Search results for "Repair"
showing 10 items of 747 documents
Urethrocutaneous fistula repair after hypospadias surgery
2003
OBJECTIVE To evaluate and compare the success rates of simple and layered repairs of urethrocutaneous fistulae after hypospadias repair. PATIENTS AND METHODS The charts of 72 children who developed fistulae after hypospadias repair were reviewed; 39 had a simple closure of the fistula, whereas 32 had a 'pants over vest' repair, in all cases after excluding an impairment of urine outflow. RESULTS The success rate at the first attempt was 74% for simple closure and 94% for the layered repair; at the second attempt it was 80% and 100%, the difference being statistically significant for both repairs. CONCLUSIONS Although probably far from an optimal technique for repairing urethrocutaneous fist…
Preface to special issue on "Peripheral Nerve Repair and Regeneration"
2015
Editorial
Mouse embryonic stem cells are hypersensitive to apoptosis triggered by the DNA damage O(6)-methylguanine due to high E2F1 regulated mismatch repair.
2007
Exposure of stem cells to genotoxins may lead to embryonic lethality or teratogenic effects. This can be prevented by efficient DNA repair or by eliminating genetically damaged cells. Using undifferentiated mouse embryonic stem (ES) cells as a pluripotent model system, we compared ES cells with differentiated cells, with regard to apoptosis induction by alkylating agents forming the highly mutagenic and killing DNA adduct O(6)-methylguanine. Upon treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ES cells undergo apoptosis at much higher frequency than differentiated cells, although they express a high level of the repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Apo…
Stem cells, cancer stem-like cells, and natural products.
2012
Somatic stem cells can be found in many rapidly regenerating tissues, e.g., the skin, gastrointestinal mucosa, and hematopoietic system, but are also present at low numbers in non-regenerative organs such as the heart and brain. In these organs, somatic stem cells aid in normal tissue homeostasis and repair after injury as well as self-renewal and the generation of specific progenitor cells during differentiation. Cancer stem-like cells are a small subpopulation of self-renewing cells that are able to proliferate upon appropriate stimulation and differentiate into heterogeneous lineages in tumors. Modulation of the behavior of normal tissue stem cells and cancer stem-like cells is an emergi…
“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres
2020
Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome in interphase, is a typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort the damaged DNA into the cytoplasm. In this study, we explored MS in the MDA-MB-231 cell line treated with doxorubicin (DOX). We found selective release into the cytoplasm of telomere fragments enriched in telomerase reverse transcriptase (hTERT), telomere capping protein TRF2, and DNA double-strand breaks marked by γH2AX, in association with ubiquitin-binding protein SQSTM1/p62. This occurs along with the alternative lengthening of telomeres (ALT) and DNA repa…
Injuries of the lateral collateral ligaments of the ankle: assessment with MR imaging.
1999
The aim of this study was to evaluate the ability of MRI to display injuries of the lateral collateral ligamentous complex in patients with an acute ankle distorsion trauma. The MR examinations of 36 patients with ankle pain after ankle distorsion were evaluated retrospectively without knowledge of clinical history, outcome and/or operative findings. The examinations were performed on a 1. 5-T whole-body imager using a flexible surface coil. The signs for ligamentous abnormality were as follows: complete or partial discontinuity, increased signal within, and irregularity and waviness of the ligament. The results were compared with operative findings in 18 patients with subsequent surgical r…
Cell fate regulation upon DNA damage : p53 Serine 46 kinases pave the cell death road
2019
Mild and massive DNA damage are differentially integrated into the cellular signaling networks and, in consequence, provoke different cell fate decisions. After mild damage, the tumor suppressor p53 directs the cellular response to cell cycle arrest, DNA repair, and cell survival, whereas upon severe damage, p53 drives the cell death response. One posttranslational modification of p53, phosphorylation at Serine 46, selectively occurs after severe DNA damage and is envisioned as a marker of the cell death response. However, the molecular mechanism of action of the p53 Ser46 phospho-isomer, the molecular timing of this phosphorylation event, and its activating effects on apoptosis and ferropt…
DNA damage-induced cell death by apoptosis
2006
Following the induction of DNA damage, a prominent route of cell inactivation is apoptosis. During the last ten years, specific DNA lesions that trigger apoptosis have been identified. These include O6-methylguanine, base N-alkylations, bulky DNA adducts, DNA cross-links and DNA double-strand breaks (DSBs). Repair of these lesions are important in preventing apoptosis. An exception is O6-methylguanine-thymine lesions, which require mismatch repair for triggering apoptosis. Apoptosis induced by many chemical genotoxins is the consequence of blockage of DNA replication, which leads to collapse of replication forks and DSB formation. These DSBs are thought to be crucial downstream apoptosis-tr…
Loss of ATM sensitizes against O6-methylguanine triggered apoptosis, SCEs and chromosomal aberrations.
2003
A critical pre-cytotoxic and -apoptotic DNA lesion induced by methylating carcinogens and chemotherapeutic drugs is O6-methylguanine (O6MeG). The mechanism by which O6MeG causes cell death via apoptosis is only partially understood. The current model ascribes a role to DNA replication and mismatch repair, which converts O6MeG into a critical distal lesion (presumably a DNA double-strand break) that is finally responsible for genotoxicity and apoptosis. Here we analysed whether the PI3-like kinase ATM is involved in this process. ATM is a major player in recognizing and signaling DNA breaks, but most reports are limited to ionizing radiation. Comparing mouse ATM knockout fibroblasts (ATM-/-)…
Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O6-methylguanine triggered apoptosis, DSBs and chromosomal aberrations by …
2008
Abstract O 6 -methylguanine (O 6 MeG) is a highly critical DNA adduct induced by methylating carcinogens and anticancer drugs such as temozolomide, streptozotocine, procarbazine and dacarbazine. Induction of cell death by O 6 MeG lesions requires mismatch repair (MMR) and cell proliferation and is thought to be dependent on the formation of DNA double-strand breaks (DSBs) or, according to an alternative hypothesis, direct signaling by the MMR complex. Given a role for DSBs in this process, either homologous recombination (HR) or non-homologous end joining (NHEJ) or both might protect against O 6 MeG. Here, we compared the response of cells mutated in HR and NHEJ proteins to temozolomide and…