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  1. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

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    Franklin, J.M., E-mail: jamiemfranklin@hotmail.com [Churchill Hospital, Headington, Oxford (United Kingdom); Anderson, E.M.; Gleeson, F.V. [Churchill Hospital, Headington, Oxford (United Kingdom)

    2012-06-15

    Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having {>=}80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

  2. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

    International Nuclear Information System (INIS)

    Franklin, J.M.; Anderson, E.M.; Gleeson, F.V.

    2012-01-01

    Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

  3. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Kristiansen, C.; Loft, A.; Berthelsen, Anne Kiil

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography Udgivelsesdato: 2008/1...... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic...

  4. Repair of bone defect by nano-modified white mineral trioxide aggregates in rabbit: A histopathological study.

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    Saghiri, Mohammad-Ali; Orangi, Jafar; Tanideh, Nader; Asatourian, Armen; Janghorban, Kamal; Garcia-Godoy, Franklin; Sheibani, Nader

    2015-09-01

    Many researchers have tried to enhance materials functions in different aspects of science using nano-modification method, and in many cases the results have been encouraging. To evaluate the histopathological responses of the micro-/nano-size cement-type biomaterials derived from calcium silicate-based composition with addition of nano tricalcium aluminate (3CaO.Al2O3) on bone healing response. Ninety mature male rabbits were anesthetized and a bone defect was created in the right mandible. The rabbits were divided into three groups, which were in turn subdivided into five subgroups with six animals each based on the defect filled by: white mineral trioxide aggregate (WMTA), Nano-WMTA, WMTA without 3CaO.Al2O3, Nano-WMTA with 2% Nano-3CaO.Al2O3, and empty as control. Twenty, forty and sixty days postoperatively the animals were sacrificed and the right mandibles were removed for histopathological evaluations. Kruskal-Wallis test with post-hoc comparisons based on the LSMeans procedure was used for data analysis. All the experimental materials provoked a moderate to severe inflammatory reaction, which significantly differed from the control group (pbone formation and bone regeneration data showed significant differences between groups at 40- and 60- day intervals in all groups. Absence of 3CaO.Al2O3 leads to more inflammation and foreign body reaction than other groups in all time intervals. Both powder nano-modification and addition of 2% Nano-3CaO.Al2O3 to calcium silicate-based cement enhanced the favorable tissue response and osteogenesis properties of WMTA based materials.

  5. Human longevity and variation in DNA damage response and repair

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette; Flachsbart, Friederike

    2014-01-01

    others. Data were applied on 592 SNPs from 77 genes involved in nine sub-processes: DNA-damage response, base excision repair (BER), nucleotide excision repair, mismatch repair, non-homologous end-joining, homologous recombinational repair (HRR), RecQ helicase activities (RECQ), telomere functioning...... in genotyping procedures and investigated SNPs, potentially inducing differences in the coverage of gene regions. Specifically, five genes were not covered at all in the German data. Therefore, investigations in additional study populations are needed before final conclusion can be drawn....

  6. PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Loft, Annika; Berthelsen, Anne K

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography....... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral(R) (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared...

  7. Hemolymph chemistry and histopathological changes in Pacific oysters (Crassostrea gigas) in response to low salinity stress.

    Science.gov (United States)

    Knowles, Graeme; Handlinger, Judith; Jones, Brian; Moltschaniwskyj, Natalie

    2014-09-01

    This study described seasonal differences in the histopathological and hemolymph chemistry changes in different family lines of Pacific oysters, Crassostrea gigas, in response to the stress of an abrupt change to low salinity, and mechanical grading. The most significant changes in pallial cavity salinity, hemolymph chemistry and histopathological findings occurred in summer at low salinity. In summer (water temperature 18°C) at low salinity, 9 (25.7% of full salinity), the mean pallial cavity salinity in oysters at day 3 was 19.8±1.6 (SE) and day 10 was 22.8±1.6 (SE) lower than oysters at salinity 35. Associated with this fall in pallial cavity salinity, mean hemolymph sodium for oysters at salinity 9 on day 3 and 10 were 297.2mmol/L±20(SE) and 350.4mmol/L±21.3(SE) lower than oysters at salinity 35. Similarly mean hemolymph potassium in oysters held at salinity 9 at day 3 and 10 were 5.6mmol/L±0.6(SE) and 7.9mmol/L±0.6 (SE) lower than oysters at salinity 35. These oysters at low salinity had expanded intercellular spaces and significant intracytoplasmic vacuolation distending the cytoplasm of epithelial cells in the alimentary tract and kidney and hemocyte infiltrate (diapedesis) within the alimentary tract wall. In contrast, in winter (water temperature 8°C) oyster mean pallial cavity salinity only fell at day 10 and this was by 6.0±0.6 (SE) compared to that of oysters at salinity 35. There were limited histopathological changes (expanded intercellular spaces and moderate intracytoplasmic vacuolation of renal epithelial cells) in these oysters at day 10 in low salinity. Mechanical grading and family line did not influence the oyster response to sudden low salinity. These findings provide additional information for interpretation of non-lethal, histopathological changes associated with temperature and salinity variation. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review.

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    García-Castellano, José M; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H

    2012-01-01

    Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into "good" and "poor" responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

  9. Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review

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    José M. García-Castellano

    2012-01-01

    Full Text Available Ewing’s sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing’s sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing’s sarcoma into “good” and “poor” responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing’s sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

  10. Tributyltin toxicity in abalone (Haliotis diversicolor supertexta) assessed by antioxidant enzyme activity, metabolic response, and histopathology.

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    Zhou, Jin; Zhu, Xiao-shan; Cai, Zhong-hua

    2010-11-15

    A toxicity test was performed to investigate the possible harmful effects of tributyltin (TBT) on abalone (Haliotis diversicolor supertexta). Animals were exposed to TBT in a range of environmentally relevant concentrations (2, 10 and 50 ng/L) for 30 days under laboratory conditions. TBT-free conditions were used as control treatments. The activity of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA), along with levels of haemolymph metabolites, and hepatopancreas histopathology were analyzed. The results showed that TBT decreased SOD activity, and increased POD level and MDA production in a dose-dependent way, indicating that oxidative injury was induced by TBT. Haemolymph metabolite measurements showed that TBT increased alanine and glutamate levels, and decreased glucose content, which suggested perturbation of energy metabolism. Elevated levels of acetate and pyruvate in the haemolymph indicated partial alteration of lipid metabolism. A decrease in lactate and an increase in succinate, an intermediate of the tricarboxylic acid (TCA) cycle, indicated disturbance of amino acid metabolism. Hepatopancreas tissues also exhibited inflammatory responses characterized by histopathological changes such as cell swelling, granular degeneration, and inflammation. Taken together, these results demonstrated that TBT was a potential toxin with a variety of deleterious effects on abalone. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Comparison between CT volume measurement and histopathological assessment of response to neoadjuvant therapy in rectal cancer

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    Pomerri, Fabio, E-mail: fabio.pomerri@unipd.it [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy); Department of Medicine, University of Padua, via Giustiniani 2, 35128 Padua (Italy); Pucciarelli, Salvatore, E-mail: puc@unipd.it [Department of Oncological and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padua (Italy); Gennaro, Gisella, E-mail: gisella.gennaro@pd.infn.it [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy); Maretto, Isacco, E-mail: isac77@gmail.com [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy); Nitti, Donato, E-mail: donato.nitti@unipd.it [Department of Oncological and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padua (Italy); Muzzio, Pier Carlo, E-mail: pcmuzzio@unipd.it [Veneto Institute of Oncology IOV-IRCCS, via Gattamelata 64, 35128 Padua (Italy)

    2012-12-15

    Objectives: The aim of this study was to compare volume measurements on computed tomography (CT) images with histopathological assessments of chemoradiotherapy (CRT)-induced tumor regression in locally advanced rectal cancer (RC). Methods: In 25 patients (13 males, 12 females; median age, 63 years; age range, 44–79 years) with locally advanced RC treated with preoperative CRT and surgery, two radiologists measured tumor volume on CT images before and after CRT. CT-based tumor volumetry and the modified response evaluation criteria in solid tumors (mRECISTs) were compared with T and N downstaging after CRT, and with the tumor regression grade (TRG). Results: Tumor volumes were significantly smaller on CT images after CRT. The tumors regressed in 52% (13/25), 36% (9/25) and 40% (10/25) of patients, based on T downstaging, TRG and mRECIST findings, respectively. In terms of T downstaging, the pre- and post-CRT tumor volumes of responders and non-responders to the treatment differed statistically, while their tumor volume reduction rates and volume reductions according to the 65% mRECIST threshold did not. In terms of N downstaging and TRG, the differences between the responders’ and the non-responders’ pre- and post-CRT tumor volumes, tumor volume reduction rates, and mRECIST thresholds were never statistically significant. Conclusion: Measuring tumor size on CT images is of limited value in predicting the histopathological response to preoperative CRT in RC patients, so it may be unwise to select surgical treatment strategies based on CT volumetry.

  12. The Seed Repair Response during Germination: Disclosing Correlations between DNA Repair, Antioxidant Response, and Chromatin Remodeling in Medicago truncatula

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    Andrea Pagano

    2017-11-01

    Full Text Available This work provides novel insights into the effects caused by the histone deacetylase inhibitor trichostatin A (TSA during Medicago truncatula seed germination, with emphasis on the seed repair response. Seeds treated with H2O and TSA (10 and 20 μM were collected during imbibition (8 h and at the radicle protrusion phase. Biometric data showed delayed germination and impaired seedling growth in TSA-treated samples. Comet assay, performed on radicles at the protrusion phase and 4-days old M. truncatula seedlings, revealed accumulation of DNA strand breaks upon exposure to TSA. Activation of DNA repair toward TSA-mediated genotoxic damage was evidenced by the up-regulation of MtOGG1(8-OXOGUANINE GLYCOSYLASE/LYASE gene involved in the removal of oxidative DNA lesions, MtLIGIV(LIGASE IV gene, a key determinant of seed quality, required for the rejoining of DNA double strand breaks and TDP(TYROSYL-DNA PHOSPHODIESTERASE genes encoding the multipurpose DNA repair enzymes tyrosyl-DNA phosphodiesterases. Since radical scavenging can prevent DNA damage, the specific antioxidant activity (SAA was measured by DPPH (1,1-diphenyl-2-picrylhydrazyl and Folin-Ciocalteu reagent assays. Fluctuations of SAA were observed in TSA-treated seeds/seedlings concomitant with the up-regulation of antioxidant genes MtSOD(SUPEROXIDE DISMUTASE, MtAPX(ASCORBATE PEROXIDASE and MtMT2(TYPE 2 METALLOTHIONEIN. Chromatin remodeling, required to facilitate the access of DNA repair enzymes at the damaged sites, is also part of the multifaceted seed repair response. To address this aspect, still poorly explored in plants, the MtTRRAP(TRANSFORMATION/TRANSACTIVATION DOMAIN-ASSOCIATED PROTEIN gene was analyzed. TRRAP is a transcriptional adaptor, so far characterized only in human cells where it is needed for the recruitment of histone acetyltransferase complexes to chromatin during DNA repair. The MtTRRAP gene and the predicted interacting partners MtHAM2 (HISTONE ACETYLTRANSFERASE OF

  13. Repair and dose-response at low doses

    International Nuclear Information System (INIS)

    Totter, J.R.; Weinberg, A.M.

    1977-04-01

    The DNA of each individual is subject to formation of some 2-4 x 10 14 ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If the probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis

  14. 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.

  15. NA{sup +}, K{sup +}-ATPase, histopathological, and genetic responses of Corbicula fluminea to sediment-associated copper

    Energy Technology Data Exchange (ETDEWEB)

    Brown, S. [Univ. of Mississippi, Oxford, MS (United States)

    1995-12-31

    Time-dependent responses to sediment-associated copper were studies at hierarchical levels of biological organization along an extreme concentration gradient (40 to 40,000 mg/kg total Cu). Laboratory and in situ estimates of molecular to tissue-level responses (Na/K-ATPase activity, DNA content, histopathology) were monitored in Corbicula fluminea (Asiatic clam), and compared with laboratory and field based survival of Corbicula and Elimia teres (an indigenous Gastropoda). Mollusc survival was, in turn, compared with effects on macrobenthic community composition along the stream/[Cu] gradient. Relationships between selected sediment characteristics and the bioavailability and toxicity of sediment associated copper were also investigated. Sediment-associated copper depressed Na/K-ATPase activity and led to histopathological damage of renal and gill epithelia (vacuolization, degeneration), indicating that impaired ion regulation was an important mechanism of toxicity. Concurrent reductions in DNA content were believed to be secondary effects due to cell death, not an indication of genotoxicity. Sublethal responses were significantly correlated with survival in both species; however, while survival in situ was indicative of differences in community structure, laboratory-based survival was not. Copper levels in tissues were indicative of exposure, but were not significantly correlated with adverse effects. Copper levels in sediments, interstitial water, and overlying water varied independently of sediment characteristics except pH. Cu/AVS ratios were predictive of Corbicula and Elimia survival, but were not significantly related to differences in community structure. Instead, macrobenthic community structure was influenced by other sediment factors (grain size, Eh, pH).

  16. Histopathological changes and inflammatory response induced by Tityus discrepans scorpion venom in rams.

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    D'Suze, G; Salazar, V; Díaz, P; Sevcik, C; Azpurua, H; Bracho, N

    2004-12-15

    Anesthetized rams envenomed s.c. with 40 microg/kg Tityus discrepans scorpion venom developed fasciculation, hypothermia, polyuria, pulmonary wet rales, tachypnea, respiratory distress and arrhythmia. Rams developed a cascade of inflammation reactions, characterized by activation of macrophages, fibroblasts and neutrophils, neutrophil infiltration and aggregation, vasculitis, arteritis and abundant fibrin deposition. At the inoculation site, venom was detected by immunohistochemistry in the extra cellular matrix, lymphatic vessels' and venules' lumen, inside macrophages and surrounding nerves. Extra cellular matrix was degraded at the inoculation site perhaps by activated neutrophils. Envenoming produced hepatocytes with Mallory body-like vacuoles which may be due to the increased plasmatic levels of TNF-alpha and IL6. Venom produced degranulation and vacuolization of acinary cells as well as interstitial swelling and necrosis. Necrosis of the Langerhan's islets occurred occasionally. Lungs showed the most deleterious effects developing wall collapse and necrosis, diffuse injury of the alveolar capillary barrier, interstitial and alveolar fibrin deposits with strong neutrophil infiltration. Massive infiltration of lymphocytes and macrophage occurred in the intestinal submucose, to the point that it modified villi and intestinal folding morphology. Envenomation developed a marked leukocyte aggregation surrounding nerves at the inoculation site. This study reveals that beyond its neurotoxicity, Tityus venom produces a severe and widespread inflammatory syndrome, expressed as histopathological changes at the site of inoculation, as well as in remote organs such as pancreas, lungs, intestine and liver. Our results suggest that not all remote targets are directly affected by the venom but that, as proposed earlier, are modified by inflammation by products produced elsewhere.

  17. Histopathologic and biochemical responses in Arctic marine bivalve molluscs exposed to experimentally spilled oil

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    Neff, J.M.; Hillman, R.E.; Carr, R.S.; Buhl, R.L.; Lahey, J.I.

    1987-01-01

    Following two experimental spills of chemically dispersed and undispersed crude oil in shallow bays on the northwest coast of Baffin Island bivalve molluscs accumulated significant amounts of petroleum hydrocarbons in bay receiving dispersed oil and in those receiving crude oil alone. Specimens of Mya truncata and Macoma calcarea for histopathologic examination were collected immediately before, immediately after and one year after the experimental oil spills. Immediately after there was increased gill and digestive tract necrosis in Mya from the chemically dispersed oil. After one year a few clams had granulocytomas throughout the tissues. Three clams receiving oil alone collected one year after the spill had invasive neoplasias. There were few lesions in Macoma immediatelly after or one year after the spill; animals had a high incidence of vacuolization of the digestive tubule epithelium. The incidence of parasitism and hemocytic infiltration also was higher in Maccoma. Clams Mya truncata were collected for biochemical analysis before, after and two weeks after the simulated oil spills. Concentations in the clam tissues of glucose, glycogen, trehalose, total lipid, and free amino acids were measured; free amino acids in adductor muscles were the most useful indices of pollutant stress. The results of the biochemical analyses indicate that Mya were not severely stressed by either dispersed oil or oil alone. After two weeks, clams from the dispersed oil bays were nearly normal, while those from the bay receiving oil alone appeared stressed. These results seem to corroborate results that the acute effects of dispersed oil are greater than those of undispersed oil, but effects of undispersed oil on infaunal molluscs develop more slowly and persist longer than those from dispersed oil. 43 refs., 2 figs., 6 tabs.

  18. Histopathological analysis of the therapeutic response to cryotherapy with liquid nitrogen in patients with multiple actinic keratosis.

    Science.gov (United States)

    Oliveira, Marina Câmara de; Trevisan, Flávia; Pinto, Clovis Antônio Lopes; Xavier, Célia Antônia; Pinto, Jaqueline Campoi Calvo Lopes

    2015-01-01

    Actinic keratoses are premalignant lesions of the skin caused by excessive sun exposure. Lesions may become mainly squamous cell carcinoma. Cryotherapy with liquid nitrogen is one of the main treatments. In order to evaluate the response of actinic keratosis to cryotherapy by histopathology, two lesions were selected in each of 14 patients with multiple actinic keratoses. In one lesion a biopsy was performed and in the other lesion a biopsy was performed after cryotherapy. Subsequently, both biopsies were compared histologically. Of the thirteen patients who completed the study, the best results were obtained in lesions undergoing cryotherapy concerning the atypia of keratinocytes, epithelial thickness and corneal layer and lymphocytic infiltrate. Despite the small number of patients, it was concluded that, if performed correctly, cryotherapy has high efficacy in the treatment of actinic keratoses.

  19. Role of repair saturation in the response of plateau-phase Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Braby, L.A.; Nelson, J.M.; Metting, N.F.

    1987-01-01

    Two repair rates are seen in split-dose experiments on starved plateau-phase CHO cells. It has been assumed that this indicates two different processes repairing two distinct types of sublethal damage. However results of experiments at different dose levels are not consistent with models that assume that the damage is entirely sublethal. Another hypothesis that has been considered is the saturation of a repair mechanism having a limited pool of repair enzymes. Such saturation phenomena have been observed in biochemical repair studies and have thus formed the basis for a model of cellular response, which was shown to be capable of producing dose response curves in good agreement with experimental observations. This model can be extended to account for both dose-rate and split-dose effects

  20. Familiality of mood repair responses among youth with and without histories of depression.

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    Bylsma, Lauren M; Yaroslavsky, Ilya; Rottenberg, Jonathan; Kiss, Enikő; Kapornai, Krisztina; Halas, Kitti; Dochnal, Roberta; Lefkovics, Eszter; Baji, Ildikό; Vetrό, Ágnes; Kovacs, Maria

    2016-01-01

    Affect regulation skills develop in the context of the family environment, wherein youths are influenced by their parents', and possibly their siblings', regulatory responses and styles. Regulatory responses to sadness (mood repair) that exacerbate or prolong dysphoria (maladaptive mood repair) may represent one way in which depression is transmitted within families. We examined self-reported adaptive and maladaptive mood repair responses across cognitive, social and behavioural domains in Hungarian 11- to 19-year-old youth and their parents. Offspring included 214 probands with a history of childhood-onset depressive disorder, 200 never depressed siblings and 161 control peers. Probands reported the most problematic mood repair responses, with siblings reporting more modest differences from controls. Mood repair responses of parents and their offspring, as well as within sib-pairs, were related, although results differed as a function of the regulatory response domain. Results demonstrate familiality of maladaptive and adaptive mood repair responses in multiple samples. These familial associations suggest that relationships with parents and siblings within families may impact the development of affect regulation in youth.

  1. Histopathological effect and stress response of mantle proteome following TBT exposure in the Hooded oyster Saccostrea cucullata.

    Science.gov (United States)

    Khondee, Phattirapa; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Svasti, Jisnuson; Simpson, Richard J; Kingtong, Sutin

    2016-11-01

    Tributyltin (TBT), an environmental pollutant in marine ecosystems, is toxic to organisms. Although contamination by and bioaccumulation and toxicity of this compound have been widely reported, its underlying molecular mechanisms remain unclear. In the present study, we exposed the Hooded oyster Saccostrea cucullata to TBT to investigate histopathological effects and proteome stress response. Animals were exposed to three TBT sub-lethal concentrations, 10, 50 and 150 μg/l for 48 h. TBT produced stress leading to histopathological changes in oyster tissues including mantle, gill, stomach and digestive diverticula. TBT induced mucocyte production in epithelia and hemocyte aggregation in connective tissue. Cell necrosis occurred when exposure dosages were high. Comparative proteome analyses of mantle protein of oysters exposed to 10 μg/l and control animals were analyzed by a 2-DE based proteomic approach. In total, 32 protein spots were found to differ (p TBT induced the expression of proteins involved in defensive mechanisms (HSP-78, HSP-70, aldehyde dehydrogenase and catalase), calcium homeostasis (VDAC-3), cytoskeleton and cytoskeleton-associated proteins, energy metabolism and amino acid metabolism. Our study revealed that TBT disturbs calcium homeostasis via VDAC-3 protein in mantle and this probably is the key molecular mechanism of TBT acting to distort shell calcification. Moreover, proteins involved in cell structure (tubulin-alpha and tubulin-beta) and protein synthesis were reduced after TBT exposure. Additionally, differential proteins obtained from this work will be useful as potential TBT biomarkers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A Histopathologic Study on Pulp Response to Glass Ionomer Cements in Human Teeth

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    M. Ghavamnasiri

    2005-12-01

    Full Text Available Statement of Problem: Despite the wide range of new dental materials, there is still a need for biomaterials demonstrating high biocompatibility, antimicrobial effects and ideal mechanical properties.Purpose: The aim of this study was to histologically evaluate the pulpal response to a conventional glass ionomer, a resin modified glass ionomer and a calcium hydroxide in human teeth.Materials and Methods: Fifty five deep class V cavities were prepared in premolars of 31 patients and were divided into 3 groups based on application of the following liners:resin modified glass ionomer (Vivaglass Liner, conventional glass ionomer (ChembondSuperior and calcium hydroxide (Dycal. After applying varnish, teeth were filled with amalgam. Each group was further divided into three subgroups according to time intervals of 7, 30 and 60 days. Teeth were then extracted and their crowns were fixed in formalin. Each sample was assessed microscopically for odontoblastic changes,inflammatory cell infiltration, reactionary dentin formation, remaining dentinal thickness and presence of microorganisms. Statistical analysis including Kruskal Wallis and Mann Whitney was carried out for comparison of mean ranks. (P=0.05.Results: In the Vivaglass Liner group, pulpal response was significantly higher on day 7 as compared to days 30 and 60 (P0.05. There was no correlation between pulpal responses with micro-organisms and remaining dentin thickness (P>0.05.Conclusion: According to the results of this study, light-cured glass ionomer as well as the other tested lining materials were determined to be biologically compatible with vital pulps in deep cavities of sound human teeth.

  3. Pre-operative radiotherapy in soft tissue tumors: Assessment of response by static post-contrast MR imaging compared to histopathology

    International Nuclear Information System (INIS)

    Einarsdottir, H.; Wejde, J.; Bauer, H.C.F.

    2000-01-01

    To evaluate if static post-contrast MR imaging was adequate to assess tumor viability after pre-operative radiotherapy in soft tissue sarcoma. Post-contrast MR imaging of 36 soft tissue sarcomas performed 0 - 54 days (median 13 days) after pre-operative radiotherapy, were retrospectively reviewed and compared to post-operative histopathology reports. The contrast enhancement of the tumor was visually graded as minor, moderate or extensive. From the post-operative histopathology reports, three types of tumor response to radiotherapy were defined: Poor, intermediate or good. The size of the tumors before and after radiation was compared. Even if most viable tumors enhanced more than non-viable tumors, there was major overlapping and significant contrast enhancement could be seen in tumors where histopathological examination revealed no viable tumor tissue. Based on histopathology, there were 12 good responders; 8 of these showed minor, 3 moderate and 1 extensive contrast enhancement on MR imaging. Sixteen tumors had an intermediate response; 3 showed minor, 8 moderate and 5 extensive enhancement. Eight tumors had poor response; none showed minor enhancement, 3 moderate and 5 extensive enhancement. Both increase and Decrease in tumor size was seen in lesions with a good therapy response. Static post-contrast MR imaging cannot reliably assess tumor viability after pre-operative radiotherapy in soft tissue sarcoma. In tumors with no viable tumor tissue, moderate and extensive contrast enhancement can be seen

  4. [SOS response of DNA repair and genetic cell instability under hypoxic conditions].

    Science.gov (United States)

    Vasil'eva, S V; Strel'tsova, D A

    2011-01-01

    The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

  5. Trichothiodystrophy, a human DNA repair disorder with heterogeneity in the cellular response to ultraviolet light

    International Nuclear Information System (INIS)

    Lehmann, A.R.; Arlett, C.F.; Broughton, B.C.

    1988-01-01

    Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental and physical retardation. Some patients are photosensitive. A previous study by Stefanini et al. showed that cells from four photosensitive patients with TTD had a molecular defect in DNA repair, which was not complemented by cells from xeroderma pigmentosum, complementation group D. In a detailed molecular and cellular study of the effects of UV light on cells cultured from three further TTD patients who did not exhibit photosensitivity we have found an array of different responses. In cells from the first patient, survival, excision repair, and DNA and RNA synthesis following UV irradiation were all normal, whereas in cells from the second patient all these responses were similar to those of excision-defective xeroderma pigmentosum (group D) cells. With the third patient, cell survival measured by colony-forming ability was normal following UV irradiation, even though repair synthesis was only 50% of normal and RNA synthesis was severely reduced. The excision-repair defect in these cells was not complemented by other TTD cell strains. These cellular characteristics of patient 3 have not been described previously for any other cell line. The normal survival may be attributed to the finding that the deficiency in excision-repair is confined to early times after irradiation. Our results pose a number of questions about the relationship between the molecular defect in DNA repair and the clinical symptoms of xeroderma pigmentosum and TTD

  6. Single-nucleotide polymorphisms in base excision repair, nucleotide excision repair, and double strand break genes as markers for response to radiotherapy in patients with Stage I to II head-and-neck cancer

    International Nuclear Information System (INIS)

    Carles, Joan; Monzo, Mariano; Amat, Marta; Jansa, Sonia; Artells, Rosa; Navarro, Alfons; Foro, Palmira; Alameda, Francesc; Gayete, Angel; Gel, Bernat; Miguel, Maribel; Albanell, Joan; Fabregat, Xavier

    2006-01-01

    Purpose: Polymorphisms in DNA repair genes can influence response to radiotherapy. We analyzed single-nucleotide polymorphisms (SNP) in nine DNA repair genes in 108 patients with head-and-neck cancer (HNSCC) who had received radiotherapy only. Methods and Materials: From May 1993 to December 2004, patients with Stage I and II histopathologically confirmed HNSCC underwent radiotherapy. DNA was obtained from paraffin-embedded tissue, and SNP analysis was performed using a real-time polymerase chain reaction allelic discrimination TaqMan assay with minor modifications. Results: Patients were 101 men (93.5%) and 7 (6.5%) women, with a median age of 64 years (range, 40 to 89 years). Of the patients, 76 (70.4%) patients were Stage I and 32 (29.6%) were Stage II. The XPF/ERCC1 SNP at codon 259 and XPG/ERCC5 at codon 46 emerged as significant predictors of progression (p 0.00005 and 0.049, respectively) and survival (p = 0.0089 and 0.0066, respectively). Similarly, when variant alleles of XPF/ERCC1, XPG/ERCC5 and XPA were examined in combination, a greater number of variant alleles was associated with shorter time to progression (p = 0.0003) and survival (p 0.0002). Conclusions: Genetic polymorphisms in XPF/ERCC1, XPG/ERCC5, and XPA may significantly influence response to radiotherapy; large studies are warranted to confirm their role in HNSCC

  7. Repair and mutagenesis in procaryotes as cellular responses to ambiental agents

    International Nuclear Information System (INIS)

    Gomes, R.A.

    1982-01-01

    The correct and incorrect mechanisms of DNA repair are discussed, as well as the cellular responses induced by the DNA lesions; the reductone mollecular effects; the cellular interactions among irradiated populations of microorganisms and the utilization of microbial assays for the detection of oncogenic activities of chemicals. (M.A.) [pt

  8. Sos - response induction by gamma radiation in Escherichia coli strains with different repair capacities

    International Nuclear Information System (INIS)

    Serment Guerrero, J.H.

    1992-01-01

    The Sos - response in Escherichia coli is formed by several genes involved in mechanisms of tolerance and/or repair, and only activates when a DNA - damage appears. It is controlled by recA and lexA genes. In normal circumstances, LexA protein is linked in every Sos operators, blocking the transcription. When a DNA damage occurs, a Sos signal is generated, Rec A protein changes its normal functions, starts acting as a protease and cleaves Lex A, allowing the transcription of all Sos genes. This response can be quantified by means of Sos Chromo test, performed by Quillardet and Ofnung (1985). In using the Chromo test, it has been observed that the DNA damage made by gamma radiation in Escherichia coli depends on both the doses and the doses rate. It has been shown that the exposure of Escherichia coli PQ37 strain (uvrA) to low doses at low dose rate appears to retard the response, suggesting the action of a repair mechanism. (Brena 1990). In this work, we compare the response in Escherichia coli strains deficient in different mechanisms of repair and/or tolerance. It is observed the importance of rec N gene in the repair of DNA damage produced by gamma radiation. (Author)

  9. Radioadaptive response. Efficient repair of radiation-induced DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Ikushima, Takaji; Aritomi, Hisako; Morisita, Jun

    1996-01-01

    To verify the hypothesis that the induction of a novel, efficient repair mechanism for chromosomal DNA breaks may be involved in the radioadaptive response, the repair kinetics of DNA damage has been studied in cultured Chinese hamster V79 cells with single-cell gel electrophoresis. The cells were adapted by priming exposure with 5 cGy of γ-rays and 4-h incubation at 37C. There were no indication of any difference in the initial yields of DNA double-strand breaks induced by challenging doses from non-adapted cells and from adapted cells. The rejoining of DNA double-strand breaks was monitored over 120 min after the adapted cells were challenged with 5 or 1.5 Gy, doses at the same level to those used in the cytogenetical adaptive response. The rate of DNA damage repair in adapted cells was higher than that in non-adapted cells, and the residual damage was less in adapted cells than in non-adapted cells. These results indicate that the radioadaptive response may result from the induction of a novel, efficient DNA repair mechanism which leads to less residual damage, but not from the induction of protective functions that reduce the initial DNA damage

  10. Role of DNA damage repair capacity in radiation induced adaptive response

    International Nuclear Information System (INIS)

    Yuan Dexiao; Pan Yan; Zhao Meijia; Chen Honghong; Shao Cunlin

    2009-01-01

    This work was to explore γ-ray induced radioadaptive response (RAR) in Chinese hamster ovary(CHO) cell lines of different DNA damage repair capacities. CHO-9 cells and the two repair-deficient strains, EM-C11(DNA single strand break repair deficient) and XR-C1(DNA double strand break repair deficient), were irradiated with a priming dose of 0.08 Gy or 0.016 Gy. After 4 or 7 hours, they were irradiated again with a challenging dose of 1 Gy. The micronucleus induction and plating efficiency of the cells were assayed. Under 0.08 Gy priming dose and 4-h interval, just the CHO-9 cells showed RAR, while with the 7-h interval the CHO-9 and EM-C11 showed RAR, but XR-C1 did not. When the cells were pretreated with a lower priming dose of 0.016 Gy in a 4-h time interval, all the three cell lines showed RAR to subsequent 1 Gy irradiation. It can be concluded that RAR is not only related to the priming dose and time interval, but also has close dependence on the ability of DNA damage repair. (authors)

  11. Correlation of exercise response in repaired coarctation of the aorta to left ventricular mass and geometry.

    Science.gov (United States)

    Krieger, Eric V; Clair, Mathieu; Opotowsky, Alexander R; Landzberg, Michael J; Rhodes, Jonathan; Powell, Andrew J; Colan, Steven D; Valente, Anne Marie

    2013-02-01

    The role of exercise testing to risk stratify patients with repaired coarctation of the aorta (CoA) is controversial. Concentric left ventricular (LV) hypertrophy, defined as an increase in the LV mass-to-volume ratio (MVR), is associated with a greater incidence of adverse cardiovascular events. The objective of the present study was to determine whether a hypertensive response to exercise (HRE) is associated with increased LVMVR in patients with repaired CoA. Adults with repaired CoA who had a symptom-limited exercise test and cardiac magnetic resonance imaging examination within 2 years were identified. A hypertensive response to exercise was defined as a peak systolic blood pressure >220 mm Hg during a symptom-limited exercise test. The LV mass and volume were measured using cardiac magnetic resonance by an investigator who was unaware of patient status. We included 47 patients (median age 27.3 years, interquartile range 19.8 to 37.3), who had undergone CoA repair at a median age of 4.6 years (interquartile range 0.4 to 15.7). Those with (n = 11) and without (n = 36) HRE did not differ in age, age at repair, body surface area, arm-to-leg systolic blood pressure gradient, gender, or peak oxygen uptake with exercise. Those with a HRE had a greater mean systolic blood pressure at rest (146 ± 18 vs 137 ± 18 mm Hg, p = 0.04) and greater median LVMVR (0.85, interquartile range 0.7 to 1, vs 0.66, interquartile range 0.6 to 0.7; p = 0.04) than those without HRE. Adjusting for systolic blood pressure at rest, age, age at repair, and gender, the relation between HRE and LVMVR remained significant (p = 0.001). In conclusion, HRE was associated with increased LVMVR, even after adjusting for multiple covariates. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Incidence of systemic inflammatory response syndrome after endovascular aortic repair

    DEFF Research Database (Denmark)

    De La Motte, L; Vogt, K; Jensen, Leif Panduro

    2011-01-01

    : Sixty-six patients were included, 40 (60%) met the SIRS criteria within the first 5 postoperative days (95% of the 40 patients met the criteria within 3 days). We found no significant differences between the SIRS and the non-SIRS group in baseline characteristics or other data including volume...... in the groups (3% in the SIRS group vs. none in the non-SIRS group). CONCLUSION: The high incidence of SIRS after EVAR is unexpected considering the minimally invasive procedure. Further studies on the cause of this response and measures to attenuate the response seem appropriate....... during 2007, were retrospectively evaluated for SIRS within the first 5 postoperative days. The only exclusion-criteria were missing data. SIRS was assessed using the criteria defined by the American College of Chest Physicians and Society of Critical Care Medicine Consensus Conference Committee. RESULTS...

  13. Mycobacterium tuberculosis DNA repair in response to subinhibitory concentrations of ciprofloxacin.

    Science.gov (United States)

    O'Sullivan, D M; Hinds, J; Butcher, P D; Gillespie, S H; McHugh, T D

    2008-12-01

    To investigate how the SOS response, an error-prone DNA repair pathway, is expressed following subinhibitory quinolone treatment of Mycobacterium tuberculosis. Genome-wide expression profiling followed by quantitative RT (qRT)-PCR was used to study the effect of ciprofloxacin on M. tuberculosis gene expression. Microarray analysis showed that 16/110 genes involved in DNA protection, repair and recombination were up-regulated. There appeared to be a lack of downstream genes involved in the SOS response. qRT-PCR detected an induction of lexA and recA after 4 h and of dnaE2 after 24 h of subinhibitory treatment. The pattern of gene expression observed following subinhibitory quinolone treatment differed from that induced after other DNA-damaging agents (e.g. mitomycin C). The expression of the DnaE2 polymerase response was significantly delayed following subinhibitory quinolone exposure.

  14. Ada response - a strategy for repair of alkylated DNA in bacteria.

    Science.gov (United States)

    Mielecki, Damian; Grzesiuk, Elżbieta

    2014-06-01

    Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N(3)-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N(1)-methyladenine (1meA) and N(3)-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O(6)-methylguanine (O(6) meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA. © 2014 The Authors. FEMS Microbiology Letters published by John Wiley & Sons Ltd on behalf of Federation of European Microbiological Societies.

  15. Ada response – a strategy for repair of alkylated DNA in bacteria

    Science.gov (United States)

    Mielecki, Damian; Grzesiuk, Elżbieta

    2014-01-01

    Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N3-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N1-methyladenine (1meA) and N3-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O6-methylguanine (O6meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA. PMID:24810496

  16. Microtubules self-repair in response to mechanical stress

    Science.gov (United States)

    Schaedel, Laura; John, Karin; Gaillard, Jérémie; Nachury, Maxence V.; Blanchoin, Laurent; Théry, Manuel

    2015-11-01

    Microtubules--which define the shape of axons, cilia and flagella, and provide tracks for intracellular transport--can be highly bent by intracellular forces, and microtubule structure and stiffness are thought to be affected by physical constraints. Yet how microtubules tolerate the vast forces exerted on them remains unknown. Here, by using a microfluidic device, we show that microtubule stiffness decreases incrementally with each cycle of bending and release. Similar to other cases of material fatigue, the concentration of mechanical stresses on pre-existing defects in the microtubule lattice is responsible for the generation of more extensive damage, which further decreases microtubule stiffness. Strikingly, damaged microtubules were able to incorporate new tubulin dimers into their lattice and recover their initial stiffness. Our findings demonstrate that microtubules are ductile materials with self-healing properties, that their dynamics does not exclusively occur at their ends, and that their lattice plasticity enables the microtubules' adaptation to mechanical stresses.

