipitación. La escasa mejora del modelo polinómico respecto a la regresión simple, junto con una selección poco coherente de los términos más significativos de unas estaciones a otras, indican que la intensidad de la precipitación no modula de una manera clara la magnitud de los errores, que en promedio son de entre el -4 y el 22%, según la estación.

  9. O EMPREGO DA TERAPIA LASER DE BAIXA INTENSIDADE NO TRATAMENTO DA HERPES-ZÓSTER E NEURALGIA PÓS-HERPÉTICA COM ACOMETIMENTO OROFACIAL

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    Davidson Ribeiro Costa

    2016-12-01

    Full Text Available O herpes-zóster facial é definido como uma doença infecciosa, que durante seu desenvolvimento apresenta lesões dolorosas na região orofacial. A Neuralgia pós-herpética é uma complicação da HZ facial que é caracteriza pela sintomatologia  dolorosa. A terapia com laser  de baixa intensidade (TLBI tem sido amplamente divulgada nos meios científicos, devido o seu efeito positivo  na redução da dor em uma série de condições. Nesse contexto, o presente estudo objetivou analisar os principais efeitos da TLBI, com base na literatura, de forma a apresentar uma terapia alternativa, que pode ser empregada no tratamento da HZ facial e NPHT, salientando as doses e os possíveis locais para a irradiação em cada fase. A TLBI é uma terapia não invasiva, que não apresenta efeitos adversos, quando empregada de maneira correta. Essa terapia apresenta efeitos anti-álgico, anti-inflamatório, de reparo tecidual e neuronal, o que justifica a sua utilização no tratamento da HZ facial e NPHT.

  10. Treinamento em corrida de baixa intensidade: propriedades estruturais e mecânicas da epífise proximal do fêmur de ratas osteopênicas

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    Bárbara Braga Fernandes Maia

    2014-09-01

    Full Text Available Este estudo investigou os efeitos do treinamento em corrida de baixa intensidade (TCBI sobre propriedades estruturais e mecânicas da epífise proximal do fêmur de ratas osteopênicas. Ratas Wistar [idade = 20 semanas; massa corporal = 271,42 ± 17,6 g] foram submetidas à ovariectomia (OVX ou laparotomia (SHAM e alocadas em quatro grupos: corrida OVX (CO, n = 12, controle OVX (CONO, n = 12, corrida SHAM (CS, n = 12 e controle SHAM (CONS, n = 12. Quinze dias pós-cirurgia, os grupos CO e CS foram submetidos ao TCBI em esteira (16 m/min, 60 min/dia, cinco dias/semana por 10 semanas. O TCBI não alterou os efeitos deletérios da osteopenia induzida por ovariectomia sobre a densidade mineral do fêmur, a quantidade de osso trabecular no trocanter e colo do fêmur, a tenacidade e a força máxima de fratura do colo do fêmur de ratas.

  11. Estresse luminoso em plântulas de jequitibá-rosa (Cariniana legalis, Lecythidaceae: monitoramento da capacidade de aclimatação fotossintética sob duas intensidades de luz

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    Tatiane de Oliveira Vieira

    2011-12-01

    Full Text Available O conhecimento da capacidade de aclimatação e estabelecimento das espécies vegetais é importante para a implementação de programas de manejo e restauração ecológica de ecossistemas degradados. Estudos ecofisiológicos foram realizados (trocas gasosas, fluorescência da clorofila a e teores de pigmentos fotossintéticos para avaliar o efeito da intensidade luminosa sobre a atividade e capacidade fotossintética de jequitibá-rosa (Cariniana legalis Mart. Kuntze. As respostas das plântulas submetidas à condição de pleno sol sugerem que a radiação direta pode ter sido um fator estressante para a espécie, afetando seu desempenho, embora tenha sido verificada aclimatação da capacidade fotossintética em função da maior intensidade luminosa.

  12. Variação da intensidade vocal: estudo da vibração das pregas vocais em seres humanos com videoquimografia Vocal intensity variation: a study of vocal folds vibration in humans with videokymography

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    Henry U. Koishi

    2003-08-01

    Full Text Available O aumento da resistência glótica é o principal mecanismo responsável pela elevação da intensidade vocal em baixas freqüências. Esse aumento da resistência, em situações normais, é determinado pela contração dos músculos adutores das pregas vocais que promovem o aumento da tensão e a aproximação das pregas vocais em direção à linha mediana. No entanto, essas mesmas alterações podem estar presentes em algumas doenças funcionais que envolvem a laringe, como a disfonia espasmódica em adução e a disfonia hipertônica, mesmo durante a emissão vocal em baixa intensidade. OBJETIVO: Avaliar o padrão de vibração das pregas vocais em indivíduos com vozes normais em condições distintas de intensidade vocal, na tentativa de estabelecer valores que expressem a normalidade, para as diferentes fases do ciclo vibratório, de acordo com o nível de intensidade. FORMA DE ESTUDO: Clínico prospectivo. CASUÍSTICA E MÉTODOS: Foram avaliados 58 indivíduos durante emissão vocal em intensidade habitual (suave de conversação e durante emissão vocal elevada. A análise da vibração das pregas vocais foi realizada com a videoquimografia e para a análise da intensidade vocal, foi utilizado um programa de análise acústica computadorizado. RESULTADOS: Os resultados mostraram aumento involuntário da freqüência fundamental (F0 e redução do quociente de abertura, com o aumento da intensidade. CONCLUSÃO: Foram estabelecidos os valores de intensidade sonora para a condição habitual (63,46dB e elevada (72,55dB de emissão vocal e seus respectivos valores de quociente de abertura (OQ- open quotient.The increase of glottal resistance is the main mechanism to increase vocal intensity at low fundamental frequency. This increase is due to adductory forces provoked by the contraction of intrinsic laryngeal muscles that increases tension and approximates the vocal folds to the midline. However, the same behavior can be observed in

  13. Impacto da geometria do cânion urbano na intensidade de ilha de calor noturna: análise através de um modelo simplificado adaptado a um SIG

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    Camila Mayumi Nakata-Osaki

    Full Text Available Resumo A geometria urbana é um dos fatores de maior influência na intensidade da ilha de calor urbana. Seu estudo requer a caracterização de cânions urbanos, geralmente medidos pela relação entre a altura dos edifícios e a largura da rua (H/W, conceito aplicado no modelo numérico de Oke em 1981. O objetivo deste artigo é verificar o impacto da geometria do cânion urbano na intensidade de ilhas de calor noturna. Para isso, foram realizados levantamento de dados climáticos e de geometria urbana em duas cidades brasileiras. Os valores de intensidade de ilha de calor foram confrontados com os simulados pelo modelo original de Oke (1981, o qual foi calibrado e adaptado à plataforma SIG, de forma a possibilitar a incorporação de outro parâmetro de geometria, além da relação H/W: o comprimento de rugosidade. Esse processo gerou uma nova ferramenta de cálculo, que é denominda THIS (Tool for Heat Island Simulation. Aplicou-se o novo modelo para simular alguns cenários urbanos hipotéticos, que representam vários tipos de cânions urbanos. Os resultados demonstraram que cânions urbanos de maior rugosidade amenizam as intensidades de ilha de calor noturna em relação a um cânion de mesmo valor de relação H/W e menor rugosidade.

  14. Aptidão cardiorrespiratória e qualidade de vida pós-infarto em diferentes intensidades de exercício Aptitud cardiorrespiratoria y calidad de vida postinfarto en diferentes intensidades de ejercicio Cardiorespiratory fitness and quality of life at different exercise intensities after myocardial infarction

    Directory of Open Access Journals (Sweden)

    Magnus Benetti

    2010-09-01

    Full Text Available FUNDAMENTO: Estudos que relacionam exercícios físicos e saúde têm contribuído para a compreensão da influência de hábitos sedentários com a incidência de doenças cardiovasculares. OBJETIVO: Comparar o efeito de diferentes intensidades de exercício aeróbio sobre a capacidade funcional (VO2 pico e a qualidade de vida de pacientes pós-infarto agudo do miocárdio. MÉTODOS: 87 homens (57,7 anos, ± 6,1 participaram deste estudo prospectivo, com 12 semanas de treinamento físico de alta intensidade (n=29, a 85% da frequência cardíaca máxima, de intensidade moderada (n=29, a 75% da frequência cardíaca máxima, ou no grupo controle (n=29, que recebeu acompanhamento clínico. O exercício aeróbio foi realizado cinco vezes por semana, 45 minutos por sessão, além de exercícios de resistência muscular e alongamentos. O VO2 pico foi mensurado com teste cardiopulmonar, e a qualidade de vida foi avaliada pelo questionário MacNew. RESULTADOS: A ANOVA two-way revelou aumento do VO2 pico significativo (pFUNDAMENTO: Estudios que relacionan ejercicios físicos y salud han estado contribuyendo a la comprensión de la influencia de hábitos sedentarios con la incidencia de enfermedades cardiovasculares. OBJETIVO: Comparar el efecto de diferentes intensidades de ejercicio aerobio sobre la capacidad funcional (VO2 pico y la cualidad de vida de pacientes postinfarto agudo del miocardio. MÉTODOS: 87 varones (57,7 años, ± 6,1 participaron de este estudio prospectivo, con 12 semanas de entrenamiento físico de alta intensidad (n=29, al 85% de la frecuencia cardíaca máxima, de intensidad moderada (n=29, al 75% de la frecuencia cardíaca máxima, o en el grupo control (n=29, que recibió seguimiento clínico. El ejercicio aerobio se llevó a cabo cinco veces por semana, 45 minutos por sesión, además de ejercicios de resistencia muscular y alargamientos. El VO2 pico se cuantificó con prueba cardiopulmonar, y la cualidad de vida se evaluó por

  15. Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

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    Llor Xavier

    2011-01-01

    Full Text Available Abstract Background Lynch syndrome (LS is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls. Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%, seven were suspected of having hereditary CRC (2.8% and 11 were controls (2.68%. There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both

  16. Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome.

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    Abram Bunya Kamiza

    Full Text Available Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC. This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations.In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs and 95% confidence intervals (CIs to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence.Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34; however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88. The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55 and 0.54 (95% CI = 0.34-0.83 among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27 than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58 compared with those with blood group type O.The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.

  17. A associação de haloperidol, dexametasona e ondansetrona reduz a intensidade de náusea, dor e consumo de morfina após gastrectomia vertical laparoscópica

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    Márcio Luiz Benevides

    2013-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Náusea e vômito pós-operatório (NVPO ocorrem frequentemente após cirurgia bariátrica laparoscópica. A associação de haloperidol, dexametasona e ondansetrona pode reduzir esses eventos indesejáveis. O objetivo deste estudo foi avaliar a intensidade de náusea e dor, o número de episódios de vômito e o consumo de morfina no pós-operatório (PO de pacientes obesos submetidos à gastrectomia vertical laparoscópica (GVL. MÉTODO: Estudo clínico, aleatorizado, controlado e duplamente encoberto feito em 90 pacientes com índice de massa corporal > 35 kg.cm-2. Os pacientes foram distribuídos em três grupos de 30 para receberem no Grupo O: ondansetron 8 mg; no Grupo DO: ondansetron 8 mg e dexametasona 8 mg e no Grupo HDO: ondansetron 8 mg, dexametasona 8 mg e haloperidol 2 mg. Foram avaliados a intensidade de náusea e dor, por meio de escala numérica verbal, o número cumulativo de episódios de vômito e o consumo de morfina no período de 0-2, 2-12, 12-24 e 24-36 horas de PO. RESULTADOS: A intensidade de náusea foi menor no Grupo HDO comparado com o Grupo O (p = 0,001, a intensidade da dor foi menor no Grupo HDO comparado com o Grupo O (p = 0,046 e o consumo de morfina no Grupo HDO foi menor do que no Grupo O (p = 0,037. Não houve diferença do número de episódios de vômito entre os grupos (p = 0,052. CONCLUSÃO: A associação de haloperidol, dexametasona e ondansetron promoveu redução da intensidade de náusea, da dor e do consumo de morfina no PO de pacientes obesos submetidos à GVL.

  18. EFECTO DEL ASCENSO SÚBITO A UNA ALTITUD MODERADA SOBRE LA PERCEPCIÓN SUBJETIVA DE ESFUERZO A DIFERENTES INTENSIDADES DE EJERCICIO

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    P. Rodríguez

    2010-09-01

    Full Text Available

     

    RESUMEN

    Dieciséis sujetos varones y sanos (VO2max de 4,06 ± 0,7 l.min-1, fueron sometidos a un protocolo incremental máximo en sendas condiciones de normoxia (N y altitud aguda moderada (Alt en días diferentes. La percepción subjetiva de esfuerzo (RPE y demás parámetros máximos y los relacionados con el umbral de lactato (UL, fueron registrados y comparados entre ambas condiciones. No se observaron diferencias significativas entre los RPEL, RPEC y RPET entre ambas condiciones ni para la máxima capacidad de trabajo ni en el UL. Tampoco se observaron cambios significativos en las potencias de trabajo, VO2 (l.min-1, Ve (l.min-1 y Lac (mMol.l-1 a las intensidades estudiadas. Sin embargo, aunque la Fc registrada al UL no mostró diferencias con la obtenida en Alt, sí se observó una reducción importante en la Fc a la máxima carga de trabajo alcanzada en condiciones de hipoxia (188 ± 9 vs 182 ± 7 ppm para una p<0.001. El ascenso súbito a una altitud moderada no altera la percepción subjetiva de esfuerzo en el UL ni a la máxima capacidad de trabajo. En estas condiciones, la Fc no se muestra tan buen indicador de la intensidad de ejercicio como la percepción de esfuerzo.
    PALABRAS CLAVE: RPE, altitud, hipoxia, umbral láctico.

     

    ABSTRACT

    Sixteen healthy males, were submitted to a maximum incremental test in conditions of normoxia (N and of moderate acute altitude (Alt in two different days. Rating of perceived exertion (RPE, respiratory data, heart rate and lactate were measured during the test. The values at maximum work and at the lactate thresold (LT were compared between both conditions. Meaningful differences between the work, RPE, VO2 (l.min-1, Ve (l.min-1 y Lac (mMol.l-1 were not observed at

  19. ESTUDIO DEL MOVIMIENTO DE ARRANCADA EN HALTEROFILIA DURANTE CICLOS DE REPETICIONES DE ALTA INTENSIDAD MEDIANTE ANÁLISIS CINEMÁTICO: ESTUDIO DE CASO

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    J. Campos

    2010-09-01

    Full Text Available

     

    RESUMEN

    En Halterofilia uno de los objetivos de entrenamiento principales consiste en preparar a los levantadores para generar fuerza máxima a la mayor velocidad posible. En el presente estudio se analiza el patrón de ejecución de una levantadora española de élite durante ciclos de repeticiones de alta intensidad (90% de 1RM en situación controlada de entrenamiento. Se utiliza la metodología de fotogrametría 3D con dos cámaras de video sincronizadas (50 Hz. Se realiza un estudio correlacional y cálculo de las medidas de tendencia central así como del coeficiente de variación para cada uno de los parámetros considerados. Los resultados muestran la tendencia a una mayor estabilización del modelo en algunos de lo parámetros cinemáticos considerados a medida que se incrementa el peso para ajustarlo a la exigencia de aproximadamente el 90% de 1RM. Esta tendencia se hace más patente en las últimas series y repeticiones de cada ciclo. Con todo, se plantea la necesidad de seguir avanzando en el análisis del modelo individual aplicando cargas ajustadas a 3, 4 y 5RM de intensidad para conseguir una mejor adaptación del patrón individual a los requerimientos del movimiento de competición. Se propone también ampliar la muestra a un número mayor de levantadores/as de nivel élite para poder comprobar si se siguen confirmando las tendencias encontradas en este trabajo.
    PALABRAS CLAVE: Arrancada, Biomecánica; Halterofilia; Fuerza; Potencia.

     

    ABSTRACT

    Power capacity is one of the keys to optimizing athletic performance. In weihtllifting, it is necessary to train the atlete to generate the maximum muscular force at the most higher speed. The purpose of this study was to describe the kinematic characteristics of the

  20. Intensidade e dinâmica da modernização agrícola no Brasil e nas unidades da Federação

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    Paulo Marcelo de Souza

    2003-12-01

    Full Text Available Este artigo apresenta um estudo cujo objetivo foi caracterizar a evolução do processo de modernização agrícola nas unidades da Federação brasileira, utilizando a análise fatorial aplicada a um conjunto de variáveis relacionadas ao emprego das principais tecnologias modernas. Os resultados permitiram concluir que a intensidade do processo de modernização foi significativamente diferente entre as unidades da Federação. Esse processo sofreu retração a partir de 1980, com a redução nos valores associados ao nível de financiamento e investimentos no setor, fenômeno relacionado à redução na oferta de crédito rural e à elevação de seu custo, e possivelmente influenciado pelos efeitos da retração do mercado, da redução das expectativas e do aumento de riscos observados na década de 1980.This paper presents a study whose goal was to characterize the evolution of the agricultural modernization process in the Brazilian states. Factor analysis was applied to a group of variables related to the use of the main modern technologies. The results have led to the conclusion that the intensity of the modernization process was significantly different among the states. Since 1980, that process is becoming less intense, with the reduction in the values associated to the financing level and investments in agriculture, phenomenon related to the decrease in the offer of rural credit and the elevation of its cost. Possibly, this was also influenced by market retraction, lower expectations and increasing risks, events observed in the 1980s.

  1. ACÚMULO DE MASSA SECA E DINÂMICA DO SISTEMA RADICULAR DO ESTILOSANTE MINEIRÃO SUBMETIDO A DUAS INTENSIDADES DE DESFOLHAÇÃO

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    Allan Kardec Braga Ramos

    2006-10-01

    Full Text Available Este trabalho objetivou avaliar os efeitos de duas intensidades de desfolhação (15 e 30 cm sobre a produção de MS, resíduo, área foliar residual (AFR, capacidade de rebrota no escuro (CRE e dinâmica do sistema radicular do estilosante Mineirão (Stylosanthes guianensis cv.Mineirão. As desfolhações foram realizadas de outubro de 2000 a setembro de 2001. O intervalo de cortes foi de 64+ 7 e 82 + 4 dias nas épocas chuvosa e seca do ano, respectivamente. Após análises estatísticas, as médias foram comparadas pelo teste de Tukey (10%. O acúmulo de MS foi afetado pela interação altura x época de desfolhação. No corte a 15 cm, o acúmulo de folhas não diferiu de novembro a abril, mas declinou de 1.700 kg/ha no mês de abril para 317kg/ha no mês de setembro. No resíduo, houve aumento da MS total e da AFR até fevereiro, em ambas as alturas de corte. A densidade das raízes finas (< 2 mm de diâmetro diminuiu na época seca. A CRE foi menor no mês de fevereiro. O corte na altura de 15 cm proporcionou maiores produções de MS de folhas sem afetar o resíduo e o sistema radicular das plantas do estilosantes Mineirão. PALAVRAS-CHAVE: Área foliar, forragem, resíduo, raízes, Stylosanthes guianensis.

  2. Laser de baixa intensidade em deiscência aguda de safenectomia: proposta terapêutica Low level laser therapy in acute dehiscence saphenectomy: therapeutic proposal

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    Nathali Cordeiro Pinto

    2009-03-01

    Full Text Available Deiscência é uma complicação temida em cirurgias de grande porte. Paciente submetida a revascularização miocárdica evoluiu com deiscência de safenectomia em membro inferior, edema e dor no 15º dia pós-operatório (PO, tendo sido realizado inicialmente o tratamento convencional no ambulatório sem melhora clínica. No 30º PO, aplicou-se somente Laser de Baixa Intensidade (LBI ao redor da borda da ferida, pontualmente. A lesão respondeu com tecido de granulação, diminuição do processo inflamatório e analgesia desde a primeira aplicação. Neste estudo piloto, a laserterapia mostrou ter um papel importante como agente facilitador de cicatrização, por meio de uma terapia nãoinvasiva, eficaz e segura.Dehiscence is a feared complication after major surgeries. Patient who had undergone coronary artery bypass grafting developed saphenectomy's dehiscence on lower limb with edema and pain on the 15th postoperative day. Conventional treatment had been initially performed without clinical improvement. On the 30th postoperative day only Low Level Laser Therapy (LLLT was applied punctually around surgical wounds edge. The results revealed granulated tissue, reduction of inflammatory process and analgesic effect since the first application. In this pilot study, LLLT has shown a considerable role as a wound healing agent, through a new proposal for efficient, safe and noninvasive therapy.

  3. Efectos del entrenamiento intermitente de alta intensidad en la condición física de jugadores de baloncesto en silla de ruedas

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    Cristina Granados Domínguez

    2016-01-01

    Full Text Available El objetivo de este estudio fue analizar los efectos del entrenamiento intermitente de alta intensidad (EIAI en el rendimiento físico, las respuestas fisiológicas y la percepción subjetiva del esfuerzo en jugadores de baloncesto en silla de ruedas (BSR. Para ello, 12 jugadores masculinos (32.6 ± 10.7 años de primera división de la Liga Española participaron en este estudio. La batería de test (sprint en 5 y 20 m, sprint con arrastre de peso en 5 y 20 m, test de cambio de dirección y test de resistencia multi-stage fitness test –MSFT– se realizó en una única sesión midiéndose antes (T1 y después (T2 del programa de entrenamiento de EIAI. El tiempo en 5 m en T2 fue un 7.14% significativamente mayor (p < 0.05, d = 0.88, alto que en T1. No hubo diferencias significativas en el tiempo en 20 m ni en el sprint con arrastre de peso en 5 y 20 m ni en el test de cambio de dirección. Tampoco se obtuvieron diferencias en la distancia recorrida, la frecuencia cardiaca máxima (FCmax, la concentración de lactato sanguíneo (LA y la temperatura timpánica. Además, aunque no fue significativo, se observó un mayor esfuerzo percibido en el T2 respecto al T1, tanto a nivel respiratorio (RPEres, 16%, d = -0.64, moderado como a nivel muscular (RPEmus, 9%, d = 0.50, moderado. El programa de EIAI de 10 semanas no produjo ninguna mejora en jugadores de BSR, incluso disminuyó un 7% el rendimiento en el sprint en 5 m.

  4. Respuesta fotosintética de Eucalyptus grandis W. Hill a la disponibilidad de agua en el suelo y a la intensidad de luz

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    María Sara Mejía de Tafur

    2014-12-01

    Full Text Available En condiciones de campo en la Universidad Nacional de Colombia sede Palmira (950 m.s.n.m., 24°C y 75% de humedad relativa se evaluó la respuesta fotosintética de cuatro clones de Eucalyptus grandis (28-3, 18-3, 24A-5, 19-1 al estrés hídrico: capacidad de campo (1 cc, 0.5 cc, 0.25 cc y a la saturación de agua e intensidades lumínicas variables de 1500, 1000, 500, 250, y 0 µmol/m²/s en el primer ensayo y de 1500, 1000, 435, 87, 70, 52, 35, 26, y 0 µmol/m²/s en el segundo. En ambos estudios, se utilizó un diseño experimental de parcelas divididas con cuatro repeticiones, donde la parcela principal correspondió al nivel de humedad en el suelo y la subparcela a los clones. El análisis estadístico mostró que E. grandis reduce la tasa de fotosíntesis de manera significativa cuando se presenta estrés hídrico en el suelo y que el grado de la respuesta depende del clon, lo que sugiere la presencia de mecanismos fisiológicos dependientes del genotipo para responder al estrés hídrico. Se presentaron curvas de luz típicas con puntos de compensación bajos (0.9 - 7.0 µmol/m²/s, tasas de fotosíntesis altas (68 - 39 µmol CO2 /m²/s y alta eficiencia fotosintética (0.0003 - 0.0086 mol CO2 /mol luz

  5. Inclusão do equivalente energético do lactato na regressão VO2-intensidade em corrida horizontal e inclinada (10,5%

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    Victor Machado REIS

    Full Text Available Resumo O estudo teve por objetivo analisar o efeito da adição do equivalente energético do lactato sanguíneo com a medida de VO2 durante a corrida em esteira horizontal (0% e inclinada (10,5%, como forma de estimativa do custo energético da corrida. Treze corredores de meia e longa distância (idade 28,1 ± 4,2 anos; estatura 1,75 ± 0,07 m; massa corporal 65,2 ± 4,9 kg; VO2max 70,3 ± 4,9 ml·kg-1·min-1 cumpriram dois testes em esteira rolante (0% e 10,5% que incluíram vários estágios em intensidade constante. Foram calculadas para cada atleta as regressões VO2-velocidade, bem como regressões alternativas com a adição de um equivalente energético de 3 ml O2 Eq·kg-1·mM [La-] às medições de VO2. Não se verificou interação significativa entre a adição do equivalente do lactato e a inclinação da esteira. A ANOVA indicou um efeito significativo da adição do equivalente do lactato na inclinação da reta de regressão e na estimativa do custo energético. Os tamanhos do efeito obtidos indicam que este efeito é mais forte na corrida horizontal. Estes resultados sugerem que em testes laboratoriais com corredores treinados se deverá considerar a adição dos valores de VO2 com os equivalentes energéticos do lactato.

  6. Vitamin E Modifies High-Fat Diet-Induced Increase of DNA Strand Breaks, and Changes in Expression and DNA Methylation of Dnmt1 and MLH1 in C57BL/6J Male Mice

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    Marlene Remely

    2017-06-01

    Full Text Available Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD or a control diet (CD with and without vitamin E supplementation (4.5 mg/kg body weight (b.w. for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1 were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1. Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity—and oxidative stress—induced health risks.

  7. Vitamin E Modifies High-Fat Diet-Induced Increase of DNA Strand Breaks, and Changes in Expression and DNA Methylation of Dnmt1 and MLH1 in C57BL/6J Male Mice.

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    Remely, Marlene; Ferk, Franziska; Sterneder, Sonja; Setayesh, Tahereh; Kepcija, Tatjana; Roth, Sylvia; Noorizadeh, Rahil; Greunz, Martina; Rebhan, Irene; Wagner, Karl-Heinz; Knasmüller, Siegfried; Haslberger, Alexander

    2017-06-14

    Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene ( MLH1 ) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1 . Vitamin E reduced DNA damage and showed organ-specific effects on MLH1 and Dnmt1 gene expression and methylation. These results suggest that interventions with antioxidants and epigenetic active food ingredients should be developed as an effective prevention for obesity-and oxidative stress-induced health risks.

  8. Efeito de métodos e intensidades de pastejo sobre a ressemeadura natural de azevém anual = Effect of grazing methods and intensities on annual ryegrass under natural reseedling

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    Cristina Maria Pacheco Barbosa

    2008-10-01

    Full Text Available Este trabalho foi conduzido na E.E.A da UFRGS/RS (30°05’S e 51°39’W com o objetivo de avaliar o efeito de métodos e intensidades de pastejo na dinâmica populacional de azevém (Lolium multiflorum Lam. em ressemeadura natural. Conduziu-se a pastagem em dois métodos de pastejo (lotação contínua e rotacionada e duas intensidades de pastejo (moderada e baixa, em um delineamento em blocos casualizados, em esquema fatorial com três repetições (2x2x3. No ano seguinte, após um ciclo de lavoura de soja no verão, foi contado o número de perfilhos de azevém estabelecidos via essemeadura natural. Os resultados demonstraram não ter havido interação (p > 0,05 entre os métodos e as intensidades de pastejo, e seus efeitos foram analisados de forma independente. Enquanto os diferentes métodos de pastejo não afetaram a ressemeadura do azevém (p = 0,4636, asdiferentes intensidades de pastejo a influenciaram significativamente (p = 0,0003. O número de perfilhos de azevém estabelecidos via ressemeadura natural, na intensidade de pastejo baixa, foi maior (6.776 perfilhos m-2 do que na intensidade de pastejo moderada(211 perfilhos m-2. O controle da intensidade de pastejo é um fator determinante para a manutenção do azevém em sistemas de produção baseados na persistência dessa forrageira via ressemeadura natural.This work was conducted at EEA/UFRGS, in Eldorado do Sul, RioGrande do Sul state, Brazil (30°05’S e 51°39’W, to evaluate the effects of different grazing intensities and methods on the population dynamics of ryegrass (Lolium multiflorum Lam. under natural reseedling. Two grazing intensities (moderate and low were used, under continuous and rotational grazing. The experimental design included randomized blocks with 2x2x3 factorial arrangements (2 grazing intensities x 2 grazing methods x 3 replicates.The following year, the fields were desiccated with herbicides and a soybean plant crop cycle was established during the

  9. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas.

