238 research outputs found

    Error-Prone Translesion DNA Synthesis by Escherichia coli DNA Polymerase IV (DinB) on Templates Containing 1,2-dihydro-2-oxoadenine

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    Escherichia coli DNA polymerase IV (Pol IV) is involved in bypass replication of damaged bases in DNA. Reactive oxygen species (ROS) are generated continuously during normal metabolism and as a result of exogenous stress such as ionizing radiation. ROS induce various kinds of base damage in DNA. It is important to examine whether Pol IV is able to bypass oxidatively damaged bases. In this study, recombinant Pol IV was incubated with oligonucleotides containing thymine glycol (dTg), 5-formyluracil (5-fodU), 5-hydroxymethyluracil (5-hmdU), 7,8-dihydro-8-oxoguanine (8-oxodG) and 1,2-dihydro-2-oxoadenine (2-oxodA). Primer extension assays revealed that Pol IV preferred to insert dATP opposite 5-fodU and 5-hmdU, while it inefficiently inserted nucleotides opposite dTg. Pol IV inserted dCTP and dATP opposite 8-oxodG, while the ability was low. It inserted dCTP more effectively than dTTP opposite 2-oxodA. Pol IV's ability to bypass these lesions decreased in the order: 2-oxodA > 5-fodU~5-hmdU > 8-oxodG > dTg. The fact that Pol IV preferred to insert dCTP opposite 2-oxodA suggests the mutagenic potential of 2-oxodA leading to A:T→G:C transitions. Hydrogen peroxide caused an ~2-fold increase in A:T→G:C mutations in E. coli, while the increase was significantly greater in E. coli overexpressing Pol IV. These results indicate that Pol IV may be involved in ROS-enhanced A:T→G:C mutations

    Dysbiosis of the gut microbiota as a susceptibility factor for Kawasaki disease

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    IntroductionGut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD. MethodsFecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.ResultsFor alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia. Discussion and conclusionRuminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD

    Early gastric cancer detection in high-risk patients: a multicentre randomised controlled trial on the effect of second-generation narrow band imaging

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    Objective: Early detection of gastric cancer has been the topic of major efforts in high prevalence areas. Whether advanced imaging methods, such as second-generation narrow band imaging (2G-NBI) can improve early detection, is unknown. Design: This open-label, randomised, controlled tandem trial was conducted in 13 hospitals. Patients at increased risk for gastric cancer were randomly assigned to primary white light imaging (WLI) followed by secondary 2G-NBI (WLI group: n=2258) and primary 2G-NBI followed by secondary WLI (2G-NBI group: n=2265) performed by the same examiner. Suspected early gastric cancer (EGC) lesions in both groups were biopsied. Primary endpoint was the rate of EGC patients in the primary examination. The main secondary endpoint was the positive predictive value (PPV) for EGC in suspicious lesions detected (primary examination). Results: The overall sensitivity of primary endoscopy for the detection of EGC in high-risk patients was only 75% and should be improved. 2G-NBI did not increase EGC detection rate over conventional WLI. The impact of a slightly better PPV of 2G-NBI has to be evaluated further. Trial registration number: UMIN000014503

    Rituximab-combination chemotherapy achieves a 10th cycle of remission for Burkitt's lymphoma.

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    A 14-year-old girl with multiple intra-abdominal tumors was diagnosed with stage III Burkitt's lymphoma. She achieved complete remission after multi-drug chemotherapy, but she relapsed after six courses. Autologous peripheral blood stem cells (PBSC) or allogeneic PBSC harvested from an HLA-identical sibling were insufficient, and her family did not agree to bone marrow collection from the sibling. Although the patient relapsed nine times (the relapses involved intra-abdominal organs or bone) during the following 4 years 7 months, treatment with rituximab monotherapy or in combination with ifosphamide, carboplastin, and etoposide, or local irradiation (33.8-40.0 Gy) to treat the bone metastases, proved effective, resulting in complete or partial remission. At the time of writing, the patient was in a 10th cycle of remission lasting 1 year 6 months and had not required transplantation. Thus, a chemotherapy regimen including rituximab might be effective for Burkitt's lymphoma in patients experiencing multiple relapse
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