  17. Responses to accelerated heavy ions of spores of Bacillus subtilis of different repair capacity

    International Nuclear Information System (INIS)

    Baltschukat, K.; Horneck, G.

    1991-01-01

    Inactivation, mutagenesis of histidine reversion and the involvement of DNA repair were studied in spores of Bacillus subtilis irradiated with heavy ions at LBL, Berkeley and GSI, Darmstadt. Five groups of ions (from boron to uranium) were used with residual energies from 0.2 MeV/u up to 18.6 MeV/u; in addition, carbon ions were used with a residual energy of 120 MeV/u. Action cross sections of both inactivation and mutagenesis show a similar dependence on ion mass and energy: For lighter ions (Z≤10), the lethal response is nearly energy independent (Z=10) or decreasing with energy (Z≤6); these light ions, up to 18.6 MeV/u, induce hardly any mutations. For heavier ions (Z≥26), the lethal as well as the mutagenic responses increase with ion mass and energy up to a maximum or saturation. The efficiency of DNA repair to improve survival and the mutagenic efficiency per lethal event, both, increase with ion energy up to a saturation value which, depending on strain and endpoint, either roughtly coincides with the X-ray value or is smaller than that after X-ray treatment. For repair based on recombination events, the increase in the survival effects with ion energy is more pronounced than for that based on repair replication. At energies of 1 MeV/u or below, neither DNA repair nor mutation induction appear to be significant. The results support previous suggestions on the importance of the radial distribution of the energy around the ion track in biological action cross section and the evidence that the entire core of the spore represents the sensitive site in responses to heavy ions. (orig.)

  18. Histopathological assessment and inflammatory response in the digestive gland of marine mussel Mytilus galloprovincialis exposed to cadmium-based quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Thiago Lopes [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Laboratory of Cellular Behavior, Biological Sciences Institute, Federal University of Goiás, Goiânia, Goiás (Brazil); Sabóia-Morais, Simone Maria Teixeira [Laboratory of Cellular Behavior, Biological Sciences Institute, Federal University of Goiás, Goiânia, Goiás (Brazil); Bebianno, Maria João, E-mail: mbebian@ualg.pt [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2016-08-15

    Highlights: • Digestive gland of marine mussels is target for Cd-based QDs toxicity. • Both Cd forms increase the frequency of atrophic digestive tubules in a time dependent pattern. • QDs induce higher inflammatory responses when compared to dissolved Cd. • Multiparametric tissue-levels biomarkers show distinct mode of action in the digestive gland. - Abstract: Although tissue-level biomarkers have been widely applied in environmental toxicology studies, the knowledge using this approach in marine invertebrates exposed to engineered nanomaterials (ENMs) remains limited. This study investigated histopathological alterations and inflammatory responses induced by Cd-based quantum dots (QDs), in comparison with their dissolved counterparts, in the marine mussel Mytilus galloprovincialis. Mussels were exposed to CdTe QDs and dissolved Cd at the same concentration (10 μg Cd L{sup −1}) for 14 days and a total of 15 histopathological alterations and 17 histomorphometric parameters were analysed in the digestive gland along with the determination of histopathological condition indices (I{sub h}). A multivariate analysis showed that the mussel response to QDs was more related to exposure time, inflammatory conditions (frequency of haemocytic infiltration and granulocytomas) and changes of cell-type composition (especially the rate between basophilic and digestive cells) when compared to dissolved Cd, while the response to dissolved Cd was associated with histomorphometric parameters of the epithelium and lumen of digestive tubules and increase of the atrophic tubule frequency. Both Cd forms induced higher I{sub h} compared to unexposed mussels indicating a significant decrease in the health status of digestive gland in a Cd form and time-dependent pattern. Results indicate that the multiparametric tissue-level biomarkers in the digestive gland provide a suitable approach to assess the ecotoxicity and mode of action of metal-based ENMs in marine bivalves.

  19. Static Tensile and Transient Dynamic Response of Cracked Aluminum Plate Repaired with Composite Patch - Numerical Study

    Science.gov (United States)

    Khalili, S. M. R.; Shariyat, M.; Mokhtari, M.

    2014-06-01

    In this study, the central cracked aluminum plates repaired with two sided composite patches are investigated numerically for their response to static tensile and transient dynamic loadings. Contour integral method is used to define and evaluate the stress intensity factors at the crack tips. The reinforcement for the composite patches is carbon fibers. The effect of adhesive thickness and patch thickness and configuration in tensile loading case and pre-tension, pre-compression and crack length effect on the evolution of the mode I stress intensity factor (SIF) (KI) of the repaired structure under transient dynamic loading case are examined. The results indicated that KI of the central cracked plate is reduced by 1/10 to 1/2 as a result of the bonded composite patch repair in tensile loading case. The crack length and the pre-loads are more effective in repaired structure in transient dynamic loading case in which, the 100 N pre-compression reduces the maximum KI for about 40 %, and the 100 N pre-tension reduces the maximum KI after loading period, by about 196 %.

  20. Crisis strategies in BP's Deepwater Horizon response : An image repair and situational crisis communication study

    OpenAIRE

    Johansson, Mikael

    2017-01-01

    The BP Deepwater Horizon crisis in 2010 was one the largest catastrophes in the history of the oil industry. BP was sued over the disaster, and lost several billion dollars. This study examines the crisis response strategies and/or image repair strategies, which can be found in BP's press releases following the Deepwater Horizon crisis. In particular, the study looks closer at what established crisis communication strategies could be discerned in the material, and how they are used discursive...

  1. Fixation free femoral hernia repair with a 3D dynamic responsive implant. A case series report.

    Science.gov (United States)

    Amato, G; Romano, G; Agrusa, A; Gordini, L; Gulotta, E; Erdas, E; Calò, P G

    2018-04-23

    To date, no gold standard for the surgical treatment of femoral hernia exists. Pure tissue repair as well as mesh/plug implantation, open or laparoscopic, are the most performed methods. Nevertheless, all these techniques need sutures or mesh fixation. This implies the risk of damaging sensitive structures of the femoral area, along with complications related to tissue tear and postoperative discomfort consequent to poor quality mesh incorporation. The present retrospective multicenter case series highlights the results of femoral hernia repair procedures performed with a 3D dynamic responsive implant in a cohort of 32 patients during a mean follow up of 27 months. Aiming to simplify the surgical procedure and reduce complications, a 3D dynamic responsive implant was delivered for femoral hernia repair, in a patient cohort. After returning the hernia sack to the abdominal cavity, the implant was simply delivered into the hernia defect where it remained, thanks to its inherent centrifugal expansion, obliterating the hernia opening without need of fixation. Postoperative pain assessment was determined using the VAS score system. The use of the 3D prosthetic device allowed for easier and faster surgical repair in a fixation free fashion. None of the typical fixation related complications occurred in the examined patients. Postoperative pain assessment with VAS score showed a very low level of pain, allowing the return of patients to normal activities in extremely reduced times. In the late postoperative period, no discomfort or chronic pain was reported. Femoral hernia repair with the 3D dynamic revealed a quick and safe placement procedure. The reduced pain intensity, as well as the absence of adverse events consequent to sutures or mesh fixation, seems to be a significant benefit of the motile compliance of the device. Furthermore, this 3D prosthesis has already proven to induce an enhanced probiotic response showing ingrowth in the implant of the typical tissue

  2. Endocrine, Physiological and Histopathological Responses of Fish and their Larvae to Stress with Emphasis on Exposure to Crude Oil and Various Petroleum Hydrocarbons

    Directory of Open Access Journals (Sweden)

    A. Y. A. AL-Kindi

    2000-12-01

    Full Text Available Various endocrine and physiological responses of fish exposed to forceful physical and chemical stimuli are reviewed with emphasis on the effects of crude oils and their hydrocarbon constituents. The chemistry and toxicity of petroleum hydrocarbons are examined and methods for experimental exposure of fish to crude oil and petroleum hydrocarbons are considered. A variety of blood-borne parameters recognized as reliable tools in determining the relative severity of stress in fish are reviewed. The effects of stress and petroleum hydrocarbons on endocrine responses including changes in plasma catecholamines, corticosteroids, and thyroid hormones are reviewed. The physiological responses: changes in plasma glucose, osmotic and ionic regulation, blood oxygen, hematocrit and hemoglobin concentration are explored, and histopathological effects of crude oil on fish are reviewed. Recent studies of the effects of petroleum hydrocarbons on fish larvae are considered and the increased sensitivity of the early life stages of fish are highlighted.

  3. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    David A. Boothman

    1999-08-11

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed.

  4. Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Hammond, Dianne; Mehta, Satish K.; Jeevarajan, Antony S.; Pierson, Duane L.; Wu, Honglu

    2009-01-01

    Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR

  5. Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Takaji Ikushima

    1997-01-01

    The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

  6. Repair response for DNA double-strand damage through ubiquitylation of chromatin

    International Nuclear Information System (INIS)

    Nakada, Shinichiro

    2011-01-01

    The chromatin modulation (remodeling) via lysine63 (K63)-linked ubiquitin (U) has been found important in the repair response for DNA double-strand damage, and the sequential signaling events at the damage site are explained. As the first step of the repair, MRN (MRE11, RAD50 and nibrin) complex recognizes the damage site and binds to it followed by many linked reactions by recruited and activated enzymes of various protein kinases and phosphatases, which resulting in the enhanced early signaling. As well, gamma-H2AX (phosphorylated histone H2AX) is yielded by the process, to which phosphorylated MDC1 (mediator of DNA-damage checkpoint 1) binds to produce their complex. Then further binding of RNF8-HERC2-UBC13 (ring finger protein 8, hect domain and RCC1 (CHC1)-like domain, and U conjugating enzyme E2N, respectively) occurs for starting the cumulative ubiquitylation of H2AX via K63 as the middle phase response. Signaling in the late phase occurs on the U chain formed at the damage site by binding of RAP (receptor-associated protein) 80 and other recruited 5 proteins like BRCA1 (breast cancer 1, early onset) to repair DNA by the homologous recombination after 53BP1 (tumor protein p53 binding protein) binding followed by methylation of histone H4. In a case of human compound heterozygous RNF168 defect, RIDDLE syndrome (radiosensitivity, immunodeficiency, dysmorphic features and learning difficulties), cells have no and slight abnormality of G2/M and intra-S checkpoint, respectively. Another defecting case with homozygous nonsense mutation has high radiosensitivity, intra-S checkpoint abnormality and others. Abnormality of immuno-globulins observed in both cases is similar to that in the RNF8-knockout mouse. Many tasks in chromatin ubiquitylation in the repair are still remained to be solved for protection and treatment of related diseases. (T.T.)

  7. The response of tenocytes to commercial scaffolds used for rotator cuff repair

    Directory of Open Access Journals (Sweden)

    RDJ Smith

    2017-01-01

    Full Text Available Surgical repairs of rotator cuff tears have high re-tear rates and many scaffolds have been developed to augment the repair. Understanding the interaction between patients’ cells and scaffolds is important for improving scaffold performance and tendon healing. In this in vitro study, we investigated the response of patient-derived tenocytes to eight different scaffolds. Tested scaffolds included X-Repair, Poly-Tape, LARS Ligament, BioFiber (synthetic scaffolds, BioFiber-CM (biosynthetic scaffold, GraftJacket, Permacol, and Conexa (biological scaffolds. Cell attachment, proliferation, gene expression, and morphology were assessed. After one day, more cells attached to synthetic scaffolds with dense, fine and aligned fibres (X-Repair and Poly-Tape. Despite low initial cell attachment, the human dermal scaffold (GraftJacket promoted the greatest proliferation of cells over 13 days. Expression of collagen types I and III were upregulated in cells grown on non-cross-linked porcine dermis (Conexa. Interestingly, the ratio of collagen I to collagen III mRNA was lower on all dermal scaffolds compared to synthetic and biosynthetic scaffolds. These findings demonstrate significant differences in the response of patient-derived tendon cells to scaffolds that are routinely used for rotator cuff surgery. Synthetic scaffolds promoted increased cell adhesion and a tendon-like cellular phenotype, while biological scaffolds promoted cell proliferation and expression of collagen genes. However, no single scaffold was superior. Our results may help understand the way that patients’ cells interact with scaffolds and guide the development of new scaffolds in the future.

  8. What role for DNA damage and repair in the bystander response?

    International Nuclear Information System (INIS)

    Prise, Kevin M.; Folkard, Melvyn; Kuosaite, Virginija; Tartier, Laurence; Zyuzikov, Nikolai; Shao, Chunlin

    2006-01-01

    The radiation-induced bystander effect challenges the accepted paradigm of direct DNA damage in response to energy deposition driving the biological consequences of radiation exposure. With the bystander response, cells which have not been directly exposed to radiation respond to their neighbours being targeted. In our own studies we have used novel targeted microbeam approaches to specifically irradiate parts of individual cells within a population to quantify the bystander response and obtain mechanistic information. Using this approach it has become clear that energy deposited by radiation in nuclear DNA is not required to trigger the effect, with cytoplasmic irradiation required. Irradiated cells also trigger a bystander response regardless of whether they themselves live or die, suggesting that the phenotype of the targeted cell is not a determining factor. Despite this however, a range of evidence has shown that repair status is important for dealing with the consequences of a bystander signal. Importantly, repair processes involved in the processing of dsb appear to be involved suggesting that the bystander response involves the delayed or indirect production of dsb-type lesions in bystander cells. Whether these are infact true dsb or complexes of oxidised bases in combination with strand breaks and the mechanisms for their formation, remains to be elucidated

  9. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    International Nuclear Information System (INIS)

    Alexander, Brian M.; Wang Xiaozhe; Niemierko, Andrzej; Weaver, David T.; Mak, Raymond H.; Roof, Kevin S.; Fidias, Panagiotis; Wain, John; Choi, Noah C.

    2012-01-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  10. Alteration of cellular radiation response as a consequence of defective DNA mismatch repair

    International Nuclear Information System (INIS)

    Weese, Theodore L. de; Bucci, Jennifer M.; Larrier, Nicole A.; Cutler, Richard G.; Riele, Hein te; Nelson, William G.

    1997-01-01

    Purpose/Objective: A number of genes have been implicated in the response of mammalian cells to ionizing radiation. Among these include the genes P53 and P21. Disruption of these genes can alter the predicted cellular behavior following radiation-induced DNA damage. Similarly, cells defective in mismatch repair are known to be tolerant to the lethal effects of alkylating agents. We hypothesized that mammalian cells which are defective in mismatch repair and tolerant to alkylating DNA damage might also be tolerant to the effects of oxidative DNA damage inflicted by ionizing radiation. Materials and Methods: Mouse embryonic stem cells homozygous for disrupted Msh2 alleles (Msh2-/-), heterozygous for a disrupted Msh2 allele (Msh2+/-) or intact cells (Msh2+/+) were exposed to both acute dose (1 Gy/min) and low dose rate (LDR) radiation (0.004 Gy/min) and cell survival was determined by clonogenic assay. Apoptosis induced by LDR was assessed by a terminal transferase assay. Immunoblot analysis was performed in order to evaluate induction of the polypeptides p53 and p21. Another measure of radiation damage tolerance may be accumulation of oxidative DNA species. Therefore, we monitored levels of 8-hydroxyguanine (8-OHG) and 8-hydroxyadenine (8-OHA) by gas chromatography - mass spectrometry with selected ion monitoring (GC-MS/SIM). Results: Cells containing either one or two disrupted Msh2 alleles (Msh2+/-, Msh2-/-) were found to be less sensitive to LDR than cells containing a complete complement of Msh2 alleles (Msh2+/+). Interestingly, all three cell lines had a nearly identical radiosensitivity to acute dose ionizing radiation despite differences in mismatch repair capacity. Apoptosis after LDR also varied between cells, with the Msh2+/+ cells exhibiting higher levels of apoptosis as compared to either the Msh2+/- or Msh2-/- cell lines. In addition, GC-MS/SIM revealed the Msh2+/- and Msh2-/- cell lines to have an approximately ten fold greater accumulation of the

  11. Repair capability and the cellular age response for killing and mutation induction after UV

    International Nuclear Information System (INIS)

    Wood, R.D.; Burki, H.J.; California Univ., Berkeley

    1982-01-01

    The cell-cycle response for killing and mutation induction by ultraviolet irradiation was measured in synchronous Chinese hamster ovary cells (CHO wild-type) and in a UV-hypersensitive mutant (43-3B) derived from this line. The CHO 43-3B line shows a greatly enhanced sensitivity to killing (D 0 of 0.3 as compared to 3.2 J/m 2 for the wild-type), is hypermutable, and deficient in DNA repair. For the wild-type, a characteristic age response is seen for killing by UV, with maximum sensitivity in early-S and resistance increasing through the S-phase. There is also a life-cycle specificity for induction of diphtheria-toxin resistance in late-G 1 and early-S. Relatively little variation is seen through the cell cycle for induced 6-thioguanine and ouabain resistance. In contrast, the 43-3B cell line shows a relatively 'flat' response to UV throughout the cell cycle, for both killing and mutation induction. Therefore it appears that the characteristic age responses seen in the wild-type CHO are associated with the function of an essentially error-free repair process. (orig./AJ)

  12. Neural Responses to Injury: Prevention, Protection and Repair; Volume 7: Role Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury

    National Research Council Canada - National Science Library

    Bazan, Nicolas

    1996-01-01

    ...: Prevention, Protection, and Repair, Subproject: Role of Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury, are as follows: Species Rat(Albino Wistar), Number Allowed...

  13. Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents.

    Science.gov (United States)

    Klapacz, Joanna; Pottenger, Lynn H; Engelward, Bevin P; Heinen, Christopher D; Johnson, George E; Clewell, Rebecca A; Carmichael, Paul L; Adeleye, Yeyejide; Andersen, Melvin E

    2016-01-01

    From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance of a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

    Science.gov (United States)

    Klapacz, Joanna; Pottenger, Lynn H.; Engelward, Bevin P.; Heinen, Christopher D.; Johnson, George E.; Clewell, Rebecca A.; Carmichael, Paul L.; Adeleye, Yeyejide; Andersen, Melvin E.

    2016-01-01

    From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. PMID:27036068

  15. Repair and cell cycle response in cells exposed to environmental biohazards. Final report, January 1, 1973-December 31, 1984

    International Nuclear Information System (INIS)

    Hadden, C.T.; Billen, D.

    1986-01-01

    These studies have focussed on agents which cause damage to DNA leading to inhibition of DNA synthesis or faulty DNA replication or repair. The overall goal of this project has been to understand how environmental agents interact with the DNA of cells and how cells cope with any resulting damage. In particular we have been concerned with the nature of the repair systems involved in restoration of damaged DNA and the cellular responses to radiation or chemical damage

  16. Real-time fluorescence imaging of the DNA damage repair response during mitosis.

    Science.gov (United States)

    Miwa, Shinji; Yano, Shuya; Yamamoto, Mako; Matsumoto, Yasunori; Uehara, Fuminari; Hiroshima, Yukihiko; Toneri, Makoto; Murakami, Takashi; Kimura, Hiroaki; Hayashi, Katsuhiro; Yamamoto, Norio; Efimova, Elena V; Tsuchiya, Hiroyuki; Hoffman, Robert M

    2015-04-01

    The response to DNA damage during mitosis was visualized using real-time fluorescence imaging of focus formation by the DNA-damage repair (DDR) response protein 53BP1 linked to green fluorescent protein (GFP) (53BP1-GFP) in the MiaPaCa-2(Tet-On) pancreatic cancer cell line. To observe 53BP1-GFP foci during mitosis, MiaPaCa-2(Tet-On) 53BP1-GFP cells were imaged every 30 min by confocal microscopy. Time-lapse imaging demonstrated that 11.4 ± 2.1% of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells had increased focus formation over time. Non-mitotic cells did not have an increase in 53BP1-GFP focus formation over time. Some of the mitotic MiaPaCa-2(Tet-On) 53BP1-GFP cells with focus formation became apoptotic. The results of the present report suggest that DNA strand breaks occur during mitosis and undergo repair, which may cause some of the mitotic cells to enter apoptosis in a phenomenon possibly related to mitotic catastrophe. © 2014 Wiley Periodicals, Inc.

  17. Bridging Plant and Human Radiation Response and DNA Repair through an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Zacharenia Nikitaki

    2017-06-01

    Full Text Available The mechanisms of response to radiation exposure are conserved in plants and animals. The DNA damage response (DDR pathways are the predominant molecular pathways activated upon exposure to radiation, both in plants and animals. The conserved features of DDR in plants and animals might facilitate interdisciplinary studies that cross traditional boundaries between animal and plant biology in order to expand the collection of biomarkers currently used for radiation exposure monitoring (REM in environmental and biomedical settings. Genes implicated in trans-kingdom conserved DDR networks often triggered by ionizing radiation (IR and UV light are deposited into biological databases. In this study, we have applied an innovative approach utilizing data pertinent to plant and human genes from publicly available databases towards the design of a ‘plant radiation biodosimeter’, that is, a plant and DDR gene-based platform that could serve as a REM reliable biomarker for assessing environmental radiation exposure and associated risk. From our analysis, in addition to REM biomarkers, a significant number of genes, both in human and Arabidopsis thaliana, not yet characterized as DDR, are suggested as possible DNA repair players. Last but not least, we provide an example on the applicability of an Arabidopsis thaliana—based plant system monitoring the role of cancer-related DNA repair genes BRCA1, BARD1 and PARP1 in processing DNA lesions.

  18. Load response and gap formation in a single-row cruciate suture rotator cuff repair.

    Science.gov (United States)

    Huntington, Lachlan; Richardson, Martin; Sobol, Tony; Caldow, Jonathon; Ackland, David C

    2017-06-01

    Double-row rotator cuff tendon repair techniques may provide superior contact area and strength compared with single-row repairs, but are associated with higher material expenses and prolonged operating time. The purpose of this study was to evaluate gap formation, ultimate tensile strength and stiffness of a single-row cruciate suture rotator cuff repair construct, and to compare these results with those of the Mason-Allen and SutureBridge repair constructs. Infraspinatus tendons from 24 spring lamb shoulders were harvested and allocated to cruciate suture, Mason-Allen and SutureBridge repair groups. Specimens were loaded cyclically between 10 and 62 N for 200 cycles, and gap formation simultaneously measured using a high-speed digital camera. Specimens were then loaded in uniaxial tension to failure, and construct stiffness and repair strength were evaluated. Gap formation in the cruciate suture repair was significantly lower than that of the Mason-Allen repair (mean difference = 0.6 mm, P = 0.009) and no different from that of the SutureBridge repair (P > 0.05). Both the cruciate suture repair (mean difference = 15.7 N/mm, P = 0.002) and SutureBridge repair (mean difference = 15.8 N/mm, P = 0.034) were significantly stiffer than that of the Mason-Allen repair; however, no significant differences in ultimate tensile strength between repair groups were discerned (P > 0.05). The cruciate suture repair construct, which may represent a simple and cost-effective alternative to double-row and double-row equivalent rotator cuff repairs, has comparable biomechanical strength and integrity with that of the SutureBridge repair, and may result in improved construct longevity and tendon healing compared with the Mason-Allen repair. © 2017 Royal Australasian College of Surgeons.

  19. SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response

    DEFF Research Database (Denmark)

    Mund, Andreas; Schubert, Tobias; Staege, Hannah

    2012-01-01

    -dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after γ-irradiation (γ-IR), non...

  20. Immunological responses, histopathological finding and disease resistance of blue mussel (Mytilus edulis) exposed to treated and untreated municipal wastewater

    International Nuclear Information System (INIS)

    Akaishi, Fabiola M.; St-Jean, Sylvie D.; Bishay, Farida; Clarke, John; Rabitto, Ines da S.; Oliveira Ribeiro, Ciro A. de

    2007-01-01

    This study provides new information on the response of the immune system of Mytilus edulis exposed to untreated and treated sewage, linking immune response to ecologically relevant endpoints, such as disease resistance. Our goal was to assess the potential effects of sewage on the immune system (phagocytic activity and production of cytotoxic metabolites, disease resistance) and gills (light microscope) of mussels through a bioassay and field study in an estuarine receiving environment (RE). A semi-static experiment was developed in a wastewater treatment plant in New Glasgow, NS Canada. Mussels were exposed for 21 days to 12.5%, 25%, 50% and 100% of untreated sewage influent and artificial seawater control. Sampling occurred after 7, 14 and 21 days of exposure. In the field study, eight sites were selected in East River and Pictou Harbour, NS, positioned upstream and downstream of sewage effluents outfalls. Caged mussels were exposed to the RE for 90 days (May-July 2005). Mussels were challenged to test their efficiency at eliminating the bacteria, Listonella anguillarium in the bioassay and field studies. The bioassay results showed that higher concentrations of untreated sewage could modulate the immune system of mussels through increased of phagocytic activity (PA), nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ) production during 14 days of exposure, and decreased activity and production at 21 days, with the exception of H 2 O 2 production which was high even at 21 days. Mussels exposed to untreated sewage RE also presented a high PA, NO and H 2 O 2 production and lower number of haemocytes compared to mussels from reference sites. In the bacterial challenge, mussels pre-exposed to 100% sewage died 24 h after being infected with L. anguillarium, while mussels pre-exposed to 50% eliminated bacteria had a mortality rate of 30%. Mussels from the control, 12.5% and 25% groups eliminated bacteria and no mortality was observed. No significant difference was

  1. Genetic and Histopathological Responses to Cadmium Toxicity in Rabbit's Kidney and Liver: Protection by Ginger (Zingiber officinale).

    Science.gov (United States)

    Baiomy, Ahmed A; Mansour, Ahmed A

    2016-04-01

    This study aimed to examine the protective effects of ginger (G) on the genetic response induced by cadmium (Cd) and immunohistochemical expression of Caspase3 and MKI67 in the kidney and liver of rabbits. Male rabbits were divided into three groups; each group contains 10 animals: group (C) received basic diet and tap water for 12 weeks, the second group (Cd) received 200 mg/kg b.w CdCl2 in water for 12 weeks, group (Cd + G) was given 200 mg/kg b.w CdCl2 in water and 400 mg ginger/kg b.w in food for 12 weeks. Cd administration increased the activity of mRNA expression of the examined apoptotic (Caspase3), proliferation (MKI67), proto-oncogene (C-fos), and antioxidant (GST), while decreased the expression of anti-apoptotic (Bcl2). Ginger counteracted the effects of Cd in (Cd + G) group and downregulated the previously upregulated genes under Cd administration appeared in (Cd) group. The immunohistochemical expression of Caspase3 and MKI67 in the liver and kidney cells of the (C) group was shown very faint to negative reactions, strong staining in hepatocytes and the tubular epithelium in cadmium-treated group, while slight staining in some hepatocytes and tubular epithelium in co-administration with ginger in (Cd + G) group. In conclusion, ginger administration showed a protective effect against cadmium toxicity.

  2. Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yarosh, Daniel B

    2002-11-30

    The goal of DNA repair enzyme therapy is the same as that for gene therapy: to rescue a defective proteome/genome by introducing a substitute protein/DNA. The danger of inadequate DNA repair is highlighted in the genetic disease xeroderma pigmentosum. These patients are hypersensitive to sunlight and develop multiple cutaneous neoplasms very early in life. The bacterial DNA repair enzyme T4 endonuclease V was shown over 25 years ago to be capable of reversing the defective repair in xeroderma pigmentosum cells. This enzyme, packaged in an engineered delivery vehicle, has been shown to traverse the stratum corneum, reach the nuclei of living cells of the skin, and enhance the repair of UV-induced cyclobutane pyrimidine dimers (CPD). In such a system, changes in DNA repair, mutagenesis, and cell signaling can be studied without manipulation of the genome.

  3. Quantitative assessment of the dose-response of alkylating agents in DNA repair proficient and deficient ames tester strains.

    Science.gov (United States)

    Tang, Leilei; Guérard, Melanie; Zeller, Andreas

    2014-01-01

    Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even "thresholded" dose-response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada-), YG7104 (Ogt-/Ada+) and YG7108 (Ogt-/Ada-). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose-response curves were statistically fitted by the PROAST benchmark dose model and the Lutz-Lutz "hockeystick" model. These dose-response curves suggest efficient DNA-repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl-transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Copyright © 2013 Wiley Periodicals, Inc.

  4. Prognostic Role of Hypertensive Response to Exercise in Patients With Repaired Coarctation of Aorta.

    Science.gov (United States)

    Yogeswaran, Vidhushei; Connolly, Heidi M; Al-Otaibi, Mohamad; Ammash, Naser M; Warnes, Carole A; Said, Sameh M; Egbe, Alexander C

    2018-05-01

    This study aimed to determine the prevalence of hypertensive response to exercise (HRE) and its association with cardiovascular adverse events (CAEs) in patients with repaired coarctation of aorta (rCOA). We retrospectively reviewed records of adult patients with rCOA who had cardiopulmonary exercise tests (CPETs) and follow-up from 1994 to 2014 at Mayo Clinic. Patients with residual COA, defined as aortic isthmus peak velocity >2.5 m/s, were excluded. HRE was defined as peak systolic blood pressure >200 mm Hg; CAEs were defined as cardiovascular death, stroke, acute coronary syndrome, heart failure hospitalization, and left ventricular ejection fraction (LVEF) HRE occurred in 26 (19%) patients, and 24 (92%) of the patients with HRE had normal resting blood pressure. There were no differences in age, blood pressure at rest, and CPET findings between patients with HRE and those with normotensive response to exercise. There were 28 CAEs in 24 patients (17%), and HRE was an independent risk factor for CAE (hazard ratio [HR], 1.46 [1.13-2.52]; P = 0.04). HRE can occur even in the setting of normal blood pressure at rest, and it is a risk factor for CAE. We speculate that patients with HRE represent a high-risk group of patients who, presumably, have occult, advanced vascular dysfunction. CPET can identify these patients. The benefit of intensive antihypertension therapy needs to be confirmed. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  5. Impact of DNA repair on the dose-response of colorectal cancer formation induced by dietary carcinogens.

    Science.gov (United States)

    Fahrer, Jörg; Kaina, Bernd

    2017-08-01

    Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, which is causally linked to dietary habits, notably the intake of processed and red meat. Processed and red meat contain dietary carcinogens, including heterocyclic aromatic amines (HCAs) and N-nitroso compounds (NOC). NOC are agents that induce various N-methylated DNA adducts and O 6 -methylguanine (O 6 -MeG), which are removed by base excision repair (BER) and O 6 -methylguanine-DNA methyltransferase (MGMT), respectively. HCAs such as the highly mutagenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) cause bulky DNA adducts, which are removed from DNA by nucleotide excision repair (NER). Both O 6 -MeG and HCA-induced DNA adducts are linked to the occurrence of KRAS and APC mutations in colorectal tumors of rodents and humans, thereby driving CRC initiation and progression. In this review, we focus on DNA repair pathways removing DNA lesions induced by NOC and HCA and assess their role in protecting against mutagenicity and carcinogenicity in the large intestine. We further discuss the impact of DNA repair on the dose-response relationship in colorectal carcinogenesis in view of recent studies, demonstrating the existence of 'no effect' point of departures (PoDs), i.e. thresholds for genotoxicity and carcinogenicity. The available data support the threshold concept for NOC with DNA repair being causally involved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Effect of cadmium exposure on hepatopancreas and gills of the estuary mud crab (Scylla paramamosain): Histopathological changes and expression characterization of stress response genes.

    Science.gov (United States)

    Zhu, Qi-Hui; Zhou, Zhong-Kai; Tu, Dan-Dan; Zhou, Yi-Lian; Wang, Cong; Liu, Ze-Peng; Gu, Wen-Bin; Chen, Yu-Yin; Shu, Miao-An

    2018-02-01

    Cadmium (Cd) is a heavy metal that accumulates easily in organisms and causes several detrimental effects, including tissue damage. Cd contamination from anthropogenic terrestrial sources flows into rivers, and through estuaries to the ocean. To evaluate the toxic effects of Cd on estuary crustaceans, we exposed the mud crab Scylla paramamosain to various Cd concentrations (0, 10.0, 20.0, and 40.0mg/L) for 24h. We also exposed mud crabs to a fixed Cd concentration (20.0mg/L) for various periods of time (0, 6, 12, 24, 48, and 72h). We observed that after exposure to Cd, the surfaces of the gill lamellae were wrinkled, and the morphologies of the nuclei and mitochondria in the hepatopancreas were altered. We analyzed the expression profiles of 36 stress-related genes after Cd exposure, including those encoding metallothioneins, heat shock proteins, apoptosis-related proteins, and antioxidant proteins, with quantitative reverse transcription PCR. We found that exposure to Cd altered gene expression, and that some genes might be suitable bioindicators of Cd stress. Gene expression profiles were organ-, duration-, and concentration-dependent, suggesting that stress-response genes might be involved in an innate defense system for handling heavy metal exposure. To the best of our knowledge, this study is the first one of histopathology and stress-response gene expression pattern of Scylla paramamosain after Cd exposure. Our work could increase our understanding of the effect of environmental toxins on estuary crustaceans. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Hsueh-Fen Juan

    2012-08-01

    Full Text Available Helicobacter pylori (H. pylori, the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+, single mutant (ΔvacA or ΔcagA or double mutant (ΔvacA/ΔcagA strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca2+ influx. Ca2+-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.

  8. Model System for Live Imaging of Neuronal Responses to Injury and Repair

    Directory of Open Access Journals (Sweden)

    Mathieu Gravel

    2011-11-01

    Full Text Available Although it has been well established that induction of growth-associated protein-43 (GAP-43 during development coincides with axonal outgrowth and early synapse formation, the existence of neuronal plasticity and neurite outgrowth in the adult central nervous system after injuries is more controversial. To visualize the processes of neuronal injury and repair in living animals, we generated reporter mice for bioluminescence and fluorescence imaging bearing the luc (luciferase and gfp (green fluorescent protein reporter genes under the control of the murine GAP-43 promoter. Reporter functionality was first observed during the development of transgenic embryos. Using in vivo bioluminescence and fluorescence imaging, we visualized induction of the GAP-43 signals from live embryos starting at E10.5, as well as neuronal responses to brain and peripheral nerve injuries (the signals peaked at 14 days postinjury. Moreover, three-dimensional analysis of the GAP-43 bioluminescent signal confirmed that it originated from brain structures affected by ischemic injury. The analysis of fluorescence signal at cellular level revealed colocalization between endogenous protein and the GAP-43-driven gfp transgene. Taken together, our results suggest that the GAP-43-luc/gfp reporter mouse represents a valid model system for real-time analysis of neurite outgrowth and the capacity of the adult nervous system to regenerate after injuries.