    Science.gov (United States)

    Felsberg, Jörg; Thon, Niklas; Eigenbrod, Sabina; Hentschel, Bettina; Sabel, Michael C; Westphal, Manfred; Schackert, Gabriele; Kreth, Friedrich Wilhelm; Pietsch, Torsten; Löffler, Markus; Weller, Michael; Reifenberger, Guido; Tonn, Jörg C

    2011-08-01

    Epigenetic silencing of the O(6) -methylguanine-DNA methyltransferase (MGMT) gene promoter is associated with prolonged survival in glioblastoma patients treated with temozolomide (TMZ). We investigated whether glioblastoma recurrence is associated with changes in the promoter methylation status and the expression of MGMT and the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 in pairs of primary and recurrent glioblastomas of 80 patients, including 64 patients treated with radiotherapy and TMZ after the first operation. Among the primary tumors, the MGMT promoter was methylated in 31 patients and unmethylated in 49 patients. In 71 patients (89%), the MGMT promoter methylation status of the primary tumor was retained at recurrence. MGMT promoter methylation, but not MGMT protein expression, was associated with longer progression-free survival, overall survival and postrecurrence survival (PRS). Moreover, PRS was increased under salvage chemotherapy. Investigation of primary and recurrent glioblastomas of 43 patients did not identify promoter methylation in any of the four MMR genes. However, recurrent glioblastomas demonstrated significantly lower MSH2, MSH6 and PMS2 protein expression as detected by immunohistochemistry. In conclusion, reduced expression of MMR proteins, but not changes in MGMT promoter methylation, is characteristic of glioblastomas recurring after the current standards of care. Copyright © 2011 UICC.

  10. Mismatch Repair Proteins and Microsatellite Instability in Colorectal Carcinoma (MLH1, MSH2, MSH6 and PMS2): Histopathological and Immunohistochemical Study.

    Science.gov (United States)

    Ismael, Nour El Hoda S; El Sheikh, Samar A; Talaat, Suzan M; Salem, Eman M

    2017-03-15

    Colorectal cancer (CRC) is one of the most common cancers worldwide. Microsatellite instability (MSI) is detected in about 15% of all colorectal cancers. CRC with MSI has particular characteristics such as improved survival rates and better prognosis. They also have a distinct sensitivity to the action of chemotherapy. The aim of the study was to detect microsatellite instability in a cohort of colorectal cancer Egyptian patients using the immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Cases were divided into Microsatellite stable (MSS), Microsatellite unstable low (MSI-L) and Microsatellite unstable high (MSI-H). This Microsatellite stability status was correlated with different clinicopathological parameters. There was a statistically significant correlation between the age of cases, tumor site & grade and the microsatellite stability status. There was no statistically significant correlation between the gender of patients, tumor subtype, stage, mucoid change, necrosis, tumor borders, lymphocytic response, lymphovascular emboli and the microsatellite stability status. Testing for MSI should be done for all colorectal cancer patients, especially those younger than 50 years old, right sided and high-grade CRCs.

  11. Modelo dinámico para lámparas de descarga de alta intensidad en alta frecuencia; Dynamic model for high intensity discharge lamps in high frequency

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    Leonardo Cedeño Rodríguez

    2015-04-01

    Full Text Available En este trabajo se desarrolla el modelado dinámico de lámparas de descarga de alta intensidad (HID en inglés, de manera que pueda contribuir al desarrollo posterior de un sistema de control avanzado sobre la etapa de potencia de un balasto electrónico, que permita operar este tipo de lámparas en alta frecuencia. El modelo tiene en cuenta la presencia del fenómeno de la resonancia acústica (RA, que usualmente se presenta en las lámparas HID a frecuencias elevadas. Para el modelado se emplean técnicas híbridas, teniendo como punto de partida las ecuaciones de balance de energía en el interior de la lámpara, en tanto para la parametrización, se aplica identificación de sistemas y optimización mediante algoritmos genéticos. La implementación del modelo se realiza con el software Matlab R2011a. Como resultado se obtiene un modelo dinámico para lámparas HID en alta frecuencia, validado para lámparas de alta presión de sodio.In this paper the dynamic modeling of high intensity discharge lamps (HID is developed. This will contribute to the further development of an advanced control system on the power stage of an electronic ballast, which allows these lamps operate at high frequency. The model must take into account the presence of the acoustic resonance’s phenomenon (AR, which usually occurs when HID lamps operates at high frequency. Hybrid modeling techniques were employed, the balance equations and the empirical expressions were obtained and the model was parameterized by identification techniques and optimization based on genetic algorithms. The implementation of the model has performed using Simulink tool of Matlab R2011a software. As a result, a dynamic model for HID lamps in high frequency has achieved and validated for high-pressure sodium lamps (HPS.

  12. Comparação de resposta da pressão intraocular frente a duas diferentes intensidades e volumes do treinamento resistido

    Directory of Open Access Journals (Sweden)

    Marcelo Conte

    2014-01-01

    Full Text Available Objetivo: Verificar a influência de duas diferentes intensidades e volumes de treinamento resistido na pressão intraocular. Método: Dezenove boxeadores (13 homens e 6 mulheres; idade média de 22 ± 3 anos foram randomicamente submetidos a duas diferentes sessões de exercícios resistidos: resistência muscular com 3 séries de 15 repetições máximas e hipertrofia muscular com 4 séries de 8RM. A pressão intraocular foi obtida com Tonometro de Perkins antes, durante e após as sessões de exercício resistido. Os dados foram expressos em média e desvio padrão. Foi realizada análise de variância (ANOVA com medidas repetidas e pós teste de Tukey. Resultados: Foi observada redução da pressão intraocular durante as sessões de treinamento resistido. Contudo, a sessão de exercício para resistência muscular promoveu uma redução significativa da pressão intraocular comparada a de hipertrofia muscular. Ao final da sessão de resistência muscular a pressão intraocular retornou aos valores prévios ao exercício, por outro lado na sessão de hipertrofia muscular a pressão intraocular após o término dos exercícios apresentou-se acima dos valores iniciais. Conclusão: O treinamento resistido pode influenciar os valores da pressão intraocular, especificamente 3 séries de 15 repetições com 60% de 1RM promoveu respostas hipotensivas mais expressivas na pressão intraocular do que 3 séries de 8 repetições com 80% de 1RM. Esses achados podem contribuir para prescrição de exercício resistido para pessoas com fatores de risco para o glaucoma.

  13. Consumo de oxigênio de recuperação em resposta a duas sessões de treinamento de força com diferentes intensidades

    Directory of Open Access Journals (Sweden)

    Ana Paula Viola de Almeida

    2011-04-01

    Full Text Available O objetivo do presente estudo foi comparar o comportamento do consumo de oxigênio (VO2 em resposta a uma sessão de treinamento de força (TF com objetivo em hipertrofia muscular (HP com uma sessão com objetivo em resistência muscular localizada (RML. Nove indivíduos do sexo masculino (23,1 ± 2,1 anos foram recrutados para este estudo. A força muscular dinâmica foi mensurada através do teste de 1RM. O VO2 foi coletado durante o repouso e 10 minutos de recuperação com um analisador de gases (CPX/D. As sessões foram compostas por um exercício de membros superiores (supino e um de membros inferiores (agachamento, e compreenderam a execução de três séries de 6-8 repetições máximas (RM a 80% de 1RM para HP e 15-20 RM a 55% de 1RM para RML. Foram analisados os dados de VO2 pós-exercício (EPOC, gasto energético (GE de recuperação e constante de tempo de VO2 (CT. Foi observado que ambas sessões provocaram comportamento significativamente elevado de VO2 durante os 10min de recuperação em relação aos valores de repouso. Não houve diferenças significativas entre os valores de EPOC (litros para HP (2,21 ± 0,54 e RML (2,60 ± 0,44, GE (kcal para HP (10,36 ± 2,53 e RML (12,18 ± 2,04 e CT (segundos para HP (56 ± 7 e RML (57 ± 6 (p > 0,05. Esses resultados demonstraram que uma sessão de TF com objetivo em RML é capaz de causar distúrbios metabólicos semelhantes àqueles provocados por uma sessão de HP, mesmo que seja em menor intensidade relativa a carga máxima.

  14. El control de la intensidad del entrenamiento de los ejercicios competitivos individuales con Cuerda, en la preparación deportiva de las gimnastas élites cubanas de 1ra Categoría en Gimnasia Rítmica

    Directory of Open Access Journals (Sweden)

    Yolainy Govea Díaz

    2007-12-01

    Full Text Available El proceso de preparación deportiva de las gimnastas élites cubanas de Gimnasia Rítmica en los últimos años ha ido modificándose debido a los cambios de las exigencias del código de puntuación planteadas por la FIG. Se han realizado investigaciones alrededor del asunto pero aún existen deficiencias como es el control de la carga de entrenamiento y fundamentalmente el indicador intensidad. La intensidad resulta muy difícil de valorar y controlar en los entrenamientos de Gimnasia Rítmica, debido a la variabilidad de ejercicios técnicos que se ejecutan, pero además por lo individualizado que se hace el entrenamiento de los ejercicios competitivos, pues las gimnastas ejecutan los ejercicios o elementos en dependencia de nivel técnico y físico que tengan. Por esta razón se determinó como objetivo de esta investigación elaborar un conjunto de indicaciones metodológicas para el control de la intensidad del entrenamiento de los ejercicios competitivos individuales de las gimnastas elites cubanas (adultas de Gimnasia Rítmica. Fueron utilizados diferentes métodos teóricos y empíricos que permitieron el desarrollo de la investigación. Se hicieron diferentes mediciones durante los entrenamientos de la preparación especial, ya que en esta etapa la gimnasta se encuentra lista para realizar el ejercicio competitivo con música, como lo realizará en las competencias.

  15. Persistencia de las ideas previas sobre potencial eléctrico, intensidad de corriente y ley de Ohm en los estudiantes de segundo curso de Ingeniería

    OpenAIRE

    Periago Oliver, María Cristina; Bohigas Janoher, Xavier

    2005-01-01

    El objetivo del trabajo que se presenta es la evaluación y el análisis de los conocimientos previos sobre los contenidos conceptuales de Teoría de circuitos que tienen los alumnos de segundo curso de Ingeniería Industrial e Ingeniería Química, con la finalidad de detectar la persistencia de estos conocimientos desde niveles educativos anteriores. Concretamente, nos hemos centrado en los conceptos básicos de potencial eléctrico e intensidad de la corriente, así como la relación fundamental ent...

  16. Efeitos da experiência nas dimensões de intensidade, direção e frequência da ansiedade e autoconfiança competitiva: Um estudo em atletas de desportos individuais e coletivos

    OpenAIRE

    Fernandes, Marcos Gimenes; Nunes, Sandra Adriana Neves; Raposo, José Vasconcelos; Fernandes, Helder Miguel

    2014-01-01

    O presente estudo teve os seguintes objetivos: i) examinar as correlações inter-escalas entre as três dimensões de respostas (intensidade, direção e frequência) do CSAI-2R e sua relação com a experiência competitiva; e ii) verificar o efeito da experiência competitiva na ansiedade (cognitiva e somática) e na autoconfiança na amostra total e em função de diferentes tipos de modalidades (individuais vs. coletivas). A amostra foi composta por 267 atletas (196 do sexo masculino e 71 do sexo femin...

  17. Análise dos efeitos agudos do laser de baixa intensidade. (660nm) sobre os níveis de estresse oxidativo de ratos diabéticos com feridas na pele

    OpenAIRE

    Denadai, Amanda Silveira

    2013-01-01

    Introdução: O termo estresse oxidativo é utilizado quando se evidencia um desequilíbrio entre os sistemas pró e antioxidantes. A laserterapia influencia parâmetros de estresse oxidativo como a alteração da atividade das enzimas antioxidantes e a produção de espécies reativas de oxigênio (ERO). Objetivo: Analisar o efeito da laserterapia de baixa intensidade - LLLT sobre o estresse oxidativo provocado por ferida cirúrgica aguda em ratos diabéticos. Materiais e métodos: ...

  18. Avaliação do efeito da laserterapia em baixa intensidade na reparação óssea após radioterapia externa – estudo experimental em ratos

    OpenAIRE

    Paixão, Darcy de Almeida

    2013-01-01

    Esse estudo teve como objetivo avaliar o efeito da Laserterapia em baixa intensidade na reparação de feridas cirúrgicas produzidas no tecido ósseo de ratos da raça Wistar. Para isso, foi artificialmente produzido um orifício no fêmur dos ratos e quatro dias após, os ratos foram submetidos a radioterapia externa com fonte de cobalto radioativo na dosagem de 3000 cGys. O grupo experimental recebeu adicionalmente sete sessões de Laserterapia de 780 hm, 40 nW, 100 J/cm2, por 100 seg. (qu...

  19. Intensidade-duração-frequência de chuvas para o Estado de Mato Grosso do Sul Intensity-duration-frequency of rainfall for the State of Mato Grosso do Sul

    Directory of Open Access Journals (Sweden)

    Glenio G. Santos

    2009-12-01

    Full Text Available A ausência de equações de chuvas intensas para o Estado do Mato Grosso do Sul e a necessidade de maior segurança na elaboração de projetos e dimensionamento de obras hidráulicas, foram o alicerce para, com este estudo, se obtivessem e espacializassem as relações de intensidade, duração e frequência de precipitações para o Estado. Utilizou-se, então, da metodologia da desagregação da chuva de 24 h e se utilizaram dados pluviométricos consistidos de 109 estações disponíveis no banco de dados da Agência Nacional de Águas. As equações de chuvas intensas apresentaram bom ajuste, com coeficientes de determinação acima de 0,99 para todas as localidades estudadas. Os parâmetros ajustados apresentaram alta variabilidade resultando em grandes diferenças nos valores de precipitações intensas esperadas para as diferentes localidades. A espacialização permitiu boa visualização das diferenças evidenciando maiores intensidades esperadas na região centro-norte e as menores intensidades nas regiões sudeste e sudoeste do Estado. Os resultados demonstram a importância da obtenção da equação de intensidade-duração-frequência para cada localidade e sua utilização para a realização de estudos e projetos hidráulicos.Rain intensity data are necessary to increase security of hydraulic projects. The objective of this study was to determine the rain storm equations and the spatial distribution of rain intensity for the State of Mato Grosso do Sul, Brazil. The equations were obtained by disaggregation of 24 h rain data from 109 pluviometric stations available in the National Water Agency (ANA data bank. These equations resulted in coefficients of determination above 0,99 for all localities. The adjusted parameters showed high variability, resulting from different rain intensities in different places of the State. The interpolation of data allowed good visualization of the differences, evidencing higher intensities of rains

  20. Grazing ecology of female lambs on Italian ryegrass plus red clover pasture under different defoliation intensities Ecologia do pastejo por cordeiras em pastagem de azevém e trevo-vermelho sob diversas intensidades de desfolha

    Directory of Open Access Journals (Sweden)

    Carine Lisete Glienke

    2010-01-01

    Full Text Available The relationship between pasture dynamics and ingestive behavior of female lambs was studied on Italian ryegrass (Lolium multiflorum Lam. plus red clover (Trifolium pratense L. mixture under a range of defoliation intensities. Rotational grazing was used and the grazing interval was determined by the thermal sum of 313 degree days. The initial pre-grazing canopy height disappearance values were 65 (very high, 58 (high, 47 (medium and 37% (low. The sward vertical structure was similar among defoliation intensities. The forage allowance decreased linearly as defoliation intensities increased, with 0.35 bite/minute reduction for each 1% increase in forage allowance. The bite rate and number of bites/feeding station decreased with reduced contribution of leaves in the sward structure. It was associated, respectively, with an increase and a decrease of NDF and CP levels in forage as grazed by female lambs. The pasture cycle proves to be more important than defoliation intensities as a source for changes in feeding stations and displacement patterns of female lambs.Estudou-se a relação entre a dinâmica do pasto e o comportamento ingestivo de cordeiras em pastagem de azevém (Lolium multiflorum Lam. e trevo-vermelho (Trifolium pratense L. em diferentes intensidades de desfolha. O pastejo foi rotacionado e o intervalo entre pastejos foi determinado pela soma térmica de 313 graus-dia. Os valores de desaparecimento da altura do dossel no pré-pastejo foram de 65 (muito alta, 58 (alta, 47 (média e 37% (baixa, respectivamente. A estrutura vertical do pasto foi semelhante entre as intensidades de desfolha testadas. A oferta de forragem diminuiu linearmente com o aumento da intensidade de desfolha, com redução de 0,35 bocado/minuto a cada 1% a mais na oferta de forragem. A taxa de bocados e o número de bocados/estação alimentar reduziram com a diminuição da contribuição de folhas na estrutura da pastagem, acompanhada do aumento do teor de FDN e

  1. DIFERENTES MODELOS DE REGRESIÓN PARA DESCRIBIR LA RELACIÓN V.O2-FC Y PARA ESTIMAR EL V.O2 A DIFERENTES INTENSIDADES DE ESFUERZO

    Directory of Open Access Journals (Sweden)

    Nuria Garatachea Vallejo

    2005-01-01

    Full Text Available Muchos son los estudios que demuestran el potencial de la frecuencia cardiaca (FC para estimar el coste energético de una actividad física, ya que se relaciona directamente con el consumo de oxígeno (V. O2. La mayoría de estudios describen la relación V. O2- FC como lineal para un amplio rango de esfuerzo, exceptuando los valores de reposo aunque se han propuesto diferentes funciones matemáticas continuas no lineales sin existir todavía un acuerdo en la ecuación más apropiada. También existen estudios que apuntan un cambio en la relación V. O2-FC en función de la intensidad del esfuerzo. Nuestro objetivo fue determinar cuál es la mejor función matemática que describe la relación entre la FC y el V. O2 y decidir cuál es la mejor función matemática para estimar el V. O2 a diferentes intensidades de esfuerzo. Participaron 14 sujetos que realizaron una prueba de esfuerzo máxima sobre cicloergómetro y una prueba que consistía en pedalear a 5 intensidades de esfuerzo (40, 50, 60, 70 y 80% del V. O2max durante 3 minutos. Durante ambas pruebas se midió V. O2 y frecuencia cardiaca. El modelo lineal y potencial fueron los modelos matemáticos más exactos para describir la relación V. O2-FC. El mayor error de estimación se produjo a bajas intensidades de esfuerzo. En conclusión, la elección de un tipo u otro de regresión influye en la exactitud del método de monitorización de la frecuencia cardiaca.

  2. Aplicación de Pulsos Eléctricos de Alta Intensidad en una bebida mezcla de zumo de naranja y leche: Efectos sobre Escherichia coli, Saccharomyces cerevisiae, componentes nutricionales y calidad

    OpenAIRE

    RIVAS SOLER, ALEJANDRO

    2012-01-01

    Los Pulsos Eléctricos de Alta Intensidad (PEAI) es una tecnología no térmica de conservación de alimentos que se está siendo evaluada como alternativa a las tecnologías convencionales de conservación basadas en el calor. Esta tecnología se caracteriza por permitir obtener un producto seguro microbiológicamente, con un mayor respeto de los componentes nutricionales que el tratamiento térmico convencional. Los trabajos que componen la presente tesis doctoral tratan de evaluar la idoneidad de...

  3. Tissue expression of MLH1, PMS2, MSH2, and MSH6 proteins and prognostic value of microsatellite instability in Wilms tumor: experience of 45 cases.

    Science.gov (United States)

    Diniz, Gulden; Aktas, Safiye; Cubuk, Cankut; Ortac, Ragip; Vergin, Canan; Olgun, Nur

    2013-05-01

    Although the importance of microsatellite instability (MSI) and mismatch repair genes (MMR) is strongly established in colorectal cancer seen in the Lynch syndrome, its significance has not been fully established in Wilms tumor (WT). The aim of this study was to determine the prognostic value of MSI and MMR proteins in WT. This study included 45 pediatric cases with nephroblastoma. Protein expression was analyzed by immunohistochemistry of archival tissue sections. Real-time PCR melting analysis and fluorescence capillary electrophoresis (FCE) were performed to evaluate the MSI markers BAT25, BAT26, NR21, NR24, MONO27, penta D, and penta C in DNA extracted from tumor and normal tissues. Lower levels of MSI were observed in six cases (13.3%). There were no statistically significant correlations between MSI and some clinical prognostic factors such as stage of the tumors, and survival rates. Nineteen tumors (42.2%) showed loss of protein expression of MLH1, PMS2, MSH2, or MSH6. MMR protein defects were correlated with size (P = .021), and stage (P = .019) of the tumor, and survival rates (P < .01).Similarly MSI was also correlated with the size of the tumor (P = .046). This study showed that a small proportion of WT might be associated with the presence of MSI, as is the case with defects of DNA mismatch repair genes in the pathogenesis of WT. However, there was no concordance with the frequency of tissue expression of MMR proteins and MSI. These findings suggest that MMR genes may play an important role in the development of WT via different pathways.

  4. Stress Analysis of the D-Zero Solenoid Magnet Lifting Fixture PPD Fixture No.102

    International Nuclear Information System (INIS)

    Zaczek, M.

    1997-01-01

    This engineering note presents stress analysis calculations for the below the hook lifting fixture which will be used to move the D-Zero solenoid magnet during installation work at the D-Zero Assembly building. Load bearing structural members are shown to have a minimum design factor of 3 based on yield strength as required by ASME B30.20. All bolts were analyzed and shown to be kept below allowable loads/stresses listed in the American Institute of Steel Construction (AISC) manual. The lifting fixture will be manufactured at Fermilab using some material scavenged from an existing lifting fixture that was shipped with the magnet from the magnet manufacturer, Toshiba Corporation. The fixture is designed with built in versatility so that the solenoid magnet can be maneuvered through the stages of preparation and installation into it's final mounted position. The structure has been analyzed for all phases of its use, although the analysis of the structure as a below the hook lifting device is the main purpose of this note.

  5. Quantitative PCR high-resolution melting (qPCR-HRM) curve analysis, a new approach to simultaneously screen point mutations and large rearrangements: application to MLH1 germline mutations in Lynch syndrome.

    Science.gov (United States)

    Rouleau, Etienne; Lefol, Cédrick; Bourdon, Violaine; Coulet, Florence; Noguchi, Tetsuro; Soubrier, Florent; Bièche, Ivan; Olschwang, Sylviane; Sobol, Hagay; Lidereau, Rosette

    2009-06-01

    Several techniques have been developed to screen mismatch repair (MMR) genes for deleterious mutations. Until now, two different techniques were required to screen for both point mutations and large rearrangements. For the first time, we propose a new approach, called "quantitative PCR (qPCR) high-resolution melting (HRM) curve analysis (qPCR-HRM)," which combines qPCR and HRM to obtain a rapid and cost-effective method suitable for testing a large series of samples. We designed PCR amplicons to scan the MLH1 gene using qPCR HRM. Seventy-six patients were fully scanned in replicate, including 14 wild-type patients and 62 patients with known mutations (57 point mutations and five rearrangements). To validate the detected mutations, we used sequencing and/or hybridization on a dedicated MLH1 array-comparative genomic hybridization (array-CGH). All point mutations and rearrangements detected by denaturing high-performance liquid chromatography (dHPLC)+multiplex ligation-dependent probe amplification (MLPA) were successfully detected by qPCR HRM. Three large rearrangements were characterized with the dedicated MLH1 array-CGH. One variant was detected with qPCR HRM in a wild-type patient and was located within the reverse primer. One variant was not detected with qPCR HRM or with dHPLC due to its proximity to a T-stretch. With qPCR HRM, prescreening for point mutations and large rearrangements are performed in one tube and in one step with a single machine, without the need for any automated sequencer in the prescreening process. In replicate, its reagent cost, sensitivity, and specificity are comparable to those of dHPLC+MLPA techniques. However, qPCR HRM outperformed the other techniques in terms of its rapidity and amount of data provided.

  6. DETERMINAÇÃO DA CURVA DE INTENSIDADE, DURAÇÃO E FREQUÊNCIA DO MUNICÍPIO DE IPAMERI – GOIÁS

    Directory of Open Access Journals (Sweden)

    Daniela Carneiro Pereira

    2017-08-01

    Full Text Available RESUMO: A caracterização das chuvas intensas para utilização em projetos de engenharia é fundamental, especificadamente no que tange à obras hidráulicas. O estudo das chuvas intensas é feito por meio da relação entre a intensidade, a duração e a frequência das mesmas. Este artigo trata da determinação de tais relações para o município de Ipameri, Goiás, devido à falta de estudos relacionados a esta localidade. Foi feito o ajustamento à distribuição estatística de Gumbel de forma a obter os valores de precipitação máxima para os períodos de retorno de 2, 5, 10, 15, 20, 25, 50 e 100 anos. Para verificação do ajuste dos dados observados a distribuição de Gumbel, realizou-se os testes de aderência de Kolmogorov-Smirnov, Anderson-Darling e Qui-Quadrado, ao nível de significância de 1%. A desagregação dos valores de precipitação máxima em durações menores que 24 horas foi feita utilizando o método das Relações de Durações. Os parâmetros K (881,7487, a (0,1333, b (10,5332 e c (0,7519 da equação de chuvas intensas foram obtidos utilizando o método do Gradiente Reduzido Generalizado. Para avaliação da equação obtida foi utilizado o coeficiente de determinação (R², o índice de concordância de Willmott (d e índice de confiança (Ic, com resultados respectivos de 0,9986, 0,9997 e 0,9990. Assim esta pesquisa contribuiu para a determinação da equação de chuvas intensas, permitindo seu uso no dimensionamento de estruturas hidráulicas do local. ABSTRACT: Heavy rains characterization for use in engineering design projects is essential, specifically with regard to the hydrological researches and structures. In this way the study of heavy rains is done relating the intensity, duration and frequency of the events. This paper deals with the determination of such relations for the city of Ipameri, Goiás - Brazil, due to lack of studies related to the municipality. Adjusting the statistical Gumbel

  7. Efeito de variáveis ambientais, épocas e métodos de plantio na intensidade da seca da haste (Botrytis cinerea em Hibiscus sabdariffa

    Directory of Open Access Journals (Sweden)

    Carlos Alberto de Oliveira

    2011-06-01

    Full Text Available O presente estudo objetivou avaliar o efeito da temperatura (15, 20, 25 e 30ºC, do período de molhamento foliar (0, 6, 12 e 24 h, de épocas (setembro, outubro, novembro e dezembro e métodos de plantio (semeadura direta e transplantio de mudas, na intensidade da seca da haste (Botrytis cinerea do hibisco (Hibiscus sabdariffa. As variáveis ambientais foram avaliadas em condições controladas com inoculação artificial e as épocas e métodos de plantio foram avaliados em condições de infecção natural em campo. Os dados de frequência de infecção analisados, como área abaixo da curva de progresso da frequência de infecção (AACPF e comprimento de lesões relacionados às variáveis ambientais, foram submetidos à análise de variância e regressão e, em seguida, plotadas as superfícies de resposta. Os dados de incidência (AACPI relacionados às épocas e métodos de plantio foram submetidos à análise de variância, utilizando-se o programa estatístico Sisvarâ/UFLA. A interação da temperatura e da duração do período de molhamento foliar influenciou a frequência de infecção e o comprimento de lesões da seca da haste. Houve aumento na frequência de infecção e no comprimento de lesões com o incremento do período de molhamento foliar e redução da temperatura. As lesões apresentaram maior tamanho na temperatura de 15ºC e 24 horas de molhamento foliar. Na ausência de molhamento foliar houve manifestação de sintomas somente a 15ºC. A 30ºC houve dependência de maior período de molhamento foliar para a manifestação de sintomas. Houve interação significativa de métodos e épocas de plantio na incidência da doença. Constatou-se menor incidência da seca da haste em transplantio de mudas comparado à semeadura direta em todas as épocas de plantio. Verificou-se aumento da incidência proporcionado pelo atraso na época de plantio nos dois métodos. Registrou-se uma relação direta entre queda de

  8. Intensidade da dor em pacientes com síndrome do ombro doloroso Pain severity in patients with painful shoulder syndrome

    Directory of Open Access Journals (Sweden)

    Daniela Dias da Silva Garzedin

    2008-01-01

    Full Text Available O objetivo do estudo é avaliar intensidade da dor e associações com características clínicas em grupo de pacientes com Síndrome do Ombro Doloroso (SOD. Realizou-se estudo descritivo utilizando dados retrospectivos de 77 prontuários. Como instrumento de avaliação utilizamos Escala Visual Numérica (EVN. Foram consideradas variáveis de interesse: EVN (77, diagnóstico (57, ombro acometido (77, sexo (77, idade (76, localização da dor (77, uso de medicamentos (59 e problema cervical associado (77. Destes 53,2% eram do sexo feminino com média de idade 50,4±15,7 anos. O ombro direito foi o mais afetado (57,1%. Dor intensa foi referida por 41,6% dos pacientes sendo mais freqüente no sexo feminino (56,1% vs 25,0%; p=0,006. Os pacientes queixaram-se de dor intensa com mais freqüência em ombro esquerdo (57,7% vs 31,8%, p=0,034. Dos pacientes estudados, 59 (81,3% usavam medicamentos, sendo mais freqüente o antinflamatório. A síndrome do manguito rotador estava presente em 80,7% (57 e dor cervical associada em 15,6% (77. Localização da dor exclusivamente no ombro correspondeu a 76,6%. Evidenciamos que a síndrome do manguito rotador foi causa mais freqüente da SOD, sendo mais comum e intensa em mulheres com idade próxima de 51 anos. A EVN mostrou-se instrumento relevante para mensurar a dor na SOD.The aim of this study was to assess the severity of pain and its correlations to clinical characteristics in Painful Shoulder Syndrome (PSS patients. A descriptive study was conducted using retrospective data from 77 medical record files. The Visual Numerical Scale (VNS was used as an assessment instrument. The following variables of interest were considered: VNS (77, diagnosis (57, affected shoulder (77, sex (77, age (76, pain site (77, use of medications (59 and associated cervical pain (77. 53.2% of the patients were females and the mean age was 50.4±15.7 years. The right shoulder was the most affected side (57.1%. Severe pain was

  9. Caracterização fisiológica de sorgo sacarino em diferentes intensidades de irrigação

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    Luciano Rezende Moreira

    2013-10-01

    Full Text Available O sorgo [Sorghum bicolor (L. Moench] é uma planta de origem africana, da mesma família do milho. O sorgo tipo sacarino é utilizado como matéria prima para bionergia (etanol e apresenta elevada eficiência no uso da água. Este trabalho teve como objetivo caracterizar cultivares de sorgo sacarino quanto às características fisiológicas em diferentes intensidades de irrigação, analisar trocas gasosas e fluorescência de clorofila a fim de subsidiar programas de melhoramento genético direcionados à obtenção de genótipos produtivos de sorgo em situações de déficit hídrico. Foram avaliados quatro cultivares, tolerantes à seca: Rio, Ramada, BRS 501, BRS 506. O tratamento consistiu de três disponibilidades de água no solo: 80%, 60% e 40% da capacidade de campo (c.c.. Foram avaliadas a condutância estomática (gs, a taxa de fotossíntese líquida (A, a transpiração foliar (E e a eficiência intrínseca do uso da água (EIUA, A/gs. Também foi determinada a eficiência quântica ideal (Fv/Fm do fotossistema II (FSII, o rendimento quântico basal dos processos fotoquímicos no FSII (Fo/Fm e a eficiência fotoquímica no FSII (Fv/Fo. A disponibilidade hídrica não causou alteração (P > 0,05 na transpiração dos cultivares Ramada e BRS 501, mas afetou (P < 0,05 os cultivares Rio e BRS 506 que responderam positivamente ao aumento da irrigação. Resultado semelhante ocorreu com a fotossíntese, já que as diferentes disponibilidades hídricas influenciaram positivamente apenas os cultivares Rio e BRS 506. Com o incremento da irrigação houve um acréscimo (P < 0,05 na condutância estomática dos cultivares avaliados. Os resultados referentes à fluorescência da clorofila mostraram superioridade dos cultivares BRS 506, Rio e Ramada com valores maiores (P < 0,05 de Fv/Fm e Fv/Fo. Os distintos níveis de disponibilidade hídrica e os diferentes cultivares não promoveram (P > 0,05 alteração na EIUA. Esta metodologia, comum

  10. Efeitos do ultra-som de baixa intensidade na veia auricular de coelhos Effects of low intensity ultrasound in the auricular vein of rabbits

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    Marcelo Araújo

    2003-01-01

    Full Text Available OBJETIVO: Estudar a ação do ultra-som na veia auricular de coelhos. MÉTODOS: Vinte coelhos foram divididos em dois grupos de dez animais diferindo com relação ao local da aplicação, do ultra-som, o modo e o intervalo de tempo para a análise histopatológica (3 e 7 dias. Os animais foram submetidos à aplicação de ultra-som contínuo e pulsado em dois segmentos venosos da orelha previamente determinados. Cada animal foi o seu próprio controle. Empregou-se a freqüência de 3MHz, intensidade de 3W/cm² nos ciclos pulsado e contínuo por 10 minutos, de forma estacionária. O grupo I foi submetido a eutanásia após 3 dias e o grupo II em 7 dias contemplando a fase aguda do processo inflamatório. Empregou-se o teste exato de Fisher e o teste de Mc Nemar para análise estatística. RESULTADOS: Obteve-se trombose venosa e aumento de linfócitos de forma significativa (p= 0,032 nos grupos tratados com o modo contínuo. O modo pulsado não provocou efeitos deletérios. Outros achados foram congestão, edema, hemorragia e lesão da parede vascular. CONCLUSÕES: O ultra-som pulsado não provoca qualquer alteração na parede vascular nas condições do experimento.O ultra-som contínuo induz a trombose venosa e aumento dos linfócitos de forma significativa.PURPOSE: The purpose of this experimental work was evaluate the effects of low intensity in the auricular vein of rabbits. METHODS: Twenty rabbits were divided in two groups of ten animals. The groups differed about the place where the continuous and pulsed ultrasound were applied and the period that the material was collected for the morphologic examination (3 and 7 days. Acoustic coupling gel was used on marginal ear vein, each animal underwent continuous and pulsed ultrasound treatment, in segments previously marked with indelible ink. Each animal provided its own control. Ultrasound was used in the frequency of 3MHz, intensity of 3W/cm² in the pulsed and continuous modes during 10min

  11. Substratos e intensidades de luz no cultivo de orquídea denfal Substrates and light intensity on cultivation of Denphal orchid

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    Marichel C Macedo

    2011-06-01

    Full Text Available Foi avaliada a influência da luminosidade e de substratos alternativos ao xaxim, no desenvolvimento e floração de plantas de Dendrobium phalaenopsis var. schroederianum x Dendrobium bigibbum var. compactum. O experimento foi conduzido na UFGD-FCA, de outubro de 2007 a agosto de 2008. Foram utilizadas plantas com quatro anos oriundas de cultivo in vitro, aclimatizadas em viveiro com intensidade luminosa de 12.800, 8.300, 6.200, 5.300 e 4.500 lux, e plantadas em vasos plásticos contendo como substrato carvão, fibra de coco ou uma mistura de carvão + fibra de coco. Durante o período experimental foram avaliados a redução de massa fresca (%, o diâmetro de pseudobulbos (%, brotações (%, início da floração, plantas com flores (%, comprimento da haste floral, botões florais (nO, diâmetro das flores e duração do florescimento. As menores reduções da massa fresca e do diâmetro foram observados sob 12.800 lux. Para brotações os maiores valores foram observados em substrato carvão sob 12.800 lux, ou em substrato fibra de coco e carvão + fibra de coco sob 4.500 lux. Nas condições em que o trabalho foi conduzido recomenda-se que esta orquídea seja cultivada em carvão sob 12.800 lux, uma vez que o maior percentual de plantas com flores, número de botões por planta, diâmetro das flores e comprimento da haste floral produzidos foram observados nestas condições.The influence of light and alternative substrates to fern tree fiber was evaluated on the development and flowering of Dendrobium phalaenopsis var. schroederianum x Dendrobium bigibbum var. compactum plants. The experiment was carried out from October 2007 to August 2008. Four-year old plants from in vitro cultivation, and acclimatized in nursery with light intensities of 12,800, 8,300, 6,200, 5,300 and 4,500 lux, were used. Plants were planted in plastic vases filled with charcoal, coconut fiber or a mix of charcoal + coconut fiber as substrate. During the experimental

  12. Análises macro e microscópicas de enxertos cutâneos por semeadura após laserterapia de baixa intensidade Macro and microscopic analysis of island skin grafts after low-level laser therapy

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    Elisângela Barboza da Silva

    2013-02-01

    Full Text Available OBJETIVO: observar se a laserterapia de baixa intensidade acelera o processo inflamatório, a cicatrização e epitelização de enxertos cutâneos por semeadura. MÉTODOS: vinte ratos foram submetidos a esta técnica de enxertia e divididos em dois grupos iguais, um tratado com laser e outro controle. RESULTADOS: houve menor tempo de reação inflamatória, maior velocidade de cicatrização, epitelização e queratinização nos animais tratados com laser em relação aos não tratados. CONCLUSÃO: a laserterapia de baixa intensidade é efetiva no auxílio ao tratamento de enxertos por semeadura.OBJECTIVE: To observe the effects of low intensity laser therapy in inflammation, wound healing and epithelialization of island skin grafts. METHODS: Twenty rats were subjected to this grafting technique and divided subsequently into two equal groups, one treated with laser and the other control. RESULTS: there was less inflammation, faster healing, epithelialization and keratinization in the laser-treated animals when compared to the untreated. CONCLUSION: Low intensity laser therapy is helpful to island skin grafting.

  13. Sample intensity in ombrophilous open forest at Verde Para Sempre Extractive Reserve, Porto de Moz, PA = Intensidade amostral em Floresta Ombrófila Aberta na Resex Verde Para Sempre, Porto de Moz, PA

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    Fabio Miranda Leão

    2018-03-01

    Full Text Available Determining the ideal sampling intensity is important to guarantee data closer to reality with less cost and time in the forest inventory. The objective of this paper was to evaluate the influence of different sample intensities to estimate the floristic composition, species diversity and the timber volume, beyond compare the results with their respective parameters obtained in the census of an ombrophilous open forest area in Verde Para Sempre Extractive Reserve. Was simulated a random sampling with sampling units of 1 ha and several sample intensities: 5%, 10%, 15% and 20% in an area of 200 ha that it was submitted to a forest census. It was evaluated the phytosociological parameters such as structure and diversity, and the estimated errors in the sampling intensities for the volume. The forest has a structure with high diversity and species of high economic value, indicating the existence of an aptitude for sustainable forest management. The treatment with 5% and 10% sample intensity were not enough to contemplate all the species in the area and estimate the volume inside to the required accuracy limit, maximum of 10% sampling error. The treatments of 15% and 20% resembled the parametric value regarding floristic composition, species diversity and volumetry of the forest census of the area, showing no significant difference between them. The analysis of the phytosociological structure showed the importance of using sample inventories to evaluate the economic potential of an area and its suitability for forest management. = Determinar a intensidade amostral ideal é importante para garantir dados mais próximos da realidade com menor custo e tempo na realização do inventário florestal. Assim, objetivou-se avaliar a influência de diferentes intensidades amostrais para estimar a composição florística, a diversidade de espécies e o volume de madeira, bem como comparar esses resultados com seus respectivos parâmetros obtidos pelo censo de

  14. Efeito da intensidade do exercício físico sobre o controle inibitório, afeto, controle autonômico cardíaco e oxigenação do córtex pré-frontal

    OpenAIRE

    Silva, Weslley Quirino Alves da

    2016-01-01

    Introdução: A baixa aderência na maior parte da população em programas de atividade física tem sido associada a experiências emocionais de desprazer provocada pela intensidade do exercício físico. Estudos teóricos propõem o controle inibitório como elemento fundamental para a regulação emocional de prazer durante o exercício executado em diferentes intensidades. No entanto, ainda é desconhecida a relação do controle inibitório com as respostas afetivas acerca da intensidade do exercício. Obje...

  15. Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells

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    Katja Zappe

    2018-01-01

    Full Text Available Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l and high (4.5 g/l glucose cell culture condition. Malondialdehyde (MDA as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1 and the DNA methyltransferase 1 (DNMT1 as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 μM vitamin E proved to be more efficient than did 50 μM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

  16. Intensidades de treinamento resistido e pressão arterial de idosas hipertensas - um estudo piloto Resistance training intensities and blood pressure of hypertensive older women - a pilot study

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    Eline Silva da Cunha

    2012-12-01

    Full Text Available INTRODUÇÃO: Observa-se que a literatura apresenta uma lacuna acerca da intensidade ideal de treinamento resistido para idosos hipertensos, os poucos estudos existentes utilizam treinamentos com diferentes intensidades. OBJETIVO: Verificar o efeito de duas intensidades de treinamento resistido sobre a pressão arterial de idosas hipertensas controladas. Métodos: Dezesseis idosas hipertensas, controladas por medicação anti-hipertensiva, foram divididas em dois grupos através de sorteio. Nove pacientes foram submetidas a treinamento resistido moderado (G1 e sete, a treinamento resistido leve (G2. As pacientes realizaram oito semanas de treinamento resistido, com frequência de três vezes por semana em dias alternados, no período vespertino. Os exercícios realizados foram respectivamente: leg press, supino reto, extensão de joelhos, puxada frontal, flexão de joelhos, abdução de ombro, abdução unilateral de quadril com cross over e rosca direta com barra. RESULTADOS: As pacientes do G1 apresentaram redução tanto nos valores de repouso da pressão arterial diastólica (PAD p BACKGROUND: The optimum intensity of resistance training for hypertensive elderly has not been studied yet and the few studies in the literature used training with distinct intensities. Objective: To verify the effect of two resistance training intensities on blood pressure (BP of elderly women with controlled hypertension. METHODS: Sixteen older women with hypertension controlled by anti-hypertensive drug were randomly divided into two groups. Nine patients were submitted to moderate resistance training (G1 and seven patients were submitted to mild resistance training (G2. The patients underwent eight weeks of resistance training, with frequency of three times per week on alternate days in the afternoon. The exercises performed were: leg press, bench press, knee extension, lat pull-down, knee flexion, shoulder abduction, standing cable hip abduction and biceps

  17. Épocas e intensidades de poda de frutificação na goiabeira ' Paluma' , em Pinheiros-ES Effect of pruning time and intensity on ' Paluma' guava trees, in Pinheiros, ES, Brazil

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    Luiz Augusto Lopes Serrano

    2008-12-01

    Full Text Available Este trabalho teve como objetivo avaliar os efeitos de diferentes intensidades de poda de frutificação realizadas em diferentes épocas do ano sobre a fenologia e a produção da goiabeira 'Paluma', em Pinheiros-ES. As plantas foram submetidas a três intensidades de poda de frutificação (curta, média e longa, em quatro diferentes épocas (25-11-2005, 21-12-2005, 27-01-2006 e 23-02-2006. O ciclo da goiabeira 'Paluma', entre a poda até o início da colheita dos frutos, variou de 189 dias (podas em novembro e dezembro a 203 dias (poda em fevereiro. Independentemente da época de poda, as plantas submetidas à poda longa apresentaram maior emissão de brotos novos e maior número de ramos estabelecidos. As plantas submetidas à poda curta apresentaram menores números de brotos emitidos e de ramos estabelecidos, bem como menor índice de pegamento de frutos, menor número de frutos por planta e, conseqüentemente, menor produção; entretanto produziram frutos de maior peso médio em relação às plantas submetidas à poda longa. A maior produção e o maior número de frutos colhidos por planta ocorreram nas plantas podadas em fevereiro. A época e a intensidade da poda de frutificação afetam a brotação e a produção da goiabeira 'Paluma'.The objective of this work was to evaluate the effects of different pruning times and intensities on the phenology and yield of 'Paluma' guava trees, in Pinheiros, Espírito Santo State, Brazil. The plants were submitted to three pruning intensities (heavy, medium and light, in four dates (November 25, 2005; December 21, 2005; January 27, 2006 and February 23, 2006. The period between pruning and the beginning of fruit ripening varied from 189 (pruning in November and December to 203 days (pruning in February. Regardless of pruning time, the larger numbers of buds and established branches occurred in plants submitted to light pruning. Plants submitted to heavy pruning produced the smallest numbers of

  18. Avaliação da intensidade de luz e da manutenção dos aparelhos fotopolimerizadores utilizados em clínicas odontológicas da cidade do Recife-PE

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    Rafael Antonio de Oliveira RIBEIRO

    Full Text Available Resumo Objetivo Avaliar os aparelhos fotopolimerizadores utilizados em clínicas da cidade do Recife e a manutenção realizada nesses aparelhos. Método Os profissionais participaram da avaliação de forma voluntária e não foram identificados nos questionários que foram por eles respondidos. Foi perguntado sobre os métodos de desinfecção, a frequência de troca de lâmpadas e a frequência da técnica empregada de manutenção. Também foi realizada a avaliação do aparelho fotopolimerizador, registrando as informações referentes a modelo, marca e data de aquisição. Foi realizada a mensuração da intensidade de luz utilizando-se um radiômetro (Demetron®. Resultado Todos os aparelhos fotopolimerizadores estavam com intensidade de luz inferior a 300 mW/cm2; 96,7% dos profissionais realizavam manutenção técnica de seus aparelhos apenas quando necessário; 100% trocavam a lâmpada só quando a mesma queimava; 40% dos aparelhos fotopolimerizadores encontravam-se acoplados ao equipo; 86,6% dos aparelhos apresentavam detritos na fibra óptica; 50% dos filtros apresentavam fraturas, sendo que 86,66% dos mesmos apresentavam detritos; 60% dos profissionais empregavam apenas álcool 70° como método de desinfecção; 53% dos entrevistados realizavam o método de desinfecção após cada paciente. Conclusão Todos os aparelhos fotopolimerizadores avaliados estavam com intensidade de luz abaixo do preconizado e constatou-se a inexistência de um protocolo de manutenção preventiva periódica.

  19. Respostas hormonais agudas a diferentes intensidades de exercícios resistidos em mulheres idosas Acute hormonal responses to different intensities of resistance exercises in older women

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    Ricardo Jacó de Oliveira

    2008-08-01

    Full Text Available O treinamento resistido vem sendo apontado como eficaz em retardar o declínio de força e massa muscular que acompanham o envelhecimento; contudo, a resposta hormonal aguda a esse tipo de exercício precisa ser mais bem caracterizada. Os objetivos do presente estudo foram caracterizar e comparar as respostas hormonais agudas resultantes de diferentes intensidades de exercícios resistidos realizados por mulheres idosas. A amostra foi composta por 15 mulheres com idade média de 67,5 anos, as quais realizaram, de forma aleatória, três visitas ao laboratório: 1 exercícios resistidos realizados a 50% de 1-RM (G50; 2 exercícios resistidos realizados a 80% de 1-RM (G80; e 3 sessão controle (GC. Coletas sanguíneas foram realizadas imediatamente antes e após (TO e T1, respectivamente cada sessão, bem como três e 48 horas após (T2 eT3, respectivamente, para posterior análise hormonal através do método imunoensaio quimiluminescente. ANOVA e ANCOVA foram utilizadas, respectivamente, para examinar diferenças intra e intersessões. Não foram observadas diferenças significativas entre as sessões para nenhum dos hormônios avaliados. EmT2, as concentrações do cortisol encontraram-se significativamente inferiores quando comparados com T0 nas três sessões realizadas, enquanto a testosterona apresentou-se reduzida no T2 do GC. Apenas a sessão G80 induziu elevação transitória significativa da razão testosterona/cortisol e nenhuma das sessões provocou alterações nas concentrações séricas de GH. Conclui-se que exercícios resistidos realizados a 50% ou a 80% de 1-RM não induziram agudamente elevação significativa de cortisol, testosterona ou GH na amostra estudada. Por outro lado, a sessão realizada a 80% de 1-RM promoveu aumento significativo da razão testosterona/cortisol três horas pós-exercício quando comparada com a dos valores basais, em mulheres idosas.Resistance training has been pointed as an effective intervention

  20. A intensidade da exploração agropecuária como indicador da degradação ambiental na região dos Cerrados, Brasil

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    Nina Rosa da Silveira Cunha

    2008-06-01

    Full Text Available Constituindo-se no maior fator de risco e de efetiva degradação para o Cerrado, a intervenção do homem na natureza e, em especial, na exploração agropecuária requer análise e monitoramento mais profundos. Este trabalho objetiva analisar as relações entre a exploração agropecuária e a degradação ambiental na região dos Cerrados, em 1995-1996. Em particular, pretende-se, por meio de análise estatística multivariada, verificar os fatores associados à intensidade da agropecuária, predominantes na determinação do padrão de degradação, além de obter índices de intensidade de exploração que possibilitem hierarquizar e agrupar as microrregiões em termos de potencial de degradação. Analisando os resultados alcançados verificou-se que a intensidade da exploração agropecuária manifestou-se pelo uso intensivo do solo (exploração agrícola e de tecnologias mecânica e bioquímica; pela intensidade de exploração pecuária; e outras dimensões da agricultura. As microrregiões com maiores níveis de degradação concen traram-se no noroeste de Minas Gerais, parte do sul de Goiás, e, em parte do sudeste de Mato Grosso. Os menores valores médios do índice de degradação ficaram por conta de Tocantins, Piauí e Maranhão. O maior índice coube à microrregião Primavera do Leste (MT e o menor a Jalapão (TO.Being constituted as the largest risk factor and effective degradation to the Savannah, the man's intervention in the nature and, especially, the agricultural exploration require analysis and better monitoring. This work aims to analyze the relationship between the agricultural exploration and the environmental degradation in the area of the Savannahs, in 1995-1996. In particular, it is intended, to use multivariate statistical analysis, to verify the factors associated with the intensity of farming predominant in the determination of the degradation pattern, and to obtain indexes of exploration intensity to make

  1. Efeito agudo do exercício realizado em diferentes intensidades sobre a fome, hormônios relacionados ao apetite e ingestão alimentar em homens e mulheres

    OpenAIRE

    Valéria Leme Gonçalves Panissa

    2015-01-01

    A manutenção da saúde, depende, dentre outros aspectos, do controle da massa corporal, uma vez que a obesidade está associada ao desenvolvimento de doenças crônicas. Sendo assim, o exercício pode ser considerado uma ferramenta eficaz nesse controle. Contudo, está evidenciado que o exercício realizado em alta intensidade pode ocasionar maior redução da gordura corporal. Dentre as hipóteses sugeridas para explicar tal fenômeno, a supressão do apetite pós-exercício foi levantada, no entanto, o e...

  2. Relação entre intensidade de dor e capacidade funcional em indivíduos obesos com osteoartrite de joelho Relationship between pain intensity and functional capacity of obese individuals with knee osteoarthritis

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    KSS Vasconcelos

    2006-01-01

    Full Text Available CONTEXTUALIZAÇÃO: A osteoartrite (OA de joelho é uma doença crônica que acomete a cartilagem articular, provocando alterações ósseas, dor e rigidez à movimentação. A obesidade é um dos seus principais fatores de risco. As queixas de dificuldades funcionais são freqüentes, especialmente para a locomoção, que se torna mais lenta. Com os crescentes níveis de obesidade no Brasil, torna-se importante compreender como a OA de joelho afeta a capacidade funcional humana, a fim de se elaborar medidas de tratamento e prevenção. OBJETIVO: Analisar a influência da intensidade de dor, gravidade radiográfica, grau de obesidade e duração dos sintomas na capacidade funcional de indivíduos obesos com OA de joelho. MÉTODO: A intensidade de dor foi medida pelo questionário Western Ontario and McMaster Universities Index (WOMAC e durante os testes funcionais. A gravidade radiográfica foi analisada pela classificação Kellgren-Lawrence e o grau de obesidade pelo índice de massa corporal (IMC. Foram realizados quatro testes funcionais de velocidade: marcha usual e rápida, subir e descer escadas. RESULTADOS: A amostra foi constituída de 31 mulheres e 4 homens, com idade média de 51,65 ± 10,72 anos e IMC médio de 41,16 ± 8,37 kg/m². As atividades em escadas estavam associadas a níveis mais intensos de dor. Apenas a intensidade de dor apresentou correlações significativas com os resultados nos testes de velocidade. CONCLUSÃO: A intensidade de dor é um fator que influencia a realização de atividades funcionais em indivíduos obesos com OA de joelho, mas outros estudos são necessários para identificar os fatores determinantes de capacidade funcional nesta população.BACKGROUND: Knee osteoarthritis is a chronic disease that affects joint cartilage, causing bone structure alterations, pain and stiffness during movement. Obesity is one of its principal risk factors. Complaints about functional disability are frequent, especially

  3. Aplicações do laser de baixa intensidade no tratamento da síndrome do túnel do carpo - doi: 10.5102/ucs.v7i2.996

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    João Paulo Caldas Cardozo

    2010-06-01

    Full Text Available O objetivo deste trabalho foi analisar, por meio de revisão bibliográfica, a eficiência da aplicação do Laser de baixa intensidade (LBI no tratamento da Síndrome do Túnel do Carpo (STC. Para isso foi realizada uma pesquisa de artigos nas bases de dados PUBMED e BIREME, publicados entre 1985 e 2009, nos idiomas espanhol, inglês e português. Grande parte dos artigos consultados revelou que a LBI é eficaz no tratamento de pacientes diagnosticados com Síndrome do Túnel do Carpo. Concluiu-se que, quando associada ao uso de órtese para o punho, a laserterapia é um método eficiente no tratamento da síndrome do túnel do carpo.

  4. Efeito de diferentes intensidades do treinamento de força intradialítico sobre a massa muscular e capacidade funcional e qualidade de vida de pacientes em hemodiálise: ensaio clínico randomizado

    OpenAIRE

    Lopes, Lorena Cristina Curado

    2016-01-01

    Pacientes com doença renal crônica em tratamento de hemodiálise apresentam reduções importantes na massa muscular e na capacidade funcional, estas reduções são associadas a um maior risco de mortalidade. Contudo, o treinamento de força é uma possível estratégia de atenuação ou ate mesmo de redução da perda de massa muscular e força nestes pacientes. Objetivo: Avaliar o efeito de duas intensidades de treinamento de força progressivo intradialítico sobre a massa muscular e a capa...