  9. Aged blood factors decrease cellular responses associated with delayed gingival wound repair.

    Directory of Open Access Journals (Sweden)

    María Paz Saldías

    Full Text Available Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblast for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts. We next evaluated cellular responses of primary gingival fibroblast obtained from young subjects in the presence human blood serum of individuals of different ages. Eighteen to sixty five years old masculine donors were classified into 3 groups: "young" from 18 to 22 years old, "middle-aged" from 30 to 48 years old and "aged" over 50 years old. Cell proliferation, measured through immunofluorescence for Ki67 and flow cytometry for DNA content, was decreased when middle-aged and aged serum was added to gingival fibroblast compared to young serum. Myofibroblastic differentiation, measured through alpha-smooth muscle actin (α-SMA, was stimulated with young but not middle-aged or aged serum both the protein levels and incorporation of α-SMA into actin stress fibers. High levels of PDGF, VEGF, IL-6R were detected in blood serum from young subjects when compared to middle-aged and aged donors. In addition, the pro-inflammatory cytokines MCP-1 and TNF were increased in the serum of aged donors. In old rat wound there is an increased of staining for TNF compared to young wound. Moreover, healthy gingiva (non injury shows less staining compared to a wound site, suggesting a role in wound healing. Moreover, serum from middle-aged and aged donors was able to stimulate cellular senescence in young cells as determined by the expression of senescence associated beta-galactosidase and histone H2

  10. DNA repair is responsible for the presence of oxidatively damaged DNA lesions in urine

    International Nuclear Information System (INIS)

    Cooke, Marcus S.; Evans, Mark D.; Dove, Rosamund; Rozalski, Rafal; Gackowski, Daniel; Siomek, Agnieszka; Lunec, Joseph; Olinski, Ryszard

    2005-01-01

    The repair of oxidatively damaged DNA is integral to the maintenance of genomic stability, and hence prevention of a wide variety of pathological conditions, such as aging, cancer and cardiovascular disease. The ability to non-invasively assess DNA repair may provide information regarding repair pathways, variability in repair capacity, and susceptibility to disease. The development of assays to measure urinary DNA lesions offered this potential, although it rapidly became clear that possible contribution from diet and cell turnover may influence urinary lesion levels. Whilst early studies attempted to address these issues, up until now, much of the data appears conflicting. However, recent work from our laboratories, in which human volunteers were fed highly oxidatively modified 15 N-labelled DNA demonstrates that diet does not appear to contribute to urinary levels of 8-hydroxyguanine and 7,8-dihydro-8-oxo-2'-deoxyguanosine. Furthermore, we propose that a number of literature reports form an argument against a contribution from cell death. Indeed we, and others, have presented evidence, which strongly suggests the involvement of cell death to be minimal. Taken together, these data would appear to rule out various confounding factors, leaving DNA repair pathways as the principal source of urinary purine, if not DNA, lesions enabling such measurements to be used as indicators of repair

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

    Directory of Open Access Journals (Sweden)

    Ida Casorelli

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

  12. DNA Double Strand Break Response and Limited Repair Capacity in Mouse Elongated Spermatids

    Directory of Open Access Journals (Sweden)

    Emad A. Ahmed

    2015-12-01

    Full Text Available Spermatids are extremely sensitive to genotoxic exposures since during spermiogenesis only error-prone non homologous end joining (NHEJ repair pathways are available. Hence, genomic damage may accumulate in sperm and be transmitted to the zygote. Indirect, delayed DNA fragmentation and lesions associated with apoptotic-like processes have been observed during spermatid elongation, 27 days after irradiation. The proliferating spermatogonia and early meiotic prophase cells have been suggested to retain a memory of a radiation insult leading later to this delayed fragmentation. Here, we used meiotic spread preparations to localize phosphorylate histone H2 variant (γ-H2AX foci marking DNA double strand breaks (DSBs in elongated spermatids. This technique enabled us to determine the background level of DSB foci in elongated spermatids of RAD54/RAD54B double knockout (dko mice, severe combined immunodeficiency SCID mice, and poly adenosine diphosphate (ADP-ribose polymerase 1 (PARP1 inhibitor (DPQ-treated mice to compare them with the appropriate wild type controls. The repair kinetics data and the protein expression patterns observed indicate that the conventional NHEJ repair pathway is not available for elongated spermatids to repair the programmed and the IR-induced DSBs, reflecting the limited repair capacity of these cells. However, although elongated spermatids express the proteins of the alternative NHEJ, PARP1-inhibition had no effect on the repair kinetics after IR, suggesting that DNA damage may be passed onto sperm. Finally, our genetic mutant analysis suggests that an incomplete or defective meiotic recombinational repair of Spo11-induced DSBs may lead to a carry-over of the DSB damage or induce a delayed nuclear fragmentation during the sensitive programmed chromatin remodeling occurring in elongated spermatids.

  13. Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect - a histopathological and immunohistochemical study

    International Nuclear Information System (INIS)

    Nagtegaal, Iris D; Marijnen, Corrie AM; Kranenbarg, Elma Klein; Mulder-Stapel, Adri; Hermans, Jo; Velde, Cornelis JH van de; Krieken, J Han JM van

    2001-01-01

    Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. The presence of inflammatory infiltrate and eosinophils was determined in 1530 patients with rectal adenocarcinoma from a multicenter trial. We selected 160 patients to analyze this inflammatory infiltrate in more detail using immunohistochemistry. The association with the development of local and distant relapses was determined using univariate and multivariate log rank testing. Patients with an extensive inflammatory infiltrate around the tumor had lower recurrence rates (3.4% versus 6.9%, p = 0.03), showing the importance of host response against tumor cells. In particular, peritumoral mast cells prevent local and distant recurrence (44% versus 15%, p = 0.007 and 86% versus 21%, p < 0.0001, respectively), with improved survival as a consequence. The presence of intratumoral T-cells had independent prognostic value for the occurrence of distant metastases (32% versus 76%, p < 0.0001). We showed that next to properties of tumor cells, the amount and type of inflammation is also relevant in the control of rectal cancer. Knowledge of the factors involved may lead to new approaches in the management of rectal cancer

  14. Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents.

    Science.gov (United States)

    Christmann, M; Kaina, B

    2000-11-17

    Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gene activity. Cells expressing the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT), thus having the ability to repair O(6)-methylguanine, showed no translocation of MutSalpha, whereas inhibition of MGMT by O(6)-benzylguanine provoked the translocation. The results demonstrate that O(6)-methylguanine lesions are involved in triggering nuclear accumulation of MSH2 and MSH6. The finding that treatment of cells with O(6)-methylguanine-generating mutagens results in an increase of MutSalpha and GT binding activity in the nucleus indicates a novel type of genotoxic stress response.

  15. Role of Cell Cycle Regulation and MLH1, A Key DNA Mismatch Repair Protein, In Adaptive Survival Responses. Final Report; FINAL

    International Nuclear Information System (INIS)

    David A. Boothman

    1999-01-01

    Due to several interesting findings on both adaptive survival responses (ASRs) and DNA mismatch repair (MMR), this grant was separated into two discrete Specific Aim sets (each with their own discrete hypotheses). The described experiments were simultaneously performed

  16. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.

  17. Bridging plant and human radiation response and DNA repair through an in silico approach

    Czech Academy of Sciences Publication Activity Database

    Nikitaki, Z.; Pavlopoulou, A.; Holá, Marcela; Donà, M.; Michalopoulos, I.; Balestrazzi, A.; Angelis, Karel; Georgakilas, A. G.

    2017-01-01

    Roč. 9, č. 6 (2017), č. článku 65. ISSN 2072-6694 R&D Projects: GA ČR GA16-01137S Institutional support: RVO:61389030 Keywords : Bioinformatics * DNA damage repair * In silico analysis * Ionizing radiation * Plant radiation biodosimeter * Ultraviolet radiation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Oncology

  18. Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin.

    Science.gov (United States)

    Li, Zhi; Gothard, Elizabeth; Coles, Mark C; Ambler, Carrie A

    2018-01-01

    In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s), by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

  19. Long-term anisotropic mechanical response of surgical meshes used to repair abdominal wall defects.

    Science.gov (United States)

    Hernández-Gascón, B; Peña, E; Pascual, G; Rodríguez, M; Bellón, J M; Calvo, B

    2012-01-01

    Routine hernia repair surgery involves the implant of synthetic mesh. However, this type of procedure may give rise to pain and bowel incarceration and strangulation, causing considerable patient disability. The purpose of this study was to compare the long-term behaviour of three commercial meshes used to repair the partially herniated abdomen in New Zealand White rabbits: the heavyweight (HW) mesh, Surgipro(®) and lightweight (LW) mesh, Optilene(®), both made of polypropylene (PP), and a mediumweight (MW) mesh, Infinit(®), made of polytetrafluoroethylene (PTFE). The implanted meshes were mechanical and histological assessed at 14, 90 and 180 days post-implant. This behaviour was compared to the anisotropic mechanical behaviour of the unrepaired abdominal wall in control non-operated rabbits. Both uniaxial mechanical tests conducted in craneo-caudal and perpendicular directions and histological findings revealed substantial collagen growth over the repaired hernial defects causing stiffness in the repair zone, and thus a change in the original properties of the meshes. The mechanical behaviour of the healthy tissue in the craneo-caudal direction was not reproduced by any of the implanted meshes after 14 days or 90 days of implant, whereas in the perpendicular direction, SUR and OPT achieved similar behaviour. From a mechanical standpoint, the anisotropic PP-lightweight meshes may be considered a good choice in the long run, which correlates with the structure of the regenerated tissue. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice

    International Nuclear Information System (INIS)

    Nakada, Shinichiro

    2016-01-01

    The E3 ubiquitin ligases ring finger protein (RNF) 8 and RNF168 transduce the DNA double-strand break (DSB) response (DDR) signal by ubiquitinating DSB sites. The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair. This mini-review provides a brief overview of the RNF8- and RNF168-dependent DDR-signaling and DNA-repair pathways. The choice of DNA-repair pathway when RNF8- and RNF168-mediated ubiquitination-dependent DDR signaling is negatively regulated by deubiquitinating enzymes (DUBs) is reviewed to clarify how the opposing roles of RNF8/RNF168 and DUBs regulate ubiquitination-dependent DDR signaling and the choice of DNA-repair pathway

  1. Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness

    DEFF Research Database (Denmark)

    Kari, Vijayalakshmi; Mansour, Wael Yassin; Raul, Sanjay Kumar

    2016-01-01

    The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of Ct......-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may...... serve as a marker for prostate cancer patient stratification and the utilization of targeted therapies such as PARP inhibitors, which specifically target tumors with HR defects....

  2. Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin

    Directory of Open Access Journals (Sweden)

    Zhi Li

    2018-02-01

    Full Text Available In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s, by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

  3. Repair and cell cycle response in cells exposed to environmental biohazards. Progress report, June 1, 1979-May 31, 1980

    International Nuclear Information System (INIS)

    Billen, D.; Hadden, C.T.

    1980-01-01

    Progress is reported in the following research areas: (1) DNA repair in Bacillus subtilis; (2) postreplication repair in Rec - mutants of B. subtilis; (3) photobiology of halogenated DNA; (4) effects of caffeine on pyrimidine dimer excision and postreplication repair in B. subtilis; and (5) DNA repair in toluene-treated Escherichia coli

  4. Escaping and repairing behaviors of the termite Odontotermes formosanus (Blattodea: Termitidae in response to disturbance

    Directory of Open Access Journals (Sweden)

    Hongpeng Xiong

    2018-03-01

    Full Text Available The escaping behavior of termites has been documented under laboratory conditions; however, no study has been conducted in a field setting due to the difficulty of observing natural behaviors inside wood or structures (e.g., nests, tunnels, etc.. The black-winged termite, Odontotermes formosanus (Shiraki, is a subterranean macrotermitine species which builds extensive mud tubes on tree trunks. In the present study, 41 videos (totaling ∼2,700 min were taken on 22 colonies/subcolonies of O. formosanus after their mud tubes were partially damaged by hand. In general, termites consistently demonstrated three phases of escape, including initiation (wandering near the mud-tube breach, individual escaping (single termites moving downward, and massive, unidirectional escaping flows (groups of termites moving downward. Downward moving and repairing were the dominant behavioral activities of individuals and were significantly more frequent than upward moving, turning/backward moving, or wandering. Interestingly, termites in escaping flows moved significantly faster than escaping individuals. Repairing behavior was observed shortly after the disturbance, and new mud tubes were preferentially constructed from the bottom up. When predators (i.e., ants were present, however, termites stopped moving and quickly sealed the mud-tube openings by capping the broken ends. Our study provides an interesting example that documents an animal (besides humans simultaneously carrying out pathway repairs and emergency evacuation without congestion.

  5. Escaping and repairing behaviors of the termite Odontotermes formosanus (Blattodea: Termitidae) in response to disturbance.

    Science.gov (United States)

    Xiong, Hongpeng; Chen, Xuan; Wen, Yuzhen; Layne, Michael; Sun, Zhaohui; Ma, Tao; Wen, Xiujun; Wang, Cai

    2018-01-01

    The escaping behavior of termites has been documented under laboratory conditions; however, no study has been conducted in a field setting due to the difficulty of observing natural behaviors inside wood or structures (e.g., nests, tunnels, etc.). The black-winged termite, Odontotermes formosanus (Shiraki), is a subterranean macrotermitine species which builds extensive mud tubes on tree trunks. In the present study, 41 videos (totaling ∼2,700 min) were taken on 22 colonies/subcolonies of O. formosanus after their mud tubes were partially damaged by hand. In general, termites consistently demonstrated three phases of escape, including initiation (wandering near the mud-tube breach), individual escaping (single termites moving downward), and massive, unidirectional escaping flows (groups of termites moving downward). Downward moving and repairing were the dominant behavioral activities of individuals and were significantly more frequent than upward moving, turning/backward moving, or wandering. Interestingly, termites in escaping flows moved significantly faster than escaping individuals. Repairing behavior was observed shortly after the disturbance, and new mud tubes were preferentially constructed from the bottom up. When predators (i.e., ants) were present, however, termites stopped moving and quickly sealed the mud-tube openings by capping the broken ends. Our study provides an interesting example that documents an animal (besides humans) simultaneously carrying out pathway repairs and emergency evacuation without congestion.

  6. Timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer - A comparison of magnetic resonance imaging at two time points and histopathological responses.

    Science.gov (United States)

    West, M A; Dimitrov, B D; Moyses, H E; Kemp, G J; Loughney, L; White, D; Grocott, M P W; Jack, S; Brown, G

    2016-09-01

    There is wide inter-institutional variation in the interval between neoadjuvant chemoradiotherapy (NACRT) and surgery for locally advanced rectal cancer. We aimed to assess the association of magnetic resonance imaging (MRI) at 9 and 14 weeks post-NACRT; T-staging (ymrT) and post-NACRT tumour regression grading (ymrTRG) with histopathological outcomes; histopathological T-stage (ypT) and histopathological tumour regression grading (ypTRG) in order to inform decision-making about timing of surgery. We prospectively studied 35 consecutive patients (26 males) with MRI-defined resection margin threatened rectal cancer who had completed standardized NACRT. Patients underwent a MRI at Weeks 9 and 14 post-NACRT, and surgery at Week 15. Two readers independently assessed MRIs for ymrT, ymrTRG and volume change. ymrT and ymrTRG were analysed against histopathological ypT and ypTRG as predictors by logistic regression modelling and receiver operating characteristic (ROC) curve analyses. Thirty-five patients were recruited. Inter-observer agreement was good for all MR variables (Kappa > 0.61). Considering ypT as an outcome variable, a stronger association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.064 vs. p = 0.010; Volume change - p = 0.062 vs. p = 0.007). Similarly, considering ypTRG as an outcome variable, a greater association of favourable ymrTRG and volume change at Week 14 compared to Week 9 was found (ymrTRG - p = 0.005 vs. p = 0.042; Volume change - p = 0.004 vs. 0.055). Following NACRT, greater tumour down-staging and volume reduction was observed at Week 14. Timing of surgery, in relation to NACRT, merits further investigation. NCT01325909. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. A damage-responsive DNA binding protein regulates transcription of the yeast DNA repair gene PHR1

    International Nuclear Information System (INIS)

    Sebastian, J.; Sancar, G.B.

    1991-01-01

    The PHR1 gene of Saccharomyces cerevisiae encodes the DNA repair enzyme photolyase. Transcription of PHR1 increases in response to treatment of cells with 254-nm radiation and chemical agents that damage DNA. The authors here the identification of a damage-responsive DNA binding protein, termed photolyase regulatory protein (PRP), and its cognate binding site, termed the PHR1 transcription after DNA damage. PRP activity, monitored by electrophoretic-mobility-shift assay, was detected in cells during normal growth but disappeared within 30 min after irradiation. Copper-phenanthroline footprinting of PRP-DNA complexes revealed that PRP protects a 39-base-pair region of PHR1 5' flanking sequence beginning 40 base pairs upstream from the coding sequence. Thus these observations establish that PRP is a damage-responsive repressor of PHR1 transcription

  8. Induction of the early response protein EGR-1 in human tumour cells after ionizing radiation is correlated with a reduction of repair of lethal lesions and an increase of repair of sublethal lesions

    NARCIS (Netherlands)

    Franken, Nicolaas A. P.; ten Cate, Rosemarie; van Bree, Chris; Haveman, Jaap

    2004-01-01

    The role of EGR-1 in potentially lethal damage repair (PLDR) was studied. Induction of the early response protein EGR-1 and survival after ionizing radiation of two human tumour cell lines after culturing for 48 h in serum-deprived medium was investigated. The glioblastoma cell line (Gli-6) and a

  9. perception and utilization of oral histopathology services by general ...

    African Journals Online (AJOL)

    GENERAL PRACTICE DENTIST IN SOUTHWEST NIGERIA pathology ... Keywords: Oral; Histopathology; General dental practice; Southwest Nigeria. Ann Ibd. Pg. Med .... Table 3: Distribution of responses indicating barriers and utilization of oral histopathology services. Perception of respondents χ2 p value. Poor. Good.

  10. Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms.

    Science.gov (United States)

    Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis

    2016-06-01

    Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed.

  11. Repair Responses of Dental Pulp to Tooth Injury and Biological Properties of Dentin-pulp Complex

    OpenAIRE

    大島, 勇人; Ohshima, Hayato

    2004-01-01

    Regeneration-the creation of a new tissue after the original one has been lost-is the fundamental biological capability in an organism. Numerous organs are considered to contain stem cells referred to as adult stem cells, even in the adult. Adult stem cells can give rise to a limited set of adult tissue types. In the field of clinical dentistry, it is well-known that the dentin-pulp complex is capable of repair after tooth injuries such as tooth replantation/transplantation or restorative pro...

  12. Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation

    Directory of Open Access Journals (Sweden)

    Manuel J. Muñoz

    2017-03-01

    Full Text Available We have previously found that UV irradiation promotes RNA polymerase II (RNAPII hyperphosphorylation and subsequent changes in alternative splicing (AS. We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER, and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation.

  13. DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

    LENUS (Irish Health Repository)

    Martin, Lynn M

    2013-07-10

    DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.

  14. Homologous Recombination Repair Signaling in Chemical Carcinogenesis: Prolonged Particulate Hexavalent Chromium Exposure Suppresses the Rad51 Response in Human Lung Cells

    Science.gov (United States)

    Qin, Qin; Xie, Hong; Wise, Sandra S.; Browning, Cynthia L.; Thompson, Kelsey N.; Holmes, Amie L.; Wise, John Pierce

    2014-01-01

    The aim of this study was to focus on hexavalent chromium, [Cr(VI)], a chemical carcinogen and major public health concern, and consider its ability to impact DNA double strand break repair. We further focused on particulate Cr(VI), because it is the more potent carcinogenic form of Cr(VI). DNA double strand break repair serves to protect cells against the detrimental effects of DNA double strand breaks. For particulate Cr(VI), data show DNA double strand break repair must be overcome for neoplastic transformation to occur. Acute Cr(VI) exposures reveal a robust DNA double strand break repair response, however, longer exposures have not been considered. Using the comet assay, we found longer exposures to particulate zinc chromate induced concentration-dependent increases in DNA double strand breaks indicating breaks were occurring throughout the exposure time. Acute (24 h) exposure induced DNA double strand break repair signaling by inducing Mre11 foci formation, ATM phosphorylation and phosphorylated ATM foci formation, Rad51 protein levels and Rad51 foci formation. However, longer exposures reduced the Rad51 response. These data indicate a major chemical carcinogen can simultaneously induce DNA double strand breaks and alter their repair and describe a new and important aspect of the carcinogenic mechanism for Cr(VI). PMID:25173789

  15. Repair and cell-cycle response in cells exposed to environmental biohazards. Comprehensive project report, June 1, 1979-May 31, 1982

    International Nuclear Information System (INIS)

    Billen, D.

    1982-01-01

    Agents which cause damage to DNA leading to inhibition of DNA synthesis or faulty DNA replication or repair may cause cell death or mutation. Many organisms possess the ability to circumvent some or all of this DNA damage. Many DNA mutants of E. coli and B. subtilis provide a genetic approach to measuring the role of individual components of the DNA repair and replicative system. The information obtained with prokaryotes provides leads to assess the details of DNA repair and replication in mammalian systems including man. Escherichia coli cells treated with a low concentration of toluene become permeable to a variety of compounds, including the precursors and cofactors necessary for DNA synthesis. By their manipulation various aspects of DNA replication and repair can be selectively emphasized. Observations made by use of this system include: (1) Repair synthesis induced by x irradiation or exposure to alkylating chemicals of toluene-treated cells is more extensive if polynucleotide ligase is inhibited. (2) DNA replication in E. coli is carried out by DNA polymerase III. The replication of DNA is strongly inhibited by methylmethansulfonate, N-methyl-N-nitrosourea, and N-methyl-N'-nitro-N-nitrosoguanidine. (3) Using a po1A1 po1B100 dnaB (po1I - , po1II - , po1III + ) mutant of E. coli, it was demonstrated that the dnaB gene product is not necessary for Po1III directed repair synthesis. (4) The physiological stage of cells and tissues affects their response to environmental hazards. (5) Procedures for permeabilizing mammalian cells have been developed or further refined; and (6) In earlier studies involving both alkylating agents and x rays, it was observed that the number of DNA single-strand breaks increased with dose along with repair synthesis. It appears that non-repaired sites do not serve as primer ends for Po1I-dependent repair synthesis in toluene-treated cells

  16. Response of BP cell lines to γ-radiation: evaluation of DNA repair and apoptosis

    International Nuclear Information System (INIS)

    Paris, F.E.; Martin, M.; Le Rhum, Y.; May, E.; Duriez, P; Shah, G.

    1997-01-01

    In the BP cell lines, mutation of p53 gene is associated with an increased radiosensitivity. In order to understand the relation between p53 and radiosensitivity, we looked at DNA repair and cell death. Unexpectedly, after radiation the mutated p53 cell line BPp- Tu and the wild type p53 cell line BPp- Tu cells, both ell lines died by the same non necrotic process: a programmed cell death independent of their p53 status. The cleavage of poly (ADP-ribose) polymerase (PARP) by an ICE-related protease is considered an early and critical event during apoptosis. The fate of PARP was monitored by Western extensively in the apoptotic BPp- Tu cells than in the BPp cells. This faster PARP cleavage might be linked to the increased radiosensitivity of the BPp- Tu cells. (authors)

  17. Repair and cell cycle response in cells exposed to environmental biohazards. Progress report, June 1, 1980-May 31, 1981

    International Nuclear Information System (INIS)

    Billen, D.; Hadden, C.T.

    1981-01-01

    Research progress for the period June 1, 1980 through May 31, 1981 is reported. Topics include: (1) repair of damage by psoralen plus near-uv light; (2) in vitro repair of transforming DNA; (3) photobiology of halogenated DNA; and (4) DNA repair in toluene-treated Escherichia coli containing BU-DNA

  18. Dose-response and histopathological study, with special attention to the hypophysis, of the differential effects of domoic acid on rats and mice.

    Science.gov (United States)

    Vieira, Andrés Crespo; Martínez, J Manuel Cifuentes; Pose, Roberto Bermúdez; Queijo, Álvaro Antelo; Posadas, Nuria Alemañ; López, Luis M Botana

    2015-05-01

    The effects of the neurotoxin domoic acid (DA) in the central nervous system of rodents (essentially rats and mice) after intraperitoneal administration have been profusely studied in the past. These observations have shown that the toxin induces similar symptoms and pathology in both species, but the lethality varies greatly. This article addresses the common and specific histopathological effects in rats and mice and the difference in sensitivity of these species to DA. Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8 mg/kg) to observe their neurotoxicity by using different histological techniques, and these results were compared with the pathological effects after the administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the presence of this toxin in various tissues by means of immunohistochemistry. Our results showed that rats are more vulnerable than mice to the neurotoxic effects of DA after intraperitoneal inoculation: lethality was extremely high in rats and the toxin produced hippocampal damage in rats surviving the intoxication, while lesions were not observed in DA-inoculated mice. As for similarities between rats and mice, both displayed similar clinical signs and in both the toxin was detected in the hypophysis by immunohistochemistry, a brain region not reported to date as target of the toxin. © 2015 Wiley Periodicals, Inc.

  19. Coagulation, inflammatory, and stress responses in a randomized comparison of open and laparoscopic repair of recurrent inguinal hernia

    DEFF Research Database (Denmark)

    Rahr, H B; Bendix, J; Ahlburg, P

    2006-01-01

    BACKGROUND: In previous comparisons of inflammatory and stress responses to open (OR) and laparoscopic (LR) hernia repair, all operations were performed under general anesthesia. Since local anesthesia is widely used for OR, a comparison of this approach with LR seemed relevant. METHODS: Patients...... with recurrent inguinal hernia were randomized to OR under local anesthesia (n = 30) or LR under general anesthesia (n = 31). The magnitude of the surgical trauma was assessed by measuring markers of coagulation (prothrombin fragment 1 + 2), endothelial activation (von Willebrand factor), inflammation...... [leukocytes, interleukin-6, -8 and -10, granulocyte macrophage colony-stimulating factor, and C-reactive protein (CRP)], and endocrine stress (cortisol) in blood collected before operation, 4 h postincision, and on postoperative day 2. RESULTS: Leukocyte counts and interleukin-6 and CRP levels increased...

  20. Histopathology of hepatocellular carcinoma.

    Science.gov (United States)

    Schlageter, Manuel; Terracciano, Luigi Maria; D'Angelo, Salvatore; Sorrentino, Paolo

    2014-11-21

    Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

  1. Mechanical stress is associated with right ventricular response to pulmonary valve replacement in patients with repaired tetralogy of Fallot.

    Science.gov (United States)

    Tang, Dalin; Yang, Chun; Del Nido, Pedro J; Zuo, Heng; Rathod, Rahul H; Huang, Xueying; Gooty, Vasu; Tang, Alexander; Billiar, Kristen L; Wu, Zheyang; Geva, Tal

    2016-03-01

    Patients with repaired tetralogy of Fallot account for a substantial proportion of cases with late-onset right ventricular failure. The current surgical approach, which includes pulmonary valve replacement/insertion, has yielded mixed results. Therefore, it may be clinically useful to identify parameters that can be used to predict right ventricular function response to pulmonary valve replacement. Cardiac magnetic resonance data before and 6 months after pulmonary valve replacement were obtained from 16 patients with repaired tetralogy of Fallot (8 male, 8 female; median age, 42.75 years). Right ventricular ejection fraction change from pre- to postpulmonary valve replacement was used as the outcome. The patients were divided into group 1 (n = 8, better outcome) and group 2 (n = 8, worst outcome). Cardiac magnetic resonance-based patient-specific computational right ventricular/left ventricular models were constructed, and right ventricular mechanical stress and strain, wall thickness, curvature, and volumes were obtained for analysis. Our results indicated that right ventricular wall stress was the best single predictor for postpulmonary valve replacement outcome with an area under the receiver operating characteristic curve of 0.819. Mean values of stress, strain, wall thickness, and longitudinal curvature differed significantly between the 2 groups with right ventricular wall stress showing the largest difference. Mean right ventricular stress in group 2 was 103% higher than in group 1. Computational modeling and right ventricular stress may be used as tools to identify right ventricular function response to pulmonary valve replacement. Large-scale clinical studies are needed to validate these preliminary findings. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. Toxicogenomic analysis of N-nitrosomorpholine induced changes in rat liver: Comparison of genomic and proteomic responses and anchoring to histopathological parameters

    International Nuclear Information System (INIS)

    Oberemm, A.; Ahr, H.-J.; Bannasch, P.; Ellinger-Ziegelbauer, H.; Glueckmann, M.; Hellmann, J.; Ittrich, C.; Kopp-Schneider, A.; Kramer, P.-J.; Krause, E.; Kroeger, M.; Kiss, E.; Richter-Reichhelm, H.-B.; Scholz, G.; Seemann, K.; Weimer, M.; Gundert-Remy, U.

    2009-01-01

    A common animal model of chemical hepatocarcinogenesis was used to examine the utility of transcriptomic and proteomic data to identify early biomarkers related to chemically induced carcinogenesis. N-nitrosomorpholine, a frequently used genotoxic model carcinogen, was applied via drinking water at 120 mg/L to male Wistar rats for 7 weeks followed by an exposure-free period of 43 weeks. Seven specimens of each treatment group (untreated control and 120 mg/L N-nitrosomorpholine in drinking water) were sacrificed at nine time points during and after N-nitrosomorpholine treatment. Individual samples from the liver were prepared for histological and toxicogenomic analyses. For histological detection of preneoplastic and neoplastic tissue areas, sections were stained using antibodies against the placental form of glutathione-S-transferase (GST-P). Gene and protein expression profiles of liver tissue homogenates were analyzed using RG-U34A Affymetrix rat gene chips and two-dimensional gel electrophoresis-based proteomics, respectively. In order to compare results obtained by histopathology, transcriptomics and proteomics, GST-P-stained liver sections were evaluated morphometrically, which revealed a parallel time course of the area fraction of preneoplastic lesions and gene plus protein expression patterns. On the transcriptional level, an increase of hepatic GST-P expression was detectable as early as 3 weeks after study onset. Comparing deregulated genes and proteins, eight species were identified which showed a corresponding expression profile on both expression levels. Functional analysis suggests that these genes and corresponding proteins may be useful as biomarkers of early hepatocarcinogenesis.

  3. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

  4. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Gloria A. Santa-Gonzalez

    2016-10-01

    Full Text Available Many environmental and physiological stresses are chronic. Thus, cells are constantly exposed to diverse types of genotoxic insults that challenge genome stability, including those that induce oxidative DNA damage. However, most in vitro studies that model cellular response to oxidative stressors employ short exposures and/or acute stress models. In this study, we tested the hypothesis that chronic and repeated exposure to a micromolar concentration of hydrogen peroxide (H2O2 could activate DNA damage responses, resulting in cellular adaptations. For this purpose, we developed an in vitro model in which we incubated mouse myoblast cells with a steady concentration of ~50 μM H2O2 for one hour daily for seven days, followed by a final challenge of a 10 or 20X higher dose of H2O2 (0.5 or 1 mM. We report that intermittent long-term exposure to this oxidative stimulus nearly eliminated cell toxicity and significantly decreased genotoxicity (in particular, a >5-fold decreased in double-strand breaks resulting from subsequent acute exposure to oxidative stress. This protection was associated with cell cycle arrest in G2/M and induction of expression of nine DNA repair genes. Together, this evidence supports an adaptive response to chronic, low-level oxidative stress that results in genomic protection and up-regulated maintenance of cellular homeostasis.

  5. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  6. Biaxial Mechanical Evaluation of Absorbable and Nonabsorbable Synthetic Surgical Meshes Used for Hernia Repair: Physiological Loads Modify Anisotropy Response.

    Science.gov (United States)

    Cordero, A; Hernández-Gascón, B; Pascual, G; Bellón, J M; Calvo, B; Peña, E

    2016-07-01

    The aim of this study was to obtain information about the mechanical properties of six meshes commonly used for hernia repair (Surgipro(®), Optilene(®), Infinit(®), DynaMesh(®), Ultrapro™ and TIGR(®)) by planar biaxial tests. Stress-stretch behavior and equibiaxial stiffness were evaluated, and the anisotropy was determined by testing. In particular, equibiaxial test (equal simultaneous loading in both directions) and biaxial test (half of the load in one direction following the Laplace law) were selected as a representation of physiologically relevant loads. The majority of the meshes displayed values in the range of 8 and 18 (N/mm) in each direction for equibiaxial stiffness (tangent modulus under equibiaxial load state in both directions), while a few achieved 28 and 50 (N/mm) (Infinit (®) and TIGR (®)). Only the Surgipro (®) mesh exhibited planar isotropy, with similar mechanical properties regardless of the direction of loading, and an anisotropy ratio of 1.18. Optilene (®), DynaMesh (®), Ultrapro (®) and TIGR (®) exhibited moderate anisotropy with ratios of 1.82, 1.84, 2.17 and 1.47, respectively. The Infinit (®) scaffold exhibited very high anisotropy with a ratio of 3.37. These trends in material anisotropic response changed during the physiological state in the human abdominal wall, i.e. T:0.5T test, which the meshes were loaded in one direction with half the load used in the other direction. The Surgipro (®) mesh increased its anisotropic response (Anis[Formula: see text] = 0.478) and the materials that demonstrated moderate and high anisotropic responses during multiaxial testing presented a quasi-isotropic response, especially the Infinit(®) mesh that decreased its anisotropic response from 3.369 to 1.292.

  7. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  8. Dose-response relationship of induction kinetics of In vivo DNA damage and repair in mouse leukocytes exposed to gamma radiation

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales, R.P.

    2000-01-01

    The Unicellular electrophoresis in gel technique is a useful tool in the determination of simple ruptures and labile sites to the alkali in DNA of eucariontes cells. The determination of the induction kinetics of damage and repair of DNA can give more information. The objective of this work was to determine whether the analysis of the area under the damage/repair induction kinetics curve in comets percent or the comets frequency in the two peaks of maximum induction is adequate for determining the dose-response relationship. The mice were exposed at the doses of 0.5, 1.0, 2.0 Gy. (Author)

  9. Clinical spectrum and histopathological study

    African Journals Online (AJOL)

    Manal M. Abd-Elgawad

    2013-04-23

    Apr 23, 2013 ... ciated with fatigue especially in teens and adults. Patients who ... data on the natural history and histopathology of HCV-related liver disease in children .... not performed in every affected child, it usually reveals mild le- sions.

  10. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents.

    Science.gov (United States)

    Esteller, M; Garcia-Foncillas, J; Andion, E; Goodman, S N; Hidalgo, O F; Vanaclocha, V; Baylin, S B; Herman, J G

    2000-11-09

    The DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents. We analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome. The MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.

  11. Mitosis, double strand break repair, and telomeres: a view from the end: how telomeres and the DNA damage response cooperate during mitosis to maintain genome stability.

    Science.gov (United States)

    Cesare, Anthony J

    2014-11-01

    Double strand break (DSB) repair is suppressed during mitosis because RNF8 and downstream DNA damage response (DDR) factors, including 53BP1, do not localize to mitotic chromatin. Discovery of the mitotic kinase-dependent mechanism that inhibits DSB repair during cell division was recently reported. It was shown that restoring mitotic DSB repair was detrimental, resulting in repair dependent genome instability and covalent telomere fusions. The telomere DDR that occurs naturally during cellular aging and in cancer is known to be refractory to G2/M checkpoint activation. Such DDR-positive telomeres, and those that occur as part of the telomere-dependent prolonged mitotic arrest checkpoint, normally pass through mitosis without covalent ligation, but result in cell growth arrest in G1 phase. The discovery that suppressing DSB repair during mitosis may function primarily to protect DDR-positive telomeres from fusing during cell division reinforces the unique cooperation between telomeres and the DDR to mediate tumor suppression. © 2014 The Author. Bioessays published by WILEY Periodicals, Inc.

  12. Evaluating the integrity of the reinforced concrete structure repaired by epoxy injection using simulated transfer function of impact-echo response

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Chia-Chi; Yu, Chih-peng; Wu, Jiunn-Hong; Hsu, Keng-Tsan; Ke, Ying-Tsu [Chaoyang University of Technology, Department of Construction Engineering, Taichung, Taiwan (China)

    2014-02-18

    Cracks and honeycombs are often found inside reinforced concrete (RC) structure caused by excessive external force, or improper casting of concrete. The repairing method usually involves epoxy injection. The impact-echo method, which is a sensitive for detecting of the interior voids, may not be applicable to assess the integrity of the repaired member as both air and epoxy are less in acoustic impedances. In this study, the repaired RC structure was evaluated by the simulated transfer function of the IE displacement waveform where the R-wave displacement waveform is used as a base of a simulated force-time function. The effect of different thickness of the epoxy layer to the amplitude corresponding to the interface is studied by testing on specimen containing repaired naturally delaminated cracks with crack widths about 1 mm, 3 mm and 5 mm. The impact-echo responses were compared with the drilling cores at the test positions. The results showed the cracks were not fully filled with epoxy when the peak amplitude corresponding to the interface dropped less than 20%. The peak corresponding to the thicker epoxy layer tends to be larger in amplitude. A field study was also performed on a column damaged by earthquake before and after repairing.

  13. Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Hui; Shi, Qiong; Song, Xiufang; Fu, Juanli; Hu, Lihua; Xu, Demei; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang, E-mail: songyangwenrong@hotmail.com

    2015-07-01

    Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observed phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.

  14. Repair and cell cycle response in cells exposed to environmental biohazards. Progress report, February 1, 1976--May 31, 1977

    International Nuclear Information System (INIS)

    Billen, D.

    1977-01-01

    Progress is reported on the following research projects: DNA polymerase III dependent repair of x-ray damage in Escherichia coli; regulation of reinsertation of nucleotides by DNA ligase; DNA synthesis in permeabilized CHO cells; measurement of damage to DNA in Bacillus subtilis; repair defect in rec A cells; inactivation of transforming DNA; and mutagenesis of transforming DNA

  15. Hippocampal Neurogenesis and the Brain Repair Response to Brief Stereotaxic Insertion of a Microneedle

    Directory of Open Access Journals (Sweden)

    Shijie Song

    2013-01-01

    Full Text Available We tested the hypothesis that transient microinjury to the brain elicits cellular and humoral responses that stimulate hippocampal neurogenesis. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus resulted in (a significantly increased expression of granulocyte-colony stimulating factor (G-CSF, the chemokine MIP-1a, and the proinflammatory cytokine IL12p40; (b pronounced activation of microglia and astrocytes; and (c increase in hippocampal neurogenesis. This study describes immediate and early humoral and cellular mechanisms of the brain’s response to microinjury that will be useful for the investigation of potential neuroprotective and deleterious effects of deep brain stimulation in various neuropsychiatric disorders.