  5. Índice de intensidade de infecção adaptado ao estudo de manchas de sementes de arroz Index of infection intensity adapted for the study of spotted rice seeds

    Directory of Open Access Journals (Sweden)

    Jaciro Soave

    1988-01-01

    Full Text Available A avaliação de manchas em amostras de sementes de arroz (Oryza sativa L. tem sido feita mediante o cálculo de porcentagem de sementes manchadas, o que não dá informação quantitativa sobre sua incidência. Com o objetivo de obter dados quantitativos de manchas de sementes de arroz, procurou-se adaptar o índice de intensidade de infecção proposto por Amaral e exemplificado por Silva, comparando-se os dois métodos. Foram utilizadas 128 amostras de 5g de sementes provenientes de ensaios conduzidos nos municípios paulistas de Jaboticabal e Pindorama, no ano agrícola de 1982/83, e compostos de 16 cultivares de arroz-de-sequeiro, com quatro repetições. Para calcular o índice de intensidade de infecção, cada amostra foi separada visualmente em quatro categorias: n0 = sem manchas; n1 = poucas manchas (até 5%; n2 = muitas manchas (6-25%, e n3 = extremamente manchadas (acima de 25% da superfície com manchas. A mesma amostra foi separada em sementes com e sem manchas, independente da quantidade de manchas que cada semente apresentasse, calculando-se a porcentagem das manchadas. A comparação da análise da variância e da correlação entre ambas as avaliações revelou que o índice de intensidade de infecção, denominado pelos autores de índice de intensidade de manchas, proporcionou maior discriminação entre os tratamentos que a porcentagem de sementes manchadas, sugerindo-o para a avaliação quantitativa de manchas de sementes de arroz.The evaluation of spots in rice seeds has been performed through the calculation of the percentage of spotted seeds. However this measurement is not quantitative. The objective of this experiment was to compare the percentage of spotted seeds with an index of infection intensity, which gives a more precise quantitative information about the extension of the seed surface area infected. For this comparison, 5g-rice-seed samples from two field trials, carried out in Jaboticabal and Pindorama, in the

  6. Influência dos exercícios físicos de baixa e alta intensidade sobre o limiar de hipernocicepção e outros parâmetros em ratos

    OpenAIRE

    Lana,Ademir da Costa; Paulino,Célia Aparecida; Gonçalves,Ivair Donizeti

    2006-01-01

    A prática de exercícios físicos é um hábito importante para manutenção do bem-estar físico e emocional de quem a adota com regularidade, podendo trazer grandes benefícios à saúde. Todavia, dependendo do seu tipo, intensidade, freqüência e duração, os exercícios também podem causar certos prejuízos para o organismo. Como benefício, é descrito o seu papel na função imune específica e não-específica e, nesta última, destaca-se o processo inflamatório. Assim, este trabalho teve como objetivo estu...

  7. Efectos de la suplementación de omega-3 y entrenamiento de intervalos de alta intensidad en el rendimiento físico, presión arterial y composición corporal en individuos sedentarios con sobrepeso

    OpenAIRE

    Peñailillo Escarate, Luis; Mackay Phillips, Karen; Serrano Duarte, Natalia; Canales Espinoza, Pablo; Miranda Herrera, Pamela; Zbinden-Foncea, Hermann

    2016-01-01

    Introducción: el entrenamiento de intervalos de alta intensidad (HIIT) y el consumo de ácidos grasos omega-3 (O3) ha demostrado cada uno por separado aumentar la capacidad aeróbica, el metabolismo oxidativo y la función cardiovascular. Objetivo: examinar el efecto combinado de HIIT más suplementación de O3 en el rendimiento físico, presión arterial y composición corporal en jóvenes sedentarios. Métodos: 28 jóvenes sedentarios con sobrepeso (edad = 22 ± 4 años; IMC = 25,8 ± 2,4 kg·m-2) fueron ...

  8. Efeitos agudos de diferentes intensidades de exercício sobre a ingestão alimentar pós-exercício Acute effects of exercise intensity on pos-exercise food intake in young men

    Directory of Open Access Journals (Sweden)

    Tatiana Acioli Lins

    2011-06-01

    Full Text Available O objetivo do presente estudo foi verificar os efeitos agudos de diferentes intensidades de exercício aerróbio (40 e 80% do VO2pico sobre a ingestão alimentar pós-exercício. Participaram do estudo 18 adultos jovens, eutróficos (22,20 ± 1,72 kg/m² e fisicamente ativos. Todos os sujeitos foram submetidos aleatoriamente a três condições experimentais: controle (sem exercício; EBI, exercício de baixa intensidade (40% doVO2pico e EAI, exercício de alta intensidade (80% do VO2pico. As sessões de exercício foram isocalróricas (350 kcal. Após 120 minutos de recuperação passiva, os voluntários tinham livre acesso a um "buffet" variado de alimentos, a ingestão alimentar foi determinada atravéz da pesagem dos alimentos ingeridos. Os dados alimentares obtidos foram então tabulados e analisados por meio do "software" Nutwin 6.0 (UNIFESP, 2002, para estimativa do consumo energético total (kcal e ingestão dos macronutrientes (carboidratos, proteínas e lipídeos em gramas. Os resultados não demonstram nenhuma diferença na ingesto alimentar entre as condições experimentais analisadas. Dessa forma, podemos concluir que a ingestão alimentar pós-exercício não se mostrou dependente da intensidade do esforóo em curto prazo em indivíduos adultos jovens fisicamente ativos.The aim of this study was to investigate the acute effects of different aerobic exercise intensities (40 and 80% do VO2peak on post-exercise food intake. The sample was composed of eighteen healthy, physically active young men, of normal weight (22.20 ± 1.72 kg/m². Subjects were randomly submitted to three experimental conditions: control (no exercise; low-intensity exercise (LIE -40% of VO2peak and high-intensity exercise (HIE- 80% of VO2peak. Exercise trials were iso-caloric (350 Kcal. After 120 minutes of passive recovery, the volunteers had free access to a variety food buffet, and food intake was determined thru food weight. Data was analyzed by the software

  9. Erosivity under two durations of maximum rain intensities in Pelotas/RS = Erosividade sob duas durações de intensidades máximas da chuva em Pelotas - RS

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    Jacira Porto dos Santos

    2012-04-01

    Full Text Available In the Universal Equation of Soil Loss (USLE, erosivity is the factor related to rain and express its potential to cause soil erosion, being necessary to know its kinetic energy and the maximum intensities of rain in duration of 30 min. Thus, the aim of this study was to verify and quantify the impact of the rain duration, considering 15 and 30 min, on the USLE erosivity factor. To achieve this, 863 rain gauge records were used, duiring the period of 1983 to 1998 in the city of Pelotas, RS, obtained from the Agrometeorological Station - Covenant EMBRAPA/UFPel, INMET (31o51´S; 52o21´O and altitude of 13,2 m. With the records, it was estimated the erosivity values from the maximum intensities of rain during the period evaluated. The average annual values of erosivity was 2551,3 MJ ha-1 h-1 ano-1 and 1406,1 MJ ha-1 h-1 ano-1, for the average intensities of 6,40 mm h-1 and 3,74 mm h-1, in durations of 15 and 30 min, respectively. The results of this study have shown that the percentage of erosive rainfalls in relation to the total precipitation was of 91.0%, and that the erosivity was influenced by the duration of the maximum intensity of rain.= Na Equação Universal de Perdas de Solo (EUPS a erosividade é o fator relacionado à chuva e expressa o seu potencial em provocar a erosão do solo, sendo necessário que se conheça a energia cinética da mesma e as máximas intensidades da chuva na duração de 30 min. Objetivou-se com este trabalho verificar e quantificar o impacto da duração da chuva, considerando 15 e 30 min, sobre o fator erosividade da EUPS. Para tanto foram utilizados 863 registros pluviográficos de chuva, no período de 1983 a 1998 da localidade de Pelotas, RS, obtidos na Estação Agroclimatológica – Convênio EMBRAPA/UFPel, INMET (31o51´S;52o21´O e altitude de 13,2 m. Com os registros foram estimados os valores de erosividade a partir de intensidades máximas de chuva nas durações consideradas. Os valores m

  10. Dinâmica de potássio em sistema de integração lavoura-pecuária em plantio direto sob intensidades de pastejo

    OpenAIRE

    Eric Victor de Oliveira Ferreira

    2009-01-01

    A dinâmica de potássio em sistemas de integração lavoura-pecuária diverge de outros sistemas de manejo, porque são sistemas mais complexos e envolvem, além das práticas relacionadas à cultura de interesse econômico, a introdução do animal no sistema. Assim, objetivou-se, neste trabalho, avaliar a evolução, a ciclagem e o balanço de potássio em um sistema de integração lavoura-pecuária em plantio direto, com diferentes intensidades de pastejo (aveia preta + azevém) de bovinos no inverno e sua ...

  11. Periodicidade e intensidade de oocistos do gênero Isospora Schneider, 1881 eliminados nas fezes de passeriformes oriundos do tráfico de animais silvestres e mantidos em quarentena.

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    Cleide Domingues Coelho

    2016-12-01

    Full Text Available Frequência diurna tem sido observada em espécies de parasitos intestinais, especialmente no gênero Isospora Schneider, 1881 em aves selvagens, que eliminam oocistos nas fezes mais frequentemente no final da tarde. Este estudo teve como objetivo avaliar a periodicidade e a eliminação de oocistos por pássaros mantidos no Centro de Triagem de Animais Silvestres, Seropédica, Rio de Janeiro, Brasil triagem. Amostras de uma defecação foram coletadas de 602 pássaros, no período da manhã entre 9 e 12h e à tarde entre 15 e 17h, de maio a novembro de 2010. As amostras foram diluídas em dicromato de potássio a 2,5% 1: 6 (v/v e incubou-se à temperatura ambiente durante sete dias. De cada amostra foi também determinada a OoPD (número de oocistos por defecação, onde observou –se que as amostras fecais coletadas na parte da manhã tiveram um número menor de amostras positivas (12/2% em comparação com àquelas coletadas no fim da tarde os quais apresentaram um maior número de amostras positivas (136/23%, da mesma forma, que os OoPDs de pássaros das famílias Cardinalidae, Emberizidae e Thraupidae também foram diferentes em intensidade. Ambos os resultados indicaram que a periodicidade e a intensidade de oocistos em passeriformes foram extremamente significativas (p<0,0001, quando eles foram determinados usando amostras coletadas no período da tarde.

  12. Náusea e vômito no pós-operatório: validação da versão em português da escala de intensidade de náuseas e vômitos pós-operatórios

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    Veiga Dalila

    2013-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVO: A Escala de Intensidade de Náuseas e Vômitos Pós-Operatórios (NVPO foi desenvolvida para definir NVPOs clinicamente importantes. O objetivo deste estudo foi traduzir, retraduzir e validar a Escala de Intensidade de NVPO para uso em unidades de recuperação pósanestésica (RPA portuguesas. MÉTODO: A Escala de Intensidade de NVPO foi traduzida e retraduzida de acordo com as diretrizes disponíveis. A equipe de pesquisadores conduziu um estudo prospectivo e observacional de coorte em uma RPA. Durante três semanas, avaliamos as NVPO em 157 pacientes adultos internados após cirurgia. As mensurações foram feitas com o uso da Escala Visual Analógica (EVA nos intervalos de seis e 24 horas durante o período pós-operatório. Avaliamos a confiabilidade e a discordância do observador com o uso do coeficiente de correlação interclasses (CCI e da medida de discordância baseada na informação (MDBI. Comparamos os escores EVA entre os pacientes com NVPO clinicamente significantes (> 50 e não significantes (< 50. RESULTADOS: Trinta e nove pacientes (25% apresentaram NVPO em seis horas e 54 (34% em 24 horas. Trinta e seis pacientes apresentaram náusea em seis horas e 54 em 24 horas. Entre os pacientes com NVPO, os escores de seis pacientes (15% e nove pacientes (27% foram clinicamente significantes na Escala de Intensidade de NVPO em seis e 24 horas, respectivamente. A confiabilidade foi boa tanto para os escores da Escala de Intensidade de NVPO quanto para EVA e a discordância entre observadores foi ligeiramente superior para EVA. A mediana dos escores EVA foi maior nos pacientes com escores clinicamente significantes na Escala de Intensidade de NVPO. CONCLUSÃO: A Escala de Intensidade de NVPO parece ser um instrumento de avaliação e monitoramento preciso e confiável de NVPO em RPA.

  13. Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

    Science.gov (United States)

    Wilczak, Waldemar; Rashed, Semin; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Büscheck, Franziska; Clauditz, Till Sebastian; Grupp, Katharina; Minner, Sarah; Tsourlakis, Maria Christina; Möller-Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Izbicki, Jakob Robert; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till; Lebok, Patrick

    2017-01-01

    DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Comparação de diferentes metodologias para estimativa de curvas intensidade-duração-freqüência para Pelotas - RS Comparison of different methodologies to estimate intensity-duration-frequency curves for Pelotas - RS, Brazil

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    Rita de C. F. Damé

    2008-06-01

    Full Text Available Nos projetos agrícolas de obras hidráulicas, onde não se dispõe de dados observados de vazão, é necessário explorar ao máximo as informações relativas às curvas Intensidade-Duração-Freqüência (IDF. Diante disso, é preciso obter maneira de desenvolver metodologias de estimativas de curvas IDF, em locais que possuam pouco ou nenhum dado pluviográfico. O objetivo do trabalho foi comparar as metodologias de desagregação de precipitações diárias para verificar o ganho de informação em termos de curvas IDF, comparadas àquela obtida a partir de dados observados (histórica. Os métodos utilizados foram: (a Método das Relações (CETESB, 1979; (b BELTRAME et al. (1991; (c ROBAINA & PEITER (1992; (d Modelo Bartlett-Lewis do Pulso Retangular Modificado (DAMÉ, 2001. Utilizou-se de série de dados de precipitação diária de Pelotas - RS, referente ao período de 1982-1998. Para estimar as curvas IDF, a partir dos registros históricos, foram estabelecidas as durações de 15; 30; 60; 360; 720 e 1.440 minutos, e os períodos de retorno de 2; 5 e 10 anos. Os valores de intensidades máximas foram comparados entre si, pelo teste "t" de Student, para os coeficientes linear e angular, e pelo Erro Relativo Médio Quadrático. O método que melhor representou as intensidades máximas de precipitação, nos períodos de retorno de 2 e 10 anos, foi o Método das Relações (CETESB, 1979.Agricultural projects which deal with hydraulic projects and do not possess observed data on outflow need to explore at the most, information about the Intensity-Duration-Frequency (IDF curves. Thus, it is necessary to create ways to develop methodologies that estimate IDF curves for locations that have little or no pluviometric data. The aim of this work was to compare disaggregation methodologies for daily precipitation, to verify the increase in quality information considering the IDF curves, as compared to those originated from observed data

  15. UNA PROPUESTA DE ESCALA DE INTENSIDAD SÍSMICA OBTENIDA DEL CÓDICE NÁHUATL TELLERIANO REMENSIS (A Proposal of a Seismic Intensity Scale Obtained from the Nahuatl Codex Telleriano Remensis

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    Víctor Hugo Garduño-Monroy

    2016-09-01

    Full Text Available Antes de la llegada de los españoles a América, entre los siglos XIV y XVI, los hechos y acontecimientos de la vida diaria fueron registrados por los pueblos nativos con símbolos en los códices. Muchos de esos códices fueron destruidos por los españoles al ser considerados una forma de idolatría. Sin embargo, en México y en el extranjero existen aún varios códices que fueron dibujados por los tlacuilos, personas con conocimientos en diferentes disciplinas como los procesos naturales, la biodiversidad, las guerras y los problemas sociales y religiosos. Uno de ellos, con una gran cantidad de información, es el códice conocido como Telleriano Remensis. Este contiene representaciones de diversos procesos naturales como el clima, las erupciones volcánicas y los sismos, así como de procesos de tipo social, político y religioso, entre otros. Un análisis geocientífico cuidadoso de este códice, consultando la literatura relacionada, ha permitido encontrar evidencias de doce eventos sísmicos que quedaron registrados en el espacio y en el tiempo. Los sismos se representaron con dos símbolos combinados correspondientes a la tierra y al movimiento. Por separado, ninguno de estos dos símbolos está relacionado con los sismos, si bien juntos sí representan un evento sísmico cuyos efectos podrían reflejar una intensidad o grado V en la escala de intensidad sísmica ambiental conocida como ESI (Environmental Seismic Intensity 2007. Pero también se plantea la posibilidad de que el pueblo náhuatl hubiera conseguido una escala de intensidades de sismos antes de las escalas modernas. ENGLISH: Before the arrival of the Spaniards in America, between the fourteenth and sixteenth centuries A.D., events and daily life were described through symbols in documents called codices. During the conquest, the Spaniards destroyed many of the codices because they were viewed as idolatrous. In Mexico and overseas there exist a number of codex that were

  16. Pruebas de velocidad aeróbica máxima con jóvenes futbolistas. Control y programación de la intensidad de los entrenamientos

    Directory of Open Access Journals (Sweden)

    Philippe Campillo

    2013-09-01

    Full Text Available Se ha realizado un estudio comparativo para analizar la importancia del entrenamiento intermitente, más precisamente la utilización de la velocidad aeróbica máxima (VAM intermitente en la práctica del fútbol. Se ha evaluado la VAM continua con la prueba VAMEVAL (evaluación de la velocidad máxima aeróbica y la VAM intermitente con la prueba 45-15 con ayuda de 21 jóvenes futbolistas. Teniendo en cuenta los resultados se han formado dos grupos homogéneos que realizan un ciclo de siete semanas de entrenamiento específico con el objetivo de desarrollar la PMA. La intensidad del entrenamiento del grupo 1 tiene como referencia el nivel máximo de la VAM continua y el de la VAM intermitente para el grupo 2. Para el conjunto de los jugadores, y para cada grupo, se observa una diferencia significativa inicial (p < 0,001 entre la VAM intermitente (16,02 ± 1,21 km/h y la VAM continua (14,12 ± 1,06 km/h. Finalizado el ciclo se mantienen las mismas diferencias entre las VAM intermitentes y continuas. Sin embargo, para el grupo 1 no hay diferencias significativas entre las dos pruebas 45-15 inicial y final; por el contrario, para el grupo 2 existe una clara diferencia (p < 0,01 entre las dos pruebas intermitentes (15,86 ± 1,50 km/h / 17,0 ± 0,97 km/h. Aunque los dos grupos han mejorado su VAM continua se observa un aumento superior de la velocidad en el grupo 2. Es muy importante tener en cuenta los resultados de las pruebas de VAM continua y sobre todo intermitente para programar y adaptar con precisión la intensidad de los entrenamientos, puesto que existen diferencias que no siempre se valoran.

  17. Metodología de inspección higrotérmica para la determinación de un factor intensidad de evaporación en edificios históricos

    Directory of Open Access Journals (Sweden)

    García-Morales, S.

    2012-12-01

    Full Text Available This paper presents what we call “Hygrothermal Inspection”. It consists in a first step in the way to quantify real water flux across constructions. Theoretical aspects are related to the fact that a wall, affected by rising damp, suctions water that will then evaporate from the surface, towards the internal and external air. This flux increases the humidity ratio of the internal air, mainly in the thin air coat in contact with the wall or pavement. This fact allows us to measure the relative evaporation intensity by means of a thermohygrometer and to map evaporation zones. Measuring method and results analysis are shown. Different evaporation levels from the walls or pavements are established by means of calculating what we call “Evaporation Intensity Factor (Fi”. Some results from several years work on Heritage Buildings are presented.

    En este artículo se presenta lo que hemos denominado “inspección higrotérmica”, que consiste en un primer paso en el diagnóstico de flujos de agua a través de los elementos constructivos. El fundamento se basa en que un muro afectado por un problema de capilaridad está sometido a una succión con un determinado caudal y esta agua evaporará en la superficie del muro o del suelo, incrementando el contenido en humedad (W de la lámina de aire en contacto con el paramento. Se describe el método de inspección y de análisis de los resultados. Se utiliza un termohigrómetro de lectura directa, y las lecturas se hacen siguiendo un protocolo que permite el análisis de variables. Los niveles de intensidad de los focos se establecen a partir de lo que hemos denominado “Factor de Intensidad de evaporación (Fi”. Se ilustra el método con ejemplos de estudios en varios edificios históricos.

  18. Avaliação da intensidade de tráfego e carga de um forwarder sobre a compactação de um Latossolo Vermelho-Amarelo

    Directory of Open Access Journals (Sweden)

    Arystides Resende Silva

    2011-06-01

    Full Text Available A operação de baldeio florestal está relacionada ao uso de máquinas, as quais trafegam numa mesma linha várias vezes ou aleatoriamente, o que pode causar compactação do solo, alterando o meio onde o sistema radicular se desenvolve e reduzindo a produtividade. Além do número de passadas, a carga de madeira transportada pode afetar a compactação do solo quando as pressões aplicadas pelas máquinas excederem a capacidade de suporte de carga desse solo. Os objetivos deste estudo foram: a propor modelo de capacidade de suporte de carga para Latossolo Vermelho-Amarelo no Município de Santa Maria de Itabira, MG, em razão da pressão de pré-consolidação e da umidade; e b determinar, com o uso deste modelo, o efeito da intensidade de tráfego e da carga de Forwarder sobre a estrutura do solo. Para a obtenção dos modelos de capacidade de suporte de carga, 20 amostras indeformadas de solo foram coletadas nas profundidades de 0-3 e 10-13 cm no local onde não houve tráfego. Foram também coletadas 10 amostras indeformadas em cada profundidade, onde o Forwarder trafegou duas, quatro e oito vezes e no local onde o Forwarder trafegou quatro vezes com 1/3 (3 m³, 2/3 (6 m³ e 3/3 (9 m³ de sua carga. As amostras indeformadas foram utilizadas nos ensaios de compressão uniaxial. Determinaram-se também a textura, o teor de matéria orgânica e a densidade de partículas e densidade dos solos. O modelo de capacidade de suporte de carga do LVA é expresso pela equação s p = 10(2,71 - 1,36 U. Todas as intensidades de tráfego causaram compactação no solo nas duas profundidades estudadas, sendo quatro passadas as que causaram maior compactação do solo, e, à medida que a carga do Forwarder aumentou, a compactação do solo também aumentou nas duas profundidades.

  19. Benefícios sobre a intensidade da dor, qualidade de vida e incapacidade de mulheres com dismenorreia submetidas a exercícios gerais versus método de Pilates: estudo-piloto

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    Bruna Cristina Taques Peruzzo

    2015-05-01

    Full Text Available Introdução: Dismenorreia primária é um distúrbio ginecológico caracterizado por dor relacionada à menstruação, sem causa patológica. Objetivo: Verificar e comparar a intensidade da dor, a incapacidade e a qualidade de vida em mulheres com dismenorreia primária submetidas a exercícios gerais versus Pilates. Métodos: Participaram do estudo 14 mulheres aleatorizadas em grupo de exercícios gerais (19,14±1 anos e de Pilates (20,57±1,8 anos. Ambos os grupos realizaram duas sessões por semana durante 50 minutos, no período de dois meses e meio, totalizando 20 sessões. O grupo de exercícios gerais realizou alongamentos e fortalecimentos dos músculos abdominais, lombares e assoalho pélvico. O grupo de Pilates, por sua vez, praticou exercícios para conscientização de pelve, com contrações do transverso e reto do abdômen, glúteos, períneo e eretores da coluna. As participantes responderam aos questionários de índice de incapacitação de Oswestry para dor lombar, Escala Visual Analógica (EVA, para medir a intensidade da dor e ao Questionário de Qualidade de Vida SF-36, antes e após a intervenção. Os dados foram considerados estatisticamente significantes quando p<0,05. Resultados: Foram encontradas melhoras significativas após a intervenção em ambos os grupos, em todas as avaliações. Em relação à diferença entre os grupos, na avaliação sobre a incapacitação para dor lombar, o  grupo de exercícios gerais teve melhor resultado (p<0,003 do que o grupo de Pilates, assim como no domínio de estado da saúde (0,03 do Questionário SF-36. Conclusão: A prática de exercícios físicos gerais e Pilates por mulheres com dismenorreia podem reduzir a dor e a incapacidade e melhorar a qualidade de vida.

  20. Treinamento de natação na intensidade do limiar anaeróbio melhora a aptidão funcional de ratos idosos Swimming training at anaerobic threshold intensity improves the functional fitness of older rats

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    Verusca Najara de Carvalho Cunha

    2008-12-01

    Full Text Available Os efeitos do treinamento aeróbio em intensidade relativa ao limiar de lactato (LL foram analisados em 15 ratos idosos (~448 dias de vida. Os grupos de animais treinados (n=9 e controle (n=6 foram submetidos a um teste antes e após quatro semanas de treinamento. O teste incremental consistiu de uma carga inicial de 1% do peso corporal e incrementos de 1% a cada três minutos, com mensurações de lactato sanguíneo para identificação do LL por inspeção visual do ponto de inflexão da curva. O programa de treinamento consistiu de 30 minutos de natação/dia, cinco dias/semana, com sobrecarga de 5% do peso corporal (PC, ou controle sem exercício. Foi observado aumento significativo na intensidade do LL após o treinamento (pré = 4,5 ± 1,1 vs. Pós = 5.4 ± 0.9% PC. A carga máxima atingida ao final do teste incremental aumentou significativamente de 39,7 ± 7,5g no pré para 48,4 ± 10,5g no pós treinamento, sem mudanças para o grupo controle (44,7 ± 8 vs. 45,3 ± 9,3g. O peso corporal do grupo treinado não apresentou diferença como resultado de quatro semanas de natação em intensidade correspondente ao LL (641,0 ±62,0 para 636,0 ± 72.7g; p>0.05. Por outro lado, o grupo não treinado aumentou significativamente o PC de 614,0 ± 8,0 para 643,0 ± 74,1g. A carga máxima atingida expressa tanto em valores absolutos como relativos (%PC aumentou significativamente após o treinamento. Conclui-se que quatro semanas de treinamento de natação em intensidade correspondente ao limiar de lactato resultou em uma melhora da aptidão aeróbia e na manutenção do peso corporal em ratos idosos.The effects of aerobic training at the lactate threshold (LT intensity were analyzed in fifteen older rats (~448 days old. Both the trained (n = 9 and control (n = 6 groups were submitted to an incremental exercise test before and after four weeks of training. The incremental exercise test consisted of an initial load of 1% BM and 1% increments at each

  1. Influência dos exercícios físicos de baixa e alta intensidade sobre o limiar de hipernocicepção e outros parâmetros em ratos Influencia de los ejercicios físicos de baja y alta intensidad sobre el límite de hipernocicepción y otros parámetros en ratones Influence of low and high intensity physical exercise on hypernociception threshold and other parameters of rats

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    Ademir da Costa Lana

    2006-10-01

    Full Text Available A prática de exercícios físicos é um hábito importante para manutenção do bem-estar físico e emocional de quem a adota com regularidade, podendo trazer grandes benefícios à saúde. Todavia, dependendo do seu tipo, intensidade, freqüência e duração, os exercícios também podem causar certos prejuízos para o organismo. Como benefício, é descrito o seu papel na função imune específica e não-específica e, nesta última, destaca-se o processo inflamatório. Assim, este trabalho teve como objetivo estudar os efeitos dos exercícios físicos de baixa e alta intensidade sobre a hipernocicepção, além de avaliar a massa corporal e o peso relativo de alguns órgãos de ratos. Para isso, foram utilizados ratos machos, adultos, da linhagem Wistar, os quais foram submetidos (grupo treinado ou não (grupo não treinado a exercícios em esteira ergométrica. A inflamação aguda foi induzida pela injeção de carragenina-0,5% no coxim da pata posterior esquerda dos ratos e a nocicepção foi mensurada por meio do teste plantar antes e após 1, 2, 3, 4, 6, 8 e 24 horas. Ao final das avaliações os ratos foram submetidos a anestesia profunda, até a eutanásia, para coleta e pesagem das glândulas adrenais, coração, baço e rins e posterior estudo anatomopatológico destes tecidos. A análise estatística dos resultados mostrou aumento significante (P La práctica de ejercicios físicos es un hábito importante para la manutención del bienestar físico y emocional de quien la adopta con regularidad, pudiendo traer grandes beneficios a la salud. A pesar de esto, dependiendo de su tipo, intensidad, frecuencia y duración, los ejercicios también pueden causar ciertos perjuicios al organismo. Como beneficio, se describe su papel en la función inmune específica y no específica y, en esta última, se destaca el proceso inflamatorio. Así, este trabajo ha tenido como objetivo estudiar los efectos de los ejercicios físicos de baja y

  2. Measurement of soil aggregate stability using low intensity ultrasonic vibration Medición de la estabilidad de agregados de suelo utilizando vibración ultrasónica de baja intensidad Medição da estabilidade dos agregados do solo por vibração ultrasónica de baixa intensidade

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    Herwig Mayer

    2011-11-01

    ía aplicada por el equipo de ultrasonidos para el análisis de variaciones en la estabilidad de los agregados del suelo con respecto a diferentes tratamientos de laboreo. La combinación de los métodos de análisis de estabilidad de agregados, por tamizado en condiciones de humedad (SAS y por dispersión ultrasónica a niveles bajos de energía, permite un análisis más preciso de la estabilidad de los agregados del suelo.