  16. Histopathological study of response of Vitis vinifera cv. Cabernet Sauvignon to bark and wood injury with and without inoculation by Phaeomoniella chlamydospora

    Directory of Open Access Journals (Sweden)

    Jérôme POUZOULET

    2013-09-01

    Full Text Available Summary. Phaeomoniella chlamydospora (Pch is one of the main causal agents of tracheomycosis in grapevine. We characterize how this fungus affects the response of Vitis vinifera cv. Cabernet Sauvignon to bark and xylem-tissue wounding after six weeks post-treatment. A histological investigation shows that, in xylem tissue, cell-wall modifications in response to wounding are related to suberin deposits rather than to lignin-induced wall thickening. The xylem response does not appear to be disturbed by Pch infection. Therefore, cell-wall modification strongly inhibits the development of wound-closure tissue (WCT but does not prevent the differentiation of the necro-phylactic periderm. Hyphae localization in tissue surrounding the wound or inoculation sites indicates that Pch colonizes all cell types, such as vascular tissues, paratracheal parenchyma cells, fibers and rays. The results also suggest that efficient compartmentalization separating fascicular xylem portions is assured by thick suberized cell walls bordering the ray parenchyma.

  17. Comparison of histopathology, cultivation of tissues and rectal contents, and interferon-gamma and serum antibody responses for the diagnosis of bovine paratuberculosis

    DEFF Research Database (Denmark)

    Huda, A.; Jensen, H.E.

    2003-01-01

    contents, and (3) examination of repeated blood samples for interferon-gamma (IFN-gamma) and antibody responses. Tissue samples were taken from the small and large intestine and corresponding mesenteric lymph nodes, and from the pharyngeal tonsil and other lymphoid nodes (retropharyngeal, mediastinal...

  18. DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics.

    Science.gov (United States)

    de Rosa, Nicole; Rodriguez-Bigas, Miguel A; Chang, George J; Veerapong, Jula; Borras, Ester; Krishnan, Sunil; Bednarski, Brian; Messick, Craig A; Skibber, John M; Feig, Barry W; Lynch, Patrick M; Vilar, Eduardo; You, Y Nancy

    2016-09-01

    DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions. © 2016 by American Society of Clinical Oncology.

  19. Histopathological subgroups in knee osteoarthritis.

    Science.gov (United States)

    Wyatt, L A; Moreton, B J; Mapp, P I; Wilson, D; Hill, R; Ferguson, E; Scammell, B E; Walsh, D A

    2017-01-01

    Osteoarthritis (OA) is a heterogeneous, multi-tissue disease. We hypothesised that different histopathological features characterise different stages during knee OA progression, and that discrete subgroups can be defined based on validated measures of OA histopathological features. Medial tibial plateaux and synovium were from 343 post-mortem (PM) and 143 OA arthroplasty donations. A 'chondropathy/osteophyte' group (n = 217) was classified as PM cases with osteophytes or macroscopic medial tibiofemoral chondropathy lesions ≥grade 3 to represent pre-surgical (early) OA. 'Non-arthritic' controls (n = 48) were identified from the remaining PM cases. Mankin histopathological scores were subjected to Rasch analysis and supplemented with histopathological scores for subchondral bone marrow replacement and synovitis. Item weightings were derived by principle components analysis (PCA). Histopathological subgroups were sought using latent class analysis (LCA). Chondropathy, synovitis and osteochondral pathology were each associated with OA at arthroplasty, but each was also identified in some 'non-arthritic' controls. Tidemark breaching in the chondropathy/osteophyte group was greater than in non-arthritic controls. Three histopathological subgroups were identified, characterised as 'mild OA', or 'severe OA' with mild or moderate/severe synovitis. Presence and severity of synovitis helps define distinct histopathological OA subgroups. The absence of a discrete 'normal' subgroup indicates a pathological continuum between normality and OA status. Identifying specific pathological processes and their clinical correlates in OA subgroups has potential to accelerate the development of more effective therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Clinical response to chemotherapy in locally advanced breast cancer was not associated with several polymorphisms in detoxification enzymes and DNA repair genes.

    Science.gov (United States)

    Saadat, Mostafa; Khalili, Maryam; Nasiri, Meysam; Rajaei, Mehrdad; Omidvari, Shahpour; Saadat, Iraj

    2012-03-02

    The main aim of the present study was to investigate the association between several genetic polymorphisms (in glutathione S-transferase members and DNA repair genes) and clinical response to chemotherapy in locally advanced breast cancer. A sequential series of 101 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response was regarded as a response or no response. There was no difference between non-responders and responders for the prevalence of genotypes of the study polymorphisms. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

    Directory of Open Access Journals (Sweden)

    Michael Van Meter

    2016-09-01

    Full Text Available The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6, promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is activated by oxidative stress to promote DNA double-strand break (DSB repair. We show that the stress-activated protein kinase, c-Jun N-terminal kinase (JNK, phosphorylates SIRT6 on serine 10 in response to oxidative stress. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose polymerase 1 (PARP1 to DNA break sites and for efficient repair of DSBs. Our results demonstrate a post-translational mechanism regulating SIRT6, and they provide the link between oxidative stress signaling and DNA repair pathways that may be critical for hormetic response and longevity assurance.

  2. DNA damage response and DNA repair – dog as a model?

    International Nuclear Information System (INIS)

    Grosse, Nicole; Loon, Barbara van; Rohrer Bley, Carla

    2014-01-01

    Companion animals like dogs frequently develop tumors with age and similarly to human malignancies, display interpatient tumoral heterogeneity. Tumors are frequently characterized with regard to their mutation spectra, changes in gene expression or protein levels. Among others, these changes affect proteins involved in the DNA damage response (DDR), which served as a basis for the development of numerous clinically relevant cancer therapies. Even though the effects of different DNA damaging agents, as well as DDR kinetics, have been well characterized in mammalian cells in vitro, very little is so far known about the kinetics of DDR in tumor and normal tissues in vivo. Due to (i) the similarities between human and canine genomes, (ii) the course of spontaneous tumor development, as well as (iii) common exposure to environmental agents, canine tumors are potentially an excellent model to study DDR in vivo. This is further supported by the fact that dogs show approximately the same rate of tumor development with age as humans. Though similarities between human and dog osteosarcoma, as well as mammary tumors have been well established, only few studies using canine tumor samples addressed the importance of affected DDR pathways in tumor progression, thus leaving many questions unanswered. Studies in humans showed that misregulated DDR pathways play an important role during tumor development, as well as in treatment response. Since dogs are proposed to be a good tumor model in many aspects of cancer research, we herein critically investigate the current knowledge of canine DDR and discuss (i) its future potential for studies on the in vivo level, as well as (ii) its possible translation to veterinary and human medicine

  3. 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.

  4. Endocrine-disruptor molecular responses, occurrence of intersex and gonado-histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria

    International Nuclear Information System (INIS)

    Adeogun, Aina O.; Onibonoje, Kolawole; Ibor, Oju R.; Omiwole, Roseline A.; Chukwuka, Azubuike V.; Ugwumba, Alex O.; Ugwumba, Adiaha A.A.; Arukwe, Augustine

    2016-01-01

    Highlights: • Occurrence and severity of intersex in Nigerian aquatic environment. • Estrogenic and reproductive developmental effects of effluents from a University community. • Biomarker of endocrine disruption in fish from a developing country. • Relationship between estrogenic responses and sediment contaminants burden in a dam used for University domestic water supply and for fisheries. • Possible health consequences of environmental contamination - Abstract: In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n = 57 and 32, males and females, respectively) and Tilapia guineensis (n = 23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam

  5. Endocrine-disruptor molecular responses, occurrence of intersex and gonado-histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria

    Energy Technology Data Exchange (ETDEWEB)

    Adeogun, Aina O.; Onibonoje, Kolawole; Ibor, Oju R.; Omiwole, Roseline A.; Chukwuka, Azubuike V.; Ugwumba, Alex O.; Ugwumba, Adiaha A.A. [Department of Zoology, University of Ibadan, Ibadan (Nigeria); Arukwe, Augustine, E-mail: arukwe@bio.ntnu.no [Department of Biology, Norwegian University of Science and Technology (NTNU), 7491 Trondheim (Norway)

    2016-05-15

    Highlights: • Occurrence and severity of intersex in Nigerian aquatic environment. • Estrogenic and reproductive developmental effects of effluents from a University community. • Biomarker of endocrine disruption in fish from a developing country. • Relationship between estrogenic responses and sediment contaminants burden in a dam used for University domestic water supply and for fisheries. • Possible health consequences of environmental contamination - Abstract: In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n = 57 and 32, males and females, respectively) and Tilapia guineensis (n = 23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam

  6. Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation

    Energy Technology Data Exchange (ETDEWEB)

    Asaithamby, Aroumougame, E-mail: Aroumougame.Asaithamy@UTsouthwestern.edu [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 (United States); Chen, David J., E-mail: David.Chen@UTsouthwestern.edu [Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 (United States)

    2011-06-03

    Low-linear energy transfer (LET) radiation (i.e., {gamma}- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles is slowly repaired or is irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those treated with low-LET radiation. The types of DNA lesions induced by HZE particles have been characterized in vitro and usually consist of two or more closely spaced strand breaks, abasic sites, or oxidized bases on opposing strands. It is unclear why these lesions are difficult to repair. In this review, we highlight the potential of a new technology allowing direct visualization of different types of DNA lesions in human cells and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal characterization of complex DNA damage. We focus on the recent insights into the molecular pathways that participate in the repair of HZE particle-induced DSBs. We also discuss recent advances in our understanding of how different end-processing nucleases aid in repair of DSBs with complicated ends generated by HZE particles. Understanding the mechanism underlying the repair of DNA damage induced by HZE particles will have important implications for estimating the risks to human health associated with HZE particle exposure.

  7. Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation

    International Nuclear Information System (INIS)

    Asaithamby, Aroumougame; Chen, David J.

    2011-01-01

    Low-linear energy transfer (LET) radiation (i.e., γ- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles is slowly repaired or is irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those treated with low-LET radiation. The types of DNA lesions induced by HZE particles have been characterized in vitro and usually consist of two or more closely spaced strand breaks, abasic sites, or oxidized bases on opposing strands. It is unclear why these lesions are difficult to repair. In this review, we highlight the potential of a new technology allowing direct visualization of different types of DNA lesions in human cells and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal characterization of complex DNA damage. We focus on the recent insights into the molecular pathways that participate in the repair of HZE particle-induced DSBs. We also discuss recent advances in our understanding of how different end-processing nucleases aid in repair of DSBs with complicated ends generated by HZE particles. Understanding the mechanism underlying the repair of DNA damage induced by HZE particles will have important implications for estimating the risks to human health associated with HZE particle exposure.

  8. Endocrine-disruptor molecular responses, occurrence of intersex and gonado-histopathological changes in tilapia species from a tropical freshwater dam (Awba Dam) in Ibadan, Nigeria.

    Science.gov (United States)

    Adeogun, Aina O; Onibonoje, Kolawole; Ibor, Oju R; Omiwole, Roseline A; Chukwuka, Azubuike V; Ugwumba, Alex O; Ugwumba, Adiaha A A; Arukwe, Augustine

    2016-05-01

    In the present study, the occurrence of endocrine disruptive responses in Tilapia species from Awba Dam has been investigated, and compared to a reference site (Modete Dam). The Awba Dam is a recipient of effluents from University of Ibadan (Nigeria) and several other anthropogenic sources. A total of 132 Tilapia species (Sarotherodon malenotheron (n=57 and 32, males and females, respectively) and Tilapia guineensis (n=23 and 20, males and females, respectively)) were collected from June to September 2014. At the reference site, samples of adult male and female S. melanotheron (48 males and 47 females) and T. guineensis (84 males and 27 females) were collected. Gonads were morphologically and histologically examined and gonadosomatic index (GSI) was calculated. Hepatic mRNA transcriptions of vitellogenin (Vtg) and zona radiata protein (Zrp) genes were analyzed using validated RT-qPCR. Significant increase in Vtg and Zrp transcripts were observed in male tilapias from Awba Dam, compared to males from the reference site. In addition, male tilapias from Awba Dam produced significantly higher Vtg and Zrp mRNA, compared to females in June and July. However, at the natural peak spawning period in August and September, females produced, significantly higher Vtg and Zrp mRNA, compared to males. Fish gonads revealed varying incidence of intersex with a striking presence of two (2) pairs of testes and a pair of ovary in S. melanotheron from Awba Dam. The entire fish population examined at Awba Dam showed a high prevalence of intersex (34.8%), involving phenotypic males and females of both species. Analysis of sediment contaminant levels revealed that As, Cd, Pb, Hg and Ni (heavy metals), monobutyltin cation, 4-iso-nonyphenol and PCB congeners (138, 153 and 180) were significantly higher in Awba Dam, compared to the reference site. Principal component analysis (PCA) showed that fish variables were positively correlated with sediment contaminant burden at Awba Dam, indicating

  9. Upregulation of Soluble HLA-G5 and HLA-G6 Isoforms in the Milder Histopathological Stages of Helicobacter pylori Infection: A Role for Subverting Immune Responses?

    Science.gov (United States)

    Souza, D M B Oliveira; Genre, J; Silva, T G Alves; Soares, C P; Rocha, K Borges Ferreira; Oliveira, C Nunes; Jatobá, C A Nunes; Andrade, J Marco de Leon; Moreau, P; Medeiros, A da Cunha; Donadi, E A; Crispim, J C de Oliveira

    2016-01-01

    The subversion mechanisms employed by Helicobacter pylori (H. pylori) to escape from immune surveillance and to establish persistent infection are poorly understood. Growing evidence indicates that expression of HLA-G, a non-classical major histocompatibility complex molecule, negatively regulates immune responses in pathological conditions, including infectious diseases. In this context, we aimed to evaluate HLA-G expression in the gastric microenvironment of individuals harbouring H. pylori and to correlate it with histological variables. Fifty-four gastric specimens from patients harbouring H. pylori infection were evaluated by immunohistochemistry using anti-HLA-G monoclonal antibody. As a result, HLA-G expression was detected in 43 of 54 specimens harbouring H. pylori. The presence of HLA-G was significantly associated with milder colonization by H. pylori (P role of HLA-G during H. pylori infection is beneficial or hazardous for patients remains to be defined. © 2015 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Foundation for the Scandinavian Journal of Immunology.

  10. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2016-02-01

    Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fisher 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.

  11. Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic Escherichia coli.

    Science.gov (United States)

    Molina-Quiroz, Roberto C; Silva-Valenzuela, Cecilia; Brewster, Jennifer; Castro-Nallar, Eduardo; Levy, Stuart B; Camilli, Andrew

    2018-01-09

    Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli , as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli , the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds. Copyright © 2018 Molina-Quiroz et al.

  12. Histopathological responses of newly hatched larvae of whitefish (Coregonus lavaretus s.l.) to UV-B induced toxicity of retene

    Energy Technology Data Exchange (ETDEWEB)

    Haekkinen, Jani; Vehniaeinen, Eeva; Oikari, Aimo

    2003-04-10

    Positively phototactic fish larvae may be exposed to increased ultraviolet-B (UV-B) radiation alone or, potentially and in addition, to polycyclic aromatic hydrocarbons (PAHs) such as retene (7-isopropyl-1-methylphenanthrene) at the egg or larval stages. Suspended and sedimental particulate material near pulp and paper mills may act as sources of retene in chemically contaminated lake areas. In laboratory conditions whitefish larvae were pre-exposed to retene (10, 32 and 100 {mu}g/l), with relevant controls, and irradiated in semi-static tests for 3 h once a day (2 consecutive days) with two UV-B doses (CIE-weighted 2.8 or 5.4 kJ per m{sup 2} per day) or with visible light only. These UV-B doses correspond with slightly subambient and 80% increases relative to the natural maximum daily doses of the solar UV-B in Finland in early May. The UV-B radiation alone increased mortality only slightly (2.7 and 4.0%, respectively). Similarly, no mortality was observed due to retene alone. On the contrary, simultaneous UV-B and retene exposure caused very high mortality to whitefish and all larvae died in the highest retene concentration. The photoinduced acute LC{sub 50} for retene was 13.3 {mu}g/l. Retene treated fish exhibited signs of behavioral irritation and hypoxia during and after the exposure to UV light. Severe skin damages were detected in larvae exposed simultaneously to retene and UV-B. The structural signs of sunburn could also be seen in UV-B and solvent controls (DMSO) with UV-B. Even at the lowest retene concentration, the number of mucous cells increased significantly in simultaneous chemical and UV-B treatment. We consider the tissue reaction as protective response against UV induced retene toxicity. Further, regarding liver parenchyma, fish exposed to retene with UV-B had lesions, revealing hepatotoxicity. We suggest that synergism of the UV-B radiation and the photoactivating pollutants such as retene is a potential risk factor to be taken into

  13. Histopathological responses of newly hatched larvae of whitefish (Coregonus lavaretus s.l.) to UV-B induced toxicity of retene

    International Nuclear Information System (INIS)

    Haekkinen, Jani; Vehniaeinen, Eeva; Oikari, Aimo

    2003-01-01

    Positively phototactic fish larvae may be exposed to increased ultraviolet-B (UV-B) radiation alone or, potentially and in addition, to polycyclic aromatic hydrocarbons (PAHs) such as retene (7-isopropyl-1-methylphenanthrene) at the egg or larval stages. Suspended and sedimental particulate material near pulp and paper mills may act as sources of retene in chemically contaminated lake areas. In laboratory conditions whitefish larvae were pre-exposed to retene (10, 32 and 100 μg/l), with relevant controls, and irradiated in semi-static tests for 3 h once a day (2 consecutive days) with two UV-B doses (CIE-weighted 2.8 or 5.4 kJ per m 2 per day) or with visible light only. These UV-B doses correspond with slightly subambient and 80% increases relative to the natural maximum daily doses of the solar UV-B in Finland in early May. The UV-B radiation alone increased mortality only slightly (2.7 and 4.0%, respectively). Similarly, no mortality was observed due to retene alone. On the contrary, simultaneous UV-B and retene exposure caused very high mortality to whitefish and all larvae died in the highest retene concentration. The photoinduced acute LC 50 for retene was 13.3 μg/l. Retene treated fish exhibited signs of behavioral irritation and hypoxia during and after the exposure to UV light. Severe skin damages were detected in larvae exposed simultaneously to retene and UV-B. The structural signs of sunburn could also be seen in UV-B and solvent controls (DMSO) with UV-B. Even at the lowest retene concentration, the number of mucous cells increased significantly in simultaneous chemical and UV-B treatment. We consider the tissue reaction as protective response against UV induced retene toxicity. Further, regarding liver parenchyma, fish exposed to retene with UV-B had lesions, revealing hepatotoxicity. We suggest that synergism of the UV-B radiation and the photoactivating pollutants such as retene is a potential risk factor to be taken into consideration in lake

  14. Breast cancer histopathology image analysis

    NARCIS (Netherlands)

    Veta, M.

    2014-01-01

    Pathology labs are currently undergoing a transformation towards a fully digital workflow. In addition to the digital management of tissue samples, pathology orders and reports, this includes the digitization of histopathology slides and use of computer monitors for viewing them, which aims to

  15. Levers Histopathology of the Skin* .,

    African Journals Online (AJOL)

    Books. Levers Histopathology of the Skin*. By David Elder, Rosalie Elenitsas, Christine Jaworsky and. Bernett Johnson ... for the poor quality of most of the black and white clinical pictures, which ... R85. Long. Me~ord, UK: E B Adams, 1996.

  16. Histopathology reconstruction on digital imagery

    Science.gov (United States)

    Li, Wenjing; Lieberman, Rich W.; Nie, Sixiang; Xie, Yihua; Eldred, Michael; Oyama, Jody

    2009-02-01

    Diagnosing cervical cancer in a woman is a multi-step procedure involving examination of the cervix, possible biopsy and follow-up. It is open to subjective interpretation and highly dependent upon the skills of cytologists, colposcopists, and pathologists. In an effort to reduce the subjectiveness of the colposcopist-directed biopsy and to improve the diagnostic accuracy of colposcopy, we have developed new colposcopic imaging systems with accompanying computer aided diagnostic (CAD) techniques to guide a colposcopist in deciding if and where to biopsy. If the biopsy's histopathology, the identification of the disease state at the cellular and near-cellular level, is to be used as the gold standard for CAD, then the location of the histopathologic analysis must match exactly to the location of the biopsy tissue in the digital image. Otherwise, no matter how perfect the histopathology and the quality of the digital imagery, the two data sets cannot be matched and the true sensitivity and specificity of the CAD cannot be ascertained. We report here on new approaches to preserving, continuously, the location and orientation of a biopsy sample with respect to its location in the digital image of the cervix so as to preserve the exact spatial relationship throughout the mechanical aspects of the histopathologic analysis. This new approach will allow CAD to produce a linear diagnosis and pinpoint the location of the tissue under examination.

  17. ZTF-8 interacts with the 9-1-1 complex and is required for DNA damage response and double-strand break repair in the C. elegans germline.

    Directory of Open Access Journals (Sweden)

    Hyun-Min Kim

    2014-10-01

    Full Text Available Germline mutations in DNA repair genes are linked to tumor progression. Furthermore, failure in either activating a DNA damage checkpoint or repairing programmed meiotic double-strand breaks (DSBs can impair chromosome segregation. Therefore, understanding the molecular basis for DNA damage response (DDR and DSB repair (DSBR within the germline is highly important. Here we define ZTF-8, a previously uncharacterized protein conserved from worms to humans, as a novel factor involved in the repair of both mitotic and meiotic DSBs as well as in meiotic DNA damage checkpoint activation in the C. elegans germline. ztf-8 mutants exhibit specific sensitivity to γ-irradiation and hydroxyurea, mitotic nuclear arrest at S-phase accompanied by activation of the ATL-1 and CHK-1 DNA damage checkpoint kinases, as well as accumulation of both mitotic and meiotic recombination intermediates, indicating that ZTF-8 functions in DSBR. However, impaired meiotic DSBR progression partially fails to trigger the CEP-1/p53-dependent DNA damage checkpoint in late pachytene, also supporting a role for ZTF-8 in meiotic DDR. ZTF-8 partially co-localizes with the 9-1-1 DDR complex and interacts with MRT-2/Rad1, a component of this complex. The human RHINO protein rescues the phenotypes observed in ztf-8 mutants, suggesting functional conservation across species. We propose that ZTF-8 is involved in promoting repair at stalled replication forks and meiotic DSBs by transducing DNA damage checkpoint signaling via the 9-1-1 pathway. Our findings define a conserved function for ZTF-8/RHINO in promoting genomic stability in the germline.

  18. DNA damage and repair in peripheral blood lymphocytes from healthy individuals and cancer patients: a pilot study on the implications in the clinical response to chemotherapy.

    Science.gov (United States)

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

    2006-07-28

    Drug resistance is considered the main impediment to successful cancer chemotherapy. The quest for a method useful to predict individual responses to chemotherapy prior to treatment is highly desired. This study was designed to determine the individual influences of doxorubicin and cisplatin on the degree of DNA damage, DNA repair and hMSH2 and the hMLH1 protein expression in peripheral blood lymphocytes (PBL) and their correlations with the clinical response. PBL were obtained from 25 cancer patients (pre- and post-chemotherapy) and from 10 healthy persons, cultured and exposed to doxorubicin or cisplatin. Cells were collected at T0 (immediately after drug treatment) and 24h after damage (T24). The alkaline comet assay was employed to assess the DNA damage and repair function, and immunocytochemistry to study hMLH1 and hMSH2 expression. Clinical response was evaluated after three cycles of chemotherapy. Pre-chemotherapy PBL from cancer patients showed significantly higher levels of basal DNA damage than healthy persons, with appreciable interindividual variations between them. The in vivo administration of antineoplasic drugs was accompanied by significant DNA damage, and an increased in the number of apoptotic cells. Cancer patients with complete response showed a high number of apoptotic cells. The DNA migration increased at T0 and at T24 in cisplatin-treated patients, reflecting a decreased rate of cisplatin adducts repair than that observed in healthy individuals. The ability to repair DNA lesions in doxorubicin-damaged cells was very similar between healthy individuals and cancer patients. Cisplatin-treated patients that died by the disease showed lower DNA migration than the mean value. The expression of hMLH1 and hMSH2 was practically identical between healthy individuals and cancer patients. Nevertheless, chemotherapy induced a depletion mostly of hMLH1. In 83% of cisplatin-treated patients with CR the hMLH1 and hMSH2 expression at T24 was higher than the

  19. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...

  20. Early inflammatory response following elective abdominal aortic aneurysm repair: A comparison between endovascular procedure and conventional, open surgery

    Directory of Open Access Journals (Sweden)

    Marjanović Ivan

    2011-01-01

    Full Text Available Background/Aim. Abdominal aorta aneurysm (AAA represents a pathological enlargment of infrarenal portion of aorta for over 50% of its lumen. The only treatment of AAA is a surgical reconstruction of the affected segment. Until the late XX century, surgical reconstruction implied explicit, open repair (OR of AAA, which was accompanied by a significant morbidity and mortality of the treated patients. Development of endovascular repair of (EVAR AAA, especially in the last decade, offered another possibility of surgical reconstruction of AAA. The preliminary results of world studies show that complications of such a procedure, as well as morbidity and mortality of patients, are significantly lower than with OR of AAA. The aim of this paper was to present results of comparative clinical prospective study of early inflammatory response after reconstruction of AAA between endovascular and open, conventional surgical technique. Methods. A comparative clinical prospective study included 39 patients, electively operated on for AAA within the period of December 2008 - February 2010, divided into two groups. The group I counted 21 (54% of the patients, 58-87 years old (mean 74.3 years, who had been submited to EVAR by the use of excluder stent graft. The group II consisted of 18 (46% of the patients, 49-82 (mean 66.8 years, operated on using OR technique. All of the treated patients in both groups had AAA larager than 50 mm. The study did not include patients who have been treated as urgent cases, due to the rupture or with simptomatic AAA. Clinical, biochemical and inflamatory parameters in early postoperative period were analyzed, in direct postoperative course (number of leucocytes, thrombocytes, serum circulating levels of cytokine - interleukine (IL-2, IL-4, IL-6 and IL-10. Parameters were monitored on the zero, first, second, third and seventh postoperative days. The study was approved by the Ethics Commitee of the Military Medical Academy. Results

  1. Differential response of human and rodent cell lines to chemical inhibition of the repair of potentially lethal damage

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B.; Ueno, A.M.; Dahlberg, W.K.

    1989-07-01

    We have examined the effects of several classes of metabolic inhibitors on the repair of potentially lethal damage in density-inhibited cultures of two rodent and two human cell systems which differ in their growth characteristics. Aphidicolin, 1-..beta..-D-arabinofuranosylcytosine (ara-C) and hydroxyurea showed no effect on PLD repair, whereas the effects of 9-..beta..-D-arabinofuranosyladenine (ara-A) and 3-aminobenzamide (3-AB) were cell line dependent. For example, 3-AB suppressed PLD repair almost completely in CHO cells, but showed no inhibitory effects in human diploid fibroblasts. These results indicate that inhibitors of DNA replication and poly(ADP-ribose) synthesis are not efficient inhibitors of cellular recovery in irradiated cells and, moreover, that such effects may be cell line dependent.

  2. Fibroblast growth factor 2 and DNA repair involvement in the keratinocyte stem cells response to ionizing radiation

    International Nuclear Information System (INIS)

    Harfouche, L'Emira Ghida

    2010-02-01

    Keratinocyte stem cells (KSCs) from the human inter follicular epidermis are regarded as the major target to radiation during radiotherapy. We found herein that KSCs are more resistant to ionizing radiation than their direct progeny, and presented more rapid DNA damage repair kinetics than the progenitors. Furthermore, we provided evidence describing the effect of fibroblast growth factor 2 (FGF2) signaling on the ability of KSCs and progenitors to repair damaged DNA. Despite our knowledge of the fact, that FGF is an anti-apoptotic factor in multiple cell types, the direct link between DNA repair and FGF2 signaling has rarely been shown. Existence of such link is an important issue with implications not only to stem cell field but also to cancer therapy. (author)

  3. XRCC1 coordinates disparate responses and multiprotein repair complexes depending on the nature and context of the DNA damage

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Sundheim, Ottar

    2011-01-01

    . We demonstrate that the laser dose used for introducing DNA damage determines the repertoire of DNA repair proteins recruited. Furthermore, we demonstrate that recruitment of POLß and PNK to regions irradiated with low laser dose requires XRCC1 and that inhibition of PARylation by PARP......-inhibitors only slightly reduces the recruitment of XRCC1, PNK, or POLß to sites of DNA damage. Recruitment of PCNA and FEN-1 requires higher doses of irradiation and is enhanced by XRCC1, as well as by accumulation of PARP-1 at the site of DNA damage. These data improve our understanding of recruitment of BER......XRCC1 is a scaffold protein capable of interacting with several DNA repair proteins. Here we provide evidence for the presence of XRCC1 in different complexes of sizes from 200 to 1500 kDa, and we show that immunoprecipitates using XRCC1 as bait are capable of complete repair of AP sites via both...

  4. Plant γH2AX foci are required for proper DNA DSB repair responses and colocalize with E2F factors

    OpenAIRE

    Smetana, Ondrej; Sanchez-Calderon, Lenin; Lincker, Frédéric; Genestier, Julie; Schmit, Anne-Catherine; Houlné, Guy; Chabouté, Marie Edith

    2012-01-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (cH2AX) repair foci which are multiproteic nuclear complexes responsible for DSB sensing and signalling. However, neither the components of these foci nor their role are yet known in plants. In this paper, we describe the effects of cH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional respo...

  5. Repair and cell cycle response in cells exposed to environmental biohazards. Progress report, 1 June 1982-31 May 1983

    International Nuclear Information System (INIS)

    Billen, D.; Hadden, C.T.

    1983-01-01

    The research program has attempted to determine low environmental agents, especially ionizing radiation, interact with DNA and how the cells respond to the resulting damage. The focus has been on the spectrum of damage generated in DNA, the kinds of damage that can be repaired, and the mechanisms of repair. The effects of radioprotective agents and certain sensitizing conditions on breakage of DNA in bacterial cells by ionizing radiation, and mechanisms of enzymatic excision of pyrimidine dimers and other DNA adducts have been studied

  6. Morphologic study of three collagen materials for body wall repair.

    Science.gov (United States)

    Soiderer, Emily E; Lantz, Gary C; Kazacos, Evelyn A; Hodde, Jason P; Wiegand, Ryan E

    2004-05-15

    The search for ideal prostheses for body wall repair continues. Synthetic materials such as polypropylene mesh (PPM) are associated with healing complications. A porcine-derived collagen-based material (CBM), small intestinal submucosa (SIS), has been studied for body wall repair. Renal capsule matrix (RCM) and urinary bladder submucosa (UBS) are CBMs not previously evaluated in this application. This is the first implant study using RCM. Full-thickness muscle/fascia ventral abdominal wall defects were repaired with SIS, RCM, UBS, and PPM in rats with omentum and omentectomy. A random complete block design was used to allot implant type to each of 96 rats. Healing was evaluated at 4 and 8 weeks. Adhesion tenacity and surface area were scored. Implant site dimensions were measured at implantation and necropsy. Inflammation, vascularization, and fibrosis were histopathologically scored. Data were compared by analysis of variance (P response in contrast to the organized healing of CBM implants. CBM mean scores were lower than PPM scores for adhesion tenacity, surface area, and inflammation at each follow-up time for rats with omentums (P fibrotic response to PPM was unique and more intense compared to CBMs. These CBM implants appear morphologically acceptable and warrant continued investigation.

  7. Electiveness of photorepair, influence of dark-repair on shape of dose-response curves, and high-dose decline, in UV-induced colour mutations of Serratia

    International Nuclear Information System (INIS)

    Kaplan, R.W.

    1978-01-01

    Strain CV of Serratia marcescens mutates by UV with high frequency to 3 groups of mutants (w, h, s) differing in colour from the red wild-type. The mutational dose-response curve has a curvature corresponding to about 3 hits. It reaches a peak and declines at high doses. Inactivation curves have a broad shoulder and mostly, but not always, a break to a lesser slope at UV doses near the peak of mutations. Photo reactivation (PR) gives a dose reduction of about 2 for both inactivation and mutation including the break and peak. The dose curve with PR for w-mutations shows 1 hit-, the other types 2-hit curvature leading to a change of mutation spectrum with dose due to PR. The UV-sensitive mutant uvs21 of CV has a survival curve with a small shoulder and a long upward concavity without a break, and the mutation curve is of the one-hit type without a peak and decline. PR gives a dose reduction of 12 for inactivation and of 7.5 for mutation. The 3-hit mutation curve of CV is interpreted by assuming that 2 further hits are required to protect the 1-hit pre-mutations from being abolished by the repair lacking in uvs21. UV induction of SOS repair cannot be responsible for the 3-hit curvature because UVR of phages and induction of prophage are already saturated at rather low doses. As high-dose decline is not observed in uvs21, possibly the non-mutagenic repair lacking from uvs21 interferes with the mutation finishing processes at high doses in the repair-proficient strain CV. However, UV induction of this interference cannot be a one-hit process but requires a very large number of hits. (Auth.)

  8. Commercial formalin substitutes for histopathology

    DEFF Research Database (Denmark)

    Prentø, P; Lyon, H

    1997-01-01

    We compared the performance of six commercial fixatives proposed to be formalin substitutes with the performance of buffered formalin, Clarke's ethanol-acetic acid, and ethanol, using rat liver, small intestine, and kidney. We investigated the rate of penetration, mode of fixation, extent of prot...... was obtained by combining formalin fixation with antigen retrieval. We conclude that none of the proposed commercial substitutes for buffered formalin are adequate for critical histology or histopathology....

  9. Histopathologic analysis of appendectomy specimens

    Directory of Open Access Journals (Sweden)

    R Shrestha

    2012-03-01

    Full Text Available Background: Acute appendicitis is one of the common conditions requiring emergency surgery. A retrospective study was performed to determine various histopathological diagnoses, their demographics and the rates of perforated appendicitis, negative appendectomy and incidental appendectomy. Materials and Methods: Histopathological records of resected appendices submitted to histopathology department Chitwan medical college teaching hospital over the period of 2 yrs from May, 2009 to April 2011 were reviewed retrospectively. Results: Out of 930 specimens of appendix, appendicitis accounted for 88.8% with peak age incidence in the age group of 11 to 30 yrs in both sexes. Histopathologic diagnoses included acute appendicitis (45.6%, acute suppurative (20.8%, gangrenous (16.3%, perforated (1.7%, resolving /recurrent/non specific chronic appendicitis (2.5%, acute eosinophilic appendicitis (1.2%, periappendicitis (0.2%, and carcinoid tumour (0.1%. Other important coexisting pathologies were parasitic infestation (0.2% and Meckel’s diverticulum (0.2%. Negative appendectomy rate was 10.8% and three times more common in females with peak occurrence in the age group of 21-30 yrs. There were 10 cases of acute appendicitis in incidental appendectomies (2.5%, 24 cases with 7 times more common in females of age group of 31- 60 yrs. Conclusion: There is a high incidence of appendicitis in adolescents and young adults in central south region of Nepal. Negative appendectomy is also very common in females. Incidental appendectomy in elderly females may have preventive value. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6025 JPN 2012; 2(3: 215-219

  10. Repair and cell cycle response in cells exposed to environmental biohazards. Progress report, October 1, 1976--May 31, 1979

    International Nuclear Information System (INIS)

    Billen, D.

    1979-01-01

    A wide variety of environmental agents are known which induce damage in DNA leading to an inhibition of DNA synthesis or faulty replication. Both results may cause cell death or mutation. Both bacteria and mommalian cells are being used to assess the roles of the several known DNA polymerases and other DNA metabolic enzymes and factors in DNA repair, replication and recombination. The many DNA mutants of E. coli and B. subtilis provide a genetic approach to measuring the role of individual components of the DNA repair and replicative system. Because of the advantage of controlling pools and precursors of nucleic acid synthesis we have further developed the use of permeabilized cells for such studies. In addition a series of repair studies with Bacillus subtilis have been carried on because of the unique genetic manipulation of this system which includes the ability of cells to be easily transformed by exogenous DNA. The information obtained with prokaryotes provides leads to assess the details of DNA repair and replication in mammalian systems including man

  11. Adaptive response to ionizing radiation in normal human skin fibroblasts. Enhancement of DNA repair rate and modulation of gene expression

    International Nuclear Information System (INIS)

    Toledo, S.M. de; Mitchel, R.E.J.; Azzam, E.; Ottawa Univ., ON; Raaphorst, G.P.

    1994-01-01

    Low doses and dose rates of ionizing radiation enhance the rate of DNA repair in human fibroblasts and protect the cells against radiation-induced micronucleus formation. Chronic exposures reduce the mRNA levels of the genes topoisomerase II and FACC-1 (Fanconi's anemia, group C). (authors). 11 refs., 1 tab., 2 figs

  12. Nano-calciumphosphate scaffold generation for bone repair/replacement: elucidating the signalling response and cell cycle

    CSIR Research Space (South Africa)

    Wepnener, I

    2010-09-01

    Full Text Available Strong, bioinert materials have always been the focus for bone replacement and repair. This practice has since moved towards materials that can mimic living tissue and aid the healing process (i.e. be replaced by natural bone); thus materials...

  13. ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

    Science.gov (United States)

    Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

    2016-01-01

    Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

  14. Histopathology for the diagnosis of infectious diseases

    Directory of Open Access Journals (Sweden)

    Gupta E

    2009-01-01

    Full Text Available Histopathological examination of tissue biopsies for the identification of infectious organisms is a very important diagnostic tool. Conventional culture confirmation of tissue biopsies often fail to identify any pathogen as, first of all, invariably most of the tissue samples that are collected and sent for culture isolation are inappropriately collected in formalin, which prevents pathogen growth in culture media. Inadequate processing like grinding, etc. further hinders isolation. Presence of inhibitors like dead tissue debris, fibers, etc. also delays isolation. Microbiologists often lack expertise in identifying infectious pathogens directly from tissue biopsies by microscopic visualization. This review therefore acquaints microbiologists with the various methods available for detecting infectious agents by using histological stains. On histopathological examination of the tissue biopsy once, it is determined that a disease is likely to be due to an infection and has characterized the inflammatory response and hence associated microorganisms should be thoroughly looked for. Although some microorganisms or their cytopathic effects may be clearly visible on routine haematoxylin- and eosin-stained sections, additional histochemical stains are often needed for their complete characterization. Highly specific molecular techniques, such as immunohistochemistry, in situ hybridization and nucleic acid amplification, may be needed in certain instances to establish the diagnosis of infection. Through appropriate morphologic diagnoses and interlaboratory communication and collaboration, direct microscopic visualization of tissue samples can thus be very helpful in reaching a correct and rapid diagnosis.

  15. Meningocele repair

    Science.gov (United States)

    ... is surgery to repair birth defects of the spine and spinal membranes. Meningocele and myelomeningocele ... is covered by a sterile dressing. Your child may then be transferred to a neonatal intensive ...

  16. Evaluation of the histopathological classifications of American cutaneous and mucocutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    A. L. Bittencourt

    1991-03-01

    Full Text Available In order to evaluate the reliability of histopathological classifications of cutaneous and mucocutaneous leishmaniasis the authors compared the histopathological patterns of two biopsies taken simultaneously from the same patient, and classified the material according to Ridley et al. (1980, to Magalhães et al. (1986a, and to a more simplified classification with only three patterns. District histopathological aspects, were observed in different lesions or even in the same lesion. The authors concluded that histopathological patterns do not represent a stage of tegumentary leishmaniasis, thus they can not be correlated with prognosis and therapeutical response as suggested in the literature.

  17. Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair

    International Nuclear Information System (INIS)

    Thames, H.D. Jr.; Peters, L.J.

    1984-01-01

    A model is proposed for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing number of ever-smaller fractional doses, the model transforms into the accumulation model of survival after continuous irradiation. When adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is an advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since, in addition to determination of repair capacity, there is an estimate of repair kinetics. Results of analyses of previously published data are presented as illustration. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of β/delta were approximately 0.1 Gy -1 . From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and β/delta was 0.27 Gy -1 . In the rat spinal cord β/delta was 0.7 Gy -1 and Tsub(1/2) was 1.5 h. (U.K.)

  18. DNA repair

    International Nuclear Information System (INIS)

    Van Zeeland, A.A.

    1984-01-01

    In this chapter a series of DNA repair pathways are discussed which are available to the cell to cope with the problem of DNA damaged by chemical or physical agents. In the case of microorganisms our knowledge about the precise mechanism of each DNA repair pathway and the regulation of it has been improved considerably when mutants deficient in these repair mechanisms became available. In the case of mammalian cells in culture, until recently there were very little repair deficient mutants available, because in almost all mammalian cells in culture at least the diploid number of chromosomes is present. Therefore the frequency of repair deficient mutants in such populations is very low. Nevertheless because replica plating techniques are improving some mutants from Chinese hamsters ovary cells and L5178Y mouse lymphoma cells are now available. In the case of human cells, cultures obtained from patients with certain genetic diseases are available. A number of cells appear to be sensitive to some chemical or physical mutagens. These include cells from patients suffering from xeroderma pigmentosum, Ataxia telangiectasia, Fanconi's anemia, Cockayne's syndrome. However, only in the case of xeroderma pigmentosum cells, has the sensitivity to ultraviolet light been clearly correlated with a deficiency in excision repair of pyrimidine dimers. Furthermore the work with strains obtained from biopsies from man is difficult because these cells generally have low cloning efficiencies and also have a limited lifespan in vitro. It is therefore very important that more repair deficient mutants will become available from established cell lines from human or animal origin

  19. Social repair of relationships

    DEFF Research Database (Denmark)

    Fahnøe, Kristian Relsted

    2017-01-01

    organisations, friends and family, and communities. These social relations are viewed as the foundation of citizenship as experienced and practised. Focusing on how two dimensions of lived citizenship, namely rights-responsibilities and belonging, are affected by the social repairs, the chapter shows how...

  20. The prognostic value of histopathology on lingual nerve neurosensory recovery after micro-neurosurgery

    DEFF Research Database (Denmark)

    Hørberg, Mette; Reibel, Jesper; Kragelund, Camilla

    2016-01-01

    OBJECTIVE: Micro-neurosurgical repair is considered in permanent nerve damage but the outcome is unpredictable. We examined if histopathologic parameters of traumatic neuromas have a prognostic value for recovery in relation to lingual nerve micro-neurosurgery. MATERIALS AND METHODS: Retrospective...... case study on neurosensory recovery after micro-neurosurgery. Outcome variables were as follows: pain perception, two-point discrimination, and sum score of perception, before and 12 months after micro-neurosurgery. Predictive histopathology variables included size, nerve tissue, and inflammation...

  1. Histopathology of nymphal pentastomid infections (Sebekia mississippiensis) in paratenic hosts.

    Science.gov (United States)

    Boyce, W M; Kazacos, E A

    1991-02-01

    The histopathologic alterations occurring in mice, hamsters, turtles, and a frog were described following experimental infection with nymphs of Sebekia mississippiensis. Initially, nymphal migration caused traumatic tissue damage and hemorrhage characteristic of larva migrans. Subsequent inflammatory responses included cellular infiltration with eosinophils, macrophages, and lymphocytes, and fibrotic encapsulation of the nymphs. Dead nymphs were surrounded by a necrotic granulomatous response similar to that reported previously in humans and other animals. Differences were not seen in animals given single or multiple infections, but mice and hamsters exhibited a more marked inflammatory response than turtles. Overall, the histopathologic response to nymphal infections resembled those seen in infections resulting from ingestion of eggs, and both sources of infection should be considered in epidemiologic investigations of naturally occurring pentastomiasis.

  2. Experience of high-nitrogenous steel powder application in repairs and surface hardening of responsible parts for power equipment by plasma spraying

    Science.gov (United States)

    Kolpakov, A. S.; Kardonina, N. I.

    2016-02-01

    The questions of the application of novel diffusion-alloying high-nitrogenous steel powders for repair and surface hardening of responsible parts of power equipment by plasma spraying are considered. The appropriateness of the method for operative repair of equipment and increasing its service life is justified. General data on the structure, properties, and manufacture of nitrogen-, aluminum-, and chromium-containing steel powders that are economically alloyed using diffusion are described. It is noted that the nitrogen release during the decomposition of iron nitrides, when heating, protects the powder particles from oxidation in the plasma jet. It is shown that the coating retains 50% of nitrogen that is contained in the powder. Plasma spraying modes for diffusion-alloying high-nitrogenous steel powders are given. The service properties of plasma coatings based on these powders are analyzed. It is shown that the high-nitrogenous steel powders to a nitrogen content of 8.9 wt % provide the necessary wear resistance and hardness of the coating and the strength of its adhesion to the substrate and corrosion resistance to typical aggressive media. It is noted that increasing the coating porosity promotes stress relaxation and increases its thickness being limited with respect to delamination conditions in comparison with dense coatings on retention of the low defectiveness of the interface and high adhesion to the substrate. The examples of the application of high-nitrogenous steel powders in power engineering during equipment repairs by service companies and overhaul subdivisions of heat power plants are given. It is noted that the plasma spraying of diffusion-alloyed high-nitrogenous steel powders is a unique opportunity to restore nitrided steel products.

  3. Repair process and a repaired component

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, III, Herbert Chidsey; Simpson, Stanley F.

    2018-02-20

    Matrix composite component repair processes are disclosed. The matrix composite repair process includes applying a repair material to a matrix composite component, securing the repair material to the matrix composite component with an external securing mechanism and curing the repair material to bond the repair material to the matrix composite component during the securing by the external securing mechanism. The matrix composite component is selected from the group consisting of a ceramic matrix composite, a polymer matrix composite, and a metal matrix composite. In another embodiment, the repair process includes applying a partially-cured repair material to a matrix composite component, and curing the repair material to bond the repair material to the matrix composite component, an external securing mechanism securing the repair material throughout a curing period, In another embodiment, the external securing mechanism is consumed or decomposed during the repair process.

  4. Motorcycle Repair.

    Science.gov (United States)

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  5. Involvement of mismatch repair proteins in adaptive responses induced by N-methyl-N'-nitro-N-nitrosoguanidine against {gamma}-induced genotoxicity in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Ayumi; Sakamoto, Yasuteru; Masumura, Kenichi; Honma, Masamitsu [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Nohmi, Takehiko, E-mail: nohmi@nihs.go.jp [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)

    2011-08-01

    Highlights: {yields} Health effects of radiation should be evaluated in combination with chemicals. {yields} Here, we show that MNNG suppresses radiation-induced genotoxicity in human cells. {yields} Mismatch repair proteins play critical roles in the apparent adaptive responses. {yields} Chemical exposure may modulate radiation-induced genotoxicity in humans. - Abstract: As humans are exposed to a variety of chemical agents as well as radiation, health effects of radiation should be evaluated in combination with chemicals. To explore combined genotoxic effects of radiation and chemicals, we examined modulating effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting methylating agent, against genotoxicity of {gamma}-radiation. Human lymphoblastoid TK6 cells and its mismatch-deficient derivative, i.e., MT1 cells, were treated with MNNG for 24 h before they were exposed to {gamma}-irradiation at a dose of 1.0 Gy, and the resulting genotoxicity was examined. In TK6 cells, the pretreatments with MNNG at low doses suppressed frequencies of the thymidine kinase (TK) gene mutation and micronucleus (MN) formation induced by {gamma}-irradiation and thus the dose responses of TK and MN assays were U-shaped along with the pretreatment doses of MNNG. In contrast, the genotoxic effects of MNNG and {gamma}-irradiation were additive in MT1 cells and the frequencies of TK mutations and MN induction increased along with the doses of MNNG. Apoptosis induced by {gamma}-radiation was suppressed by the pretreatments in TK6 cells, but not in MT1 cells. The expression of p53 was induced and cell cycle was delayed at G2/M phase in TK6, but not in MT1 cells, by the treatments with MNNG. These results suggest that pretreatments of MNNG at low doses suppress genotoxicity of {gamma}-radiation in human cells and also that mismatch repair proteins are involved in the apparent adaptive responses.

  6. Turbine repair process, repaired coating, and repaired turbine component

    Science.gov (United States)

    Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

    2015-11-03

    A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

  7. Breast cancer histopathology image analysis : a review

    NARCIS (Netherlands)

    Veta, M.; Pluim, J.P.W.; Diest, van P.J.; Viergever, M.A.

    2014-01-01

    This paper presents an overview of methods that have been proposed for the analysis of breast cancer histopathology images. This research area has become particularly relevant with the advent of whole slide imaging (WSI) scanners, which can perform cost-effective and high-throughput histopathology

  8. Mature cystic teratomas: Relationship between histopathological ...

    African Journals Online (AJOL)

    ... tumor size, symptoms related to MCT and laterality of the tumor did not differ among the patients according to the MCT contents. Conclusions: Our findings suggest no relationship between the clinical features and histopathological contents of MCTs. Key words: Histopathological contents, mature cystic teratoma, ovarian, ...

  9. National Status and Trends: Contaminant body burdens and histopathology of fish and shellfish from Alaska

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — In response to the growing concerns among Chugach communities, contaminant body burden and histopathological condition of chum and sockeye salmon (Oncorhynchus keta...

  10. Role of DNA Repair Factor Xeroderma Pigmentosum Protein Group C in Response to Replication Stress As Revealed by DNA Fragile Site Affinity Chromatography and Quantitative Proteomics.

    Science.gov (United States)

    Beresova, Lucie; Vesela, Eva; Chamrad, Ivo; Voller, Jiri; Yamada, Masayuki; Furst, Tomas; Lenobel, Rene; Chroma, Katarina; Gursky, Jan; Krizova, Katerina; Mistrik, Martin; Bartek, Jiri

    2016-12-02

    Replication stress (RS) fuels genomic instability and cancer development and may contribute to aging, raising the need to identify factors involved in cellular responses to such stress. Here, we present a strategy for identification of factors affecting the maintenance of common fragile sites (CFSs), which are genomic loci that are particularly sensitive to RS and suffer from increased breakage and rearrangements in tumors. A DNA probe designed to match the high flexibility island sequence typical for the commonly expressed CFS (FRA16D) was used as specific DNA affinity bait. Proteins significantly enriched at the FRA16D fragment under normal and replication stress conditions were identified using stable isotope labeling of amino acids in cell culture-based quantitative mass spectrometry. The identified proteins interacting with the FRA16D fragment included some known CFS stabilizers, thereby validating this screening approach. Among the hits from our screen so far not implicated in CFS maintenance, we chose Xeroderma pigmentosum protein group C (XPC) for further characterization. XPC is a key factor in the DNA repair pathway known as global genomic nucleotide excision repair (GG-NER), a mechanism whose several components were enriched at the FRA16D fragment in our screen. Functional experiments revealed defective checkpoint signaling and escape of DNA replication intermediates into mitosis and the next generation of XPC-depleted cells exposed to RS. Overall, our results provide insights into an unexpected biological role of XPC in response to replication stress and document the power of proteomics-based screening strategies to elucidate mechanisms of pathophysiological significance.

  11. Histopathological effects, responses of oxidative stress, inflammation, apoptosis biomarkers and alteration of gene expressions related to apoptosis, oxidative stress, and reproductive system in chlorpyrifos-exposed common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Altun, Serdar; Özdemir, Selçuk; Arslan, Harun

    2017-11-01

    In this study, we aimed to identify the toxic effects of chlorpyrifos exposure on the tissues of common carp. For this purpose, we evaluated histopathological changes in the brain, gills, liver, kidney, testis, and ovaries after 21 days of chlorpyrifos exposure. Activation of 8-OHdG, cleaved caspase-3, and iNOS were assesed by immunofluorescence assay in chlorpyrifos-exposed brain and liver tissue. Additionally, we measured the expression levels of caspase-3, caspase-8, iNOS, MT1, CYP1A, and CYP3A genes in chlorpyrifos-exposed brain tissue, as well as the expression levels of FSH and LH genes in chlorpyrifos-exposed ovaries, using qRT-PCR. We observed severe histopathological lesions, including inflammation, degeneration, necrosis, and hemorrhage, in the evaluated tissues of common carp after both high and low levels of exposure to chlorpyrifos. We detected strong and diffuse signs of immunofluorescence reaction for 8-OHdG, iNOS, and cleaved caspase-3 in the chlorpyrifos-exposed brain and liver tissues. Furthermore, we found that chlorpyrifos exposure significantly upregulated the expressions of caspase-3, caspase-8, iNOS, and MT1, and also moderately upregulated CYP1A and CYP3A in the brain tissue of exposed carp. We also noted downregulation of FSH and LH gene expressions in chlorpyrifos-exposed ovary tissues. Based on our results, chlorpyrifos toxication caused crucial histopathological lesions in vital organs, induced oxidative stress, inflammation, and apoptosis in liver and brain tissues, and triggered reproductive sterility in common carp. Therefore, we can propose that chlorpyrifos toxication is highly dangerous to the health of common carp. Moreover, chlorpyrifos pollution in the water could threaten the common carp population. Use of chlorpyrifos should be restricted, and aquatic systems should be monitored for chlorpyrifos pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. KIN17, XPC, DNA-PKCS and XRCC4 proteins in the cellular response to DNA damages. Relations between nucleotide excision repair and non-homologous end joining in a human syn-genic model

    International Nuclear Information System (INIS)

    Despras, Emmanuelle

    2006-01-01

    The response to genotoxic stress involves many cellular factors in a complex network of mechanisms that aim to preserve the genetic integrity of the organism. These mechanisms enclose the detection and repair of DNA lesions, the regulation of transcription and replication and, eventually, the setting of cell death. Among the nuclear proteins involved in this response, kin17 proteins are zinc-finger proteins conserved through evolution and activated by ultraviolet (UV) or ionizing radiations (IR). We showed that human kin17 protein (HSAkin17) is found in the cell under a soluble form and a form tightly anchored to nuclear structures. A fraction of HSAkin17 protein is directly associated with chromatin. HSAkin17 protein is recruited to nuclear structures 24 hours after treatment with various agents inducing DNA double-strand breaks (DSB) and/or replication forks blockage. Moreover, the reduction of total HSAkin17 protein level sensitizes RKO cells to IR. We also present evidence for the involvement of HSAkin17 protein in DNA replication. This hypothesis was further confirmed by the biochemical demonstration of its belonging to the replication complex. HSAkin17 protein could link DNA replication and DNA repair, a defect in the HSAkin17 pathway leading to an increased radiosensitivity. In a second part, we studied the interactions between two DNA repair mechanisms: nucleotide excision repair (NER) and non-homologous end joining (NHEJ). NER repairs a wide variety of lesions inducing a distortion of the DNA double helix including UV-induced pyrimidine dimers. NHEJ allows the repair of DSB by direct joining of DNA ends. We used a syn-genic model for DNA repair defects based on RNA interference developed in the laboratory. Epstein-Barr virus-derived vectors (pEBV) allow long-term expression of siRNA and specific extinction of the targeted gene. The reduction of the expression of genes involved in NER (XPA and XPC) or NHEJ (DNA-PKcs and XRCC4) leads to the expected

  13. ATR-p53 restricts homologous recombination in response to replicative stress but does not limit DNA interstrand crosslink repair in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Bianca M Sirbu

    Full Text Available Homologous recombination (HR is required for the restart of collapsed DNA replication forks and error-free repair of DNA double-strand breaks (DSB. However, unscheduled or hyperactive HR may lead to genomic instability and promote cancer development. The cellular factors that restrict HR processes in mammalian cells are only beginning to be elucidated. The tumor suppressor p53 has been implicated in the suppression of HR though it has remained unclear why p53, as the guardian of the genome, would impair an error-free repair process. Here, we show for the first time that p53 downregulates foci formation of the RAD51 recombinase in response to replicative stress in H1299 lung cancer cells in a manner that is independent of its role as a transcription factor. We find that this downregulation of HR is not only completely dependent on the binding site of p53 with replication protein A but also the ATR/ATM serine 15 phosphorylation site. Genetic analysis suggests that ATR but not ATM kinase modulates p53's function in HR. The suppression of HR by p53 can be bypassed under experimental conditions that cause DSB either directly or indirectly, in line with p53's role as a guardian of the genome. As a result, transactivation-inactive p53 does not compromise the resistance of H1299 cells to the interstrand crosslinking agent mitomycin C. Altogether, our data support a model in which p53 plays an anti-recombinogenic role in the ATR-dependent mammalian replication checkpoint but does not impair a cell's ability to use HR for the removal of DSB induced by cytotoxic agents.

  14. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  15. HISTOPATHOLOGIC PATTERN OF THYROID DISEASE B ...

    African Journals Online (AJOL)

    hi-tech

    2003-10-01

    Oct 1, 2003 ... Thyroid carcinoma causes about 7000 deaths annualy in the ... included patients's age, sex and the histopathologic diagnosis. The slides were not .... help to reduce the resources spent on managing individual goiter cases ...

  16. Reversal of histopathologic pulmonary changes with indomethacin.

    Science.gov (United States)

    Kerstein, M D; Crivello, M

    1980-12-01

    There are pulmonary changes documented by light and electron microscopy in a canine model of nonhypotensive shock induced by a lower limb tourniquet. These histopathologic changes are mediated, at least in part, when the dog is treated with indomethacin.

  17. histomorphometric and histopathological studies on the effectof ...

    African Journals Online (AJOL)

    Dr Olaleye

    Histomorphometric and histopathological evaluations of the effects of fresh leaf extract of Calotropis procera on the reproductive organs of male wistar rats given 20mg\\gm body weight of the extract once daily, ..... Antifertility Drugs of India.

  18. Histopathological evaluation of dental follicles of clinically ...

    African Journals Online (AJOL)

    2015-11-02

    Nov 2, 2015 ... asymptomatic impacted third molars histopathologically for a number of characteristics. Materials and ... Introduction. Surgical removal of symptomatic impacted third molar ..... These percentages were lower compared to the.

  19. Efficient nucleus detector in histopathology images.

    NARCIS (Netherlands)

    Vink, J.P.; Leeuwen, van M.B.; Deurzen, van C.H.M.; Haan, de G.

    2013-01-01

    In traditional cancer diagnosis, (histo)pathological images of biopsy samples are visually analysed by pathologists. However, this judgment is subjective and leads to variability among pathologists. Digital scanners may enable automated objective assessment, improved quality and reduced throughput

  20. Signalization and repair of the DNA double-strand breaks of in the cerebral tumors: modulation of the radiation response with the chemotherapy treatments

    International Nuclear Information System (INIS)

    Marcinkova-Bencokova, Z.

    2007-07-01

    There are about 6000 new cases of nervous system tumours each year in France. However, the current radio chemotherapeutic approaches against brain tumours remain still insufficient to produce a satisfactory therapeutic index. In parallel, the knowledge of the early radiobiological events has considerably progressed in the last few years. This thesis aims to provide new insights in the molecular and cellular response of brain tumours to radio chemotherapy. This thesis was divided into four stages. Stage 1: a novel DNA double-strand breaks repair pathway depending on the MRE11 protein but independent of the phosphorylation of H2AX emerged from the study of artefacts of the immunofluorescence technique and a systematic analysis of the radiosensitivity of human cells. Stage 2: the radiobiological features of 3 rodent models of glioma among the most used in preclinical trials and of 7 human glioma cell lines were investigated. Functional impairments of the BRCA1 protein in response to radiation and/or cisplatin were observed in the majority of the models tested, raising the question of the role of this protein in the anti-glioma treatments and in glioma genesis. Stage 3: in order to extend our approach to genetic syndromes associated with cerebral tumours predisposition, the radiobiological characteristics of the fibroblasts resulting from patients suffering from neurofibromatosis type 1 (NF1), a pathology associated with a strong incidence of peripheral nervous system tumours, were investigated. NF1 appeared to be a syndrome with moderated radiosensitivity, associated with a weak deficiency of DNA end-joining repair but with a strong activity of MRE11. These results enabled us to propose a preliminary model involving both proteins BRCA1 and NF1. Stage 4: considering the role of BRCA1 in the inhibition of some tyrosine kinase activity and in the response to cisplatin, we tested the radiobiological effects of treatments combining radiation, cisplatin and tyrosine kinase

  1. Preliminary study of the effects of smectite granules (WoundStat) on vascular repair and wound healing in a swine survival model.

    Science.gov (United States)

    Gerlach, Travis; Grayson, J Kevin; Pichakron, Kullada O; Sena, Matthew J; DeMartini, Steven D; Clark, Beth Z; Estep, J Scot; Zierold, Dustin

    2010-11-01

    WoundStat (WS) (TraumaCure, Bethesda, MD) is a topical hemostatic agent that effectively stops severe hemorrhage in animal models. To the best of our knowledge, no survival study has been conducted to ensure long-term product safety. We evaluated vascular patency and tissue responses to WS in a swine femoral artery injury model with survival up to 5 weeks. Anesthetized swine received a standardized femoral artery injury with free hemorrhage for 45 seconds followed by WS application. One hour after application, the WS was removed, the wound copiously irrigated, and the artery repaired using a vein patch. Six groups of three animals received WS and were killed either immediately after surgery or at weekly intervals up to 5 weeks. Three control animals were treated with gauze packing and direct pressure followed by identical vascular repair and survival for 1 week. At the time of killing, angiograms were performed, and tissue was collected for histopathology. Hemostasis was complete in all WS animals. All animals survived the procedure, and there were no clinically evident postoperative complications. Vascular repairs were angiographically patent in 15 of 18 animals (83%) receiving WS. Histopathologic examination of WS animals revealed severe diffuse fibrogranulomatous inflammation, early endothelial degeneration with subsequent intimal hyperplasia, moderate myocyte necrosis, and fibrogranulomatous nerve entrapment with axonal degeneration. Although an effective hemostatic agent, WS use was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks postinjury.

  2. Comparative proteomics of oxidative stress response of Lactobacillus acidophilus NCFM reveals effects on DNA repair and cysteine de novo synthesis

    DEFF Research Database (Denmark)

    Calderini, Elia; Celebioglu, Hasan Ufuk; Villarroel, Julia

    2017-01-01

    acidophilus NCFM to H2O2, simulating an oxidative environment. Bacterial growth was monitored by BioScreen and batch cultures were harvested at exponential phase for protein profiling of stress responses by 2D gel-based comparative proteomics. Proteins identified in 19 of 21 spots changing in abundance due...

  3. uvsF RFC1, the large subunit of replication factor C in Aspergillus nidulans, is essential for DNA replication, functions in UV repair and is upregulated in response to MMS-induced DNA damage.

    Science.gov (United States)

    Kafer, Etta; Chae, Suhn-Kee

    2008-09-01

    uvsF201 was the first highly UV-sensitive repair-defective mutation isolated in Aspergillus nidulans. It showed epistasis only with postreplication repair mutations, but caused lethal interactions with many other repair-defective strains. Unexpectedly, closest homology of uvsF was found to the large subunit of human DNA replication factor RFC that is essential for DNA replication. Sequencing of the uvsF201 region identified changes at two close base pairs and the corresponding amino acids in the 5'-region of uvsF(RFC1). This viable mutant represents a novel and possibly important type. Additional sequencing of the uvsF region confirmed a mitochondrial ribosomal protein gene, mrpA(L16), closely adjacent, head-to-head with a 0.2kb joint promoter region. MMS-induced transcription of both the genes, but especially uvsF(RFC1), providing evidence for a function in DNA damage response.

  4. Validity and Responsiveness of the Short Version of the Western Ontario Rotator Cuff Index (Short-WORC) in Patients With Rotator Cuff Repair.

    Science.gov (United States)

    Dewan, Neha; MacDermid, Joy C; MacIntyre, Norma

    2018-05-01

    Study Design Clinical measurement. Background Recently, the Western Ontario Rotator Cuff Index (WORC) was shortened, but few studies have reported its measurement properties. Objective To compare the validity and responsiveness of the short version of the Western Ontario Rotator Cuff Index (Short-WORC) and the WORC (disease-specific measures) with those of the Shoulder Pain and Disability Index (SPADI) and the simple shoulder test (SST) (joint-specific measures); the Disabilities of the Arm, Shoulder and Hand (DASH) (a region-specific measure); and the Medical Outcomes Study 12-Item Short-Form Health Survey version 2 (SF-12v2) (a general health status measure) in patients undergoing rotator cuff repair (RCR). Methods A cohort of patients (n = 223) completed the WORC, SPADI, SST, DASH, and SF-12v2 preoperatively and at 3 and 6 months after RCR. Short-WORC scores were extracted from the WORC questionnaire. The construct validity (Pearson correlations) and internal responsiveness (effect size [ES], standardized response mean [SRM], relative efficiency [RE]) of the Short-WORC were calculated. Results The Short-WORC was strongly correlated with the WORC (r = 0.89-0.96) and moderately to strongly correlated with non-disease-specific measures at preoperative and postoperative assessments (r = 0.51-0.92). The Short-WORC and WORC were equally responsive (RE Short-WORC/WORC = 1) at 0 to 6 months and highly responsive overall at 0 to 3 months (ES Short-WORC , 0.72; ES WORC , 0.92; SRM Short-WORC , 0.75; SRM WORC , 0.81) and 0 to 6 months (ES Short-WORC , 1.05; ES WORC , 1.12; SRM Short-WORC , 0.89; SRM WORC , 0.89). The responsiveness of the comparator measures (SPADI, SST, DASH, SF-12v2) was poor to moderate at 0 to 3 months (ES, 0.07-0.55; SRM, 0.09-0.49) and 0 to 6 months (ES, 0.05-0.78; SRM, 0.07-0.78). Conclusion The Short-WORC and WORC have similar responsiveness in patients undergoing RCR, and are more responsive than non-disease-specific measures. Future studies

  5. Histopathological Effects of Gammalin 20 on African Catfish (Clarias gariepinus)

    International Nuclear Information System (INIS)

    Ezemonye, L.; Ogbomida, T.E.

    2010-01-01

    Clarias gariepinus fingerlings exposed to lethal and sublethal concentrations of Gammalin 20 were investigated in a renewal static bioassay with particular reference to behaviour, survival, and histopathological changes. Early symptoms of gammalin 20 lethal poisoning were, respiratory distress, increased physical activity, convulsions, erratic swimming, loss of equilibrium, and increased breathing activity. Behavioural response was dose dependent and decreased with decreased concentration. The 96-hour lethal concentration (LC 50 ) value was 30 ppb. Histopathological changes of the gill, liver, and intestinal tissues of fish treated with sublethal concentration of gammalin 20 for twelve weeks showed gill distortion and fusion of adjacent secondary lamella as a result of hyperplasia and excessive mucus accumulation. The liver showed swelling of hepatocytes with mild necrosis, pyknosis, and vacuolation, while the intestine showed yellow bodies of the lamina propria at the tip of the mucosal fold. environmental monitoring hazardous substances like heavy metals, pesticides

  6. A deficiency in chromatin repair, genetic instability, and predisposition to cancer

    International Nuclear Information System (INIS)

    Sanford, K.K.; Parshad, R.; Gantt, R.R.; Tarone, R.E.

    1989-01-01

    This review traces steps leading to malignant neoplastic transformation of rodent and human cells in culture and in vivo. Emphasis is placed on an abnormal response characterized by persistent chromatid damage following irradiation of cells in culture with X-rays or fluorescent light during G2 phase of the cell cycle. Evidence is presented that deficient or unbalanced DNA repair during G2 accounts for the abnormal response. This G2 repair deficiency can be inherited or acquired by normal tissue cells during the process of or following attainment of infinite lifespan. It appears as an early, possibly initiating step in neoplastic transformation. It characterizes all human tumor cells examined irrespective of histopathology or tissue of origin. It has a genetic basis. In an animal model, the BALB/c mouse, this phenotype is associated with genes on chromosomes 1 and 4. It characterizes skin fibroblasts and blood lymphocytes from individuals with genetic or familial conditions predisposing to cancer and can be used to identify clinically normal family members carrying a gene(s) for any one of the three cancer-prone genetic disorders studied to date. Furthermore, it can provide the basis of a test for carriers of genes predisposing to a high risk of cancer. We conclude that the G2 repair deficiency, whether inherited or acquired, is a prerequisite for cancer development and that it accounts for the genetic instability of the cancer cell. 167 refs

  7. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  8. Eukaryotic initiation factor 2α--a downstream effector of mammalian target of rapamycin--modulates DNA repair and cancer response to treatment.

    Directory of Open Access Journals (Sweden)

    Liron Tuval-Kochen

    Full Text Available In an effort to circumvent resistance to rapamycin--an mTOR inhibitor--we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy. We found that rapamycin, at nM concentrations, increased phosphorylation of eukaryotic initiation factor (eIF 2α in rapamycin-sensitive and estrogen-dependent MCF-7 cells, but had only a minimal effect on eIF2α phosphorylation in the rapamycin-insensitive triple-negative MDA-MB-231 cells. Addition of salubrinal--an inhibitor of eIF2α dephosphorylation--decreased expression of a surface marker associated with capacity for self renewal, increased senescence and induced clonogenic cell death, suggesting that excessive phosphorylation of eIF2α is detrimental to the cells' survival. Treating cells with salubrinal enhanced radiation-induced increase in eIF2α phosphorylation and clonogenic death and showed that irradiated cells are more sensitive to increased eIF2α phosphorylation than non-irradiated ones. Similar to salubrinal--the phosphomimetic eIF2α variant--S51D--increased sensitivity to radiation, and both abrogated radiation-induced increase in breast cancer type 1 susceptibility gene, thus implicating enhanced phosphorylation of eIF2α in modulation of DNA repair. Indeed, salubrinal inhibited non-homologous end joining as well as homologous recombination repair of double strand breaks that were induced by I-SceI in green fluorescent protein reporter plasmids. In addition to its effect on radiation, salubrinal enhanced eIF2α phosphorylation and clonogenic death in response to the histone deacetylase inhibitor--vorinostat. Finally, the catalytic competitive inhibitor of mTOR--Ku-0063794--increased phosphorylation of eIF2α demonstrating further the involvement of mTOR activity in modulating eIF2α phosphorylation. These experiments suggest that excessive phosphorylation of eIF2α decreases survival of cancer cells; making eIF2α a worthy target for

  9. Metabolic modulation of mammalian DNA excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Schrader, T.J.

    1988-01-01

    First, ultraviolet light (UVL)- and dimethylsulfate (DMS)-induced excision repair was examined in quiescent and lectin-stimulated bovine lymphocytes. Upon mitogenic stimulation, UVL-induced repair increased by a factor of 2 to 3, and reached this maximum 2 days before the onset of DNA replication. However, DMS-induced repair increased sevenfold in parallel with DNA replication. Repair patch sizes were smaller for DMS-induced damage reflecting patches of 7 nucleotides in quiescent lymphocytes compared to 20 nucleotides induced by UVL. The patch size increased during lymphocyte stimulation until one day prior to the peak of DNA replication when patch sizes of 45 and 35 nucleotides were produced in response to UVL- and DMS-induced damage, respectively. At the peak of DNA replication, the patch sizes were equal for both damaging agents at 34 nucleotides. In the second study, a small amount of repair replication was observed in undamaged quiescent and concanavalin A-stimulated bovine lymphocytes as well as in human T98G glioblastoma cells. Repair incorporation doubled in the presence of hydroxyurea. Thirdly, the enhanced repair replication induced by the poly (ADP-ribose) polymerase inhibitor, 3-aminobenzamide, (3-AB), could not be correlated either with an increased rate of repair in the presence of 3-AB or with the use of hydroxyurea in the repair protocol. Finally, treatment of unstimulated lymphocytes with hyperthermia was accompanied by decreased repair replication while the repair patches remained constant at 20 nucleotides.

  10. Complex networks under dynamic repair model

    Science.gov (United States)

    Chaoqi, Fu; Ying, Wang; Kun, Zhao; Yangjun, Gao

    2018-01-01

    Invulnerability is not the only factor of importance when considering complex networks' security. It is also critical to have an effective and reasonable repair strategy. Existing research on network repair is confined to the static model. The dynamic model makes better use of the redundant capacity of repaired nodes and repairs the damaged network more efficiently than the static model; however, the dynamic repair model is complex and polytropic. In this paper, we construct a dynamic repair model and systematically describe the energy-transfer relationships between nodes in the repair process of the failure network. Nodes are divided into three types, corresponding to three structures. We find that the strong coupling structure is responsible for secondary failure of the repaired nodes and propose an algorithm that can select the most suitable targets (nodes or links) to repair the failure network with minimal cost. Two types of repair strategies are identified, with different effects under the two energy-transfer rules. The research results enable a more flexible approach to network repair.

  11. Current Biomechanical Concepts for Rotator Cuff Repair

    Science.gov (United States)

    2013-01-01

    For the past few decades, the repair of rotator cuff tears has evolved significantly with advances in arthroscopy techniques, suture anchors and instrumentation. From the biomechanical perspective, the focus in arthroscopic repair has been on increasing fixation strength and restoration of the footprint contact characteristics to provide early rehabilitation and improve healing. To accomplish these objectives, various repair strategies and construct configurations have been developed for rotator cuff repair with the understanding that many factors contribute to the structural integrity of the repaired construct. These include repaired rotator cuff tendon-footprint motion, increased tendon-footprint contact area and pressure, and tissue quality of tendon and bone. In addition, the healing response may be compromised by intrinsic factors such as decreased vascularity, hypoxia, and fibrocartilaginous changes or aforementioned extrinsic compression factors. Furthermore, it is well documented that torn rotator cuff muscles have a tendency to atrophy and become subject to fatty infiltration which may affect the longevity of the repair. Despite all the aforementioned factors, initial fixation strength is an essential consideration in optimizing rotator cuff repair. Therefore, numerous biomechanical studies have focused on elucidating the strongest devices, knots, and repair configurations to improve contact characteristics for rotator cuff repair. In this review, the biomechanical concepts behind current rotator cuff repair techniques will be reviewed and discussed. PMID:23730471

  12. DNA repair , cell repair and radiosensitivity

    International Nuclear Information System (INIS)

    Zhestyanikov, V.D.