    Determinou-se a influência da lavoura na estabilidade dos agregados do solo (soil aggregate stability –SAS com recurso à dispersão ultrasónica. Os ensaios realizados foram executados com um equipamento de dispersão electrónica desenvolvido na nossa Universidade. Este equipamento permite a aplicação amplitudes de baixa intensidade, de 0,5 µm, 2 µm e 5 µm. A potência ultrasónica determinada por um método de balanço de energia foi de 0,7 W, 8,9 W e 22,3 W para cada amplitude ensaiada. Colheram-se amostras de agregados de 2 000 a 250 µm, num solo do tipo Chernozem franco limoso degradado, num Cambisol franco argiloso e num Cambisol franco arenoso a Este da Áustria, submetidos a diferentes tipos de lavoura: lavoura convencional (CT – conventional tillage, lavoura com eliminação mecânica de infestantes e sem lavoura (NT – no tillage, com sementeira intercalada no Inverno. A medição da estabilidade dos agregados do solo de acordo com a norma DIN (Deutsches Institut für Normung permitiu concluir que a estabilidade diminuiu pela seguinte ordem: Cambisol franco argiloso> Cambisol franco arenoso> Chernozem franco limoso. A influência do tipo de lavoura observou-se para o segundo e terceiro tipo de solos mencionados. A dispersão ultrasónica por amplitudes de baixa vibração apresentou uma estabilidade mais alta para os solos do tipo Cambisol. Observou-se uma influência significativa do tipo de lavoura na estabilidade dos agregados do solo (entre 1 e 1,7 J ml-1 no Cambisol franco argiloso e

  3. Ecocardiografia de equinos Puro Sangue Árabe após exercício de enduro de diferentes intensidades Echocardiography in Arabian horses after endurance exercise of different intensities

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    Camila Alfaro de Oliveira Bello

    2011-01-01

    Full Text Available A ecocardiografia é um método não invasivo e adequado para a avaliação das alterações cardíacas em equinos, identificando assim aqueles animais que apresentaram melhor adaptação e condicionamento ao exercício a que foram submetidos. O objetivo deste estudo foi verificar por meio de exames ecocardiográficos em modo-M e bidimensional os índices funcionais cardíacos de 15 equinos Puro Sangue Árabe, sendo nove machos e seis fêmeas, com idade variando de seis a 12 anos, submetidos a diferentes intensidades de exercício prolongado de enduro. Para tanto, foram divididos em três grupos, sendo que quatro animais percorreram 30km (GI, seis animais percorreram 90km (GII e cinco animais percorreram 120km (GIII. As avaliações ocorreram antes do início de cada prova, sendo considerado o momento zero (M0 e 30 minutos após percorrerem o último anel da correspondente prova, caracterizando o momento final (Mf. Diante do tratamento estatístico, não se verificaram diferenças significantes entre os índices obtidos no M0 e Mf do GI. De outra forma, no GII para VS, FC, VEs e VEd, assim como no GIII para VS, FC, VEs, VEd e SIVd, observou-se diferença estatística. Portanto, em equinos de enduro a ecocardiografia revelou que o exercício físico permitiu o estabelecimento de índices funcionais cardíacos próprios, de acordo com a intensidade do exercício imposto.Echocardiography is a noninvasive and accurate evaluation of cardiac abnormalities in horses, thereby determining those animals that show better adaptation to exercise and conditioning to which they were submitted. The aim of this study was to verify by echocardiographic M-mode and two-dimensional cardiac functional indices of 15 purebred Arabian horses, nine males and six females, ranging in age from 6 to 12 years, subjected to different intensities prolonged endurance exercise. Thus, both groups were divided into three, in which four animals traveled 30km (GI, six animals

  4. Fenologia da goiabeira 'Paluma' sob diferentes sistemas de cultivos, épocas e intensidades de poda de frutificação Phenology of 'Paluma' guava trees under different cultivation systems, times and intensities of fruit pruning

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    Luiz Augusto Lopes Serrano

    2008-01-01

    Full Text Available O trabalho teve como objetivo avaliar os efeitos de diferentes épocas e intensidades de poda de frutificação sobre a fenologia da goiabeira 'Paluma', em dois sistemas de cultivo, em Pedro Canário (ES. O delineamento experimental foi o de blocos ao acaso, em esquema de parcelas sub-subdivididas. As parcelas foram os sistemas de cultivo irrigado e sequeiro; as subparcelas foram as épocas de poda (10/11/2005, 9/12/2005, 13/1/2006 e 10/2/2006; e as sub-subparcelas foram as intensidades de poda (curta, média e longa. O ciclo da goiabeira 'Paluma', entre a poda até o início da colheita dos frutos, variou de 182 (poda em novembro e dezembro a 203 dias (poda em fevereiro. A queda fisiológica dos frutos ocorreu até os 56 dias após o final do florescimento. A irrigação e a poda longa proporcionaram maior brotação e estabelecimento dos ramos. As plantas submetidas à poda longa em fevereiro produziram maior número de frutos por ramo. Independentemente da época de poda, as plantas submetidas à poda curta apresentaram menor número de frutos por ramo e menor índice de pegamento de frutos. A irrigação e as podas realizadas em dezembro e janeiro favoreceram a produção de frutos maiores.The objective of this work was to evaluate the effects of different fruit pruning times and intensities on the phenology of 'Paluma' guava trees in two cultivation systems, in Pedro Canário, Espírito Santo State, Brazil. The experimental design was a randomized complete block in a split split plots scheme. The main plots were the cultivation systems (with and without irrigation, the split plots were the pruning times (November 10, 2005; December 9, 2005; January 13, 2006 and February 10, 2006, and the split split plots were the pruning intensities (heavy, medium and light. The period between pruning and the beginning of fruit ripening was between 182 (pruning in November and December to 203 days (pruning in February. Fruit physiologic fall continued for

  5. Experimental model for low level laser therapy on ischemic random skin flap in rats Modelo experimental para laserterapia de baixa intensidade em retalho cutâneo randômico isquêmico em ratos

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    Rodrigo Paschoal Prado

    2006-08-01

    Full Text Available PURPOSE: To develop an experimental model to be used in the study of low level Laser therapy on viability of random skin flap in rats. METHODS: The sample was 24 Wistar-EPM rats. The random skin flap measured 10 x 4 cm and a plastic sheet was interposed between the flap and donor site. Group 1 (control underwent sham irradiation with diode laser (830 nm. Group 2 was submitted to laser irradiation with diode laser (830 nm. The animals were submitted to Laser therapy with 36 J/cm² energy density (72 seconds immediately after the surgery and on the four subsequent days. The probe was usually held in contact with the skin flap surface on a point at 2.5 cm cranial from the flap base. On the seventh postoperative day, the percentage of necrotic area was measured and calculated. RESULTS: Group 1 reached an average necrotic area of 48.86%, Group 2 - 23.14%. After the statistic analysis, compared with the control group, Group 2 showed a statistically significant increase in survival area (pOBJETIVO: Propor o desenvolvimento de um modelo experimental para verificar o efeito da laserterapia de baixa intensidade na viabilidade do retalho cutâneo randômico em ratos. MÉTODOS: A amostra constituiu-se de 24 ratos, da linhagem Wistar-EPM. O retalho cutâneo randômico foi realizado com dimensões de 10x4 cm e uma barreira plástica foi interposta entre o mesmo e o leito doador. O Grupo 1 (controle, foi submetido a uma simulação de tratamento com a irradiação laser de diodo (830 nm. O Grupo 2 foi submetido à irradiação laser de diodo (830 nm. Os animais foram submetidos a terapia a laser com densidade de energia de 36 J/cm2 (72 segundos imediatamente após a operação e nos outros quatros dias subseqüentes. A caneta do laser foi posicionada a 90 graus em contato com o retalho cutâneo em um ponto a 2,5 cm da base cranial do retalho. No sétimo dia pós-operatório foram calculadas as porcentagens da área de necrose. RESULTADOS: O Grupo 1 apresentou

  6. Caracterização de perfilhos de capim-braquiária em locais com três intensidades de pastejo Characterization of signalgrass tiller in sites of same pasture with three grazing intensities

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    Guilherme Portes Silva

    2010-12-01

    Full Text Available Objetivou-se caracterizar a densidade populacional e as características estruturais de perfilhos vegetativos e reprodutivos da Brachiaria decumbens cv. Basilisk manejada sob lotação contínua com bovinos. Os tratamentos foram três locais do mesmo pasto, subpastejado, com pastejo adequado e sobrepastejado. O delineamento foi em blocos casualizados com três repetições. O número de perfilhos basais foi menor nos locais com subpastejo, e maior no local com pastejo adequado. O número de perfilho aéreo foi superior no local com pastejo adequado. No local com superpastejo, o número de perfilho reprodutivo foi inferior, enquanto que os números de perfilhos vegetativos e mortos foram superiores em relação ao local com pastejo adequado. O local subpastejado possuiu perfilhos vegetativos e reprodutivos mais pesados do que os demais locais avaliados. Em locais do mesmo pasto com distintas intensidades de pastejo, a relação entre número e peso de perfilho vegetativo foi negativa, enquanto que a mesma relação para o perfilho reprodutivo foi positiva. Em comparação aos outros locais, no local com superpastejo, os perfilhos possuíram menores comprimentos do pseudocolmo e da lâmina foliar, inferior número de folha morta, maior número de folha pastejada e menor massa de colmo vivo e lâmina foliar viva. Os perfilhos de B. decumbens têm seu número e suas características modificadas em função da intensidade de pastejo a que são submetidos em um mesmo pasto.It were characterized the population density and structural characteristics of vegetative and reproductive tillers of Brachiaria decumbens cv. Basilisk managed under continuous stocking with cattle. The treatments were three sites of the same pasture, undergrazed, with proper grazing and overgrazed. A randomized block design with three replications was used. The number of basal tillers was lower in undergrazed and overgrazed sites, and higher in site with appropriate grazing. The

  7. Resposta da cinética de consumo de oxigênio e da eficiência mecânica delta de homens e mulheres em diferentes intensidades de esforço

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    Lucenildo S Cerqueira

    2011-08-01

    Full Text Available INTRODUÇÃO:A eficiência mecânica delta (EMΔ e a cinética do consumo de oxigênio (K2 são influenciadas por parâmetros metabólicos musculares e pelo transporte de 2. O objetivo do presente estudo foi determinar a diferença na K2 e na EMΔ em três intensidades de esforço nos dois gêneros. MÉTODOS: 56 sujeitos (26 mulheres foram submetidos ao protocolo de esforço escalonado, contínuo e máximo (GxT no cicloergômetro mecânico para determinação da potência aeróbia máxima (2máx, carga máxima (Wmax, limiar anaeróbio (AT e ponto de compensação respiratória (PCR. O AT foi determinado através dos métodos V-slope e E E / 2; o PCR através da relação 2 versus E ; ambos por dois avaliadores. A EMΔ e a K 2 foram consideradas como a inclinação entre 2 versus Watts e 2 versus tempo (s, respectivamente, do começo do teste até o AT (S1, do AT ao PCR (S2 e do PCR ao 2máx (S3, determinada por análise de regressão linear. RESULTADOS: Para a EMΔ, diferenças significativas foram observadas entre S1 versus S2 (p = 0,001, S1 versus S3 (p = 0,001 e S2 versus S3 (p = 0,006. Não foi observada diferença (p = 0,060 ou interação significativa (p = 0,062 entre homens versus mulheres. Para a K 2 diferenças significativas foram observadas entre S1 versus S3 (p = 0,001 e S2 versus S3 (p = 0,001 em ambos gêneros. Diferenças (p = 0,001 e interação significativa (p = 0,006 foram observadas entre homens versus mulheres, no último parâmetro. CONCLUSÕES: A EMΔ decresce com o incremento da intensidade de trabalho, porém, não há diferenças quando se compara homens e mulheres. Por outro lado, as mulheres apresentam K 2 mais rápida do que os homens.

  8. Aplicación de la metodología Molecular de Orbitales de Defecto Cuántico (MQDO) al cálculo de intensidades vibrónicas y vidas medias de niveles vibracionales

    Science.gov (United States)

    María Velasco Sanz, Ana

    Desde que se formuló, en 1996, la metodología Molecular de Orbitales de Defecto Cuántico (MQDO) [1], se han obtenido datos de calidad relativos a intensidades de bandas electrónicas que implican estados Rydberg para una gran variedad de sistemas moleculares [2]. Animados por los buenos resultados obtenidos, recientemente hemos abordado el estudio de transiciones vibrónicas, es decir aquellas que ocurren entre estados vibracionales que pertenecen a distintos estados Rydberg electrónicos. Como prototipo adecuado para nuestros propósitos hemos elegido la molécula de NO, importante en la química de la atmósfera, y para la cual existen en la bibliografía datos experimentales de calidad suficiente para contrastar la validez de nuestros resultados. En concreto, hemos calculado las fuerzas de oscilador y coeficientes de Einstein para transiciones electrónicas y vibrónicas de las principales bandas del NO, al igual que vidas medias radiativas de niveles vibracionales de dicha molécula. Las propiedades estudiadas son esenciales para la comprensión de los aspectos teóricos de los procesos físicos básicos relativos a la dispersión electrónica en moléculas heteronucleares con capas abiertas. Además, valores fiables de probabilidades de transición moleculares tienen importantes aplicaciones en Astrofísica, en la modelización de procesos fotodinámicos moleculares, etc., al igual que para evaluar más profundamente la validez de nuestra metodología teórica.

  9. Teores de carboidratos em pessegueiros submetidos a diferentes intensidades de poda verde em clima tropical Levels of carbohydrates in peaches submitted to different intensity of green pruning in tropical climate

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    Marcelo Rehder da Cunha Borba

    2005-04-01

    Full Text Available Com o objetivo de verificar a partição de assimilados entre a copa e raízes de pessegueiro, duas intensidades de poda verde, após a colheita dos frutos, foram efetuadas em pessegueiros 'Ouromel-2', na região de Piracicaba-SP: poda leve e poda de renovação (poda drástica. Os teores de carboidratos nas raízes e parte aérea foram determinados em vários estágios fenológicos da planta ao longo do ciclo. Verificou-se que existe uma fase de consumo de carboidratos, que vai deste a poda de dormência (poda seca até a maturação dos frutos e uma fase de acúmulo, que vai desde a maturação dos frutos até a queda das folhas. Plantas que sofreram poda leve apresentaram, de maneira geral, maiores teores de carboidratos ao longo do ciclo do que plantas que sofreram poda de renovação, apresentando, assim, maior potencial de produção.With the objective to verify the photosynthate partitioning in roots and canopy of peache trees, two intensity of green pruning: light pruning and renovation pruning (heavy pruning. After fruit harvest were evaluated in 'Ouromel-2' peach in Piracicaba-SP. The carbohydrates levels of roots and canopy were evaluated in several phonological stages of the tree during the crop cycle. It was verified that there is a phase of consumption of carbohydrates, from dormant pruning to the ripening of fruits, and a phase of accumulation of carbohydrates, from the ripening of fruits to the falling of the leaves. In general, plants lightly pruned showed higher levels of carbohydrates during the crop cycle if compared to heavily pruned plants, showing then, higher potential of production.

  10. Eficiencia térmica en soldadura de la aleación AA6061-T6 por arco eléctrico indirecto modificado y digitalización de señales de intensidad de corriente

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    Ambriz, R. R.

    2009-08-01

    Full Text Available The results of the thermal efficiency on welding by modified indirect electric arc technique (MIEA [1] of the 6061- T6 aluminum alloy are presented. These values are in a range of 90 to 94 %, which depend of the preheating employed. Thermal efficiency was obtained by means of a balance energy which considers the heat input, the amount of melted mass of the welding profiles, and welding parameters during the joining, especially of the arc current data acquisition. Also, some dimensionless parameters were employed in order to determine the approximation grade of the melted pool, the heat affected zone (HAZ, and their corresponding values with the experimental results.

    En el presente trabajo de investigación, se presentan los resultados de la eficiencia térmica en la soldadura de una aleación de aluminio 6061-T6 por medio de la técnica de arco eléctrico indirecto modificado (AEIM [1]. Los valores se encuentran en un rango de 90-94 % dependiendo de la temperatura de precalentamiento y fueron obtenidos a través de un balance térmico que considera a la energía aportada por el arco eléctrico, la cantidad de masa fundida de los perfiles de soldadura obtenidos y las variables operativas en el proceso de unión, poniendo especial atención en los datos recogidos en el proceso de digitalización para la intensidad de corriente del arco eléctrico. También se em - plearon algunos parámetros adimensionales para determinar el grado de aproximación de la porción del baño fundido, el ancho de la zona afectada por el calor (ZAC y sus correspondientes aproximaciones con los resultados experimentales.

  11. Avaliação da eficácia do laser de baixa intensidade no tratamento das disfunções têmporo-mandibular: estudo clínico randomizado

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    Maria Helena Chaves de Vasconcelos Catão

    2013-12-01

    Full Text Available OBEJTIVO: avaliar a eficácia do laser de baixa intensidade no tratamento da dor em pacientes com desordens temporomandibulares. MÉTODO:consistiu de um ensaio clínico randomizado divididos em dois grupos: Grupo 1: laser AsGaAl, Grupo 2: laser InGaAlP, do qual participaram 20 pacientes entre 19 e 35 anos de idade, com diagnóstico de sinais e sintomas de DTM. Os pacientes tinham a amplitude de movimento para abertura máxima da boca e lateralidade registados no início e no final do tratamento a laser. O Laser foi aplicado em quatro pontos pré-auriculares, totalizando 12 sessões três vezes por semana, durante um mês. Dor dos pacientes foi registrado com base na utilização da escala analógica visual (EAV e também por exame físico dos pontos álgicos. RESULTADOS: observou-se redução significante (p<0,028 do nível de dor em ambos os grupos, porém no G1 a significância foi maior. A evolução do limiar de sensibilidade muscular evidenciou diferença estatisticamente significante (p<0,05 para G1 e G2. A laserterapia no Grupo 1 melhorou a abertura bucal em média de 4,643 mm, enquanto no Grupo 2, a média foi de 3,71 mm por paciente. CONCLUSÃO: houve eficácia em ambos os lasers no controle da dor e abertura bucal dos pacientes.

  12. Impacto da nutrição enteral na toxicidade aguda e na continuidade do tratamento dos pacientes com tumores de cabeça e pescoço submetidos a radioterapia com intensidade modulada

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    Liêvin Matos Rebouças

    2011-02-01

    Full Text Available OBJETIVO: Analisar o impacto da terapia nutricional enteral na manutenção do peso corpóreo e na necessidade de replanejamento e/ou interrupção da radioterapia em pacientes com câncer de cabeça e pescoço submetidos a radioterapia de intensidade modulada (IMRT. MATERIAIS E MÉTODOS: Foram analisados, retrospectivamente, os pacientes submetidos a IMRT entre janeiro de 2005 e outubro de 2008, com a inclusão de 83 casos. RESULTADOS: A idade mediana foi de 58,6 anos. Em apenas em cinco pacientes (6% houve interrupção do tratamento, que variou de 4 a 18 dias, e em 19 casos (23% houve necessidade de replanejamento. A terapia nutricional enteral foi instituída antes do início da radioterapia em 16 pacientes (19%. Perda de peso > 5% ocorreu em 58 casos (70%, sendo mais prevalente no grupo de pacientes em que a terapia nutricional enteral não foi instituída pré-radioterapia. Na comparação entre os grupos não houve diferença significativa na realização de replanejamento (25% versus 21%; p = 0,741 ou na ocorrência e duração da interrupção da radioterapia. CONCLUSÃO: A terapia nutricional enteral tem um claro ganho na manutenção do peso corporal, porém, não houve um benefício na realização da gastrostomia percutânea endoscópica ou da sonda nasoenteral em relação à interrupção e ao replanejamento da radioterapia.

  13. Radioterapia de intensidade modulada (IMRT para pacientes do SUS: análise de 508 tratamentos em dois anos de instalação da técnica

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    Harley Francisco de Oliveira

    2014-12-01

    Full Text Available Objetivo: A oferta de radioterapia de alta tecnologia para população atendida pelo Sistema Único de Saúde (SUS é limitada, por não pertencer ao rol de procedimentos e, muitas vezes, pela capacidade instalada frente à demanda e dificuldade de retenção de recursos humanos especializados. Dessa forma, o acesso à radioterapia de intensidade modulada (IMRT é restrito a poucos serviços no Brasil. Pretendemos apresentar as características dos primeiros 508 tratamentos de IMRT durante os primeiros anos de instalação da técnica em um hospital universitário. Materiais e Métodos: Foram analisados 508 tratamentos de IMRT, de maio de 2011 a setembro de 2013, que completaram a radioterapia. A técnica empregada foi multilâminas estático. Resultados: De um total de 4.233 pacientes tratados no período, 12,5% realizaram IMRT. As principais indicações foram para crânio, cabeça e pescoço, e próstata. Aproximadamente 30% das radioterapias de crânio e 50% das de próstata foram por IMRT. A toxicidade total foi 4%. Conclusão: Em razão das restrições de acesso à radioterapia e da não cobertura deste procedimento, as indicações de IMRT para pacientes do SUS devem ser apoiadas nos protocolos clínicos das instituições em acordo com sua realidade, com especial atenção à redução da toxicidade.

  14. Diferencias relacionadas con la edad en las necesidades de apoyo: análisis de la versión española de la Escala de Intensidad de Apoyos para Niños y Adolescentes

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    Miguel A. Verdugo

    2016-01-01

    Full Text Available Antecedentes : El interés en las necesidades de apoyo de las personas con discapacidad intelectual debe centrarse en la evaluación del patrón e intensidad de los apoyos reque - ridos para realizar las actividades diarias. Cuando se evalúan estas necesidades en niños, se debe considerar además la influencia de la edad. Método : Se evaluaron 450 personas con discapacidad intelectual (5-16 años mediante la versión española de la SIS-C. La invariancia de medida y las diferencias latentes fueron analizadas relacionando la mues - tra española con la muestra normativa de la versión en inglés. Los modelos desarrollados para la creación de baremos se utilizaron para estudiar las equivalencias de medida en los distintos grupos de edad y las diferencias latentes de sus medias, varianzas y desvia - ciones típicas. Resultados : Los ítems de la versión española de la SIS-C son fiables para medir las necesidades de apoyo en personas de entre 5 y 16 años. A nivel latente, los datos mostraron diferencias en las medias de las puntuaciones de diferentes grupos de edad. Conclusiones : Pueden utilizarse los mismos ítems para medir las necesidades de apoyo de niños y adolescentes, pero debe considerarse la influencia de la edad tanto en la creación de baremos como en la planificación de apoyos.

  15. Intensidad emocional en la clase de educación física en función de la victoria: juegos de cooperación-oposición

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    María Fuensanta Caballero García

    2016-01-01

    Full Text Available Las emociones determinan constantemente el comportamiento humano, por lo que éstas no pueden desvincularse del ámbito educativo, siendo la educación emocional necesaria para el desarrollo integral de los alumnos. El área de Educación Física, generadora de situaciones motrices lúdicas, ofrece una inigualable posibilidad para crear vivencias emocionales mediante el uso del juego motor. De este modo, aparece un gran interés pedagógico por conocer las características específicas de dichas emociones. Los objetivos del presente artículo fueron analizar la vivencia emocional que suscita el dominio de cooperación-­‐oposición y analizar la incidencia de la variable competición en el tipo de vivencia emocional para el dominio de cooperación-­‐oposición. Los participantes fueron 107 alumnos de Educación Primaria, quienes tras jugar a cuatro juegos de cooperación-­‐ oposición, completaban un instrumento ad hoc de reconocimiento emocional de expresiones faciales para las emociones positivas y negativas (alegría, felicidad, humor y afecto, tristeza, miedo, rechazo e ira. Los resultados mostraron que este dominio fue principalmente generador de una mayor intensidad emocional positiva y que el hecho de ganar o perder un juego influía en la experiencia emocional, siendo mayores las emociones positivas ganando y mayores las negativas al perder.