    1983-01-01

    Data obtained in laboratory of radiation cytology and literature data testifying to a considerable role of DNA repair in cell sensitivity to radiation and chemical DNA-tropic agents have been considered. Data pointing to the probability of contribution of inducible repair of DNA into plant cells sensitivity to X-rays are obtained. Certain violations of DNA repair do not result in the increase of radiosensitivity. It is assumed that in the cases unknown mechanisms of DNA repair operate

  13. Synthesis, characterization and histomorphometric analysis of cellular response to a new elastic DegraPol® polymer for rabbit Achilles tendon rupture repair.

    Science.gov (United States)

    Buschmann, Johanna; Calcagni, Maurizio; Bürgisser, Gabriella Meier; Bonavoglia, Eliana; Neuenschwander, Peter; Milleret, Vincent; Giovanoli, Pietro

    2015-05-01

    Tendon rupture repair is a surgical field where improvements are still required due to problems such as repeat ruptures, adhesion formation and joint stiffness. In the current study, a reversibly expandable and contractible electrospun tube based on a biocompatible and biodegradable polymer was implanted around a transected and conventionally sutured rabbit Achilles tendon. The material used was DegraPol® (DP), a polyester urethane. To make DP softer, more elastic and surgeon-friendly, the synthesis protocol was slightly modified. Material properties of conventional and new DP film electrospun meshes are presented. At 12 weeks post-surgery, tenocyte and tenoblast density, nuclei and width, collagen fibre structure and inflammation levels were analyzed histomorphometrically. Additionally, a comprehensive histological scoring system by Stoll et al. (2011) was used to compare healing outcomes. Results showed that there were no adverse reactions of the tendon tissue following the implant. No differences were found whether the DP tube was applied or not for both traditional and new DP materials. As a result, the new DP material was shown to be an excellent carrier for delivery of growth factors, stem cells and other agents responsible for tendon healing. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Evidence for induction of DNA double strand breaks in the bystander response to targeted soft X-rays in repair deficient CHO cells

    International Nuclear Information System (INIS)

    Kashino, Genro; Suzuki, Keiji; Prise, K.M.

    2005-01-01

    Evidence is accumulating that irradiated cells produce some signals which interact with non-exposed cells in the same population. Here, we analysed the mechanism of such a bystander effect from targeted cells to non-targeted cells. Firstly, in order to investigate the bystander effect in Chinese hamster ovary (CHO) cell lines we irradiated a single cell within a population and scored the formation of micronuclei. When a single nucleus in the population, of double strand break repair deficient xrs5 cells, was targeted with 1 Gy of Al-K soft X-rays, elevated numbers of micronuclei were induced in the neighbouring unirradiated cells. The induction of micronuclei was also observed when conditioned medium was transferred from irradiated to non-irradiated xrs5 cells. These results suggest that DNA double strand breaks are caused by factors secreted in the medium from irradiated cells. To clarify the involvements of radical species in the bystander response, cells were treated with 0.5%DMSO 1 hour before irradiation and then bystander effects were estimated in xrs5 cells. The results showed clearly that DMSO treatment during X-irradiation suppress the induction of micronuclei in bystander xrs5 cells, when conditioned medium was transferred from irradiated xrs5 cells. Therefore, it is suggested that radical species induced by ionizing radiation are important for producing bystander signals. (author)

  15. Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair.

    Science.gov (United States)

    Lima, Michelle; Bouzid, Hana; Soares, Daniele G; Selle, Frédéric; Morel, Claire; Galmarini, Carlos M; Henriques, João A P; Larsen, Annette K; Escargueil, Alexandre E

    2016-05-03

    Trabectedin (Yondelis®, ecteinascidin-743, ET-743) is a marine-derived natural product approved for treatment of advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Lurbinectedin is a novel anticancer agent structurally related to trabectedin. Both ecteinascidins generate DNA double-strand breaks that are processed through homologous recombination repair (HRR), thereby rendering HRR-deficient cells particularly sensitive. We here characterize the DNA damage response (DDR) to trabectedin and lurbinectedin in HeLa cells. Our results show that both compounds activate the ATM/Chk2 (ataxia-telangiectasia mutated/checkpoint kinase 2) and ATR/Chk1 (ATM and RAD3-related/checkpoint kinase 1) pathways. Interestingly, pharmacological inhibition of Chk1/2, ATR or ATM is not accompanied by any significant improvement of the cytotoxic activity of the ecteinascidins while dual inhibition of ATM and ATR strongly potentiates it. Accordingly, concomitant inhibition of both ATR and ATM is an absolute requirement to efficiently block the formation of γ-H2AX, MDC1, BRCA1 and Rad51 foci following exposure to the ecteinascidins. These results are not restricted to HeLa cells, but are shared by cisplatin-sensitive and -resistant ovarian carcinoma cells. Together, our data identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors.

  16. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

    International Nuclear Information System (INIS)

    Stubbert, Lawton J; Smith, Jennifer M; McKay, Bruce C

    2010-01-01

    One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic

  17. Determination of the adaptive response induced In vivo by gamma radiation and its relation with the sensibility to the damage induction in the DNA and with the repairing capacity

    International Nuclear Information System (INIS)

    Mendiola C, M.T.

    2002-01-01

    The kinetics of damage induction and repair at different doses as well as the adaptive response induced by gamma ray exposure were determined in murine leukocytes in vivo. The damage-repair kinetics were established after the exposure to 0.5, 1.0 or 2.0 Gy in a 137 Cs source. Peripheral blood samples were obtained from the tails of mice, the percentage of damaged cells and the DNA migration in each one were analyzed by the single cell gel electrophoresis (SCG) technique or comet assay. Results indicated that there was an induction of approximately 75% comets with the doses of 1.0 and 2.0 Gy, which was considerably reduced to 22% and 42% respectively during the first 15 minutes. This evidences the presence of a rapid repair process and suggests that leucocytes are genetically well prepared to repair this kind of damage. After 15 minutes, a second increase in the percentage of damaged cells that was proportional to dose occurred, which seems to represent the breaks produced during the repair of other kind of lesions. After that a second reduction was observed, reaching values near to the basal ones, except with the dose of 2.0 Gy. The kinetics obtained with the dose of 0.5 Gy was similar to that established with 1.0 Gy, but in this case the initial damage was 50 % lower. Besides, the adaptive response was observed after the exposure of the mice to an adaptive dose of 0.01 Gy and to a challenge dose of 1.0 Gy 60 minutes later. The pretreatment reduced the percentage of damaged cells caused by the challenge dose to one third approximately, and also diminished this parameter produced during the late repair process. This indicates that the early adaptive response is caused, instead of by an increment in repair, by the induction of a process that protects DNA from damage induction by radiation, i.e synthesis of substances that increase the scavenging of free radicals. (Author)

  18. Angiography of histopathologic variants of synovial sarcoma

    International Nuclear Information System (INIS)

    Lois, J.F.; Fischer, H.J.; Mirra, J.M.; Gomes, A.S.; California Univ., Los Angeles

    1986-01-01

    Synovial sarcomas are rare soft tissue tumors which histopathologically can be divided into monophasic, biphasic and mixed variants. As part of a protocol for intra-arterial chemotherapy 12 patients with biopsy proven synovial sarcoma underwent angiography. The angiograms on these patients were reviewed to determine whether synovial sarcomas and their variants demonstrated a characteristic angiographic appearance. Synovial sarcomas appeared angiographically as soft tissue masses which showed a fine network of tumor vessels with an inhomogeneous capillary blush. Their degree of vascularity varied according to their histopathology. Monophasic synovial sarcomas demonstrated in general a higher degree of neovascularity than the biphasic form. This finding was also suggested by histopathologic analysis of the vessels in the tumor. Although angiography did not show a distinctive vascular pattern it may be useful to evaluate tumor size and vascularity. (orig.)

  19. Lymphogranuloma venereum: "a clinical and histopathological chameleon?".

    Science.gov (United States)

    Tchernev, Georgi; Salaro, Cristina; Costa, Mariana Carvalho; Patterson, James W; Nenoff, Pietro

    2010-01-01

    Lymphogranuloma venereum is an infection caused by a variety of the bacterium Chlamydia trachomatis. Both genital and extragenital manifestations of the disease can cause serious differential diagnostic difficulties, indirectly leading to progression and dissemination of the infection. This work describes cases of patients with lymphogranuloma venereum showing atypical clinical and/or histopathological findings. It also focuses on alternative therapeutic approaches, such as surgical excision at stage 1, that may lead to a positive outcome. It is not completely clear whether histopathological findings of lymphogranuloma venereum can reveal progression or changes in the course of the disease over time, as is the case in other diseases. We conclude that both clinical and histopathological observations in a larger number of patients are needed in order to further evaluate the findings presented in this article.

  20. Evaluation of genome damage and transcription profile of DNA damage/repair response genes in peripheral blood mononuclear cells exposed to low dose radiation

    International Nuclear Information System (INIS)

    Soren, D.C.; Saini, Divyalakshmi; Das, Birajalaxmi

    2016-01-01

    Humans are exposed to various physical and chemical mutagens in their life time. Physical mutagens, like ionizing radiation (IR), may induce adverse effect at high acute dose exposures in human cells. However, there are inconsistent results on the effect of low dose radiation exposure in human cells. There are a variety of DNA damage endpoints to evaluate the effect of low dose radiation in human cells. DNA damage response (DDR) may lead to changes in expression profile of many genes. In the present study, an attempt has been made to evaluate genome damage at low dose IR exposure in human blood lymphocytes. Cytochalasin blocked micronuclei (CBMN) assay has been used to determine the frequency of micronuclei in binucleated cells in PBMCs exposed to IR. Transcription profile of ATM, P53, GADD45A, CDKN1A, TRF1 and TRF2 genes was studied using real time quantitative PCR. Venous blood samples collected from 10 random healthy donors were irradiated with different doses of γ-radiation ( 137 Cs) along with sham irradiated control. Whole blood culture was set up using microculture technique. Blood samples were stimulated with phytohemagglutinin, and CBMN assay was performed. An average of 2,500 binucleated cells was scored for each dose point. For gene expression analysis, total RNA was isolated, cDNA was prepared, and gene expression analysis for ATM, P53, CDKN1A, GADD45A, TRF1 and TRF2 was done using real time PCR. Our results revealed no significant increase in the frequency of MN up to 100 mGy as compared to control. However, no significant alteration in gene expression profile was observed. In conclusion, no significant dose response was observed at the frequency of MN as well as the expression profile of DDR/repair genes, suggesting low dose radiation did not induce significant DNA damage at these acute dose exposures. (author)

  1. Morphea simulating paucibacillary leprosy clinically and histopathologically

    Directory of Open Access Journals (Sweden)

    José Saulo Torres Delgado

    2013-01-01

    Full Text Available Clinically and histopathologically paucibacillary leprosy shows similar features with initial morphea. In this case we report a 24 yr-old male patient who presented to our dermatology department with diagnosed paucibacillary leprosy by his local dermatologist, and confirmed by perineurovascular lymphocytic infiltrate in the histopathological exam. On physical examination we found new plaque lesions that were suggestive of morphea with alteration of sensitivity. A new biopsy was performed showing sclerotic superficial dermis with thickening of the collagen bundles in deep dermis and linear arrays lymphocytic infiltrate between the collagen bundles that confirm the diagnosis of morphea.

  2. A generalised formulation of the 'incomplete-repair' model for cell survival and tissue response to fractionated low dose-rate irradiation

    International Nuclear Information System (INIS)

    Nilsson, P.; Joiner, M.C.

    1990-01-01

    A generalized equation for cell survival or tissue effects after fractionated low dose-rate irradiations, when there is incomplete repair between fractions and significant repair during fractions, is derived in terms of the h- and g-functions of the 'incomplete-repair' (IR) model. The model is critically dependent on α/β, repair half-time, treatment time and interfraction interval, and should therefore be regarded primarily as a tool for the analysis of fractionation and dose-rate effects in carefully designed radiobiological experiments, although it should also be useful in exploring, in a general way, the feasibility of clinical treatment protocols using fractionated low dose-rate treatments. (author)

  3. Mathematical (diagnostic algorithms in the digitization of oral histopathology: The new frontier in histopathological diagnosis

    Directory of Open Access Journals (Sweden)

    Abhishek Banerjee

    2015-01-01

    Full Text Available The technological progress in the digitalization of a complete histological glass slide has opened a new door in the tissue based diagnosis. Automated slide diagnosis can be made possible by the use of mathematical algorithms which are formulated by binary codes or values. These algorithms (diagnostic algorithms include both object based (object features, structures and pixel based (texture measures. The intra- and inter-observer errors inherent in the visual diagnosis of a histopathological slide are largely replaced by the use of diagnostic algorithms leading to a standardized and reproducible diagnosis. The present paper reviews the advances in digital histopathology especially related to the use of mathematical algorithms (diagnostic algorithms in the field of oral histopathology. The literature was reviewed for data relating to the use of algorithms utilized in the construction of computational software with special applications in oral histopathological diagnosis. The data were analyzed, and the types and end targets of the algorithms were tabulated. The advantages, specificities and reproducibility of the software, its shortcomings and its comparison with traditional methods of histopathological diagnosis were evaluated. Algorithms help in automated slide diagnosis by creating software with possible reduced errors and bias with a high degree of specificity, sensitivity, and reproducibility. Akin to the identification of thumbprints and faces, software for histopathological diagnosis will in the near future be an important part of the histopathological diagnosis.

  4. Energy and Technology Review: Unlocking the mysteries of DNA repair

    Energy Technology Data Exchange (ETDEWEB)

    Quirk, W.A.

    1993-04-01

    DNA, the genetic blueprint, has the remarkable property of encoding its own repair following diverse types of structural damage induced by external agents or normal metabolism. We are studying the interplay of DNA damaging agents, repair genes, and their protein products to decipher the complex biochemical pathways that mediate such repair. Our research focuses on repair processes that correct DNA damage produced by chemical mutagens and radiation, both ionizing and ultraviolet. The most important type of DNA repair in human cells is called excision repair. This multistep process removes damaged or inappropriate pieces of DNA -- often as a string of 29 nucleotides containing the damage -- and replaces them with intact ones. We have isolated, cloned, and mapped several human repair genes associated with the nucleotide excision repair pathway and involved in the repair of DNA damage after exposure to ultraviolet light or mutagens in cooked food. We have shown that a defect in one of these repair genes, ERCC2, is responsible for the repair deficiency in one of the groups of patients with the recessive genetic disorder xeroderma pigmentosum (XP group D). We are exploring ways to purify sufficient quantities (milligrams) of the protein products of these and other repair genes so that we can understand their functions. Our long-term goals are to link defective repair proteins to human DNA repair disorders that predispose to cancer, and to produce DNA-repair-deficient mice that can serve as models for the human disorders.

  5. Histopathological changes in female rabbits administered with ...

    African Journals Online (AJOL)

    Grossly, catarrhal enteritis and mesenteric congestion of the small intestines, congestion of the lungs, hepatization and paleness of the liver, congestion and pallor of the kidney cortex, and congestion of the meninges were noticed. Histopathological examination of the tissues revealed mild pulmonary oedema and ...

  6. Ultrastructural and Histopathological Studies of the Digenetic ...

    African Journals Online (AJOL)

    The tegument of the cryptogonimid trematode is characterised with some markings and whitish ornamentations. The cephalic and the body region bears some compressed alae. The parasite has the distome body plan of digenetic trematode. The histopathology of the parasitized gastrointestinal tracts revealed necrosis of ...

  7. Pre-ankylosing spondylitis. Histopathological report.

    Science.gov (United States)

    Pasion, E G; Goodfellow, J W

    1975-02-01

    A novel explanation for the natural history of joint destruction in the early phase of ankylosing spondylitis is proposed on the basis of the clinical history, x-ray appearance, operative findings, and histopathology of a young patient believed to be suffering from the peripheral form of this disease.

  8. Histopathological Changes Induced By Staphylococcal Enterotoxin ...

    African Journals Online (AJOL)

    In this study, six Staphylococcus aureus strains isolated from contaminated yoghurt were evaluated for enterotoxigenicity. Two o the strains were enterotoxigenic and caused fluid accumulation in rabbit ileal loops. Fluid aspirated from the loops was bloody and histopathological changes in sections collected from rabbit ...

  9. Histopathological evaluation of Oreochromis mossambicus gills and ...

    African Journals Online (AJOL)

    Oreochromis mossambicus were sampled from a semi-intensively managed polyculture earthen pond in Bagauda, Nigeria for histopathological changes in the gills and liver as early warning signs of pond water pollution. Pond water was sourced from nearby Bagauda dam through a single 28 inches water pipe.

  10. Histopathological Diagnosis of Fungal Infections: Problems and ...

    African Journals Online (AJOL)

    Histopathology is a major diagnostic tool in mycology and has the advantage of rapid diagnosis, cost effectiveness, ability to provide initial identification of the infecting fungus and demonstrates tissue reactions and currently the means of diagnosing the infections caused by the fungi: Lodoa loboi and Rhinosporidium ...

  11. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  12. Histopathology of Tilapia tissues harbouring Clinostomum tilapiae ...

    African Journals Online (AJOL)

    Tissues obtained from infected Oreochromis niloticus were processed sectioned and stained with haemotoxylin and eosin. Good sections were selected, studied and photographed. The histopathology revealed a proliferation of eosinophiles at the secondary lamellar of the gills. The site of attachment on the fish skin ...

  13. Survivorship patterns of histopathological variants and molecular ...

    African Journals Online (AJOL)

    Objective: To study the relationship of histopathological characteristics, molecular subtypes of breast cancer and survival in a low resource setting. Design: Tumours from prospectively ascertained patients newly diagnosed with breast cancer were analyzed. Formalin-fixed and paraffin-embedded sections were constructed ...

  14. Hepatic Antioxidant, Oxidative Stress And Histopathological ...

    African Journals Online (AJOL)

    Hepatic Antioxidant, Oxidative Stress And Histopathological Changes Induced By Nicotine In A Gender Based Study In Adult Rats. ... Antioxidant status was assessed in liver by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and ...

  15. Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

    Directory of Open Access Journals (Sweden)

    Smith Jennifer M

    2010-05-01

    Full Text Available Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi was used to reduce the transcription-coupled nucleotide excision repair (TC-NER capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic.

  16. Comparative analysis of histopathologic effects of synthetic meshes based on material, weight, and pore size in mice.

    Science.gov (United States)

    Orenstein, Sean B; Saberski, Ean R; Kreutzer, Donald L; Novitsky, Yuri W

    2012-08-01

    While synthetic prosthetics have essentially become mandatory for hernia repair, mesh-induced chronic inflammation and scarring can lead to chronic pain and limited mobility. Mesh propensity to induce such adverse effects is likely related to the prosthetic's material, weight, and/or pore size. We aimed to compare histopathologic responses to various synthetic meshes after short- and long-term implantations in mice. Samples of macroporous polyester (Parietex [PX]), heavyweight microporous polypropylene (Trelex[TX]), midweight microporous polypropylene (ProLite[PL]), lightweight macroporous polypropylene (Ultrapro[UP]), and expanded polytetrafluoroethylene (DualMesh[DM]) were implanted subcutaneously in mice. Four and 12 wk post-implantation, meshes were assessed for inflammation, foreign body reaction (FBR), and fibrosis. All meshes induced varying levels of inflammatory responses. PX induced the greatest inflammatory response and marked FBR. DM induced moderate FBR and a strong fibrotic response with mesh encapsulation at 12 wk. UP and PL had the lowest FBR, however, UP induced a significant chronic inflammatory response. Although inflammation decreased slightly for TX, marked FBR was present throughout the study. Of the three polypropylene meshes, fibrosis was greatest for TX and slightly reduced for PL and UP. For UP and PL, there was limited fibrosis within each mesh pore. Polyester mesh induced the greatest FBR and lasting chronic inflammatory response. Likewise, marked fibrosis and encapsulation was seen surrounding ePTFE. Heavier polypropylene meshes displayed greater early and persistent fibrosis; the reduced-weight polypropylene meshes were associated with the least amount of fibrosis. Mesh pore size was inversely proportional to bridging fibrosis. Moreover, reduced-weight polypropylene meshes demonstrated the smallest FBR throughout the study. Overall, we demonstrated that macroporous, reduced-weight polypropylene mesh exhibited the highest degree of

  17. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  18. Emerging roles of the nucleolus in regulating the DNA damage response: the noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example.

    Science.gov (United States)

    Antoniali, Giulia; Lirussi, Lisa; Poletto, Mattia; Tell, Gianluca

    2014-02-01

    An emerging concept in DNA repair mechanisms is the evidence that some key enzymes, besides their role in the maintenance of genome stability, display also unexpected noncanonical functions associated with RNA metabolism in specific subcellular districts (e.g., nucleoli). During the evolution of these key enzymes, the acquisition of unfolded domains significantly amplified the possibility to interact with different partners and substrates, possibly explaining their phylogenetic gain of functions. After nucleolar stress or DNA damage, many DNA repair proteins can freely relocalize from nucleoli to the nucleoplasm. This process may represent a surveillance mechanism to monitor the synthesis and correct assembly of ribosomal units affecting cell cycle progression or inducing p53-mediated apoptosis or senescence. A paradigm for this kind of regulation is represented by some enzymes of the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic endonuclease 1 (APE1). In this review, the role of the nucleolus and the noncanonical functions of the APE1 protein are discussed in light of their possible implications in human pathologies. A productive cross-talk between DNA repair enzymes and proteins involved in RNA metabolism seems reasonable as the nucleolus is emerging as a dynamic functional hub that coordinates cell growth arrest and DNA repair mechanisms. These findings will drive further analyses on other BER proteins and might imply that nucleic acid processing enzymes are more versatile than originally thought having evolved DNA-targeted functions after a previous life in the early RNA world.

  19. Food availability drives plastic self-repair response in a basal metazoan-case study on the ctenophore Mnemiopsis leidyi A. Agassiz

    DEFF Research Database (Denmark)

    Bading, Katharina Tissy; Kaehlert, Sarah; Chi, Xupeng

    2017-01-01

    -animals instead. Yet, the driving factors of this phenomenon have not been addressed so far. This study sheds new light on how differences in food availability affect self-repair choice and regeneration success in cydippid larvae of M. leidyi. As expected, high food availability favored whole-body regeneration....... However, under low food conditions half-animals became the preferential self-repair mode. Remarkably, both regenerating and half-animals showed very similar survival chances under respective food quantities. As a consequence of impaired food uptake after injury, degeneration of the digestive system would...... often occur indicating limited energy storage capacities. Taken together, this indicates that half-animals may represent an alternative energy-saving trajectory which implies self-repair plasticity as an adaptive trade-off between high regeneration costs and low energy storage capacities. We conclude...

  20. Imaging of cartilage repair procedures

    International Nuclear Information System (INIS)

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts

  1. Expression of a Human Cytochrome P450 in Yeast Permits Analysis of Pathways for Response to and Repair of Aflatoxin-Induced DNA Damage†

    OpenAIRE

    Guo, Yingying; Breeden, Linda L.; Zarbl, Helmut; Preston, Bradley D.; Eaton, David L.

    2005-01-01

    Aflatoxin B1 (AFB1) is a human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In humans, AFB1 is primarily bioactivated by cytochrome P450 1A2 (CYP1A2) and 3A4 to a genotoxic epoxide that forms N7-guanine DNA adducts. A series of yeast haploid mutants defective in DNA repair and cell cycle checkpoints were transformed with human CYP1A2 to investigate how these DNA adducts are repaired. Cell survival and mutagenesis following aflatoxin B1 treatment was assayed in str...

  2. Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract

    Directory of Open Access Journals (Sweden)

    Beatriz Eugenia Fuentes-Castro

    Full Text Available BACKGROUND Dialyzable leukocyte extracts (DLEs contain molecules smaller than 10 kDa with biological activity in receptor organisms. Primarily, they participate in the regulation of the Th1 immune response, which is essential for the control of several intracellular infections, such as toxoplasmosis. This disease is associated with congenital infection, encephalitis or systemic infections in immunocompromised individuals. The clinical course of this infection fundamentally depends on a well-regulated immune response and timely treatment with the appropriate drugs. OBJECTIVE The aim of this study was to evaluate the effect of treatment with a leukocyte extract, derived from crocodile lymphoid tissue, on the histopathology and brain parasite load in NIH mice that had been infected with cysts of Toxoplasma gondii (ME-49 strain. METHODS The treatment was applied during the acute and chronic stages of the infection. Histopathological changes were evaluated in the ileum, liver and spleen at one, four and eight weeks after infection and in the brain at week 8. The parasite load was evaluated by counting the cysts of T. gondii found in the brain. FINDINGS Compared to the control mouse group, the mice infected with T. gondii and under treatment with DLE showed less tissue damage, mainly at the intestinal, splenic and hepatic levels. In addition, a greater percentage of survival was observed, and there was a considerable reduction in the parasite load in the brain. CONCLUSIONS The results suggest that DLE derived from crocodile is a potential adjunctive therapy in the conventional treatment of toxoplasmosis.

  3. Extended histopathology in immunotoxicity testing: Interlaboratory validation studies

    NARCIS (Netherlands)

    Germolec, D.R.; Nyska, A.; Kashon, M.; Kuper, C.F.; Portier, C.; Kommineni, C.; Johnson, K.A.; Luster, M.I.

    2004-01-01

    There has been considerable interest in the use of expanded histopathology as a primary screen for immunotoxicity assessment. To determine the utility of a semiquantitative histopathology approach for examining specific structural and architectural changes in lymphoid tissues, a validation effort

  4. Breast cancer histopathology image analysis: a review.

    Science.gov (United States)

    Veta, Mitko; Pluim, Josien P W; van Diest, Paul J; Viergever, Max A

    2014-05-01

    This paper presents an overview of methods that have been proposed for the analysis of breast cancer histopathology images. This research area has become particularly relevant with the advent of whole slide imaging (WSI) scanners, which can perform cost-effective and high-throughput histopathology slide digitization, and which aim at replacing the optical microscope as the primary tool used by pathologist. Breast cancer is the most prevalent form of cancers among women, and image analysis methods that target this disease have a huge potential to reduce the workload in a typical pathology lab and to improve the quality of the interpretation. This paper is meant as an introduction for nonexperts. It starts with an overview of the tissue preparation, staining and slide digitization processes followed by a discussion of the different image processing techniques and applications, ranging from analysis of tissue staining to computer-aided diagnosis, and prognosis of breast cancer patients.

  5. MRI of the breast - histopathologic correlation

    International Nuclear Information System (INIS)

    Heywang, S.H.; Fenzl, G.; Hahn, D.; Beck, R.; Krischke, I.; Bassermann, R.; Nathrath, W.; Eiermann, W.

    1987-01-01

    132 solid breast masses have been examined at our institution by MR and have consequently been histopathologically correlated. T1- and T2-weighted SE and multiecho sequences have been evaluated visually. It was found that signal intensities of tissues on T2-weighted images correlated with the contents of fibrosis, cells or water. Thus in some lesions (which consisted of different tissue components), a characteristic internal structure was visible on T2-weighted images, reflecting their histopathologic structure. Corresponding to their different composition, differences of signal intensity have also been noted between those fibroadenomas with a high contents of fibrosis and all other well-circumscribed breast lesions (fibroadenomas, carcinomas). However, for the majority of lesions with irregular contours a discrimination based on signal intensities or calculated T1- and T2-values did not seem possible. This overlap can also be explained by the macroscopically similar composition (amount of fibrosis, water or cells) of benign and malignant irregular lesions. (orig.)

  6. Histopathology of Lyme arthritis in LSH hamsters

    International Nuclear Information System (INIS)

    Hejka, A.; Schmitz, J.L.; England, D.M.; Callister, S.M.; Schell, R.F.

    1989-01-01

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis

  7. Histopathological findings after Leksell gamma knife radiosurgery

    International Nuclear Information System (INIS)

    Langmann, G.; Dexel, A.; Haller-Schober, E.M.; Koelli, H.; Kleinert, R.

    2002-01-01

    Radiosurgery for uveal melanoma can achieve tumor control according to clinical studies, yet histopathological proof has not been described. 8 eyes after radiosurgery which had to be removed either to regression failure or severe complications like neovascular glaucoma or persisting retinal detachment were investigated histopathologically and compared to 10 uveal melanomas that were treated by enucleation alone. Uveal melanomas treated with the gamma knife showed tumor necrosis (in more than 50 % total necrosis), a higher number of balloon cells, less number of mitoses and vascular changes (thickening of the vessel's walls, obliteration, thrombosis) which could not be demonstrated in enucleated eyes without irradiation. Leksell gamma knife can cause tumor necrosis and varying degrees of cell death and reduced reproducibility. Vascular changes seem to play a major role in tumor regression. (author)

  8. Congenital bronchopulmonary malformation: CT histopathological correlation.

    Science.gov (United States)

    Kyncl, Martin; Koci, Martin; Ptackova, Lea; Hornofova, Ludmila; Ondrej, Fabian; Snajdauf, Jiri; Pychova, Marcela

    2016-12-01

    This study evaluated the accuracy of postnatal computed tomography (CT) imaging in the identification of congenital bronchopulmonary malformation (BPM) in comparison with histopathological analysis. CT scans of prenatally diagnosed BPMs from 24 patients with available histology were analysed retrospectively. The CT images were reviewed blinded to histological findings by two radiologists. Specific diagnosis was assigned based on predetermined criteria. The accuracy of CT was evaluated. The agreement rate in CT diagnosis between two radiologists was 100%. In 75% the lesions were located in the lower lobes. An overlap of 71% in CT and histopathological diagnoses was reached. The least matching diagnosis was type 2 CPAM. Contrast enhanced chest CT is very accurate in characterizing the BPM spectrum and provides important information on lesion type and structure.

  9. Large Penile Mass With Unusual Benign Histopathology

    Directory of Open Access Journals (Sweden)

    Nate Johnson

    2015-09-01

    Full Text Available Pseudoepitheliomatous hyperplasia is an extremely rare condition presenting as a lesion on the glans penis in older men. Physical exam without biopsy cannot differentiate malignant from nonmalignant growth. We report a case of large penile mass in an elderly male with a history of lichen sclerosis, highly suspicious for malignancy. Subsequent surgical removal and biopsy demonstrated pseudoepitheliomatous hyperplasia, an unusual benign histopathologic diagnosis with unclear prognosis. We review the literature and discuss options for treatment and surveillance.

  10. Histopathologic grading of anaplasia in retinoblastoma.

    Science.gov (United States)

    Mendoza, Pia R; Specht, Charles S; Hubbard, G Baker; Wells, Jill R; Lynn, Michael J; Zhang, Qing; Kong, Jun; Grossniklaus, Hans E

    2015-04-01

    To determine whether the degree of tumor anaplasia has prognostic value by evaluating its correlation with high-risk histopathologic features and clinical outcomes in a series of retinoblastoma patients. Retrospective clinicopathologic study. The clinical and pathologic findings in 266 patients who underwent primary enucleation for retinoblastoma were reviewed. The histologic degree of anaplasia was graded as retinocytoma, mild, moderate, or severe as defined by increasing cellular pleomorphism, number of mitoses, nuclear size, and nuclear hyperchromatism. Nuclear morphometric characteristics were measured. The clinical and pathologic data of 125 patients were compared using Kaplan-Meier estimates of survival. Fisher exact test and multivariate regression were used to analyze the association between anaplasia grade and high-risk histologic features. Increasing grade of anaplasia was associated with decreased overall survival (P = .003) and increased risk of metastasis (P = .0007). Histopathologic features that were associated with anaplasia included optic nerve invasion (P anaplasia grading as predictors of distant metastasis and death showed that high-risk histopathology was statistically significant as an independent predictor (P = .01 for metastasis, P = .03 for death) but anaplasia was not (P = .63 for metastasis, P = .30 for death). In the absence of high-risk features, however, severe anaplasia identified an additional risk for metastasis (P = .0004) and death (P = .01). Grading of anaplasia may be a useful adjunct to standard histopathologic criteria in identifying retinoblastoma patients who do not have high-risk histologic features but still have an increased risk of metastasis and may need adjuvant therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Histopathology slide projector: a simple improvisation.

    Science.gov (United States)

    Agarwal, Akhilesh K R; Bhattacharya, Nirjhar

    2008-07-01

    The ability to examine histopathology and other hematological slides under microscope is a necessary and important service which should be available in every health facility. The slides need to be projected on to a screen. We describe an inexpensive and easily constructed technique for projecting magnified images of slides using a simple microscope. It is effective both for making observations and for use as a teaching aid.

  12. Collision Repair Campaign

    Science.gov (United States)

    The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.

  13. Retinal detachment repair

    Science.gov (United States)

    ... medicines Problems breathing You may not recover full vision. ... detachments can be repaired. Failure to repair the retina always results in loss of vision to some degree. After surgery, the quality of ...

  14. Histopathologic and immunohistochemical features of Hashimoto thyroiditis.

    Science.gov (United States)

    Amani, H Kazem

    2011-01-01

    Intrathyroid lymphoid tissue is accrued in Hashimoto thyroiditis (HT). Histologically, this acquired lymphoid tissue bears a close resemblance to mucosa-associated lymphoid tissue (MALT) and can evolve to lymphoma. To demonstrate the morphological, and immunohistochemical profiles of Hashimoto thyroiditis and to ascertain the importance of light chain restriction in distinguishing HT with extensive lymphoplasmacytoid infiltrate from MALT lymphoma. We studied histopathologically and immunohistochemically (CD20, CD3, Igk, Igl and cytokeratin) 30 cases of HT for evaluation of the lymphoid infiltrate and the presence of lymphoepithelial lesions (LELs). Distinguishing between early thyroid lymphoma and HT was evaluated by light chain restriction. These findings were compared with two cases of primary thyroid lymphoma. The histopathological findings were characteristic of HT. Immunohistochemistry confirmed inconspicuous, rare B-cell LELs as well as a prominent T-lymphocyte population. Testing for light chain restriction showed polyclonal population of plasma cells. The cases of MALT lymphoma had distinct destructive lymphoepithelial lesions, B-cell immunophenotyping and showed kappa light chain restriction in the plasmacytoid population. Hashimoto thyroiditis differs both histopathologically and immunohistochemically from thyroid lymphoma. In suspicious cases, immunohistochemistry could be helpful in reaching a definitive diagnosis.

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  16. Applying perceptual and adaptive learning techniques for teaching introductory histopathology

    Directory of Open Access Journals (Sweden)

    Sally Krasne

    2013-01-01

    Full Text Available Background: Medical students are expected to master the ability to interpret histopathologic images, a difficult and time-consuming process. A major problem is the issue of transferring information learned from one example of a particular pathology to a new example. Recent advances in cognitive science have identified new approaches to address this problem. Methods: We adapted a new approach for enhancing pattern recognition of basic pathologic processes in skin histopathology images that utilizes perceptual learning techniques, allowing learners to see relevant structure in novel cases along with adaptive learning algorithms that space and sequence different categories (e.g. diagnoses that appear during a learning session based on each learner′s accuracy and response time (RT. We developed a perceptual and adaptive learning module (PALM that utilized 261 unique images of cell injury, inflammation, neoplasia, or normal histology at low and high magnification. Accuracy and RT were tracked and integrated into a "Score" that reflected students rapid recognition of the pathologies and pre- and post-tests were given to assess the effectiveness. Results: Accuracy, RT and Scores significantly improved from the pre- to post-test with Scores showing much greater improvement than accuracy alone. Delayed post-tests with previously unseen cases, given after 6-7 weeks, showed a decline in accuracy relative to the post-test for 1 st -year students, but not significantly so for 2 nd -year students. However, the delayed post-test scores maintained a significant and large improvement relative to those of the pre-test for both 1 st and 2 nd year students suggesting good retention of pattern recognition. Student evaluations were very favorable. Conclusion: A web-based learning module based on the principles of cognitive science showed an evidence for improved recognition of histopathology patterns by medical students.

  17. Situation-dependent repair of DNA damage in yeast

    International Nuclear Information System (INIS)

    von Borstel, R.C.; Hastings, P.J.

    1985-01-01

    The concept of channelling of lesions in DNA into defined repair systems has been used to explain many aspects of induced and spontaneous mutation. The channelling hypothesis states that lesions excluded from one repair process will be taken up by another repair process. This is a simplification. The three known modes of repair of damage induced by radiation are not equivalent modes of repair; they are, instead, different solutions to the problem of replacement of damaged molecules with new molecules which have the same informational content as those that were damaged. The mode of repair that is used is the result of the response to the situation in which the damage takes place. Thus, when the most likely mode of repair does not take place, then the situation changes with respect to the repair of the lesion; the lesion may enter the replication fork and be reparable by another route

  18. Clinical and histopathological observations of autologous bone ...

    African Journals Online (AJOL)

    Jane

    2011-07-06

    Jul 6, 2011 ... technique is currently accepted as a standard method for peripheral nerve repair. ... significant improvement (p<0.05) of the motor and sensory functions in the TG animals as compared ... cells to migrate to the spinal cord, dorsal root ganglia .... marrow was collected from the ilium using a syringe (5 ml) with.

  19. DNA Damage, Repair, and Cancer Metabolism

    Science.gov (United States)

    Turgeon, Marc-Olivier; Perry, Nicholas J. S.; Poulogiannis, George

    2018-01-01

    Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair. (2) Glutamine, aspartate, and other nutrients are essential for de novo nucleotide synthesis, which dictates the availability of the nucleotide pool, and thereby influences DNA repair and replication. (3) Reactive oxygen species, which can increase oxidative DNA damage and hence the load of the DNA-repair machinery, are regulated through different metabolic pathways. Interestingly, while metabolism affects DNA repair, DNA damage can also induce metabolic rewiring. Activation of the DNA damage response (DDR) triggers an increase in nucleotide synthesis and anabolic glucose metabolism, while also reducing glutamine anaplerosis. Furthermore, mutations in genes involved in the DDR and DNA repair also lead to metabolic rewiring. Links between cancer metabolism and DNA damage/DNA repair are increasingly apparent, yielding opportunities to investigate the mechanistic basis behind potential metabolic vulnerabilities of a substantial fraction of tumors. PMID:29459886

  20. Laser-activated solid protein bands for peripheral nerve repair: an vivo study.

    Science.gov (United States)

    Lauto, A; Trickett, R; Malik, R; Dawes, J M; Owen, E R

    1997-01-01

    Severed tibial nerves in rats were repaired using a novel technique, utilizing a semiconductor diode-laser-activated protein solder applied longitudinally across the join. Welding was produced by selective laser denaturation of solid solder bands containing the dye indocyanine green. An in vivo study, using 48 adult male Wistar rats, compared conventional microsuture-repaired tibial nerves with laser solder-repaired nerves. Nerve repairs were characterised immediately after surgery and after 3 months. Successful regeneration with average compound muscle action potentials of 2.5 +/- 0.5 mV and 2.7 +/- 0.3 mV (mean and standard deviation) was demonstrated for the laser-soldered nerves and the sutured nerves, respectively. Histopathology confirmed comparable regeneration of axons in laser- and suture-operated nerves. The laser-based nerve repair technique was easier and faster than microsuture repair, minimising manipulation damage to the nerve.

  1. Histopathological nerve and skeletal muscle changes in rats subjected to persistent insulin-induced hypoglycemia

    DEFF Research Database (Denmark)

    Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Heydenreich, Annette

    2016-01-01

    femoris muscle tissue, as little is known about the response to persistent hypoglycemia in these tissues. Histopathologic changes in insulin-infused animals included axonal degeneration and myofibre degeneration. To our knowledge, this is the first study to show that persistent IIH provokes peripheral...

  2. Leiomyosarcoma of sacrum: imaging and histopathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Ganau, Sergi [Department of Radiology (CDIC), Corporacio Sanitaria Clinic, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona (Spain); Servicio de Radiodiagnostico, Hospital Clinic de Barcelona, Villarroel, 170, 08036 Barcelona (Spain); Tomas, Xavier; Macho, Juan M.; Pomes, Jaume [Department of Radiology (CDIC), Corporacio Sanitaria Clinic, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona (Spain); Mallofre, Carme [Department of Pathology (CDB), Corporacio Sanitaria Clinic, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona (Spain); Combalia, Andreu [Department of Traumatology (ICAL), Corporacio Sanitaria Clinic, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona (Spain)

    2002-07-01

    A rare case of low-grade primary leiomyosarcoma of the sacrum is described in a young woman who suffered from pain in the right sacroiliac region. A lytic sacral mass was observed on conventional radiology and CT studies. Magnetic resonance imaging clearly showed Gd-DTPA enhancement in the entire mass demonstrating its hypervascularity, which was later confirmed by angiography. Histopathology and immunohistochemical results of biopsy and curettage of the lesion confirmed the diagnosis. We report on the features of a rare tumor entity through imaging and diagnostic methods. (orig.)

  3. Histopathologically verified cerebral CT findings in AIDS

    International Nuclear Information System (INIS)

    Tosch, U.; Witt, H.; Iglesias-Rozas, J.R.; Ruf, B.

    1990-01-01

    Computer tomographic and histopathological findings in 55 patients who died of the complications of acquired immunodeficiency syndrome, were reviewed retrospectively. In 23 patients (42%) an increased space of the internal or external cerebral spinal fluid was diagnosed. 20 patients (36%) had focal lesions. We differentiated between single, multiple and ring-shaped lesions with contrast enhancement and hypodense lesions. In 12 cases (22%) no CT abnormalities were found. Focal lesions proved to be secondary to toxoplasmosis in 85%. Single lesions were never caused by toxoplasmosis. (orig.) [de

  4. Repair of DNA damage in Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Evans, D.M.

    1984-01-01

    The repair of DNA lesions in Deinococcus radiodurans was examined with particular reference to DNA excision repair of ultraviolet light (UV) induced pyrimidine dimers. The characteristics of excision repair via UV endonucleases α and β in vivo varied with respect to (a) the substrate range of the enzymes, (b) the rate of repair of DNA damage (c) the requirement for a protein synthesised in response to DNA damage to attenuate exonuclease action at repairing regions. UV endonuclease α is postulated to incise DNA in a different manner from UV endonuclease β thus defining the method of subsequent repair. Several DNA damage specific endonuclease activities independent of α and β are described. Mutations of the uvsA, uvsF and uvsG genes resulted in an increase in single-strand breaks in response to DNA damage producing uncontrolled DNA degradation. Evidence is presented that these genes have a role in limiting the access of UV endonuclease β to DNA lesions. uvsF and uvsG are also shown to be linked to the mtoA gene. Mutation of uvsH and reo-1 produces further distinct phenotypes which are discussed. An overall model of excision repair of DNA damage in Deinococcus radiodurans is presented. (author)

  5. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

    International Nuclear Information System (INIS)

    Campos-Nebel, Marcelo de; Larripa, Irene; Gonzalez-Cid, Marcela

    2008-01-01

    Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by γH2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU-induced DSB

  6. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Campos-Nebel, Marcelo de [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)], E-mail: mnebel@hematologia.anm.edu.ar; Larripa, Irene; Gonzalez-Cid, Marcela [Departamento de Genetica, Instituto de Investigaciones Hematologicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires (Argentina)

    2008-11-10

    Fludarabine (FLU), an analogue of adenosine, interferes with DNA synthesis and inhibits the chain elongation leading to replication arrest and DNA double strand break (DSB) formation. Mammalian cells use two main pathways of DSB repair to maintain genomic stability: homologous recombination (HR) and non-homologous end joining (NHEJ). The aim of the present work was to evaluate the repair pathways employed in the restoration of DSB formed following replication arrest induced by FLU in mammalian cells. Replication inhibition was induced in human lymphocytes and fibroblasts by FLU. DSB occurred in a dose-dependent manner on early/middle S-phase cells, as detected by {gamma}H2AX foci formation. To test whether conservative HR participates in FLU-induced DSB repair, we measured the kinetics of Rad51 nuclear foci formation in human fibroblasts. There was no significant induction of Rad51 foci after FLU treatment. To further confirm these results, we analyzed the frequency of sister chromatid exchanges (SCE) in both human cells. We did not find increased frequencies of SCE after FLU treatment. To assess the participation of NHEJ pathway in the repair of FLU-induced damage, we used two chemical inhibitors of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), vanillin and wortmannin. Human fibroblasts pretreated with DNA-PKcs inhibitors showed increased levels of chromosome breakages and became more sensitive to cell death. An active role of NHEJ pathway was also suggested from the analysis of Chinese hamster cell lines. XR-C1 (DNA-PKcs-deficient) and XR-V15B (Ku80-deficient) cells showed hypersensitivity to FLU as evidenced by the increased frequency of chromosome aberrations, decreased mitotic index and impaired survival rates. In contrast, CL-V4B (Rad51C-deficient) and V-C8 (Brca2-deficient) cell lines displayed a FLU-resistant phenotype. Together, our results suggest a major role for NHEJ repair in the preservation of genome integrity against FLU

  7. Cell segmentation in histopathological images with deep learning algorithms by utilizing spatial relationships.

    Science.gov (United States)

    Hatipoglu, Nuh; Bilgin, Gokhan

    2017-10-01

    In many computerized methods for cell detection, segmentation, and classification in digital histopathology that have recently emerged, the task of cell segmentation remains a chief problem for image processing in designing computer-aided diagnosis (CAD) systems. In research and diagnostic studies on cancer, pathologists can use CAD systems as second readers to analyze high-resolution histopathological images. Since cell detection and segmentation are critical for cancer grade assessments, cellular and extracellular structures should primarily be extracted from histopathological images. In response, we sought to identify a useful cell segmentation approach with histopathological images that uses not only prominent deep learning algorithms (i.e., convolutional neural networks, stacked autoencoders, and deep belief networks), but also spatial relationships, information of which is critical for achieving better cell segmentation results. To that end, we collected cellular and extracellular samples from histopathological images by windowing in small patches with various sizes. In experiments, the segmentation accuracies of the methods used improved as the window sizes increased due to the addition of local spatial and contextual information. Once we compared the effects of training sample size and influence of window size, results revealed that the deep learning algorithms, especially convolutional neural networks and partly stacked autoencoders, performed better than conventional methods in cell segmentation.

  8. The effect of OK-432 (Picibanil) injection on the histopathology of nasal turbinate.

    Science.gov (United States)

    Sengul, S; Kaygusuz, I; Akin, M M; Yalcin, Ş; Karlidag, T; Keles, E; Arslan, I

    2015-12-01

    This study aimed to assess the histopathological effect of OK-432 (Picibanil) on rabbit nasal turbinates. A total of 21 rabbits were divided into 3 treatment groups and various parts of both nasal turbinates were injected with 0.5 ml OK-432, 0.2 ml OK-432 or 0.6 ml saline (control). Bilateral nasal turbinates were later excised and studied under light microscopy to assess any histopathological changes. Animals in the 0.2 ml and 0.5 ml OK-432 groups exhibited mild ciliary loss, goblet cell loss and epithelial damage, and a marked increase in inflammatory cell infiltration, submucosal vascularisation and fibrosis. There was a significant difference in histopathological changes between the two OK-432 treated groups. In addition, each OK-432 treated group had significantly more inflammatory cell infiltration, increased submucosal vascularisation and fibrosis compared with controls. The marked fibrosis observed in OK-432-injected turbinates may be responsible for a reduction in turbinate size.

  9. Histopathological lesions associated with equine periodontal disease.

    Science.gov (United States)

    Cox, Alistair; Dixon, Padraic; Smith, Sionagh

    2012-12-01

    Equine periodontal disease (EPD) is a common and painful condition, the aetiology and pathology of which are poorly understood. To characterise the histopathological lesions associated with EPD, the skulls of 22 horses were assessed grossly for the presence of periodontal disease, and a standard set of interdental tissues taken from each for histopathological examination. Histological features of EPD included ulceration and neutrophilic inflammation of the gingival epithelium. Mononuclear and eosinophilic inflammation of the gingival lamina propria and submucosa was commonly present irrespective of the presence or degree of periodontal disease. Gingival hyperplasia was present to some degree in all horses, and was only weakly associated with the degree of periodontal disease. In all horses dental plaque was present at the majority of sites examined and was often associated with histological evidence of peripheral cemental erosion. Bacteria (including spirochaetes in four horses) were identified in gingival samples by Gram and silver impregnation techniques and were significantly associated with the presence of periodontal disease. This is the first study to describe histological features of EPD, and the first to identify associated spirochaetes in some cases. Histological features were variable, and there was considerable overlap of some features between the normal and diseased gingiva. Further investigation into the potential role of bacteria in the pathogenesis and progression of EPD is warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Repairable-conditionally repairable damage model based on dual Poisson processes.

    Science.gov (United States)

    Lind, B K; Persson, L M; Edgren, M R; Hedlöf, I; Brahme, A

    2003-09-01

    The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

  11. Myrid of histopathological features of malignancy in Xeroderma pigmentosum

    Directory of Open Access Journals (Sweden)

    S Karki

    2013-10-01

    Full Text Available Background: Xeroderma pigmentosum is a rare autosomal recessively inherited disorder affecting 1 in 2,50,000 population. It shows genetic heterogeneity with at least ten different complementation groups identified which have different clinical presentations. They tend to have a more than 1000 fold increased risk of developing cancers in sun-exposed areas as a result of a DNA repair defect. This study presents a myriad of histopathological features of malignancies seen in individuals with this rare. Materials and Methods: Biopsies received from patients with a clinical diagnosis of Xeroderma Pigemntosa at the department of pathology, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, from April 2008 to June 2012 were included in the study. Hematoxylin and eosin stained sections were examined. Clinical history was retrieved from the computer data base of the department. Results: During the study period, a total of eleven cases of Xeroderma pigmentosum presented with a biopsied lesion. All of these were malignant lesions. No benign lesions were seen. The age range of these patients was 6-30years with a mean of 18.8 years. The male to female ratio was 4.5:1. The most common malignancy seen was squamous cell carcinoma 7/11 (63.6% followed by basal cell carcinoma 2/11 (27.2%. A single case presented with basal cell carcinoma of face and melanoma of trunk. The frequently observed site of malignancy was skin of the face followed by conjunctiva. Conclusion: In our population, non melanotic skin cancers affecting the face are more common in young individuals with Xeroderma pigmentosum. DOI: http://dx.doi.org/10.3126/jpn.v3i6.8996   Journal of Pathology of Nepal (2013 Vol. 3, 472-475

  12. Adaptive repair induced by small doses of γ radiation in repair-defective human cells

    International Nuclear Information System (INIS)

    Zasukhina, G.D.; L'vova, G.N.; Vasil'eva, I.M.; Sinel'shchikova, T.A.; Semyachkina, A.N.

    1993-01-01

    Adaptive repair induced by small doses of gamma radiation was studied in repair-defective xeroderma pigmentosum, gout, and homocystinuria cells. The adaptation of cells induced by small doses of radiation was estimated after subsequent exposure to gamma radiation, 4-nitroquinoline-1-oxide, and N-methyl-N-nitro-N-nitrosoguanidine by three methods: (1) by the reduction in DNA breaks; (2) by induction of resistant DNA synthesis; and (3) by increased reactivation of vaccinia virus. The three cell types in response to the three different mutagens revealed differences in the mechanism of cell defense in excision repair, in the adaptive response, and in Weigl reactivation

  13. 'Regular' and 'emergency' repair

    International Nuclear Information System (INIS)

    Luchnik, N.V.

    1975-01-01

    Experiments on the combined action of radiation and a DNA inhibitor using Crepis roots and on split-dose irradiation of human lymphocytes lead to the conclusion that there are two types of repair. The 'regular' repair takes place twice in each mitotic cycle and ensures the maintenance of genetic stability. The 'emergency' repair is induced at all stages of the mitotic cycle by high levels of injury. (author)

  14. Repair of radiation damage in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis.

  15. Repair of radiation damage in mammalian cells

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1981-01-01

    The responses, such as survival, mutation, and carcinogenesis, of mammalian cells and tissues to radiation are dependent not only on the magnitude of the damage to macromolecular structures - DNA, RNA, protein, and membranes - but on the rates of macromolecular syntheses of cells relative to the half-lives of the damages. Cells possess a number of mechanisms for repairing damage to DNA. If the repair systems are rapid and error free, cells can tolerate much larger doses than if repair is slow or error prone. It is important to understand the effects of radiation and the repair of radiation damage because there exist reasonable amounts of epidemiological data that permits the construction of dose-response curves for humans. The shapes of such curves or the magnitude of the response will depend on repair. Radiation damage is emphasized because: (a) radiation dosimetry, with all its uncertainties for populations, is excellent compared to chemical dosimetry; (b) a number of cancer-prone diseases are known in which there are defects in DNA repair and radiation results in more chromosomal damage in cells from such individuals than in cells from normal individuals; (c) in some cases, specific radiation products in DNA have been correlated with biological effects, and (d) many chemical effects seem to mimic radiation effects. A further reason for emphasizing damage to DNA is the wealth of experimental evidence indicating that damages to DNA can be initiating events in carcinogenesis

  16. Repair kinetics in tissues

    International Nuclear Information System (INIS)

    Thames, H.D.

    1989-01-01

    Monoexponential repair kinetics is based on the assumption of a single, dose-independent rate of repair of sublethal injury in the target cells for tissue injury after exposure to ionizing radiation. Descriptions of the available data based on this assumption have proved fairly successful for both acutely responding (skin, lip mucosa, gut) and late-responding (lung, spinal cord) normal tissues. There are indications of biphasic exponential repair in both categories, however. Unfortunately, the data usually lack sufficient resolution to permit unambiguous determination of the repair rates. There are also indications that repair kinetics may depend on the size of the dose. The data are conflicting on this account, however, with suggestions of both faster and slower repair after larger doses. Indeed, experiments that have been explicitly designed to test this hypothesis show either no effect (gut, spinal cord), faster repair after higher doses (lung, kidney), or slower repair after higher doses (skin). Monoexponential repair appears to be a fairly accurate description that provides an approximation to a more complicated picture, the elucidation of whose details will, however, require very careful and extensive experimental study. (author). 30 refs.; 1 fig

  17. [Histopathological and immunohistochemical studies on mucous cysts].

    Science.gov (United States)

    Kuroda, N

    1989-01-01

    The present study investigated the histopathology, histochemistry of mucopolysaccharides, and immunohistochemistry of oral mucous cysts. The materials were obtained from ninety cases that were histopathologically diagnosed as oral mucous cysts at the Department of Oral Pathology, Meikai University School of Dentistry. Mucopolysaccharide staining was done with PAS, alcian blue (AB, pH 2.5) and high iron diamine (HID). Immunohistochemical studies were focused on secretory component (SC), lactoferrin (Lf), alpha-amylase (Am), IgA, lysozyme (Ly), and keratin (Kr). The following results were obtained: 1. Histopathological findings. (1) Retention and/or retention-like type cysts occurred in was twenty-six cases and the extravasation type in sixty-four cases. (2) Cases showing epithelial lining of the cystic wall were only eight in number, and many cystic walls were contained granulation tissue (fifty cases). (3) As for inflammation of the cystic wall, the degree was slight, and infiltrated cells were mainly macrophages (so-called mucinophages) and lymphocytes. (4) Regarding adjoining salivary glands, acinar cells showed atrophic changes, and hypertrophy of mucous acinar cells was evident. Many ducts showed dilatation, and stromal connective tissue showed fibrosis and hyalinization. 2. Histochemical findings on mucopolysaccharides. (1) Mucous materials in cystic cavity, mucous acinar cells, and secretory materials in ductal lumens were intensely stained by PAS and AB. But stainability with AB was less than that with PAS staining. Serous acinar cells and ductal epithelium were negative to PAS and AB staining. (2) Stainability of the above with HID was less than at with PAS or AB. Cystic walls were not stained by HID. Mucous acinar cells reactive with HID were intensely stained, but the number of the positive cells was limited when compared with the numbers of PAS-and AB-positive cells. 3. Immunohistochemical findings. (1) As for mucous materials in the cystic cavity

  18. Cellular response of healing tissue to DegraPol tube implantation in rabbit Achilles tendon rupture repair: an in vivo histomorphometric study.

    Science.gov (United States)

    Buschmann, Johanna; Meier-Bürgisser, Gabriella; Bonavoglia, Eliana; Neuenschwander, Peter; Milleret, Vincent; Giovanoli, Pietro; Calcagni, Maurizio

    2013-05-01

    In tendon rupture repair, improvements such as higher primary repair strength, anti-adhesion and accelerated healing are needed. We developed a potential carrier system of an electrospun DegraPol tube, which was tightly implanted around a transected and conventionally sutured rabbit Achilles tendon. Histomorphometric analysis of the tendon tissue 12 weeks postoperation showed that the tenocyte density, tenocyte morphology and number of inflammation zones were statistically equivalent, whether or not DegraPol tube was implanted; only the collagen fibres were slightly less parallelly orientated in the tube-treated case. Comparison of rabbits that were operated on both hind legs with ones that were operated on only one hind leg showed that there were significantly more inflammation zones in the two-leg cases compared to the one-leg cases, while the implantation of a DegraPol tube had no such adverse effects. These findings are a prerequisite for using DegraPol tube as a carrier system for growth factors, cytokines or stem cells in order to accelerate the healing process of tendon tissue. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Histopathological audit of salivary gland neoplasms

    International Nuclear Information System (INIS)

    Memon, J.M.; Sheikh, B.

    2014-01-01

    Salivary gland neoplasms are uncommon but important presentation to general surgeons. Objective: To analyze the relative frequency and distribution of Salivary gland neoplasms in our division. Setting: Department of surgery and pathology, Peoples Medical University hospital and GMMMC hospital Sukkur. Study design: Descriptive (case series) Subjects and methods: A total of 40 patients registered for salivary gland tumors from oct 2008 to 0ct 2013 were included in the study. A thorough history, clinical examination, routine haematological and biochemical studies were done in all patients. FNAC was done in all cases. All patients were subjected to surgical intervention on standard rules. Each resected specimen was sent for histopathology. Information about age, gender and tumor location was obtained from clinical record and frequency of different neoplasms was studied from histopathological report. All data was collected on especially designed proforma. Data analysis was done using spss version 17. Results: A total of 40 patients were registered for salivary gland neoplasms. 28 patients (70%) had parotid lesions, 10 patients (25%) had submandibular gland involvement and 2 patients ( 5%) had minor salivary gland tumors. Patients were between 15 - 80 years of age( mean age =34.7 years) 24 patients(60%) were male and 16 (40%) were female,with male to female ratio of 1.5:1.32 . 22 (80%) had benign lesions and 8 patients (20%) had malignant lesions. Pleomorphic adenoma was the most common benign tumor affecting the parotid gland. Adenocarcinoma represented as the most prevelant parotid malignancy. Benign neoplasms occurred in third and fourth decades of life and malignant neoplasms were diagnosed in sixth and seventh decades of life. Conclusion:Salivary gland neoplasms are uncommon but they have occasioned much interest and debate because of broad histological spectrum. The data presented in this study is corroborated with most of the studied literature worldwide. (author)

  20. Metastatic myxoid liposarcomas: imaging and histopathologic findings

    International Nuclear Information System (INIS)

    Sheah, Kenneth; Ouellette, Hugue A.; Torriani, Martin; Kattapuram, Susan; Bredella, Miriam A.; Nielsen, G.P.

    2008-01-01

    The objective was to describe the imaging and histopathologic characteristics of metastatic myxoid liposarcomas. This retrospective study was approved by the institutional review board and complied with HIPAA guidelines. The study group comprised 12 patients with metastatic myxoid liposarcoma who underwent MRI, CT, or FDG-PET. The location and imaging characteristics of the metastatic lesions were recorded, and the histopathology of all metastatic lesions was reviewed. There were 23 histologically proven metastases in 12 patients. Based on imaging criteria, there were 41 metastases. The mean time from the diagnosis of primary tumor to the first metastasis was 4.4 years. Sixty-seven percent of patients had bone and soft tissue metastases, 33% had pulmonary metastases, 33% had liver metastases, 25% had intra-abdominal, and 16% retroperitoneal metastases. CT demonstrated well-defined lobulated masses with soft tissue attenuation in all cases, without macroscopic fat component. In cases of osseous metastases, CT showed mixed lytic and sclerotic foci, with bone destruction in advanced cases. MRI demonstrated fluid-like signal intensity with mild heterogeneous enhancement in cases of soft tissue metastases. In osseous metastases, MRI showed avid heterogeneous enhancement. FDG-PET showed no significant FDG uptake for all metastases. MRI was the most useful imaging modality for osseous and soft tissue metastases. Myxoid liposarcomas are soft tissue sarcomas, with a high prevalence of extrapulmonary metastases. The bones and soft tissues were the most common site of involvement, followed by the lungs and liver. MRI was the most sensitive modality in the detection of osseous and soft tissue metastases, and is the recommended modality for the diagnosis and follow-up of bone and soft tissue involvement. (orig.)

  1. Macrophage diversity in renal injury and repair

    NARCIS (Netherlands)

    Ricardo, Sharon D.; van Goor, Harry; Eddy, Allison A.

    Monocyte-derived macrophages can determine the outcome of the immune response and whether this response contributes to tissue repair or mediates tissue destruction. In addition to their important role in immune-mediated renal disease and host defense, macrophages play a fundamental role in tissue

  2. Snowmobile Repair. Teacher Edition.

    Science.gov (United States)

    Hennessy, Stephen S.; Conrad, Rex

    This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…

  3. DNA repair genes

    International Nuclear Information System (INIS)

    Morimyo, Mitsuoki

    1995-01-01

    Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)

  4. Faulty DNA-polymerase δ/ε-mediated excision-repair in response to gamma-radiation or ultraviolet-light in P53-deficient fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome

    International Nuclear Information System (INIS)

    Mirzayans, R.; Enns, L.; Dietrich, K.; Barley, R.D.C.; Paterson, M.C.; Alberta Univ., Edmonton, AB; Alberta Univ., Edmonton, AB

    1996-01-01

    Dermal fibroblast strains cultured from affected members of a cancer-prone family with Li-Fraumeni syndrome (LFS) harbor a point mutation in one allele of the p53 tumor suppressor gene, resulting in loss of normal p53-deficient strains to carry out the long-patch mode of excision repair, mediated by DNA polymerases delta and epsilon, after exposure to Co-60 gamma radiation or far ultraviolet (UV) (chiefly 254 mm) light. Repair was monitored by incubation of the irradiated cultures in the presence of aphidicolin (ape) or 1-beta-D-arabinofuranosylcytosine (araC), each a specific inhibitor of long-patch repair, followed by measurement of drug-induced DNA strand breaks (reflecting non-ligated strand incision events) by alkaline surcrose velocity sedimentation. The LFS strains displayed deficient repair capacity in response to both gamma rays and UV light. The repair anomaly in UV-irradiated LFS cultures was manifested not only in the overall genome, but also in the transcriptionally active, preferentially repaired c-myc gene. Using autoradiography we also assessed unscheduled DNA synthesis (UDS) after UV irradiation and found this conventional measure of repair replication to be deficient in LFS strains. Moreover, both ape and araC decreased the level of UV-induced UDS by similar to 75% in normal cells, but each had only a marginal effect on LFS cells. We further demonstrated that the LFS strains are impaired in the recovery of both RNA and replicative DNA syntheses after UV treatment, two molecular anomalies of the DNA repair deficiency disorders xeroderma pigmentosum and Cockayne's syndrome. Together these results imply a critical role for wild-type p53 protein in DNA polymerase delta/epsilon-mediated excision repair, both the mechanism operating on the entire genome and that acting on expressed genes. (Author)

  5. Repair-modification of radiodamaged genes

    International Nuclear Information System (INIS)

    Volpe, P.; Institute of Experimental Medicine, Rome; Eremenko, T.

    1995-01-01

    It is proposed that through repair-modification, the modified base 5mC may have facilitated the divergent evolution of coding (hypomethylated exon) and uncoding (hypermethylated promoter and intron) sequences in eukaryotic genes. The radioinduced repair patches appearing in regions lacking 5mC are fully reconstructed by excision-repair, whereas those appearing in regions containing 5mC are incompletely reconstructed by this conventional mechanism. Such a second class of repair patches may, however, become fully reconstructed, in the S phase, by repair-modification. In fact, while DNA polymerase β - which is a key enzyme of excision-repair - is active through the whole interphase. DNA methylase - which is responsible for post-synthetic DNA modification - is essentially active in S. Uncoupling of these two enzyme systems, outside S, might explain why in unsynchronised cells repair patches of non-replicating strands are hypomethylated when compared with specific methylation of replicating strands. In other words, excision-repair would always be able to re-establish the primary ATGC language of both damaged unmethylated and methylated regions, while repair-modification would be able to re-establish the modified ATGC(5mC) language of the damaged methylated regions, only in S, but not in G 1 or G 2 . In these two phases, when DNA methylation is inversely correlated with pre-mRNA transcription (as in the case of many tissue-specific genes), such demethylation might induce a silent transcriptional unit to become active. (Author)

  6. DNA replication and repair in Tilapia cells

    International Nuclear Information System (INIS)

    Yew, F.H.; Chang, L.M.

    1984-01-01

    The effect of ultraviolet radiation on a cell line established from the warm water fish Tilapia has been assessed by measuring the rate of DNA synthesis, excision repair, post-replication repair and cell survival. The cells tolerate ultraviolet radiation better than mammalian cells with respect to DNA synthesis, post-replication repair and cell survival. They are also efficient in excision repair, which in other fish cell lines has been found to be at a low level or absent. Their response to the inhibitors hydroxyurea and 1-β-D-arabinofuranosylcytosine is less sensitive than that of other cell lines, yet the cells seem to have very small pools of DNA precursor. (author)

  7. An audit of colorectal cancer histopathology reports in a Tertiary ...

    African Journals Online (AJOL)

    Objective: To audit the completeness of histopathologic reports of Colorectal Cancer for prognostic information in a tertiary care hospital in the light of the minimum reporting standards for colorectal cancer resections recently proposed for use in Nigeria. Material and Methods: Twenty–five histopathology reports of colorectal ...

  8. The accuracy of extended histopathology to detect immunotoxic chemicals

    NARCIS (Netherlands)

    Germolec, D.R.; Kashon, M.; Nyska, A.; Kuper, C.F.; Portier, C.; Kommineni, C.; Johnson, K.A.; Luster, M.I.

    2004-01-01

    The accuracy of extended histopathology to detect immunotoxic chemicals in female B6C3F1 mice was evaluated under the auspices of the National Toxicology Program (NTP). A workgroup was formed consisting of four pathologists who conducted extended histopathological evaluation of lymphoid tissues

  9. Cell factory-derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits.

    Science.gov (United States)

    Gupta, Ankur; Bhat, Sumrita; Chaudhari, Bhushan P; Gupta, Kailash C; Tägil, Magnus; Zheng, Ming Hao; Kumar, Ashok; Lidgren, Lars

    2017-06-01

    We have explored the potential of cell factory-derived bioactive molecules, isolated from conditioned media of primary goat chondrocytes, for the repair of subchondral cartilage defects. Enzyme-linked immunosorbent assay (ELISA) confirms the presence of transforming growth factor-β1 in an isolated protein fraction (12.56 ± 1.15 ng/mg protein fraction). These bioactive molecules were used alone or with chitosan-agarose-gelatin cryogel scaffolds, with and without chondrocytes, to check whether combined approaches further enhance cartilage repair. To evaluate this, an in vivo study was conducted on New Zealand rabbits in which a subchondral defect (4.5 mm wide × 4.5 mm deep) was surgically created. Starting after the operation, bioactive molecules were injected at the defect site at regular intervals of 14 days. Histopathological analysis showed that rabbits treated with bioactive molecules alone had cartilage regeneration after 4 weeks. However, rabbits treated with bioactive molecules along with scaffolds, with or without cells, showed cartilage formation after 3 weeks; 6 weeks after surgery, the cartilage regenerated in rabbits treated with either bioactive molecules alone or in combinations showed morphological similarities to native cartilage. No systemic cytotoxicity or inflammatory response was induced by any of the treatments. Further, ELISA was done to determine systemic toxicity, which showed no difference in concentration of tumour necrosis factor-α in blood serum, before or after surgery. In conclusion, intra-articular injection with bioactive molecules alone may be used for the repair of subchondral cartilage defects, and bioactive molecules along with chondrocyte-seeded scaffolds further enhance the repair. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Histopathological correlations to ureteral lesions visualized during ureteroscopy

    DEFF Research Database (Denmark)

    Lildal, Søren Kissow; Sørensen, Flemming Brandt; Andreassen, Kim Hovgaard

    2017-01-01

    PURPOSE: To correlate ureteral lesions visualized during ureteroscopy with histopathological findings.MATERIALS AND METHODS: Ureteral access sheaths (UAS) sized 13/15 Fr. were inserted bilaterally in 22 laboratory pigs. During retraction of the UAS with a semirigid ureteroscope inside, ureteral......) stained. Histopathological scoring of ureteral wall lesions was subsequently performed according to PULS.RESULTS: In 72.1% of ureters, the highest histopathological score was at least 1 grade higher than the highest endoscopic PULS score. For 12 (27.9%) lesions, the difference was 2 scores higher......, and for 1 (2.3%), it was 3 scores higher. The histopathological PULS grade was higher than the endoscopical PULS grade at all minimum, quartile, and maximum scores. There was a significant difference in the distribution of highest lesional scores between the endoscopic and histopathological PULS (p = 0...

  11. DNA repair and radiation sensitivity in mammalian cells

    International Nuclear Information System (INIS)

    Chen, D.J.C.; Stackhouse, M.; Chen, D.S.

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population

  12. Mutagenic DNA repair in enterobacteria

    International Nuclear Information System (INIS)

    Sedgwick, S.G.; Chao Ho; Woodgate, R.

    1991-01-01

    Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium u mu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umuDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention

  13. Repairing fuel for reinsertion

    International Nuclear Information System (INIS)

    Krukshenk, A.

    1986-01-01

    Eqiupment for nuclear reactor fuel assembly repairing produced by Westinghouse and Brawn Bovery companies is described. Repair of failed fuel assemblies replacement of defect fuel elements gives a noticeable economical effect. Thus if the cost of a new fuel assembly is 450-500 thousand dollars, the replacement of one fuel element in it costs approximately 40-60 thousand dollars. In simple cases repairing includes either removal of failed fuel elements from a fuel assembly and its reinsertion with the rest of fuel elements into the reactor core (reactor refueling), or replacement of unfailed fuel elements from one fuel assembly to a new one (fuel assembly overhaul and reconditioning)

  14. Histopathological development of equine cutaneous papillomas.

    Science.gov (United States)

    Hamada, M; Oyamada, T; Yoshikawa, H; Yoshikawa, T; Itakura, C

    1990-05-01

    The histopathological development of equine cutaneous papillomas was studied in 78 warts naturally occurring in 50 one to 3-year-old Thoroughbred or Arab horses and in 54 warts experimentally induced in three 2-year-old Thoroughbreds. Lesions in the natural cases were categorized into three phases, growth, development and regression. Main lesions of the growing phase were marked hyperplasia of the basal cells and mild to moderate acanthosis, hyper- and parakeratosis with a few intranuclear inclusion bodies (IIB) which were positive with anti-bovine papillomavirus serum. In the developing phase, there was prominent acanthosis with cellular swelling and fusion, and marked hyper- and parakeratosis. Many IIB were also present in swollen or degenerative prickle cells and granular cells, with a high degree of parakeratosis in keratinocytes. In the regressing phase, epidermal layers were almost normal with only slight hyperplastic change. However, there was rete peg proliferation downward into the dermis with moderate proliferation of fibroblasts and collagen fibres. In addition, in 10 spontaneous and one experimental wart, the lesions were fibropapillomas and this has never been described in horses previously. It was concluded that papillomas were initiated by basal cell hyperplasia without viral antigen production, with formation of acanthosis and hyper- and parakeratosis with IIB production. These findings were confirmed by examination of the experimental cases on the basis of the gross diameter of the warts.

  15. Histopathologic study on irradiated human developing teeth

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Yasunori (Iwate Medical Coll., Morioka (Japan). School of Dentistry)

    1982-12-01

    The patient was a 7-year-old boy who had been suffering from Ewing's sarcoma originating in the mandible. Irradiation with 8000 rad of Linac was performed on the mandible prior to mandibulectomy. The results of the histopathologic examination of the teeth including resected material were as follows: 1. Although the tumor tissue was not found in the resected material, complete resoption of the medullar trabecular bone with fibrosis was noted in the area between the first molar region and the mandibular ramus. 2. The first and the second premolar teeth were in the early stage of root formation, and conglomerates of dysplastic dentin were formed in the proliferative zones. This dysplastic dentin was surrounded by loose fibrous connective tissues. 3. The dysplastic dentin showed low mineralization, embedded irregular arranged-fibrous tissue matrix and scattered various-sized lacunae containing a few tiny and pyknotic cells. 4. Irregularly arranged odontoblasts with a pyknotic appearance were found along the tubular dentin, but diffuse fibrosis occurred in the pulpal tissues. 5. The first molar tooth had completed its root formation. Various amounts of osteodentin were formed at the secondary dentin layer. Inner-resorption of dentin and fibrosis of the pulpal tissue were also found. These changes concerning the first molar tooth were also due to the effects of irradiation. 6. The second molar tooth was resorbed by tumor infiltration, and dysplastic dentin was on the resorbed surface of the dentin.

  16. Histopathological studies on the irradiated brain tumors

    International Nuclear Information System (INIS)

    Narita, Tadao

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy. (J.P.N.)