  16. Ultra-som pulsado de baixa intensidade em fraturas diafisárias: aplicação clínica em cães Low-intensity pulsed ultrasound in diaphyseal fractures: clinical application in dogs

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    Valéria Lima de Sousa

    2008-08-01

    Full Text Available Os efeitos da estimulação ultra-sônica sobre a consolidação óssea têm sido demonstrados por trabalhos experimentais e clínicos. Este estudo teve por objetivo investigar a aplicação clínica do ultra-som pulsado de baixa intensidade como tratamento adjuvante de fraturas diafisárias em cães. Foram utilizados 16 cães de raças variadas, com faixa etária entre sete meses e seis anos, peso corpóreo entre 2,5 e 43kg, portadores de fraturas diafisárias fechadas recentes localizadas no rádio e ulna, fêmur ou tíbia e fíbula, estabilizadas por procedimentos de osteossíntese (fixação esquelética externa, pinos intramedulares ou a associação desses métodos. Os cães foram divididos em dois grupos: fraturas estabilizadas tratadas por ultra-som de baixa intensidade (grupo tratado, n=8; fraturas estabilizadas, não tratadas por estimulação ultra-sônica, (grupo controle, n=8. Os animais foram avaliados por exames clínicos e radiográficos nos períodos pré-operatório, pós-operatório imediato e a cada 30 dias posteriores aos procedimentos cirúrgicos. Realizou-se tratamento com ultra-som pulsado (sinal senoidal com freqüência de 1,5MHz, largura de pulso de 200µs e freqüência de repetição de 1kHz de baixa intensidade (30mW cm-2, aplicado de modo estacionário no foco de fratura. A terapia ultra-sônica foi realizada 20 minutos por dia, durante 21 dias consecutivos, a partir do período compreendido entre o 1° e o 9° dia pós-operatório. O teste t de Student, empregado na análise estatística, mostrou diferença significante (PThe effects of ultrasound stimulation on bone healing have been demonstrated in experimental and clinical studies. The purpose of this study was to investigate the clinical application of low-intensity pulsed ultrasound as an adjuvant for the treatment of diaphyseal fractures in dogs. Sixteen dogs of different breeds, ages ranging from seven months to six years, weighing from 2.5 to 43kg, were

  17. Applicability of the Spanish Version of the Supports Intensity Scale (SIS, in the Mexican Population with Severe Mental Illness Aplicabilidad de la escala de intensidad de apoyos (SIS, en población mexicana con enfermedad mental severa Aplicabilidade da versão espanhola da escala de intensidade de apoio, na população mexicana com doença mental severa

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    Maribel Cruz Ortiz

    2010-10-01

    Full Text Available This study presents the results obtained from the evaluation, by specialist judges, of the Supports Intensity Scale (SIS, Spanish version, to determine its suitability for the Mexican population with severe mental illness (SMI. The instrument, originally designed for people with intellectual disabilities, is consistent with the multidimensional concept of quality of life and the social model of disability. The semantic equivalence of the items adjusted by specialist judges, the reliability of the subscales, using Cronbach’s alpha, and the concurrent validity between the SIS and the Global Functioning Assessment (GAF were analyzed. The mean similarity to the original was 9.91 from a total of 10 (sd=0.14. The reliability coefficients were above 0.95 and the correlations between the SIS and the GAF were medium to high and significant. In conclusion, in the Mexican context, the SIS scale can be used to understand the needs and expectations of people with mental illness.Mostramos resultados obtenidos en la evaluación de jueces expertos en la Escala de Intensidad de Apoyos (SIS, versión española, para determinar su adecuación a la población mexicana con Enfermedad Mental Severa (EMS. El instrumento, originalmente diseñado para personas con discapacidad intelectual, es congruente con el concepto multidimensional de calidad de vida y el modelo social de discapacidad. Se analizó la equivalencia semántica de los ítems adaptados a través de jueces expertos, la fiabilidad de las subescalas mediante el coeficiente Alfa de Cronbach y la validez concurrente entre la SIS y la GAF. El promedio de semejanza con el original fue 9,91 sobre 10 (DE=0,14. Los coeficientes de fiabilidad fueron superiores a 0,95 y las correlaciones entre la SIS y la GAF fueron entre medias y altas y significativas. Los resultados confirman que la escala SIS, con mínimas adecuaciones de forma, puede usarse para conocer las necesidades y expectativas en personas con

  18. Perdas de solo e água em um Argissolo Vermelho Amarelo, submetido a diferentes intensidades de chuva simulada Soil and water losses in a Red Yellow Argissol under different intensities of simulated rainfall

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    Daniel F. de Carvalho

    2002-12-01

    Full Text Available Este trabalho foi desenvolvido com o objetivo de se estimar as perdas de solo e água em um Argissolo Vermelho Amarelo, utilizando-se um simulador de chuvas pendular. Para testes com 35 min de duração, o simulador foi regulado adequadamente, a fim de aplicar chuvas com cinco diferentes valores de energia cinética (138, 184, 229, 275 e 321 J m-2 correspondendo às intensidades de 30, 40, 50, 60 e 70 mm h-1, respectivamente. Com os resultados obtidos, pôde-se ajustar equações de regressão entre as perdas de solo e de água, e o tempo de precipitação. Utilizando-se as equações ajustadas, obtiveram-se valores de perda que variaram de 2,83 a 26,82 g m-2 (solo e de 0,00209 a 0,01370 m³ m-2 (água quando a energia cinética da chuva variou de 138 para 321 J m-2, respectivamente. Comparando-se os valores simulados com os dados de campo, verificaram-se variações máximas de 3,4 e 5,7%, para as perdas de solo e água, respectivamente.The objective of this research was to estimate soil and water losses of a Red Yellow Argissol, using a pendulum rainfall simulator. Rainfall was simulated for 35 min at the intensities of 30, 40, 50, 60 and 70 mm h-1, which corresponded to kinetic energy values of 138, 184, 229, 275 and 321 J m-2, respectively. Cumulative soil and water losses were recorded with time at 5 min intervals. The results of soil and water losses were then fitted by regression equations. The fitted equations yielded soil and water losses that varied from 2.83 to 26.82 g m-2 (for soil and from 0.00209 to 0.01370 m³ m-2 (for water when the rainfall kinetic energy varied from 138 to 321 J m-2. Fitted and field measured soil and water losses showed a maximum variation of 3.4 and 5.7%, respectively.

  19. Efeito do espaçamento e da cultivar de feijoeiro sobre a intensidade do mofo-branco e a sanidade de sementes Effect of plant spacing and bean cultivar on white mold and seed sanity

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    Reginaldo Napoleão

    2006-03-01

    Full Text Available Dois ensaios de campo foram realizados para avaliar o efeito do espaçamento entre linhas (30, 45 e 60 cm e entre plantas de feijoeiro com hábitos de crescimento diferentes, sobre a intensidade do mofo-branco e a sanidade de sementes. No primeiro, foi mantida a mesma população de plantas por área, 27 plantas/m², reduzindo-se o espaçamento entre plantas. No segundo ensaio, manteve-se o mesmo espaçamento entre plantas, que resultou em populações de 40, 27 e 20 plantas/m². A porcentagem de plantas infectadas e a severidade da doença não diferiram estatisticamente quanto ao hábito de crescimento da cultivar, ao espaçamento ou à interação entre eles, mesmo a incidência tendo atingido valores de 98,4% em 1998 e de 2,7% em 1999. A porcentagem de sementes infectadas não foi afetada pelo espaçamento, mas diferiu erraticamente em relação às cultivares; em 1998, a cultivar Pérola não apresentou sementes infectadas, o mesmo acontecendo com a cultivar Diamante Negro em 1999.The effect of spacing among rows and among bean plants, as well as two plant growth habits were evaluated on the intensity of white mold and seed health in two field trials in Brasilia, DF, Brazil. In the first trial, the same population of 27 plants/m² was maintained in rows of 30, 45 and 60 cm apart. In the second trial, the spacing among rows was maintained, which resulted in different plant populations of 40, 27 and 20 plants/m², respectively. Disease incidence and severity did not differ statistically within plants of different growth habits or different spacing, even with divergent disease incidences of 98.4% and 2.7% observed in 1998 and 1999, respectively. The percentage of infected seeds was not affected by spacing either, however the cultivar effect was erratic; in 1998, 'Perola' had no infected seeds and the same occurred with 'Diamante Negro' in 1999.

  20. Intensidade de ataque de tripes, de alternaria e da queima-das-pontas em cultivares de cebola Intensity of attacks of thrips, purple blotch and gray mold on onion cultivars

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    Germano L.D. Leite

    2004-03-01

    Full Text Available Avaliou-se a intensidade de ataque de Thrips tabaci Lind., a incidência de Alternaria porri (Ellis e Botrytis squamosa J.C. Walker em nove cultivares de cebola [Aurora, Primavera, CNPH 6400, Crioula Alto-Vale, Vale-Ouro (IPA 11, Franciscana (IPA-16, Piraouro, Conquista e Serrana], num experimento no delineamento em blocos casualizados com cinco repetições. Foram feitas avaliações semanais, do transplantio até a colheita, em dez plantas/parcela do número de T. tabaci presente na bainha das folhas bem como da percentagem de área foliar danificada pelo mesmo a partir da primeira folha expandida e também da presença ou da ausência de lesões causadas por A. porri e B. squamosa. A cv. Franciscana mostrou-se mais resistente em relação às demais ao ataque de T. tabaci. Não houve diferença significativa de plantas afetadas por A. porri e B. squamosa. T. tabaci e A. porri foram ambos afetados positiva e negativamente pela temperatura e pela umidade relativa do ambiente, respectivamente.The intensity of attack of T. tabaci and incidence of Alternaria porri (Ellis Cif and Botrytis squamosa J.C. Walker in nine onion cultivars [Aurora, Primavera, CNPH 6400, Crioula Alto-Vale, Vale-Ouro (IPA 11, Franciscana (IPA-16, Piraouro, Conquista and Serrana] was evaluated, in an experiment in randomized blocks design, with five replications. Weekly evaluations were done from the transplanting until harvesting date, in ten plants/parcel of the number of T. tabaci on the leaves, the percentage of damaged foliar area from the first expanded leaf up and the presence or absence of injuries caused by A. porri and B. squamosa. The cv. Franciscana was more resistant to the attack of T. tabaci in comparison to the other onion cultivars. There was no significant difference between cvs for A. porri and Botrytis squamosa resistance. T. tabaci and A. porri were influenced positively and negatively by temperature and relative humidity, respectively.

  1. Intensidade da cercosporiose da alface em cultivos convencionais e orgânicos em Pernambuco Intensity of Cercospora leaf spot of lettuce in conventional and organic farming systems in State of Pernambuco, Brazil

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    Andréa Maria André Gomes

    2006-09-01

    Full Text Available Foram realizados levantamentos da intensidade da cercosporiose da alface, causada por Cercospora longissima, em 25 plantios manejados no sistema convencional e 25 no sistema orgânico, em dois períodos de plantio, janeiro-abril (I e junho-setembro (II de 2002, no estado de Pernambuco. A prevalência da doença foi elevada (> 88% em todas as situações avaliadas. Nas áreas de cultivo convencional a severidade da cercosporiose variou de 0,0 a 16,9%, enquanto em cultivos orgânicos de 0,0 a 22,5%. Nos dois sistemas de cultivo a severidade da doença foi significativamente mais elevada no período I, quando a precipitação pluviométrica foi quase três vezes superior ao período II. No entanto, somente no período II foram constatadas diferenças significativas na severidade da doença entre os sistemas de cultivo, sendo superior no sistema orgânico. Não foram constatadas correlações significativas entre os níveis de severidade da cercosporiose nas áreas de plantio nos dois períodos avaliados, dentro de cada sistema de cultivo.Surveys of the intensity of cercospora leaf spot of lettuce caused by Cercospora longissima were performed in 25 conventional and 25 organic farming areas in 2 planting periods, January-April (I and June-September (II 2002, in State of Pernambuco (Brazil. Disease prevalence was high (> 88% in all evaluated situations. Disease severity ranged from 0.0 to 16.9% in conventional farming areas and from 0.0 to 22.5% in organic farming areas. In both systems, disease severity was significantly higher in period I when precipitation was almost 3 times higher to that in period II. However, only in period II, significant differences in disease severity were found between farming systems, with high values in the organic system. There were no significant correlations among disease severity levels in the areas in both evaluated periods inside each farming system.

  2. Frequência e intensidade de poda em pomar jovem de laranjeiras 'Valência' sob manejo orgânico Frequency and intensity of pruning young 'Valencia' orange trees in orchards under organic culture system

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    Emiliano Santarosa

    2010-10-01

    Full Text Available Este trabalho teve por objetivo avaliar o efeito da frequência e intensidade de poda sobre a produção e qualidade dos frutos da laranjeira 'Valência', enxertada sobre Poncirus trifoliata, em pomar jovem, sob sistema de manejo orgânico. O plantio foi realizado em agosto de 2001, em espaçamento de 5,0x2,5m, em Montenegro, Rio Grande do Sul (RS. Os tratamentos testados foram: A - Testemunha (sem poda; B - Poda anual de 15%; C - Poda bienal de 15%; D - Poda bienal de 30%; e E - Poda trienal de 30% do volume da copa. O delineamento experimental foi de blocos ao acaso, sendo quatro repetições e quatro plantas por parcela. Nas safras de 2006, 2007 e 2008, foram avaliados: número, massa total de frutos e massa média dos frutos, teor de sólidos solúveis totais (SST, acidez total titulável (ATT e relação SST/AT do suco dos frutos. Em pomares jovens, com menos de sete anos de idade, durante três safras consecutivas, verificou-se que as podas de frutificação não alteram a produção acumulada, nem a qualidade físico-química dos frutos, mas reduzem a produção no ano subsequente à execução da poda.This study evaluated the influence of frequency and intensity of pruning on young orchards, with organic management system, on the yield and fruit quality of 'Valencia' oranges. The trees were budded on Poncirus trifoliata rootstock and implanted in August, 2001, in Montenegro-RS. The pruning tested was: A - control, without pruning; B - annual pruning of 15%; C - biennial pruning of 15%; D - biennial pruning of 30% and E - three-year 30% pruning of the canopy volume. The experiment had a randomized complete-block design, with four-trees plots and four replications. The total fruit mass production was registered and the average weight fruit in the crops 2006, 2007 and 2008 was determined. The fruit quality, total soluble solids (TSS, total acids concentration (TTA and ratio (TSS/TTA were assessed. In orchards with fewer than seven years old

  3. Laser de baixa intensidade (830 nm na recuperação funcional do nervo isquiático de ratos Low intensity laser (830 nm functional to recover of the sciatic nerve in rats

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    Alexandre Marcio Marcolino

    2010-01-01

    Full Text Available OBJETIVO: Avaliar o efeito do laser de baixa intensidade na melhora funcional da marcha de ratos após esmagamento do nervo ciático. MÉTODOS: Foram utilizados 18 ratos divididos alea-to-riamente em dois grupos: controle (sham e irradiado com densidade de energia de 40J/cm², em 21 dias consecutivos, utilizando o laser 830nm (AsGaAl. Os animais foram submetidos ao esmagamento do nervo ciático direito com o dispositivo portátil de peso morto e avaliados pelo "Índice Funcional do Ciático" (IFC. As pegadas foram coletadas no pré-operatório, 7º, 14º e 21º dias pós-operatório. RESULTADOS: Os resultados do IFC foram significantes quando comparados os grupos no 7º e 14º dia pós-operatório (pOBJECTIVE: This study aimed to evaluate the effect of low-intensity laser on functional improvement of the walking of rats after sciatic nerve axonotmesis. METHODS: We used 18 rats divided randomly in two groups: control (Sham and irradiated with an energy density of 40J/cm² for 21 consecutive days, using 830nm laser (AsGaAl. The animals were subjected to right sciatic nerve crushing by a portable device and assessed by the "Sciatic Functional Index" (SFI at an acrylic platform through video recorded by a digital camera. The footprints were collected preoperatively, and on the 7th, 14th and 21st postoperative days. RESULTS: The results of the SFI were significant when comparing the groups on the 7th and 14th postoperative day (p<0.05. On the 21st postoperative day there was no difference between groups. There were intra-group differences detected in each evaluated week (p<0.01. The irradiated animals showed improvement in motion pattern, shown by the SFI values in the initial periods, but after 3 weeks, there was a similar recovery. CONCLUSION: The low-intensity laser has shown to be effective in accelerating regeneration of the sciatic nerve of rats after crushing.

  4. Gasto energético aeróbico y anaeróbico en un circuito con cargas a seis intensidades diferentes. (Aerobic and anaerobic energy expenditure during at circuit weight training through six different intensities.

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    Rocío Cupeiro Coto

    2011-07-01

    Full Text Available ResumenEl entrenamiento con cargas es una actividad anaeróbica glucolítica intensa y se ha comprobado que el error en las estimaciones del gasto energético en esta actividad varía entre un 13 y un 30%. El principal objetivo de este trabajo es describir la contribución anaeróbica de energía en un circuito con cargas. Doce hombres (20-26 años y diecisiete mujeres (18-29 años estudiantes de Ciencias de la Actividad Física y del Deporte realizaron un entrenamiento en circuito de cargas a 6 intensidades diferentes (entre el 30% y 80% de su 15RM. Durante la totalidad de los circuitos se registró el gasto energético aeróbico por calorimetría indirecta, la frecuencia cardiaca con pulsómetro Polar® y la concentración de lactato en sangre capilar para medir la contribución anaeróbica. El incremento que produjo la energía anaeróbica se situó entre el 5,1% y un máximo del 13,5%, lo que hace evidente que medir o no la contribución anaeróbica en el entrenamiento en circuito puede provocar un error medio del 9,65%. Existen diferencias significativas (PAbstractResistance training is an intense anaerobic glycolytic activity and has been shown that estimates of energy expenditure in this activity turn out into an error that varies between 13 and 30%. The main aim of this paper is to describe the anaerobic energy contribution in circuit weight training. Twelve men (20-26 years and seventeen women (18-29 years students in Science of Physical Activity and Sport performed circuit training at six different intensities (between 30% and 80% of 15RM. During all the circuits aerobic energy expenditure was registered by indirect calorimetry, heart rate with Polar® monitors and lactate concentration in capillary blood to measure the anaerobic contribution. The increased due to anaerobic energy was between 5,1% and a maximum of 13,5%, which clearly means that to measure or not the anaerobic contribution in circuit training can lead to an average

  5. Correlação entre a contagem dos pontos dolorosos na fibromialgia com a intensidade dos sintomas e seu impacto na qualidade de vida Correlation between the number of tender points in fibromyalgia, the intensity of symptoms and its impact on quality of life

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    José Eduardo Martinez

    2009-02-01

    Full Text Available OBJETIVO: Estabelecer se há correlação entre o número de pontos dolorosos e a intensidade da percepção de aspectos centrais da síndrome (dor, fadiga, ansiedade, depressão e do seu impacto na capacidade funcional. MATERIAL E MÉTODOS: Avaliaram-se quarenta e um prontuários de pacientes que preenchem os Critérios de Classificação para Fibromialgia do Colégio Americano de Reumatologia, considerando as seguintes variáveis: percepção da intensidade de dor, fadiga, qualidade de vida global, depressão, ansiedade e contagem de pontos dolorosos. A avaliação da capacidade funcional foi realizada através do Questionário de Avaliação de Saúde simplificado (Health Assessment Questionnaire-HAQ. RESULTADOS: Observou-se correlação entre a contagem de pontos dolorosos e a intensidade da dor e a capacidade funcional. Não houve correlação com as notas atribuídas à fadiga (p = 0,358, ansiedade (p = 0,58, depressão (p = 0,50 e qualidade de vida (p = 0,538. A correlação entre o número de pontos dolorosos e a intensidade da dor foi mais forte que com o HAQ. CONCLUSÃO: Há correlação entre contagem dos pontos dolorosos e intensidade da dor e capacidade funcional. A correlação entre os pontos dolorosos e a intensidade da dor é mais importante do que com a capacidade funcional medida pelo HAQ. Não há correlação com as demais variáveis estudadas.OBJECTIVE: to study the correlation between the number of tender points and the intensity of the perception of key aspects of the fibromyalgia syndrome (pain, fatigue, anxiety, depression, and its impact in functional capacity. MATERIAL AND METHODS: forty-one records of patients who meet the Criteria for Classification of Fibromyalgia of the American College of Rheumatology were reviewed, focusing on the following variables: perception of the intensity of pain, fatigue, quality of sleep, depression, anxiety and the tender point count. The assessment of functional capacity was done by

  6. Relación de la escala de intensidad de Mercalli y la información instrumental como una tarea de clasificación de patrones The relationships of Mercalli intensity to instrumental information as a pattern classification task

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    Jorge E. Hurtado

    2008-07-01

    Full Text Available A pesar de los progresos ocurridos en la instrumentación sísmica, la valoración de vulnerabilidad sísmica y el daño con índices cualitativos, tal como los proporcionados por Intensidad de Mercalli Modificada (IMM, siguen siendo altamente favorables y útiles para los propósitos prácticos. Para vincular las medidas cualitativas de acción del terremoto y sus efectos, es habitualmente aplicada la regresión estadística. En este artículo, se adopta un planteamiento diferente, el cual consiste en expresar la Intensidad de Mercalli, como una clase en vez de un valor numérico. Una herramienta de clasificación estadística moderna, conocida como máquina de vectores de soporte, se usa para clasificar la información instrumental con el fin de evaluar la intensidad de Mercalli correspondiente. Se muestra que el método da resultados satisfactorios con respecto a las altas incertidumbres y a la medida del daño sísmico cualitativo.Despite the progress occurred in seismic instrumentation, the assessment of seismic vulnerability and damage qualitative indexes, such as that provided by Mercalli intensity is highly valuable and useful for practical purposes. In order to link the qualitative measures of earthquake action and its effects, statistical regression is commonly applied. in the paper, a different approach is adopted. It consisten in regarding the Mercalli intensity as a class rather that a numerical value. A modern statistical classification tool known as Support Vector Machine is used for classifying the la instrumental information in order to assess the corresponding Mercalli intensity. It is shown that the method gives satisfactory results with regardto the high uncertainties linked to such a qualitative seismic damage measure.

  7. Experimentação de parâmetros ITS (intensidade, tonalidade e saturação - aplicação na imagem Landsat TM 5 do Parque Estadual da Serra do Mar, núcleo Picinguaba, SP, Brasil

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    Andrea de Castro Panizza

    2001-06-01

    Full Text Available Este artigo apresenta uma parte dos estudos realizados na preparação do DEA, na Universidade de Rennes 2, França. Mostra o interesse da utilização das imagens orbitais na visualização de extensas áreas e a riqueza de informações que podem ser extraída dessas imagens. Com o objetivo de melhorar a visualização destas, alguns experimentos foram realizados utilizando os parâmetros de intensidade, tonalidade e saturação

  8. Efectos de diferentes intensidades relativas, volúmenes, tiempos de recuperación entre repeticiones y pérdida de velocidad en la serie sobre el rendimiento en sprint, salto vertical con cargas y sin cargas y la fuerza de las extremidades inferiores

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    Mora Custodio, Ricardo

    2017-01-01

    Programa de Doctorado en Ciencias de la Actividad Física y del Deporte En la presente tesis doctoral se llevaron a cabo cuatro estudios y tuvo como objetivo analizar los efectos producidos por diferentes configuraciones del entrenamiento de fuerza sobre el rendimiento en sprint, salto vertical y la fuerza máxima. En el Estudio I se analizó el efecto producido por dos programas de entrenamiento de fuerza equivalentes en todas sus variables excepto en la intensidad relativa (Cargas bajas 40...

  9. Evaluation of muscle regeneration in aged animals after treatment with low-level laser therapy Avaliação da regeneração muscular em animais idosos após tratamento com laser de baixa intensidade

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    Adriana Pertille

    2012-12-01

    ável para a regeneração muscular. OBJETIVO: Avaliar o efeito do tratamento com laser de baixa intensidade sobre a regeneração muscular de modelos experimentais idosos após contusão. MÉTODO: Foram utilizados 25 ratos machos, com 18 meses de idade, divididos em três grupos: grupo controle (CT, sem intervenção; grupo lesão (LE, com contusão muscular e sem tratamento e grupo laser (LA, com contusão muscular e tratado com laser de baixa intensidade, 830 nm, 30 mW e 4 J/cm². A contusão foi realizada no músculo tibial anterior, e as amostras coletadas após sete e 21 sessões de tratamento. O músculo foi designado às técnicas de Microscopia de Luz e Immunoblotting. RESULTADOS: Após 21 dias de tratamento, houve redução significativa na área de inflamação/regeneração no grupo LA 21 comparado ao grupo LE 21. Na área de secção transversal das fibras em processo de regeneração, não houve diferença estatística entre os grupos LA e LE. A análise molecular evidenciou que o conteúdo de MyoD apresentou redução significativa no grupo LE 21 em relação ao CT. O conteúdo de Miogenina exibiu aumento no LE 21 comparado ao CT e, por fim, o conteúdo de TGF-β1 do grupo LE 21 aumentou em relação ao grupo CT. CONCLUSÃO: Para os parâmetros utilizados, o laser demonstrou eficácia na regeneração muscular em animais idosos somente por meio do seu efeito anti-inflamatório.

  10. Efeitos do treinamento físico de alta intensidade sobre os leucócitos de ratos diabéticos Effects of high intensity physical training on the leukocytes of diabetic rats

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    Camila Aparecida Machado de Oliveira

    2002-12-01

    Full Text Available Estudos têm demonstrado que o exercício físico regular melhora as condições do diabetes, facilitando a captação periférica da glicose e o metabolismo de glicogênio, proteínas, etc. Por outro lado, pouco se conhece sobre os efeitos do exercício intenso em diabéticos, principalmente com relação ao sistema imune desses organismos. O presente estudo teve como objetivo verificar os efeitos de um treinamento físico de alta intensidade sobre a contagem total e diferencial de leucócitos em ratos diabéticos. Ratos machos jovens Wistar foram distribuídos em quatro grupos: controle sedentário (CS, controle treinado (CT, diabético sedentário (DS e diabético treinado (DT. O diabetes foi induzido por aloxana (35mg/kg de peso corporal. Durante seis semanas os animais dos grupos CT e DT realizaram um protocolo de treinamento físico, que consistiu na realização de quatro séries de 10 saltos (intercaladas por um minuto de intervalo em piscina, com o nível da água correspondendo a 150% do comprimento corporal e sobrecarga equivalente a 50% da massa corporal dos animais. Ao final do período experimental, amostras de sangue foram coletadas para a contagem total e diferencial dos leucócitos. Os resultados foram avaliados estatisticamente por ANOVA com um nível de significância de 5%. A glicemia foi aumentada entre os diabéticos e a insulinemia diminuída. Não foram observadas diferenças significativas na contagem diferencial dos linfócitos, neutrófilos, eosinófilos e contagem total de leucócitos entre os grupos estudados. Houve aumento dos monócitos entre os treinados (CS = 10,0 ± 4,5, CT* = 25,4 ± 7,9, DS = 19,75 ± 7,4, DT* = 25,8 ± 4,4%. O peso relativo do timo foi reduzido pelo treinamento e pelo diabetes (CS = 125,0 ± 37,7, CT* = 74,6 ± 8,2, DS* = 47,5 ± 12,2, DT* = 40,1 ± 16,9mg/100g. Esses resultados permitem concluir que o treinamento físico de alta intensidade não alterou o estado geral do diabetes, mas

  11. Influência da naloxona e metisergida sobre o efeito analgésico do laser em baixa intensidade em modelo experimental de dor Influencia de la naloxona y la metisergida sobre el efecto analgésico del láser en baja intensidad en modelo experimental de dolor Influence of naloxone and methysergide on the analgesic effects of low-level laser in an experimental pain model

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    André Peres e Serra

    2010-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A fototerapia com laser (LPT é um método analgésico promissor, embora seu mecanismo de ação não seja totalmente conhecido. O objetivo deste estudo foi avaliar se a ação da LPT é dependente da ativação de receptores opioides ou serotoninérgicos periféricos. MÉTODO: Foram utilizados ratos Wistar machos. A dor produzida foi de caráter inflamatório, através da injeção de carragenina na pata posterior esquerda dos ratos. O laser utilizado foi o Photon Lase III em meio ativo InGaAIP (660 nm, fluência de 2,5 J.cm-2. Analisou-se a hiperalgesia mecânica utilizando filamentos de von Frey. Os animais foram separados em cinco grupos: Carragenina; Laser (LPT; Luz não coerente; LPT + Naloxona e LPT + Metisergida. RESULTADOS: A fototerapia com laser em baixa intensidade mostrou-se um método analgésico eficaz, enquanto o emprego de fonte de luz não coerente não mostrou ter efeito analgésico. O uso de naloxona bloqueou o efeito analgésico do LPT; já o uso de metisergida não afetou a analgesia do LPT. CONCLUSÕES: A LPT nos parâmetros utilizados apresentou efeito analgésico. A analgesia da LPT é mediada por receptores opioides periféricos. A LPT parece não interagir com receptores serotoninérgicos periféricos.JUSTIFICATIVA Y OBJETIVOS: La fototerapia con láser (LPT es un método analgésico promisorio, aunque su mecanismo de acción no se conozca en su totalidad. El objetivo de este estudio fue evaluar si la acción de la LPT es dependiente de la activación de receptores opioides o serotoninérgicos periféricos. MÉTODO: Se usaron ratones Wistar machos. El dolor generado fue de carácter inflamatorio, a través de la inyección de carragenina en la pata posterior izquierda de los ratones. El láser utilizado fue el GaIAsAl (660 nm, fluencia de 2,5 J.cm-2. Se analizó la hiperalgesia mecánica utilizando filamentos de von Frey. Los animales se dividieron en cinco grupos: Carragenina; Láser (LPT

  12. Efeito agudo da intensidade do exercício de força na modulação autonômica cardíaca pós-exercício Efecto agudo de intensidad del ejercicio de fuerza en la modulación autónoma del corazón post-ejercicio Acute effect of resistance exercise intensity in cardiac autonomic modulation after exercise

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    Aluísio Henrique Rodrigues de Andrade Lima

    2011-06-01

    Full Text Available FUNDAMENTO: O balanço simpatovagal cardíaco se altera após o exercício de força. Contudo, o impacto das características do treinamento de força nessa resposta ainda não está claro. OBJETIVO: Analisar o efeito agudo da intensidade do exercício de força para tronco e membros superiores na modulação autonômica cardíaca pós-exercício. MÉTODOS: Quinze homens jovens realizaram três sessões experimentais em ordem aleatória: controle (C, exercício de força com 50% de 1-RM (E50% e exercício de força com 70% de 1-RM (E70%. As sessões incluíram 05 exercícios para tronco e membro superior, realizados em três séries de 12, 9 e 6 repetições, respectivamente. Antes e aos 20 e 50 minutos após as intervenções, a frequência cardíaca foi medida para posterior análise espectral da sua variabilidade. RESULTADOS: Em comparação aos valores anteriores à intervenção, o intervalo RR e a banda de alta frequência (AF aumentaram (maiores alterações: + 112 ± 83 ms; +10 ± 11 un, respectivamente, p 0,05. Em comparação aos valores pré-exercício, o intervalo RR e a banda AF diminuíram (maiores alterações: -69 ± 105 ms; -13 ± 14 un, respectivamente, p FUNDAMENTO: El balance simpatovogal cardíaco se altera después del ejercicio de fuerza. Sin embargo, el impacto de las características del entrenamiento de fuerza en esta respuesta no está claro. OBJETIVO: Analizar el efecto agudo de intensidad del ejercicio de fuerza para el tronco y miembros en la modulación autonómica del corazón post-ejercicio. MÉTODOS: Quince hombres jóvenes realizaron tres sesiones experimentales en orden aleatorio: control (C, ejercicio de fuerza con el 50% de 1-RM (E50% y ejercicio de fuerza con el 70% de 1-RM (E70%. Las sesiones incluyeron 05 ejercicios para tronco y miembro superior, realizados en tres series de 12, 9 y 6 repeticiones, respectivamente. Antes y a los 20 y 50 minutos después de las intervenciones, la frecuencia cardiaca se

  13. Detección de mutaciones de los genes hMLH1 y hMSH2 del sistema de reparación de malos apareamientos del ADN en familias colombianas sospechosas de cancer colorrectal no polipósico hereditario (síndrome de Lynch.

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    Andrea Gómez

    2005-09-01

    Full Text Available Introducción. El cáncer colorrectal es la segunda causa de morbilidad y mortalidad por cáncer en los países desarrollados. En Colombia es la quinta causa de muerte entre los diferentes cánceres. Cerca del 75% de éstos corresponde a cánceres esporádicos, alrededor del 25% son familiares, y son claramente hereditarios el 5%. De éstos, el más importantes es el cáncer colorrectal no polipósico hereditario o síndrome de Lynch. Objetivo. Analizar los dos genes más importantes involucrados en el síndrome de Lynch, el hMLH1 y el hMSH2. Materiales y métodos. En 17 familias colombianas que cumplían con los criterios de Ámsterdam II o las pautas de Bethesda, se analizaron por SSCP los 35 exones de estos dos genes y las variantes electroforéticas se secuenciaron. Resultados. Se detectaron 8 mutaciones de línea germinal en las familias analizadas, 7 en el gen hMLH1 y 1 en hMSH2, y se encontró una tasa de detección de mutaciones del 47%. Seis de las 8 mutaciones encontradas en este estudio han sido previamente reportadas en la literatura. Un cambio de una base en el sitio donador de empalme en el exón 9 del gen hMLH1 (G>A (dos familias, un cambio A>G en el codón 755 del exón 17, y un cambio G>A en el exón 18. Se detectaron dos nuevas mutaciones, una en el exón 17, un cambio C>T en el codón 640, y una deleción de TG en el codón 184 del exón 3 del gen hMSH2. También se detectó en dos familias un polimorfismo del intrón 13 del hMLH1. Conclusión. Este es el primer estudio realizado en Colombia que detecta mutaciones en el síndrome de Lynch y pretende establecer un programa integral de manejo y prevención.

  14. Comportamento de variáveis cardiorrespiratórias em idosos e jovens durante 15 minutos de recuperação após esforços de diferentes intensidades

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    Paulo T.V. Farinatti

    1999-12-01

    Full Text Available Sabe-se pouco sobre os efeitos do envelhecimento na recuperação pós-esforço (RP. O estudo observou a RP em 15 idosos (GI, idade = 61 ± 1 anos e 15 jovens (GJ, idade = 22 ± 2 anos após atividades de três intensidades (IE em cicloergômetro. Realizaram-se testes máximos, com incremento de 30W/min para GJ e de 25W/min após detecção de steady-state para GI. Posteriormente, os grupos pedalaram a 40% e 75% da carga máxima, respectivamente, 25 e 15 minutos. Foram acompanhados VO2, VCO2, V E e FC nos primeiros 15 minutos da RP nas três IE. O tratamento dos resultados compreendeu: a teste de ajustamento das curvas experimentais a equações com uma ou duas exponenciais; b cálculo do valor dos componentes para a equação mais ajustada; c análise das constantes extraídas. Os desvios de ajustamento foram inferiores para uma curva de duas exponenciais, definida por integral de tempo na forma A/a +B/b. A/a designa a componente rápida da recuperação e B/b a lenta. Quando comparados os grupos, GI mostrou constantes maiores que GJ, evidenciando recuperação mais lenta nas duas fases. Subdividindo os componentes, em GI e GJ as constantes de velocidade de recuperação rápida (1/a para VO2 e VCO2 foram semelhantes nas três IE, enquanto para a constante lenta (1/b, os valores para GI indicaram maior dependência em relação à carga. A recuperação da FC revelou-se extremamente dependente da IE para GJ. Para GI isso foi menos evidente, talvez por menor possibilidade de elevação da FC. A V E em GJ comportou-se de forma similar ao VO2 e VCO2. Porém, para GI as constantes de tempo foram mais lentas, mais associadas à IE que os demais parâmetros. Conclui-se: a pode existir uma constante comum para a chamada 'fase alática' da curva de recuperação do VO2 e do VCO2, independentemente da IE e da idade; b as diferenças entre GJ e GI podem dever-se às menores potência aeróbia máxima, termorregulação e eficácia do tampão respirat

  15. Treinamento em natação com baixa intensidade não protege músculo esquelético contra lesões induzidas por exercício exaustivo em ratos

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    Edson da Silva

    2011-06-01

    Full Text Available Enquanto o exercício aeróbico regular promove adaptações benéficas ao músculo esquelético, o exercício físico exaustivo induz lesões musculares. O objetivo deste estudo foi verificar se um programa de natação com baixa intensidade é capaz de proteger músculos esqueléticos contra lesões induzidas por exercício exaustivo. Ratos Wistar (peso: 376,50 ± 4,36g; idade: 90 dias foram divididos aleatoriamente em quatro grupos: controle sedentário (CS; sedentário submetido a teste de exaustão (SE; treinado em natação (TN; treinado em natação submetido a teste de exaustão (TNE. Animais dos grupos TN e TNE foram submetidos a um programa de natação sem sobrecarga por 90 minutos/dia, cinco dias/semana, durante 17 semanas. Após este período, os grupos SE e TNE foram submetidos a um teste de exaustão em natação. Após eutanásia, fragmentos dos músculos sóleo e reto femoral foram coletados e submetidos à análise histológica e de proteínas de choque térmico (HSP70. Os resultados mostraram que o tempo até a exaustão foi maior no grupo TNE que no SE (125,0 ± 6,0 vs. 90,0 ± 8,5min, respectivamente, P < 0,05. Os níveis de lactato sanguíneo durante o teste e exaustão foram menores no grupo TNE que no SE (5,31 ± 0,22 vs. 8,76 ± 0,59mmol/L, respectivamente, P < 0,05. A frequência de fibras lesadas nos músculos foi maior nos grupos SE (sóleo: 34,86 ± 0,04; reto femoral: 37,57 ± 0,07 e TNE (sóleo: 41,57 ± 0,08; reto femoral: 39,57 ± 0,05, comparada aos grupos CS (sóleo: 13,88 ± 0,81; reto femoral: 16,75 ± 0,79 e TN (sóleo: 24,14 ± 0,06; reto femoral: 24,0 ± 0,05, respectivamente (P < 0,05. Não houve diferença significativa nos níveis de HSP70 dos músculos analisados entre os quatro grupos. Concluimos que apesar do treinamento em natação melhorar o desempenho dos animais no teste de exaustão, não promoveu proteção aos seus músculos esqueléticos contra as lesões induzidas pelo exercício exaustivo

  16. Laserterapia de baixa intensidade no pós-operatório da síndrome do túnel do carpo Low-level laser therapy after carpal tunnel release

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    Marcelo de Pinho Teixeira Alves

    2011-01-01

    Full Text Available OBJETIVO: Avaliar o tratamento pós-operatório da síndrome do túnel do carpo (STC, utilizando-se a laserterapia de baixa intensidade (LBI. MÉTODO: Foram avaliados prospectivamente 58 pacientes portadores de STC, divididos aleatoriamente em dois grupos: tratamento com LBI (grupo 1 e placebo (grupo 2. Foi utilizado laser de 830nm, de gálio-alumínio-arsênico, e potência de 30mW. RESULTADOS: Houve predominância do sexo feminino, em ambos os grupos. A média de idade dos pacientes do grupo 1 foi de 44,3 anos e do grupo 2, de 51,9 anos. A média do tempo de evolução da doença foi aproximadamente dois anos em ambos os grupos. A média do tempo decorrido para alta do tratamento foi de 3,6 meses, em ambos os grupos, com menor número de pacientes queixosos no pós-operatório do grupo 1 do que do grupo 2. Ao fim do tratamento, no grupo 1, 29,41% dos pacientes apresentavam eletroneuromiografia alterada, enquanto que, no grupo 2, foram 63,64% dos pacientes após seis meses. CONCLUSÕES: Trata-se de estudo inicial sobre a terapêutica adjuvante utilizando LBI no pós-operatório da STC. A metodologia apresentada foi suficiente para a avaliação pós-operatória dos pacientes do estudo. Os pacientes submetidos à LBI após a cirurgia para STC foram beneficiados e obtiveram melhores resultados funcionais quando comparados ao grupo controle. A técnica foi eficaz e sem efeitos adversos nos pacientes estudados.OBJECTIVE: Evaluate the post-operative treatment of CTS, using the LLLT. METHOD: We prospectively evaluated 58 patients with CTS, randomly divided into two groups: treatment with LLLT (Group 1 and placebo (Group 2. A 830 nm gallium-aluminum-arsenic laser was used, with a power of 30 mW. RESULTS: There was female predominance in both groups. The mean age of the patients in Group 1 was 44.3 years and in Group 2, 51.9 years. The average duration of disease progression was around two years in both groups. The average time elapsed since discharge

  17. Laserterapia de baixa intensidade na expressão de colágeno após lesão muscular cirúrgica Low-level laser therapy in the expression of collagen after muscular surgical injury

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    Flávia Fonseca Moreira

    2011-03-01

    Full Text Available A laserterapia é um procedimento utilizado em larga escala nas lesões musculoesqueléticas, devido as suas diversas propriedades, antiinflamatórias, cicatrizantes entre outras. Além disso, há tipos distintos de aparelhos de laser. Mesmo com os diversos modelos experimentais existentes na literatura, não há um consenso sobre a faixa de utilização, bem como o tipo de laser que promove melhor reparo no tecido muscular. Este estudo visa analisar os efeitos da laserterapia de baixa intensidade na expressão de colágeno após lesão muscular. Camundongos Swiss albinos (n=18 foram submetidos à lesão muscular cirúrgica e divididos em dois grupos, controle (C e teste (T. Os animais foram submetidos a uma irradiação diária de 5 J/cm² pelos lasers AsGaAl 830 nm e AsGa 904 nm e, em diferentes tempos de sacrifício (7 e 14 dias. Os resultados não demonstraram diferença estatística significativa na expressão de colágeno em ambos os grupos analisados. Contudo, os dados apontam que a dose de 5 J/cm² do laser AsGa 904 nm promoveu maior deposição de fibras colágenas após 14 dias de tratamento, sugerindo que a terapia seja efetiva na síntese de colágeno. Outros estudos experimentais, em humanos, devem ser propostos para maiores inferências sobre os resultados do laser no tratamento da lesão muscular.The laser therapy is a procedure utilized at long scale in the musculoskeletal injuries, due its anti-inflammatory and reparatory proprieties and others. Besides, there are differents types of laser equipments. Despites with the many experimental models at literature, there is no consensus about the range of application as well as the type of laser that promove of the best repair in muscular tissue. The aim of this study is to analyze the effects of the low level laser therapy in the expression of collagen after muscular injury. Mice Swiss albinos (n=18 were subjected to the muscular surgical injury and separated in two groups, control (C

  18. Distribución e intensidad de los estudios faunísticos sobre mariposas diurnas en la Península Ibérica e islas Baleares (Lepidoptera, Papilionoidea y Hesperioidea

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    Romo Benito, H.

    2005-06-01

    Full Text Available The distribution of the sampling effort of current faunistic data on the butterflies in the Iberian Peninsula and Balearic Islands has been analysed, using 10 and 50 km UTM grids. The number of records in the database ATLAMAR1 was selected as the sampling effort unit. Three approaches were attempted to evaluate the geographic coverage of the data: First, based on criteria of minimal conditions. Second, based on indirect estimators derived from 25 10 x 10 km UTM squares whose butterfly fauna is believed to be well sampled. Finally, accumulation curves were used to evaluate the completeness of faunistic knowledge in the 50 km UTM squares.

    The different approaches were broadly coincident in indicating an adequate degree of knowledge for 6.8% of the 10 x 10 squares, and 62.3% of the 50 x 50 UTM squares. Approximately one third of the territory is characterised by a remarkable scarcity of butterfly records. This is especially true for some regions, namely Galicia, Castilla-La Mancha and inland Andalusia.

    The results provide a reliable and objective basis for subsequent work on butterfly diversity, biogeography and conservation within the Iberian area.

    Se ha analizado la distribución actual de la intensidad de muestreo de las mariposas diurnas en la Península Ibérica e Islas Baleares, usando el sistema de proyección UTM, con una red de malla de cuadrículas de 10 y 50 km de lado. Se realizaron tres tipos de aproximaciones para valorar la cobertura geográfica de los datos, seleccionando el número de registros de la base de datos ATLAMAR1 como unidad de esfuerzo de muestreo: Una basada en criterios mínimos, otra en estimadores indirectos derivados de 25 cuadrículas UTM de 10 km de lado bien muestreadas, y una última mediante la utilización de curvas de acumulación que se aplicó a las cuadrículas de 50 km de lado.

    Los resultados de todos los análisis coinciden en señalar un 6,8% de las cuadr

  19. Avaliação da intensidade de contaminação de pontas de seringa tríplice Evaluation of the bacterial contamination of air/water syringes tips

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    Eliza Maria Agueda RUSSO

    2000-09-01

    Full Text Available O controle de infecção cruzada em consultórios odontológicos inclui cuidados especiais com as seringas tríplices. Os autores pesquisaram a intensidade de contaminação pela microbiota bucal, de pontas de seringas tríplices usadas no atendimento a pacientes de Dentística Restauradora. Cinqüenta pontas descartáveis (Riskcontrol, Injecta Prod. Odontológicos foram avaliadas: 10, imediatamente após a abertura da embalagem; 30, após o uso em pacientes; e 10, após o uso e a desinfecção com álcool etílico 70% P/V, friccionado por um minuto. Em câmara de fluxo laminar, as pontas foram "roladas" sobre a superfície de Tryptic Soy Agar, suplementado com 5% de sangue desfibrinado de carneiro. Após 96 horas de incubação anaeróbia, foi feita a avaliação da quantidade de unidades formadoras de colônias (ufc desenvolvidas. Confirmando a informação do fabricante, as pontas estavam estéreis quando retiradas da embalagem. Em todas as pontas usadas em pacientes, observou-se um número incontável de ufc (maior que 300, revelando intensa contaminação. Nas pontas usadas e desinfetadas com álcool etílico 70% P/V, verificou-se apreciável redução na contagem de colônias (1 a 100 ufc, mas incompatível com a segurança biológica. Os resultados sugerem, como condição ideal, o uso de pontas descartáveis nas seringas tríplices.Effective infection control procedures to prevent cross-contamination in the dental office include care with air/water syringes. The authors had the purpose to verify the bacterial contamination of air/water syringes used in patients seen at the Restorative Dental Clinic, School of Dentistry, University of São Paulo, Brazil. Fifty disposable tips (Riskcontrol, Injecta Prod. Odontológicos were analysed: 10, immediately after the package was opened; 10, after a single use followed by disinfection with 70% alcohol for one minute; 30, after a single use without any posterior disinfection. The samples were

  20. Perennial grasses traits as functional markers of grazing intensity in basaltic grasslands of Uruguay Rasgos de gramíneas perennes como marcadores funcionales de la intensidad de pastoreo en pastizales de basalto en Uruguay

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    Martin Jaurena

    2012-12-01

    los grupos funcionales se determinó la respuesta al incremento de la intensidad de pastoreo en un experimento con dos cargas de capones (0,78 and 1,56 unidades ganaderas ha-1 cuantificando la cobertura de dichas especies y los valores de sus rasgos. El contenido de MS y el área foliar específica fueron los rasgos que mejor describieron la respuesta de las gramíneas perennes al incremento de la carga animal y podrían ser utilizados como marcadores funcionales. Tres grupos funcionales fueron identificados. El nivel más bajo de carga animal se relacionó con el grupo funcional A (especies estivales, altas, con baja área foliar específica y alto contenido de MS y con el grupo funcional B (especies invernales altas y con niveles intermedios de rasgos foliares. Por otro lado, el nivel más elevado de carga animal se relacionó con el aumento del grupo funcional C (especies estivales, postradas, con alta área foliar específica y bajos contenidos de MS. Esta clasificación de una comunidad con alta diversidad de especies en tres grupos funcionales es un nuevo enfoque para desarrollar métodos simples y generales para el diagnóstico del estado de praderas naturales de la región basáltica en Uruguay y generar recomendaciones para su manejo.

  1. Influência da nutrição mineral na intensidade da mancha-de-olho-pardo em mudas de cafeeiro Influence of the mineral nutrition on intensity of brown-eye spot in young coffee plants

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    Adélia Aziz Alexandre Pozza

    2001-01-01

    Full Text Available Objetivando avaliar a intensidade da mancha-de-olho-pardo do cafeeiro, variedade Catuaí Vermelho, com relação ao estado nutricional das plantas quanto a N e K, realizou-se um experimento no viveiro da Universidade Federal de Viçosa, em Viçosa, MG, utilizando solução nutritiva circulante. Empregaram-se 16 tratamentos, em delineamento inteiramente casualizado, com três repetições e duas plantas por parcela, em esquema fatorial com quatro doses de K (3, 5, 7 e 9mmol/L e quatro doses de N (3, 7, 11 e 15mmol/L. Após sete inoculações de conídios, e avaliações, colheram-se as plantas. A produção de matéria seca total, a área foliar total, e a área abaixo da curva de progresso (AACP do número total de folhas não foram influenciadas pelas doses de K, mas aumentaram com o incremento das doses de N. Observou-se elevação, na AACP, do número de lesões por folha, e na desfolha com o aumento das doses de K e a redução das doses de N. A elevação nas doses de K promoveu redução nos teores foliares de Ca e Cu. Osteores foliares de P, Mg, Mn e Fe não foram influenciados pelas doses de K e tiveram pequena redução com o aumento de N na solução, elevando-se a seguir.The experiment was carried out at the coffee nursery of the Universide Federal de Viçosa, in Viçosa, MG, Brazil, using nutrient circulating solution to evaluate the intensity of brown-eye spot (Cercospora coffeicola, variety Catuaí Vermelho, as a function of N and K. Acompletely randomized design with 16 treatments, three replicates, and two plants per plot was used in a factorial with four levels of K (3, 5, 7 and 9mmol/L combined with four levels of N (3, 7, 11 and 15mmol/L. After seven inoculations and evaluations, the plants were picked. Total dry matter production, total leaf area, and the area below the curve of progress (AACP for the total number of leaves were not influenced by the levels of K, but increased with increasing levels of N. There was increase

  2. Análise da frequência e da intensidade das chuvas em Ponta Grossa, Estado do Paraná, no período entre 1954 E 2001 - doi: 10.4025/actascitechnol.v33i1.6957

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    Maysa de Lima Leite

    2011-03-01

    Full Text Available Este trabalho teve por objetivo realizar uma avaliação da frequência e da intensidade da precipitação pluvial em Ponta Grossa, Estado do Paraná, no período de 1954 a 2001, utilizando técnicas estatísticas de análise exploratória de dados com o auxílio dos softwares Microsoft Office Excel e Microcal Origin. A média dos totais anuais de precipitação para a série analisada foi de 1.546,2 mm, revelando tendência a aumentar com o passar dos anos. O mês com maior total médio de precipitação foi janeiro com o mês de agosto sendo o de menor total médio. Para todos os meses do ano foi observada assimetria positiva na distribuição de frequência dos dados, e nos meses mais secos essa tendência se mostrou mais acentuada. Em relação à intensidade de precipitação acumulada diariamente, os totais foram classificados como chuvisco, chuva fraca, chuva moderada, chuva forte e chuva extrema. O intervalo de precipitação predominante para a maioria dos meses foi o de chuva fraca, entre 2,5 e 10,0 mm.

  3. Soil compaction and eucalyptus growth in response to forwarder traffic intensity and load Compactação do solo e crescimento de eucalipto influenciados pela intensidade de tráfego e carga de um forwarder

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    Sérgio Ricardo da Silva

    2008-06-01

    tree height were not affected by soil compaction. Two passes of the forwarder were enough to cause the disturbances at the highest levels. The compaction effects were still persistent 441 days after forwarder traffic.Em povoamentos florestais, durante a retirada de madeira, as máquinas trafegam numa mesma linha várias vezes, o que pode causar a compactação do solo e, como conseqüência, facilitar o processo erosivo e dificultar o crescimento de raízes. O grau de compactação, além do número de passadas da máquina, pode também ser afetado pelo peso de madeira transportado. Este trabalho teve como objetivo avaliar a compactação do solo e o crescimento de eucalipto de acordo com a intensidade de trânsito e a carga de madeira de um forwarder. O estudo foi realizado no município de Santa Maria de Itabira, MG, em um Latossolo Vermelho-Amarelo (LVA oxídico-gibbsítico. Um povoamento de eucalipto com sete anos de idade foi abatido por motosserra, sendo a madeira retirada da área manualmente. Em seguida, demarcaram-se parcelas de quatro entrelinhas de árvores com 12 m de comprimento (espaçamento 3 x 2 m, com área de 144 m² cada. Dois ensaios foram feitos. No primeiro, testou-se o efeito da intensidade de trânsito, no qual um forwarder, com tara de 11.900 kg, foi carregado com 12 m³ de madeira (densidade de 480 kg m-3 e dirigido sobre a mesma entrelinha por 0, 2, 4 e 8 vezes. No segundo, o forwarder recebeu cargas correspondentes a 4, 8 e 12 m³ de madeira e dirigido quatro vezes sobre a mesma entrelinha. Em cada parcela, quatro entrelinhas foram compactadas pelas rodas. Foi realizado o plantio de eucalipto em covas de 30 x 30 x 30 cm, abertas sobre as trilhas compactadas. O teor de carbono orgânico total (COT era de 406 e 272 g kg-1 e a umidade atual do solo era de 248 e 249 g kg-1 nas camadas de 0-5 e 5-10 cm de profundidade, respectivamente. O teor de argila era de 470 e de areia 440 g kg-1. As avaliações realizadas após a aplicação dos

  4. Association Between Genetic Polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT Genes and Radiosensitivity in Breast Cancer Patients

    International Nuclear Information System (INIS)

    Mangoni, Monica; Bisanzi, Simonetta; Carozzi, Francesca; Sani, Cristina; Biti, Giampaolo; Livi, Lorenzo; Barletta, Emanuela; Costantini, Adele Seniori; Gorini, Giuseppe

    2011-01-01

    Purpose: Clinical radiosensitivity varies considerably among patients, and radiation-induced side effects developing in normal tissue can be therapy limiting. Some single nucleotide polymorphisms (SNPs) have been shown to correlate with hypersensitivity to radiotherapy. We conducted a prospective study of 87 female patients with breast cancer who received radiotherapy after breast surgery. We evaluated the association between acute skin reaction following radiotherapy and 11 genetic polymorphisms in DNA repair genes: XRCC1 (Arg399Gln and Arg194Trp), XRCC3 (Thr241Met), XPD (Asp312Asn and Lys751Gln), MSH2 (gIVS12-6T>C), MLH1 (Ile219Val), MSH3 (Ala1045Thr), MGMT (Leu84Phe), and in damage-detoxification GSTM1 and GSTT1 genes (allele deletion). Methods and Materials: Individual genetic polymorphisms were determined by polymerase chain reaction and single nucleotide primer extension for single nucleotide polymorphisms or by a multiplex polymerase chain reaction assay for deletion polymorphisms. The development of severe acute skin reaction (moist desquamation or interruption of radiotherapy due to toxicity) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Radiosensitivity developed in eight patients and was increased in carriers of variants XRCC3-241Met allele (hazard ratio [HR] unquantifiably high), MSH2 gIVS12-6nt-C allele (HR = 53.36; 95% confidence intervals [95% CI], 3.56-798.98), and MSH3-1045Ala allele (HR unquantifiably high). Carriers of XRCC1-Arg194Trp variant allele in combination with XRCC1-Arg399Gln wild-type allele had a significant risk of radiosensitivity (HR = 38.26; 95% CI, 1.19-1232.52). Conclusions: To our knowledge, this is the first report to find an association between MSH2 and MSH3 genetic variants and the development of radiosensitivity in breast cancer patients. Our findings suggest the hypothesis that mismatch repair mechanisms may be

  5. Rendimento de soja em sistema de integração lavoura-pecuária: efeito de métodos e intensidades de pastejo Soybean yield in an animal-crop rotation system: effects of grazing methods and intensities

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    Robson Lunardi

    2008-06-01

    Full Text Available Sistemas de integração lavoura-pecuária têm despertado o interesse de produtores que buscam a diversificação das atividades e o aumento da rentabilidade. O objetivo deste trabalho foi avaliar a influência de métodos e intensidades de pastejo de ovinos no rendimento da soja cultivada em dois espaçamentos entre linhas, em um sistema de integração lavoura-pecuária. O experimento foi conduzido no município de Eldorado do Sul - RS, na Estação Experimental Agronômica - UFRGS na safra 2003/2004, cujas coordenadas geográficas são 30005'22" S de latitude e 51039'08" W de longitude. O delineamento experimental foi em blocos casualizados num fatorial com duas intensidades de pastejo, baixa e moderada, dois métodos de pastejo, contínuo e rotacionado, e dois espaçamentos entre fileiras de soja, 0,2 e 0,4m, com quatro repetições. Uma área foi adicionada como testemunha sem pastejo. Avaliaram-se o rendimento e os componentes do rendimento da soja. A produção de soja foi superior nos tratamentos submetidos a pastejo em comparação aos não-pastejados. Dentre os pastejados, o rendimento de soja foi superior na intensidade de pastejo baixa em comparação com a intensidade moderada. A intensidade de pastejo utilizada no inverno é o principal determinante do sucesso desse sistema de integração lavoura-pecuária.Animal-crop rotation systems are fostering the interest of farmers searching for diversification and the increase of profitability. The experiment aimed to evaluate the influence of grazing methods and intensities applied on winter pastures grazed by lambs and its consequence for soybean yield cultivated in succession. This crop-animal rotation trial was conducted in 2003/2004 at UFRGS Agricultural Research Station (Universidade Federal do Rio Grande do Sul in Eldorado do Sul, Rio Grande do Sul state, Brazil, whose geographical coordinates are 30005'22" S latitude and 51039'08" W longitude. The experimental design was a

  6. Effect of light intensity and growth substratum on plant development and production of secondary metabolites in Cordia curassavica (Jacq. Roem. & Schult Efeito da intensidade de luz e substrato no crescimento da planta e produção de metabólitos secundários em Cordia curassavica (Jacq. Roem. & Schult

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    Maria Terezinha Silveira Paulilo

    2010-06-01

    Full Text Available Cordia curassavica (Jacq. Roem. & Schult. (Boraginaceae, also referred to as Cordia verbenacea DC, has been traditionally used for medicinal purposes. This study was driven to verify the behavior of the species in similar conditions to its natural environment, such as high light intensity and sandbank soil, and in conditions of low light intensity and fertilized substratum (dystroferric red nitosoil plus earthworm humus. The growth of the plant, the income of leaf crude extracts and, in the alcoholic extract, the number of substances found in thin layer cromatography and the toxicity of the substratum was observed. The results indicated that the growth of the root biomass, stem and leaves in discharge or lower light intensity was similar, but smaller in sandbank soil than in fertilized soil. The relative income of extracts in ether of petroleum and alcohol was larger in high light intensity and fertilized substratum. The light intensity and the substratum type didn't affect the number of substances detected in the alcoholic extract or the toxicity of this extract. Stains corresponding to the rosmarinic acid were only evidenced in some samples of the alcoholic extract, not allowing the verification of the effect of the treatments about its production.Cordia curassavica (Jacq. Roem. & Schult. (= Cordia verbenacea DC., Boraginaceae, tem sido tradicionalmente utilizada com propósitos medicinais. Este estudo verificou o comportamento da espécie em condições similares ao ambiente natural, alta intensidade de luz e solo de restinga e em condição de baixa intensidade de luz e substrato adubado (solo distroférrico mais húmus de minhoca. valiaram-se o crescimento da planta, o rendimento de extratos brutos de folha, o número de substâncias encontradas em cromatografia de placa no extrato alcoólico e a toxicidade do substrato. Os resultados indicaram que o crescimento da biomassa de raiz, de caule e de folhas em alta ou baixa intensidade de luz

  7. Influência da forma de indução à acidose na determinação da intensidade de lactato mínimo em corredores de longa distância Influence of the acidosis induction manner in the determination of minimal lactate threshold in endurance runners

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    Vanessa Santhiago

    2008-08-01

    Full Text Available O objetivo principal deste estudo foi verificar se diferentes formas de indução à acidose interferem na determinação da intensidade do lactato mínimo (LACmin em corredores de longa distância. Desse modo, 14 corredores de provas fundas do atletismo participaram do estudo. Os atletas realizaram três protocolos: 1 teste incremental em esteira rolante, com incrementos de 1km.h-1 a cada três minutos até a exaustão, para a determinação das intensidades de limiar anaeróbio (OBLA, de limiar aeróbio (Laer, consumo máximo de oxigênio (VO2max e intensidade de consumo máximo de oxigênio (vVO2max; 2 teste de lactato mínimo em pista de atletismo (LACminp, que consistiu de dois esforços máximos de 233m na pista de atletismo com intervalo de um minuto entre cada repetição, com oito minutos de recuperação passiva, seguido de um teste incremental semelhante ao do protocolo 1; e 3 teste de lactato mínimo em esteira rolante (LACmine, constituído de dois esforços máximos de um minuto e 45 segundos com intervalo de um minuto, na intensidade de 120% da vVO2max, seguido dos mesmos procedimentos do protocolo 2. Foram coletadas amostras de sangue do lóbulo da orelha ao final de cada estágio em todos os protocolos e no 7º minuto de recuperação passiva dos testes de LACmine e LACminp. A análise de variância (ANOVA mostrou que ocorreram diferenças significativas entre as intensidades de LACmine (13,23 ± 1,78km.h-1 e OBLA (14,67 ± 1,44km.h-1. Dessa maneira, a partir dos resultados obtidos no presente estudo, é possível concluir que a determinação da intensidade correspondente ao lactato mínimo é dependente do protocolo utilizado para a indução à acidose. Além disso, o LACmine subestimou a intensidade correspondente ao OBLA, não podendo ser utilizado para a mensuração da capacidade aeróbia de corredores fundistas.The purpose of this study was to verify if different induction forms to the acidosis can interfere in the

  8. INTENSIDADE-DURAÇÃO-FREQÜÊNCIA DE CHUVAS INTENSAS PARA LOCALIDADES NO ESTADO DE GOIÁS E DISTRITO FEDERAL INTENSITY-DURATION-FREQUENCY RELATIONSHIP OF INTENSIVE RAINFALL FOR SITES IN THE GOIÁS STATE AND THE FEDERAL DISTRICT

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    Nori Paulo Griebeler

    2007-09-01

    Full Text Available

    Este trabalho teve como objetivo a obtenção das relações intensidade-duração-frequência para algumas localidades do Estado de Goiás e Distrito Federal, empregando-se a metodologia da desagregação da chuva de um dia. Os resultados das intensidades de precipitação obtidos pelas equações geradas neste trabalho foram comparados com os obtidos pelas equações ajustadas com base em dados de pluviogramas. As relações geradas com o método de desagregação de chuvas de um dia apresentaram desvios relativos médios que variaram de -1,6% a 43,9%, para alguns municípios nessa região. Isso limita a sua utilização nas localidades para as quais não se ajustaram as equações de regressão.

    PALAVRAS-CHAVE: Chuva intensa; drenagem; intensidade-duração-frequência.

    This study had the objective of obtaining rain intensityduration- frequency information for some sites in the State of Goiás and Distrito Federal, using the one-day rain disaggregation method. The precipitation intensities obtained through the equations generated in this paper were compared to those obtained by adjusted equations based on pluviographic data. The intensityduration-frequency relationships generated through pluviometric data using the one-day rain disaggregation method presented relative mean deviations varying between -1.6% and 43.9%, for some municipalities in this region. This limits its use in sites where regression equations were not adjusted.

    KEY-WORDS: Intense rainfall; drainage; intensity-durationfrequency.

  9. Serum macro minerals in adults Thoroughbred horses, before and after the high intensity exercise. Macrominerais séricos em equinos atletas da raça Puro Sangue Inglês, antes e após exercício físico de alta intensidade

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    Regina Kiomi Takahira

    2009-12-01

    Full Text Available With the aim of analyzing the effect of high intensity physical activity on the serum values of macro minerals, 19 clinically health adults Thoroughbred horses, males and females from 3 to 5 years of age, were submitted to a galloping in a 2,000 meters sand track. Two blood samples were collected from each animal, one before and another after the high intensity exercise. The results had shown some significative changes (p<0.05 with an increase in the serum values of calcium and magnesium and a decrease in serum and potassium. Meanwhile, there were no alterations (p>0.05 in the concentration of phosphorus and potassium. It is concluded, therefore, that the high intensity exercise leads to transitory and physiologic changes in the serum concentration of macro minerals.Com o objetivo de analisar o efeito da atividade física de alta intensidade sobre os valores séricos dos macrominerais, 19 equinos adultos, com idade entre três e cinco anos, machos e fêmeas, clinicamente saudáveis da raça Puro Sangue Inglês, foram submetidos ao galope de corrida em pistas de areia, na distância de 2000 metros. De cada animal foram colhidas duas amostras de sangue, uma antes e outra após a realização do exercício físico de alta intensidade. A análise dos resultados obtidos demonstrou que houve alterações significativas nos valores séricos do cálcio e magnésio, que apresentaram elevação, e do sódio e cloreto, que apresentaram redução, enquanto não foram verificadas variações significativas nos teores séricos do fósforo e potássio. Conclui-se, portanto, que a atividade física de alta intensidade (galope de corrida altera, transitória e fisiologicamente, a concentração sérica dos macrominerais.

  10. Estimativa das contribuições dos sistemas anaeróbio lático e alático durante exercícios de cargas constantes em intensidades abaixo do VO2max Estimation of contributions of the anaerobic lactic and alactic systems during constant-load exercises at intensities below the VO2max

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    Marcos David Silva-Cavalcante

    2013-01-01

    Full Text Available O objetivo do estudo foi estimar as contribuições do metabolismo anaeróbio lático (MAL e alático (MAA em intensidades abaixo do consumo máximo de oxigênio (VO2max. Dez homens (23 ± 4 anos, 176,4 ± 6,8 cm, 72,4 ± 8,2 kg, 12,0 ± 4,5 % de gordura corporal realizaram um teste progressivo até a exaustão voluntária para identificação do VO2max, da potência correspondente ao VO2max (WVO2max e do segundo limiar ventilatório (LV2. Na segunda e na terceira visita foram realizados seis testes de cargas constantes (três testes por sessão com intensidades abaixo do VO2max. Houve uma predominância do MAL sobre o MAA durante os exercícios submáximos a partir da intensidade correspondente ao LV2, sendo significativamente maior em 90% VO2max (p The purpose this study was that estimated contributions of the anaerobic lactic (MAL and alactic (MAA metabolism during constant load exercises at intensities below the maximal oxygen capacity uptake (VO2max. Ten males (23 ± 4 years, 176.4 ± 6.8 cm, 72.4 ± 8.2 kg, 12.0 ± 4.5 % of fat body performed in the first visit a progressive test until exhaustion to identification of VO2max, power output corresponding to the VO2max (WVO2max and second ventilatory threshold (LV2. On the second and third visit, the participants performed six constant workload tests (3 per session with intensities below VO2max. There was a predominance of MAL about MAA during the exercises sub-maximal from intensity corresponding to the LV2, being significantly higher at 90% VO2max (p < 0.05. Thus, these results may help coaches to implement training loads appropriate to their athletes, according to the metabolic demand of the competition.

  11. Intensidad del síndrome climatérico y su relación con algunos factores socioambientales Climateric syndrome intensity and its relation to some socio-environmental factors

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    Margeris Yanes Calderón

    2009-12-01

    Full Text Available Introducción: expresiones como ….estoy menopáusica, estoy vieja, lo que pasa es que estoy en el climaterio o es el cambio de edad…. suelen no faltar en la consulta multidisciplinaria de climaterio y menopausia del Policlínico «Ana Betancourt», del municipio Playa. Ello motivó la realización de esta investigación, dejando atrás el enfoque biomédico con el que se ha manejado el período climatérico hasta nuestros días para avanzar hacia un enfoque médico social. Objetivo: determinar cómo influyen los factores socioambientales en la intensidad del síndrome climatérico. Métodos: se realizó un estudio descriptivo transversal de 192 mujeres climatéricas pertenecientes a 3 consultorios médicos del Policlínico Universitario «Ana Betancourt», en el municipio Playa de Ciudad de La Habana, en el período comprendido entre junio del año 2006 y mayo de 2007. Resultados: el síndrome climatérico leve prevaleció en el 42,18 % de las mujeres estudiadas, y aquellas con elevado grado de escolaridad tienen una incidencia mayor de síndrome climatérico asintomático o leve; se demostró una estrecha relación entre las mujeres con síndrome climatérico moderado y el funcionamiento familiar disfuncional; las mujeres trabajadoras tienen una tendencia a presentar un síndrome climatérico menos intenso y así lo refleja más del 33 % de ellas, y quedó demostrado que más del 30 % de las mujeres con buena satisfacción de sus necesidades básicas y un entorno higiénico habitacional bueno, tienen una mayor incidencia de síndrome climatérico asintomático o leve, lo cual guarda una estrecha relación con las características socioculturales y económicas del área de salud estudiada. Conclusiones: las mujeres con mayor grado de escolaridad, con estabilidad conyugal y vínculo laboral, que formen parte, además, de familias funcionales o moderadamente funcionales, y que tengan un entorno higiénico habitacional bueno en correspondencia

  12. Efectos de un protocolo de entrenamiento de alta intensidad sobre marcadores fisiológicos de estrés en ratas. [Physiological effects of the stress induced by a high-intensity exercise protocol in rats].

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    Gerardo Medina

    2015-04-01

    Full Text Available El objetivo del presente estudio fue examinar los posibles efectos del estrés fisiológico producidos por un programa de entrenamiento de alta intensidad (EAI en ratas. Cuarenta ratas Wistar fueron aleatoriamente distribuidas en 2 grupos experimentales: grupo EAI o grupo control, durante 12 semanas. Se estimaron índices biológicos, parámetros musculares, urinarios, plasmáticos, de perfil lipídico hepático y morfológicos renales. Tanto la ingesta media (P<0.05 como el peso final y de la canal (ambos, P<0,001 fueron menores en el grupo EAI. Los marcadores hormonales reflejaron mayores concentraciones de corticosterona (P<0.05 junto con una disminución de las de testosterona (P<0.05 en el grupo EAI, por lo que la ratio corticosterona/testosterona fue mayor y la de testosterona/corticosterona menor (ambas, P<0.01. A nivel lipídico plasmático, el grupo EAI mostró menores concentraciones de triglicéridos (P<0.01, pero también mayores de colesterol-LDL (P<0.01. A nivel lipídico hepático, la cantidad de grasa fue mayor en el grupo EAI (P<0.01, aunque dicho grupo también presentó menores niveles de triglicéridos (P<0.05. El análisis de morfología renal mostró un aumento del tejido conectivo intersticial en el grupo de EAI (P<0.05. El estrés inducido por el protocolo de EAI pudo conllevar un estado catabólico que podría haber anulado las esperadas ganancias musculares, alteró el perfil lipídico plasmático y hepático y un perfil renal con mayor predisposición a patologías futuras El presente estudio trata de reproducir un modelo de estrés/sobreentrenamiento que podría darse en deportistas con la intención de profundizar algo más en el conocimiento del alcance que este estado fisiológico pudiera inducir a largo plazo en órganos poco estudiados y con ello, en la salud futura del deportista. Abstract The objective of this study was to examine the possible stress physiological effects of a high-intensity training (HIT in

  13. Análisis estacional de la frecuencia diaria y la intensidad de los extremos de precipitación sobre el sudeste de Sudamérica Seasonal analysis of daily frequency and extreme intensity of precipitation in the Southeast of South America

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    Federico A. Robledo

    2007-12-01

    Full Text Available En este trabajo se profundiza en el conocimiento de la variabilidad espacial de la precipitación, estudiando la cantidad de días con precipitación y la intensidad media diaria (en milímetros por día, con énfasis en los extremos, definidos a partir de diferentes umbrales. La base de datos utilizada en este trabajo consta de 58 estaciones pluviométricas ubicadas al sudeste de Sudamérica, para la segunda mitad del siglo XX. De noviembre a marzo, dos áreas núcleos centradas en 68º O - 25º S y 45º O - 22º S, presentan más de 50% de días de precipitación por encima de 0,1 mm, mientras que para el resto de la región no se supera el 32%. El patrón de extremos de precipitación, por encima del percentil 75, no muestra grandes diferencias espaciales y estacionales con respecto a los del umbral 0,1mm. Sin embargo la intensidad media diaria de precipitación extrema se incrementa considerablemente con respecto al umbral 0,1mm. En el área núcleo centrada en 45º O - 22º S, la intensidad es de 36 mm/día en verano, y de 20 mm/día en invierno. Mientras que sobre el noroeste de Argentina, supera 38mm/día (8 mm/día en verano (invierno. En la provincia de Buenos Aires la intensidad media diaria extrema de precipitación es de 32mm/día (20mm/día en verano (invierno.In this paper the climatology of the different components that composed the monthly rainfall was actualized and extended. For this purpose, we calculated the frequency of daily rainfall and the mean daily intensity for the second half of the century. 58 stations were used for this study. In addition we calculated the climatology for the daily extreme rainfall and its intensity, defining different thresholds according to the regions. Between November and March, we observed two centers (65º W -25º S and 45º W - 22º S with more than 50% of days with daily rainfall above 0.1 millimeters (mm , and lower values in the rest of the region. Spatial patterns and seasonal variation

  14. Adaptações fisiológicas e anatômicas de Melissa officinalis L. (Lamiaceae cultivadas sob malhas termorrefletoras em diferentes intensidades luminosas Physiological and morphological adaptations of Melissa officinalis L. (Lamiaceae cultivated under thermo-reflector shading nets at different luminous intensities

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    R.S. Brant

    2011-01-01

    Full Text Available Objetivou-se, com a realização da pesquisa, avaliar modificações fisiológicas e anatômicas em plantas de melissa, cultivadas sob malhas termorrefletoras (Aluminet®, em diferentes níveis de sombreamento, visando conhecer a plasticidade fenotípica em resposta de adaptação a diferentes quantidades de luz. Os tratamentos foram caracterizados por plantas submetidas a pleno sol e a 20 e 60% de intensidade luminosa, e arranjados conforme o delineamento inteiramente casualizado (DIC. As quantificações de clorofila foram feitas em quatro repetições, as medições das epidermes e parênquimas foram repetidas 15 vezes e utilizou-se 10 repetições para as avaliações das características de cloroplastos e grãos de amido destes. Plantas submetidas a 20% de intensidade luminosa apresentaram maior quantidade de clorofila a e, portanto, maior razão clorofila a/b. Comparativamente, as folhas de melissa a pleno sol e a 60% de luz apresentaram células da epiderme adaxial mais espessas, mas as células da epiderme abaxial mostraram características encontradas em folhas de sombra, ou seja, mais finas. Quanto maior a intensidade luminosa, maior o número de cloroplastos, porém, a pleno sol mostraram-se mais finos e com menor área. Os grãos de amido de plantas cultivadas sob ambientes sombreados tiveram maior área e ocuparam maior parte nos cloroplastos de plantas a 60% de intensidade luminosa. Assim, plantas de melissa, quando submetidas ao sombreamento, tiveram plasticidade fenotípica.The aim of this study was to evaluate physiological and anatomical modifications in lemon balm plants, cultivated under thermo-reflector nets (Aluminet® at different levels of shading, in order to understand the phenotypic plasticity in adaptation response to different light quantities. The treatments were characterized by plants subjected to full sun and 20 and 60% of luminous intensity, and arranged in completely randomized design (CRD. The quantifications

  15. Grazing intensity and nitrogen in oat dry mass and yield of corn crop livestock systemsIntensidade de pastejo e adubação nitrogenada na massa seca de aveia e produtividade do milho na integração lavoura-pecuária

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    Claudete Reisdorfer Lang

    2012-08-01

    Full Text Available This study aimed to evaluate the impact of different grazing intensities and nitrogen fertilization applied on oats and its effect upon maize cultivated in succession in a no tillage system. The experiment was carried out at Abelardo Luz municipality during the winter and summer seasons of 2004/2005. The experimental design was a completely randomized block in a split-plot arrangement with four replicates. Treatments were five different grazing intensities, represented by utilization periods in an oat culture grazed for 0, 3, 6, 9 and 12 weeks, and at sub-plot level nitrogen doses were applied at 0 and 150 kg/ ha. The availability and residual dry matter of oat was evaluated each three weeks after the beginning of grazing until the drying of the pasture. Was also evaluated the yield of maize after oat under different intensities of grazing and nitrogen fertilization. Results indicated the existence of interaction between grazing and winter nitrogen fertilization, which affected maize nutrition and yield. Moreover, the oat residual dry matter availability was positively influenced by applied nitrogen. The nitrogen in the pasture, besides favoring the production of residual dry matter of oats, determines the greatest potential productivity of corn in sequence. In the absence of nitrogen fertilization on winter pastures, the grazing intensity should be reduced so as not to affect the productivity of maize.Este trabalho objetivou verificar o impacto da aplicação de diferentes intensidades de pastejo e da adubação nitrogenada na cultura da aveia, e sua influência na cultura do milho em sucessão, em sistema de plantio direto. O experimento foi implantado no município de Abelardo Luz – SC, durante o período de inverno e verão de 2004/2005. O delineamento foi o de blocos ao acaso com parcelas subdivididas e quatro repetições. Os tratamentos constituíram-se em cinco diferentes intensidades de pastejo na parcela, representadas por per

  16. Intensidade de colonização do córtex radicular e sua relação com a absorção de fósforo pelo capim-pensacola Intensity of root cortex colonization and its relation with phosphorus uptake by pensacola grass

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    Danilo dos Santos Rheinheimer

    1995-01-01

    Full Text Available Em plantas micorrizadas, após a colonização do córtex radicular, as hifas fúngicas extendem-se no solo absorvendo uma maior quantidade de nutrientes, especialmente o fósforo. Este trabalho tem por objetivo avaliar a relação entre porcentagem e intensidade de colonização do córtex radicular com a absorção de fósforo. Usou-se os resultados de três experimentos desenvolvidos no Departamento de Solos da Universidade Federal de Santa Maria, no período de 1989 a 1992. No primeiro, usou-se cinco níveis de calagem representados por valores de pH (4,6; 5,0; 5,5; 6, 1 e 6,6 e duas doses de P2O5 (0 e 20mg/kg; no segundo, os mesmos valores de pH e quatro doses de P2O5 (0, 20, 50 e 70mg/kg e no terceiro, dois valores de pH (4,6 e 6,1 e três doses de P2O5, (50, 150 e 250mg/kg. Em todos os experimentos usaram-se três níveis de micorrização (solo fumigado, solo fumigado + esporos de fungos micorrízicos arbusculares (fMA nativos e solo natural e pensacola como planta hospedeira. Avaliou-se o fósforo absorvido pela parte aérea, a porcentagem e intensidade de colonização. Na avaliação da intensidade levou-se em consideração a presença de hifas internas e arbúsculos, atribuindo-se notas de 1 a 5. O córtex apresentou-se densamente colonizado pelas estruturas fúngicas em condições de solo ácido e com baixa disponibilidade de fósforo, coincidindo com as maiores absorções de fósforo. Em todos os experimentos e tratamentos a intensidade mostrou-se ser um parâmetro confiável na predição de absorção de fósforo pela pensacola.Plants colonized by mycorrhizal fungi are able to uptake more nutrients, especially phosphorus, than those without colonization due to the increase in the uptake área. The objective of this study was to evaluate the rate and the intensity of mycorrhizal colonization in Paspalum notatum roots and their correlation with P uptake. The data were obtained from three different experiment carried out in a

  17. Biomarcadores de estresse em ratos exercitados por natação em intensidades igual e superior à máxima fase estável de lactato Biomarkers of stress in rats exercised in swimming at intensities equal and superior to the maximal estable lactate phase

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    Ricardo Vinicius Ledesma Contarteze

    2007-06-01

    Full Text Available INTRODUÇÃO: O estresse alcançado durante exercício agudo/crônico é relevante, pois altos índices de estresse podem prejudicar o bem-estar dos animais. As concentrações dos hormônios adrenocorticotrófico (ACTH e corticosterona, bem como as concentrações de ácido ascórbico e colesterol das glândulas adrenais são importantes biomarcadores de estresse. OBJETIVO: Analisar a sensibilidade de diferentes biomarcadores de estresse em ratos durante exercício agudo de natação em diferentes intensidades. MÉTODO: Ratos (18 adaptados à natação foram submetidos a três testes de 25 minutos suportando cargas 5,0; 5,5 e 6,0% do peso corporal (PC, para obtenção da máxima fase estável de lactato (MFEL. Em seguida, os animais foram divididos em dois grupos: M (n = 9, sacrificado após 25 minutos de exercício na intensidade de MFEL e S (n = 9, sacrificado após exercício exaustivo, em intensidade 25% superior a MFEL. Para comparações, um grupo controle C (n = 10 foi sacrificado em repouso. RESULTADOS: As concentrações séricas de ACTH e corticosterona foram superiores após exercício em ambas as intensidades comparadas com o grupo controle (P INTRODUCTION: The level of stress during acute/chronic exercise is important, since higher levels of stress may impair animal welfare. The adrenocorticotrophic (ACTH and corticosterone hormone concentrations, as well as cholesterol and ascorbic acid concentrations in adrenal gland, are considered an important stress biomarker. PURPOSE: To analyze the sensitivity of the different biomarkers during acute swimming exercise in different intensities performed by rats. METHODS: Male Wistar adult rats (n = 18 previously adapted to swimming were submitted to three 25 min. swimming tests with loads of 5.0; 5.5 and 6.0% of their body weight (BW, for maximum lactate steady state (MLSS determination. After MLSS attainment, the animals were divided into two groups: M (n = 9 sacrificed shortly after a 25

  18. Efeitos da intensidade do exercício e da neuromodulação sobre o controle inibitório, oxigenação cerebral e regulação autonômica cardíaca: estudo de intervenção randomizado

    OpenAIRE

    Fonteles, André Igor

    2017-01-01

    Existe um crescente interesse nos efeitos das intervenções não farmacológicas sobre as funções cognitivas. O exercício físico e a estimulação transcraniana por corrente continua (ETCC) promovem aumento da oxigenação cerebral no qual beneficia a função cerebral, e também, o controle inibitório. O objetivo do estudo foi analisar os efeitos da intensidade do exercício físico e da estimulação transcraniana por corrente contínua associado ao exercício físico agudo sobre controle ...

  19. Intervalo e intensidade de desfolhação nas taxas de crescimento, senescência e desfolhação e no equilíbrio de gramíneas em associação Interval and intensity of defoliation on the growth, senescence and defoliation fluxes and equilibrium of associated grasses

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    Andréa Machado Groff

    2002-09-01

    Full Text Available O experimento foi realizado no INRA (Institut National de la Recherche Agronomique em Theix, França. Duas gramíneas (azevém perene e festucaforam semeadas em caixas (0,13 m² e submetidas a três intervalos (3,5, 7 e 14 dias e três intensidades (160, 320 e 640 bocados.m-2 a cada desfolhação de desfolhação, com quatro repetições por tratamento. Quatro meses após a semeadura, a cada data de desfolhação, as caixas foram oferecidas, individualmente, a quatro ovelhas secas e retiradas após a realização de um determinado número de bocados. Para cada gramínea foram estudadas as taxas de crescimento, senescência e desfolhação. Os resultados mostraram que o intervalo e a intensidade de desfolhação tiveram efeitos diferenciados nas taxas de crescimento, senescência e desfolhação e no equilíbrio da associação.The experiment was carried in INRA (Institut National de la Recherche Agronomique at Theix, France. Two grasses (perennial ryegrass and tall fescue were grown in sward boxes (0,13 m² and submitted to three defoliation intervals (3,5, 7 and 14 days between two successive defoliation and three defoliation intensities (160, 320 and 640 bites.m-2 at each defoliation. Four months after sowing, at defoliation date, sward boxes were offered to four individual dry ewes and removed after a given number of bites had been taken. For each grass species, the growth, senescence and defoliation fluxes were studied. The results showed that the interval and the intensity of grazing had distinct effects on the growth, senescence and defoliation fluxes as well as on the equilibrium of grass mixtures.

  20. Effects of Variable Dose-Rates on Radiation Damage in the Rust-Red Flour Beetle, Tribolium Castaneum Herbst; Effets du debit de dose sur les dommages radioinduits chez le tenebrion roux (Tribolium Castaneum Herbst); Vliyanie razlichnykh moshchnostej doz na radiatsionnoe povrezhdenie krasnogo muchnogo zhuka, Tribolium Castaneum (Herbst); Radio lesiones que sufre el Tribolium Castaneum Herbst cuando se le somete a dosis de radiaciones de diversas intensidades

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    Nair, K. K.; Subramanyam, G. [Biology Division, Atomic Energy Establishment, Trombay, Bombay (India)

    1963-09-15

    In order to find out whether a change in dose-rate would significantly alter a radiation response, eggs as well as the adults of Tribolium castaneum were tested for viability and fertility respectively after exposure to gamma radiation at different dose-rates. The doses employed were 2000 and 5000 rad and the dose-rates ranged from 126 rad/h to 140 000 rad/h. It was observed that with an increase in dose-rate there was a decline in the fertility of the adults. Similarly the viability of the eggs was considerably reduced as the dose-rate increased, but at very high dose-rates there was a significant increase in viability. The significance of these findings is discussed. (author) [French] En vue de determiner si une variation du debit de dose modifie de maniere significative la reponse aux rayonnements, on a fait des essais sur des oeufs et des adultes de Tribolium castaneum, dont on a etudie respectivement la viabilite et la fecondite apres exposition a des doses de rayons gamma d'intensites differentes. On a administre des doses de 2000 et 5000 rad, le debit de dose variant de 126 a 140 000 rad/h. On a constate que la fecondite des adultes diminuait a mesure que le debit de dose augmentait. De meme, la viabilite des oeufs etait considerablement reduite a mesure que le debit de dose augmentait, mais pour des debits de dose tres eleves la viabilite augmentait sensiblement. Les auteur