  17. Menstruation and suicide: a histopathological study.

    Science.gov (United States)

    Leenaars, Antoon A; Dogra, T D; Girdhar, Shalini; Dattagupta, S; Leenaars, Lindsey

    2009-01-01

    Previous research, albeit limited, has reported mixed findings on the impact of menstruation cycle on suicidal behavior. The contribution of menstruation to completed suicide is also controversial; the studies are, in fact, very limited and are not carefully designed. To examine whether the menstruation cycle impacts on suicide. In order to explore this relationship, 56 autopsies on completed suicides in females were performed and matched to a control group of 44 females who had died from other causes, at the All India Institute of Medical Sciences in New Delhi. Histopathological examination, a method of collecting tissue from the uterus through biopsy, was used to determine the stage of the menstrual cycle. The results show that 25% of women who had died by suicide were menstruating at the time, compared to 4.5% of the control group; this is statistically (chi2) significant at the p Menstruation in the women who completed suicide, compared to a control group, appeared to have an association, though more research is warranted. Not only there are serious methodological problems in the study of menstruation and suicide (largely because of problematic tissue storage and examination), but also because of the need to understand the impact within a larger psychological, social, and cultural frame.

  18. Myelodysplastic syndromes: histopathology as prognostic factor

    Directory of Open Access Journals (Sweden)

    Romeo Maura

    2001-01-01

    Full Text Available Bone marrow biopsy allows evaluation of cellularity, abnormal localization of immature precursors and fibrosis in myelodysplastic syndrome. It has been considered important to make diagnosis and prognosis of this disorder. The object of this study evaluated the influence of histopathological parameters, such as cellularity, erythroid/myeloid ratio, abnormal localization of immature precursors and marrow fibrosis, on survival of myelodysplastic syndrome patients. Forty-six patients, admitted from April 1985 to June 1998, and diagnosed as being myelodysplastic syndrome according to French-American-British criteria, were selected. There were 20 males and 26 females, with median age of 61 years. Forty-six bone marrow smears and 36 trephine biopsies were reviewed. Mean survival of hypocellular cases was 64.8 months and of hyper and normocellular cases was 31.8 months. Patients with predominance of erythroid hyperplasia had mean survival of 50.8 months, greater than those with predominance of myeloid hyperplasia (20.3 months. There was no statistical difference in survival of patients with or without abnormal localization of immature precursors and with or without marrow fibrosis. Bone marrow biopsy is a useful tool for the identification of parameters that influence prognosis in myelodysplastic syndrome. Hypocellularity and erythroid hyperplasia were correlated with longer survival while myeloid hyperplasia with poorer survival.

  19. Histopathological studies on the irradiated brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Narita, T [Gunma Univ., Maebashi (Japan).School of Medicine

    1980-01-01

    Of 43 cases of irradiated brain tumor, histological findings showed extensive necrosis or disappearance of the neoplasm, considered to be attributable to radiation treatment, in 30 (70%). Extensive necrosis of the tumor in areas exposed to radiation was found in 16 treated cases (37.2%). The histopathology of massive necrosis was that of simple coagulative necrosis, sometimes with marked vascular alterations and extravasation of fibrinoid material into the necrotic tissue. Necrosis was almost always incomplete, and foci of residual tumors were found at the periphery of the tumors. The terminal picture in cases of massive necrosis was often that of widespread intra- and extracranial metastasis. Almost complete disappearance of the tumor was observed in some cases with subsequent diffuse degenerative changes in the brain parenchyma exposed to radiation. In 5 cases of irradiated tumors, autopsy findings suggested that the growth of the primary tumor might have been restricted. And in 5 cases tumor cytology revealed the marked presence of a large number of multinucleated, bizarre giant cells with evidence of degeneration in both the cytoplasm and the nucleus. Multifocal necrosis of the brain, with axonal swelling and sponginess of the tissue, was observed in two patients following combined radiation and antineoplastic chemotherapy. Diffuse loss and degeneration of nerve cells of the cerebral cortex in pseudo-laminar fashion was observed in 7 patients with or without bilateral necrosis of the globus pallidus. Histological findings revealed typical anoxic encephalopathy.

  20. Nucleotide excision repair in differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Wees, Caroline van der [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Jansen, Jacob [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Laarse, Arnoud van der [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert van [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands)]. E-mail: l.mullenders@lumc.nl

    2007-01-03

    Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions and operates via two NER subpathways, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Although detailed information is available on expression and efficiency of NER in established mammalian cell lines, little is known about the expression of NER pathways in (terminally) differentiated cells. The majority of studies in differentiated cells have focused on repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4PP) because of the high frequency of photolesions at low level of toxicity and availability of sensitive technologies to determine photolesions in defined regions of the genome. The picture that emerges from these studies is blurred and rather complex. Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression. This repair phenotype is clearly different from human terminal differentiated neurons. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. In contrast, in intact rat spermatogenic cells repair was very inefficient at the genome overall level and in transcriptionally active genes indicating that GGR and TCR are non-functional. Also, non-differentiated mouse embryonic stem (ES) cells exhibit low levels of NER after UV irradiation. However, the mechanisms that lead to low NER activity are clearly different: in differentiated spermatogenic cells differences in chromatin compaction and sequestering of NER proteins may underlie the lack of NER activity in pre-meiotic cells, whereas in non-differentiated ES cells NER is impaired by a strong apoptotic response.

  1. DNA Repair Systems

    Indian Academy of Sciences (India)

    DNA molecule which makes it ideal for storage and propagation of genetic information. ... of these errors are broadly referred to as DNA repair. DNA can ... changes occur in the human genome per day. ..... nails, frequent physical and mental.

  2. Brain aneurysm repair - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000123.htm Brain aneurysm repair - discharge To use the sharing features ... this page, please enable JavaScript. You had a brain aneurysm . An aneurysm is a weak area in ...

  3. Ventral hernia repair

    Science.gov (United States)

    ... incarcerated) in the hernia and become impossible to push back in. This is usually painful. The blood supply ... you are lying down or that you cannot push back in. Risks The risks of ventral hernia repair ...

  4. Omphalocele repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100033.htm Omphalocele repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Omphalocele is an abdominal wall defect at the base ...

  5. Chronic pain after childhood groin hernia repair

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Kehlet, Henrik

    2007-01-01

    BACKGROUND: In contrast to the well-described 10% risk of chronic pain affecting daily activities after adult groin hernia repair, chronic pain after childhood groin hernia repair has never been investigated. Studies of other childhood surgery before the age of 3 months suggest a risk of increased...... pain responsiveness later in life, but its potential relationship to chronic pain in adult life is unknown. METHODS: This was a nationwide detailed questionnaire study of chronic groin pain in adults having surgery for a groin hernia repair before the age of 5 years (n = 1075). RESULTS: The response...... rate was 63.3%. In the 651 patients available for analysis, pain from the operated groin was reported by 88 (13.5%) patients whereof 13 (2.0%) patients reported frequent and moderate or severe pain. Pain occurred primarily when exercising sports or other leisure activities. Patients operated on before...

  6. Celebrating DNA's Repair Crew.

    Science.gov (United States)

    Kunkel, Thomas A

    2015-12-03

    This year, the Nobel Prize in Chemistry has been awarded to Tomas Lindahl, Aziz Sancar, and Paul Modrich for their seminal studies of the mechanisms by which cells from bacteria to man repair DNA damage that is generated by normal cellular metabolism and stress from the environment. These studies beautifully illustrate the remarkable power of DNA repair to influence life from evolution through disease susceptibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 46 CFR Sec. 2 - Submission of repair entries.

    Science.gov (United States)

    2010-10-01

    ... MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY GENERAL AGENT'S RESPONSIBILITY IN CONNECTION WITH FOREIGN REPAIR CUSTOM'S ENTRIES Sec. 2 Submission of repair entries. At the... with the District Director of Customs as defined in 19 CFR 1.1(d) an affidavit on Custom's Form 3417...

  8. Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

    Directory of Open Access Journals (Sweden)

    Brett M. Lowenthal

    2017-01-01

    Full Text Available Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1 and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

  9. Breast multidetector-row CT with histopathologic correlation

    International Nuclear Information System (INIS)

    Takeuchi, Makiko; Yamashita, Akiyoshi; Ohgi, Kazuyuki; Kobori, Kenichi; Furukawa, Takashi

    2004-01-01

    The purpose of this study was to evaluate the correlation between multidetector-row CT (MDCT) and histopathologic findings using the same MDCT image as the histopathologic cross-section. MDCT with contrast enhancement was performed in 10 patients with breast cancers (8 invasive ductal carcinomas, one invasive lobular carcinoma, and one non-invasive ductal carcinoma). We tried to reconstruct multiplanar reconstructions (MPR) in the same plane as the histopathologic cross-section, and we evaluated the histopathologic findings of the false-positive lesions. In all cases, we obtained the same MDCT image as the histopathologic cross-section. There were 10 main lesions and 18 other lesions. In the other lesions, we found no false-negative lesions and 11 false-positive lesions. False-positive lesions included periductal fibrosis, cystic change, duct papillomatosis, sclerosing adenosis, fibroadenoma, and others. Using MDCT of the breast, it is possible to obtain good correlation between CT images and histopathologic findings. MDCT is thought to be useful in the evaluation CT findings on the basis of histopathologic evidence. (author)

  10. Sclerosteosis involving the temporal bone: histopathologic aspects.

    Science.gov (United States)

    Nager, G T; Hamersma, H

    1986-01-01

    Sclerosteosis is a rare, potentially lethal, autosomal recessive, progressive craniotubular sclerosing bone dysplasia with characteristic facial and skeletal features. The temporal bone changes include a marked increase in overall size, extensive sclerosis, narrowing of the external auditory canal, and severe constriction of the internal auditory meatus, fallopian canal, eustachian tube, and middle ear cleft. Attenuation of the bony canals of the 9th, 10th, and 11th cranial nerves, reduction in size of the internal carotid artery, and severe obliteration of the sigmoid sinus and jugular bulb also occur. Loss of hearing, generally bilateral, is a frequent symptom. It often manifests in early childhood and initially is expressed as sound conduction impairment. Later, a sensorineural hearing loss and loss of vestibular nerve function often develop. Impairment of facial nerve function is another feature occasionally present at birth. In the beginning, a unilateral intermittent facial weakness may occur which eventually progresses to a bilateral permanent facial paresis. The histologic examination of the temporal bones from a patient with sclerosteosis explains the mechanisms involved in the progressive impairment of sound conduction and loss of cochlear, vestibular, and facial nerve function. There is a decrease of the arterial blood supply to the brain and an obstruction of the venous drainage from it. The histopathology reveals the obstacles to decompression of the middle ear cleft, ossicular chain, internal auditory and facial canals, and the risks, and in many instances the contraindications, to such procedures. On the other hand, decompression of the sigmoid sinus and jugular bulb should be considered as an additional life-saving procedure in conjunction with the prophylactic craniotomy recommended in all adult patients.

  11. Histopathological evaluation of carcinoma of breast

    Directory of Open Access Journals (Sweden)

    R Pathak

    2016-03-01

    Full Text Available Background: Carcinoma of breast has become the major public health problem among females in developing as well as developed countries. InNepal it comprises 6% of total cancers cases and often diagnosed at advanced stage. Surgical removal or modified radical mastectomy (MRM is the most commonly used tools for disease management. The objective of this study is to identify the clinical, macroscopic and microscopic features of MRM specimens.Materials and methods: This prospective cross-sectional study was carried out at Department of Pathology, Bhaktapur Cancer Hospital, Bhaktapur, Nepal. Macroscopic and microscopic examination provided the tumor size, stage, grade, lymph node status, lympho-vascular invasion and perineural invasion. Data were collected and analyzed using SPSS 16.Results: The study comprised 112 breast cancer patients of which 109 (97.3% were females and 3 (2.7% were males. Invasive ductal carcinoma no specific type was the most common type of breast carcinoma. (84 cases accounting 75% of total cases. Carcinoma with medullary features was second most common (6 cases comprising 5.4% cases followed by lobular, papillary, apocrine, mucinious and NST mixed types. Grade II tumors were most frequent grade observed in 76.79% cases followed by Grade I (12.50% and Grade III (10.71%.Conclusion: As a conclusion invasive ductal carcinoma was the most common histological type breast cancer and the tumors were found at T2 and N3 stage i.e maximum at grade II. Our study provides prognostic significance of histo-pathological information in breast cancer management.

  12. Flexible Plug Repair for Shuttle Wing Leading Edge

    Science.gov (United States)

    Camarda, Charles J.; Sikora, Joseph; Smith, Russel; Rivers, H.; Scotti, Stephen J.; Fuller, Alan M.; Klacka, Robert; Reinders, Martin; Schwind, Francis; Sullivan, Brian; hide

    2012-01-01

    In response to the Columbia Accident Investigation Board report, a plug repair kit has been developed to enable astronauts to repair the space shuttle's wing leading edge (WLE) during orbit. The plug repair kit consists of several 17.78- cm-diameter carbon/silicon carbide (C/SiC) cover plates of various curvatures that can be attached to the refractory carbon-carbon WLE panels using a TZM refractory metal attach mechanism. The attach mechanism is inserted through the damage in the WLE panel and, as it is tightened, the cover plate flexes to conform to the curvature of the WLE panel within 0.050 mm. An astronaut installs the repair during an extravehicular activity (EVA). After installing the plug repair, edge gaps are checked and the perimeter of the repair is sealed using a proprietary material, developed to fill cracks and small holes in the WLE.

  13. Characteristics of repair following very low doses

    International Nuclear Information System (INIS)

    Braby, L.A.; Metting, N.F.; Nelson, J.M.

    1987-01-01

    The effects of ionizing radiation on living systems being with the physical processes of energy deposition and develop through many stages of chemical reaction and biological response. The modeling effort attempts to organize the available data and theories of all of these stages into self-consistent models that can be compared and tested. In some cases, important differences among models result in only small differences in cell survival within the ranges of dose and dose rate that are normally investigated. To overcome this limitation, new ways of irradiating cells at extremes of dose rate, or ways of evaluating the effects of very small doses, are developed. Mathematical modeling and cellular studies complement each other. It has recently been found that some mechanisms are not adequate to account for the interaction of dose and repair time as they affect the reproductive survival of plateau-phase Chinese hamster ovary (CHO) cells. Repair of radiation-induced cellular damage plays a central role in the survival of cells exposed to doses of 1 Gy or more. This repair is responsible for the dose rate, split-dose and delayed plating effect and can be evaluated. Because split-dose and dose-rate experiments involve repair during irradiation and delayed plating experiments involve repair after irradiation is completed, it was originally thought that different repair processes were involved. It is now clear that this is not necessarily the case. Appropriately designed models can account for observed effects at conventional doses (1 Gy or more) whether they assume all damage is lethal unless repaired or some damage is innocuous unless it interacts with additional damage. The fact that the survival following a plating delay is always less than the survival following immediate plating at low doses indicates that the damage produced is probably not potentially lethal

  14. Variability Study between Pap Smear, Colposcopy and Cervical Histopathology Findings

    International Nuclear Information System (INIS)

    Akhter, S.; Bari, A.; Hayat, Z.

    2015-01-01

    Objective: To determine the agreement/variability between colposcopic findings, Pap smear cytology and histopathological diagnosis in gynaecology patients. Methods: The cross-sectional cohort study was conducted from October 2010 to September 2011 at the Fauji Foundation Hospital, Rawalpindi, and comprised women who presented to the out-patient department with various gynaecological complaints. Colposcopy was performed in all women with unhealthy cervix during gynaecological examination, abnormal Pap smear report, recurrent vaginal discharge and postcoital bleeding. Pap smear was performed before colposcopy if not done earlier. Colposcopic findings were recorded on a specially-designed proforma. Biopsies from abnormal areas were taken and sent for histopathology. Colposcopic findings were compared with histopathology and Pap smear reports The agreement between the methods was evaluated by using Kappa coefficient and chi square test at a significance level of 5 percent. Results: The mean age of the 143 women was 44 8.5 years (range: 25-72 years). Colposcopic findings were normal in 66(46 percent) women, while 77(54 percent) had abnormal findings and among the latter, 62(80.5 percent) had abnormal histopathology, indicating strong agreement (K=0.65; p<0.001). Pap smear report was abnormal in 48(33.5 percent) cases and among them histopathology was abnormal in 28(58 percent). In the remaining 95(66.4 percent) patients with normal Pap smear, histopathology was abnormal in 44((46 percent), indicating weak agreement between Pap smear and histopathological diagnosis (K=0.10; p=0.08). Conclusion: There was a strong agreement between colposcopic findings and histopathological diagnosis. However, agreement between cytological findings and colposcopic findings and cytology and histopathological diagnosis remained weak. (author)

  15. Quantification in histopathology-Can magnetic particles help?

    International Nuclear Information System (INIS)

    Mitchels, John; Hawkins, Peter; Luxton, Richard; Rhodes, Anthony

    2007-01-01

    Every year, more than 270,000 people are diagnosed with cancer in the UK alone; this means that one in three people worldwide contract cancer within their lifetime. Histopathology is the principle method for confirming cancer and directing treatment. In this paper, a novel application of magnetic particles is proposed to help address the problem of subjectivity in histopathology. Preliminary results indicate that magnetic nanoparticles cannot only be used to assist diagnosis through improving quantification but also potentially increase throughput, hence offering a way of dramatically reducing costs within the routine histopathology laboratory

  16. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Heravi, Mitra [Department of Human Genetics, McGill University, Montreal (Canada); Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Kumala, Slawomir [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Rachid, Zakaria; Jean-Claude, Bertrand J. [Cancer Drug Research Laboratory, McGill University Health Center, Montreal (Canada); Radzioch, Danuta [Department of Human Genetics, McGill University, Montreal (Canada); Muanza, Thierry M., E-mail: tmuanza@yahoo.com [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada)

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  17. DNA repair in neurons: So if they don't divide what's to repair?

    International Nuclear Information System (INIS)

    Fishel, Melissa L.; Vasko, Michael R.; Kelley, Mark R.

    2007-01-01

    Neuronal DNA repair remains one of the most exciting areas for investigation, particularly as a means to compare the DNA repair response in mitotic (cancer) vs. post-mitotic (neuronal) cells. In addition, the role of DNA repair in neuronal cell survival and response to aging and environmental insults is of particular interest. DNA damage caused by reactive oxygen species (ROS) such as generated by mitochondrial respiration includes altered bases, abasic sites, and single- and double-strand breaks which can be prevented by the DNA base excision repair (BER) pathway. Oxidative stress accumulates in the DNA of the human brain over time especially in the mitochondrial DNA (mtDNA) and is proposed to play a critical role in aging and in the pathogenesis of several neurological disorders including Parkinson's disease, ALS, and Alzheimer's diseases. Because DNA damage accumulates in the mtDNA more than nuclear DNA, there is increased interest in DNA repair pathways and the consequence of DNA damage in the mitochondria of neurons. The type of damage that is most likely to occur in neuronal cells is oxidative DNA damage which is primarily removed by the BER pathway. Following the notion that the bulk of neuronal DNA damage is acquired by oxidative DNA damage and ROS, the BER pathway is a likely area of focus for neuronal studies of DNA repair. BER variations in brain aging and pathology in various brain regions and tissues are presented. Therefore, the BER pathway is discussed in greater detail in this review than other repair pathways. Other repair pathways including direct reversal, nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination and non-homologous end joining are also discussed. Finally, there is a growing interest in the role that DNA repair pathways play in the clinical arena as they relate to the neurotoxicity and neuropathy associated with cancer treatments. Among the numerous side effects of cancer treatments, major clinical effects

  18. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    International Nuclear Information System (INIS)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.

    2014-01-01

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting

  19. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

    2014-08-05

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

  20. Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

    Science.gov (United States)

    Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

    2011-09-01

    Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

  1. Three-dimensional digital breast histopathology imaging

    Science.gov (United States)

    Clarke, G. M.; Peressotti, C.; Mawdsley, G. E.; Eidt, S.; Ge, M.; Morgan, T.; Zubovits, J. T.; Yaffe, M. J.

    2005-04-01

    We have developed a digital histology imaging system that has the potential to improve the accuracy of surgical margin assessment in the treatment of breast cancer by providing finer sampling and 3D visualization. The system is capable of producing a 3D representation of histopathology from an entire lumpectomy specimen. We acquire digital photomicrographs of a stack of large (120 x 170 mm) histology slides cut serially through the entire specimen. The images are then registered and displayed in 2D and 3D. This approach dramatically improves sampling and can improve visualization of tissue structures compared to current, small-format histology. The system consists of a brightfield microscope, adapted with a freeze-frame digital video camera and a large, motorized translation stage. The image of each slide is acquired as a mosaic of adjacent tiles, each tile representing one field-of-view of the microscope, and the mosaic is assembled into a seamless composite image. The assembly is done by a program developed to build image sets at six different levels within a multiresolution pyramid. A database-linked viewing program has been created to efficiently register and display the animated stack of images, which occupies about 80 GB of disk space per lumpectomy at full resolution, on a high-resolution (3840 x 2400 pixels) colour monitor. The scanning or tiling approach to digitization is inherently susceptible to two artefacts which disrupt the composite image, and which impose more stringent requirements on system performance. Although non-uniform illumination across any one isolated tile may not be discernible, the eye readily detects this non-uniformity when the entire assembly of tiles is viewed. The pattern is caused by deficiencies in optical alignment, spectrum of the light source, or camera corrections. The imaging task requires that features as small as 3.2 &mum in extent be seamlessly preserved. However, inadequate accuracy in positioning of the translation

  2. ACUTE APPENDICITIS- SONOLOGICAL AND HISTOPATHOLOGICAL CORRELATION

    Directory of Open Access Journals (Sweden)

    Anjani M. Reddy

    2016-12-01

    Full Text Available BACKGROUND The aim of the study is to study the- 1. Correlation between sonological and histopathological diagnosis of acute appendicitis. 2. Prevalence of acute appendicitis in various age groups. MATERIALS AND METHODS The study was conducted in the Department of Radiodiagnosis, MVJ Medical College and Research Hospital, Bangalore, for a period of 2 years from March 2013 to February 2015. Data collection was prospective. A computer-assisted search of all the reports of ultrasonography with the diagnosis of acute appendicitis was conducted within the departmental database. A total of 244 patients (128 male patients and 116 female patients with acute appendicitis were identified and the study was conducted. RESULTS In the study, total of 244 patients were diagnosed with acute appendicitis. Out of these, 128 patients were males and 116 patients were females. The incidence of acute appendicitis was most prevalent in age group between 21 to 30 years (36.5% in our study. The least incidence was noted in age group of above 60 yrs. with only 1 out of 244 patients (0.4% was diagnosed with acute appendicitis. The histological features noted were suppuration/inflammation, gangrenous, lymphoid hyperplasia and perforation. In our study, 143 inflammation/suppuration (58.6%, 37 gangrenous (15.1%, 24 lymphoid hyperplastic (9.8% and 1 perforation (0.4% was noted. Hence, the incidence of inflammation/suppuration was found to be most common and perforation was found to be the least finding. The suppurative/inflammatory feature was most common histological type in all the age groups except for the age group above 60 yrs. The gangrenous features were most commonly seen in the age group between 11 to 20 yrs. followed by 20 to 30 yrs. Faecolith was most commonly found in age group of 21 to 30 yrs. (12 cases followed by age group of 11 to 20 yrs. (10 cases. CONCLUSION It was noted that the incidence of acute appendicitis was most commonly noted in younger age group

  3. Optic nerve histopathology in a case of Wolfram Syndrome

    DEFF Research Database (Denmark)

    Ross-Cisneros, Fred N; Pan, Billy X; Silva, Ruwan A

    2013-01-01

    Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis...

  4. Placental histopathology after Coxiella burnetii infection during pregnancy

    NARCIS (Netherlands)

    Munster, J. M.; Leenders, A. C. A. P.; Hamilton, C. J. C. M.; Hak, E.; Aarnoudse, J. G.; Timmer, A.

    Symptomatic and asymptomatic Coxiella burnetii infection during pregnancy have been associated with obstetric complications. We described placental histopathology and clinical outcome of five cases with asymptomatic C burnetii infection during pregnancy and compared these cases with four symptomatic

  5. histopathological evaluation of h. pylori associated gastric lesions in ...

    African Journals Online (AJOL)

    2012-12-12

    Dec 12, 2012 ... HISTOPATHOLOGICAL EVALUATION OF H. PYLORI ASSOCIATED GASTRIC LESIONS IN BENIN CITY,. NIGERIA. M. O. Udoh, MBBS, FMCPath, Consultant Pathologist, Department of Pathology, D. E. Obaseki, MBBS, FMCPath,. Consultant Pathologist, Department of Pathology, University of Benin ...

  6. Diagnosis of endometrial tuberculosis: culture versus histopathological examination

    International Nuclear Information System (INIS)

    Zaman, G.; Karamat, K.A.; Hafeez-ud-Din; Yousaf, A.; Abbasi, S.A.; Rafi, S.

    2002-01-01

    Objective: To compare the relative efficacy of histopathological examination and culture method in the diagnosis of endometrial tuberculosis. Design: It was a prospective, comparative in-vitro study. Place and Duration of Study: The study was conducted at the Armed Forces Institute of Pathology, Rawalpindi and Department of Obstetrics and Gynecology, Military Hospital, Rawalpindi from August 1998 to April 1999. Materiel and Methods: A total number of 50 cases of primary and secondary infertility were selected. Endometrial biopsies of all patients were subjected to histopathological as well as culture examination on BACTEC. Results: Culture method yielded 10% (n=5) positive results compared with 6% (n=3) positive results obtained by histopathological examination. P value was 0.096 by chi-square test. Conclusion: Culture is a more effective method compared with histopathological examination in the diagnosis of endometrial tuberculosis. (author)

  7. Perceived and Real Histopathology Turnaround Time: A Teaching ...

    African Journals Online (AJOL)

    2018-03-05

    Mar 5, 2018 ... Background: This study aims to audit analytic turnaround time (TAT) in a histopathology ... facility where not only pathology services are rendered, but residency ..... pathology as a tool for quality assurance. Niger J Med. 2008 ...

  8. Correlation between clinical and histopathological diagnoses in periapical inflammatory lesions.

    Science.gov (United States)

    Diegues, Liliane Lopes; Colombo Robazza, Carlos Roberto; Costa Hanemann, João Adolfo; Costa Pereira, Alessandro Antônio; Silva, Cléverson O

    2011-08-01

      The purpose of the present study was to evaluate the correlation between clinical and histopathological diagnoses of periapical inflammatory lesions, focusing mainly on cystic conditions.   Files dating from 1998 to 2006 at the Oral Pathology Laboratory, School of Dentistry, Alfenas Federal University, Brazil, were reviewed to identify cases with histopathological diagnoses of periapical inflammatory lesions. A total of 1788 files were analyzed, and 255 cases were identified with clinical diagnoses of periapical inflammatory lesions.   The most prevalent clinical diagnosis was apical periodontal cyst (59%), followed by periapical granuloma (20%), and dentoalveolar abscess (2%). After histopathological analysis, 53% of the cases represented apical periodontal cyst, 42% periapical granuloma, and 5% dentoalveolar abscess.   The outcomes of the present study show a high prevalence of periapical cysts among periapical inflammatory lesions. Moreover, this study highlights the importance of histopathological evaluation for the correct diagnosis of periapical inflammatory lesions. © 2011 Blackwell Publishing Asia Pty Ltd.

  9. Central neurocytoma: a histopathological and radiologic study of six cases

    International Nuclear Information System (INIS)

    Fugita, Dalton Yukio Araujo; Souza, Andrea Silveira de; Monteiro, Soraya Silveira; Lederman, Henrique M.; Caldas, Jose Guilherme Pereira; Frudit, Michel; Stavale, Jose Norberto

    1998-01-01

    Central neurocytoma is a rare intraventricular tumor with benign behavior which affects young adults. We describe six cases of central neurocytoma, discussing the histopathological and radiologic diagnosis, and briefly comment some aspects about treatment. (author)

  10. DNA damage repair and radiosensitivity

    International Nuclear Information System (INIS)

    Suzuki, Norio

    2003-01-01

    Tailored treatment is not new in radiotherapy; it has been the major subject for the last 20-30 years. Radiation responses and RBE (relative biological effectiveness) depend on assay systems, endpoints, type of tissues and tumors, radiation quality, dose rate, dose fractionation, physiological and environmental factors etc, Latent times to develop damages also differ among tissues and endpoints depending on doses and radiation quality. Recent progress in clarification of radiation induced cell death, especially of apoptotic cell death, is quite important for understanding radiosensitivity of tumor cure process as well as of tumorigenesis. Apoptotic cell death as well as dormant cells had been unaccounted and missed into a part of reproductive cell death. Another area of major progress has been made in clarifying repair mechanisms of radiation damage, i.e., non-homologous end joining (NHEJ) and homologous recombinational repair (HRR). New approaches and developments such as cDNA or protein micro arrays and so called informatics in addition to basic molecular biological analysis are expected to aid identifying molecules and their roles in signal transduction pathways, which are multi-factorial and interactive each other being involved in radiation responses. (authors)

  11. Influence of combined loading state on FRP repaired steel pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Shouman, A. [Dalhousie Univ., Halifax, NS (Canada). Dept. of Civil Engineering; Taheri, F. [Dalhousie Univ., Halifax, NS (Canada). Ocean Research Centre

    2009-07-01

    This paper discussed a comprehensive computational investigation conducted to assess the response of fiber reinforced polymer (FRP) repaired pipes subjected to combined loading states. The finite element method (FEM) was used to consider the response of both repaired and unrepaired pipes. Internal pressure, pure bending, and combined pure bending and internal pressures. The analysis examined damaged pipes repaired with FRP as well as damaged unrepaired pipes. The study showed that the defect region endured higher internal pressures than unrepaired pipes. The FRP repair restored the pipe to its specified minimum yield strength capacity without interrupting internal fluid transportation. It was concluded that in addition to preventing strain localization or wrinkling in the defect region, the FRP repair also significantly increases the limit bending capacity of the pipes. 6 refs., 2 figs.

  12. Acute pulmonary injury: high-resolution CT and histopathological spectrum

    Science.gov (United States)

    Obadina, E T; Torrealba, J M

    2013-01-01

    Acute lung injury usually causes hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS). Although diffuse alveolar damage is the hallmark of ARDS, other histopathological patterns of injury, such as acute and fibrinoid organising pneumonia, can be associated with acute respiratory failure. Acute eosinophilic pneumonia can also cause acute hypoxaemic respiratory failure and mimic ARDS. This pictorial essay reviews the high-resolution CT findings of acute lung injury and the correlative histopathological findings. PMID:23659926

  13. Dose-response relationship of induction kinetics of In vivo DNA damage and repair in mouse leukocytes exposed to gamma radiation; Relacion dosis-respuesta de la cinetica de induccion de dano y reparacion del ADN In vivo en leucocitos de raton expuestos a radiacion gamma

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M.T.; Morales, R.P. [Instituto Nacional de Investigaciones Nucleares, Gerencia de Investigacion Basica, Departamento de Biologia, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2000-07-01

    The Unicellular electrophoresis in gel technique is a useful tool in the determination of simple ruptures and labile sites to the alkali in DNA of eucariontes cells. The determination of the induction kinetics of damage and repair of DNA can give more information. The objective of this work was to determine whether the analysis of the area under the damage/repair induction kinetics curve in comets percent or the comets frequency in the two peaks of maximum induction is adequate for determining the dose-response relationship. The mice were exposed at the doses of 0.5, 1.0, 2.0 Gy. (Author)

  14. A self-repairing polymer waveguide sensor

    International Nuclear Information System (INIS)

    Song, Young J; Peters, Kara J

    2011-01-01

    This paper presents experimental demonstrations of a self-repairing strain sensor waveguide created by self-writing in a photopolymerizable resin system. The sensor is fabricated between two multi-mode optical fibers via lightwaves in the ultraviolet (UV) wavelength range and operates as a sensor through interrogation of the power transmitted through the waveguide in the infrared (IR) wavelength range. After failure of the sensor occurs due to loading, the waveguide re-bridges the gap between the two optical fibers through the UV resin. The response of the original sensor and the self-repaired sensor to strain are measured and show similar behaviors

  15. Flexor tendon repair with a knotless, bidirectional barbed suture: an in vivo biomechanical analysis.

    Science.gov (United States)

    Maddox, Grady E; Ludwig, Jonathan; Craig, Eric R; Woods, David; Joiner, Aaron; Chaudhari, Nilesh; Killingsworth, Cheryl; Siegal, Gene P; Eberhardt, Alan; Ponce, Brent

    2015-05-01

    To compare and analyze biomechanical properties and histological characteristics of flexor tendons either repaired by a 4-strand modified Kessler technique or using barbed suture with a knotless repair technique in an in vivo model. A total of 25 chickens underwent surgical transection of the flexor digitorum profundus tendon followed by either a 4-strand Kessler repair or a knotless repair with barbed suture. Chickens were randomly assigned to 1 of 3 groups with various postoperative times to death. Harvested tendons were subjected to biomechanical testing or histologic analysis. Harvested tendons revealed failures in 25% of knotless repairs (8 of 32) and 8% of 4-strand Kessler repairs (2 of 24). Biomechanical testing revealed no significant difference in tensile strength between 4-strand Kessler and barbed repairs; however, this lack of difference may be attributed to lower statistical power. We noted a trend toward a gradual decrease in strength over time for barbed repairs, whereas we noticed the opposite for the 4-strand Kessler repairs. Mode of failure during testing differed between repair types. The barbed repairs tended toward suture breakage as opposed to 4-strand Kessler repairs, which demonstrated suture pullout. Histological analysis identified no difference in the degree of inflammation or fibrosis; however, there was a vigorous foreign body reaction around the 4-strand Kessler repair and no such response around the barbed repairs. In this model, knotless barbed repairs trended toward higher in vivo failure rates and biomechanical inferiority under physiologic conditions, with each repair technique differing in mode of failure and respective histologic reaction. We are unable to recommend the use of knotless barbed repair over the 4-strand modified Kessler technique. For the repair techniques tested, surgeons should prefer standard Kessler repairs over the described knotless technique with barbed suture. Copyright © 2015 American Society for Surgery

  16. Radiobiological significance of DNA repair

    International Nuclear Information System (INIS)

    Kuzin, A.M.

    1978-01-01

    A short outline is given on the history of the problem relating to the repair of radiation injuries, specifically its molecular mechanisms. The most urgent problems which currently confront the researchers are noted. This is a further study on the role of DNA repair in post-radiation recovery, search for ways to activate and suppress DNA repair, investigations into the activity balance of various repair enzymes as well as the problem of errors in the structure of repairing DNA. An important role is attached to the investigations of DNA repair in solving a number of practical problems

  17. Recombinational repair: workshop summary

    International Nuclear Information System (INIS)

    Howard-Flanders, P.

    1983-01-01

    Recombinational repair may or may not be synonymous with postreplication repair. Considerable progress has been made in the study of the relevant enzymes, particularly those from bacteria. In this workshop we focus on the recombination enzyme RecA protein. What structural changes take place in the protein and in DNA during repair. How does homologous pairing take place. How is ATP hydrolysis coupled to the stand exchange reaction and the formation of heteroduplx DNA. Turning to another enzyme needed for certain kinds of bacterial recombination, we will ask whether the purified recB protein and recC protein complement each other and are sufficient for exonuclease V activity. In higher cells, we would like to know whether sister exchanges, which occur in bacteria after uv irradiation, are also seen in animal cells

  18. MR imaging and histopathologic correlations of thermal injuries induced by interstitial laser applications

    International Nuclear Information System (INIS)

    Anzai, Y.; Lufkin, R.B.; Castro, D.J.; Farahani, K.; Chen, H.W.; Hirchowiz, S.

    1991-01-01

    Interstitial laser phototherapy for deep-seated tumors may become an attractive therapeutic modality when a noninvasive, accurate monitoring system is developed. In this paper, to devaluate the ability of MR imaging to differentiate reversible and irreversible thermal injuries induced by laser therapy, the precise correlation of MR and histopathologic findings are investigated in the in vivo model. Nd:YAG lasers were applied to normal musculature of rabbits, and MR examinations were performed immediately after laser exposure and followed up for up to 10 weeks. The sequential MR images were correlated with histopathologic findings. T2-weighted MR imaging clearly showed laser-induced thermal injuries on any postoperative day. MR imaging of acute thermal injuries showed a central cavity, low-signal zone of coagulative necrosis and a peripheral high-signal layer of interstitial edema. The infiltration of neutrophils followed by fibrovascular response was identified on the marginal edema layer after 6 postoperative days

  19. DNA repair in ultraviolet-irradiated spores of Bacillus subtilis

    International Nuclear Information System (INIS)

    Wang, T.C.V.

    1976-01-01

    It has been shown previously by others that at least two independent repair mechanisms are present in Bacillus subtilis for removing ''spore photoproduct'' from DNA of ultraviolet (254 nm)-irradiated spores after germination. One of these, designated as ''spore repair,'' is shown in this study to restore ''spore photoproduct'' to two thymine residues, leaving the DNA backbone intact at the end of the process in vivo. The circumstances under which this repair can occur and some characteristics of its energy requirements have been clarified. The second repair process is identified as excision repair, which can excise both ''spore photoproduct'' from DNA of irradiated spores and cyclobutane-type pyrimidine dimers from DNA of irradiated vegetative cells. In this study it is shown that the gene hcr 1 affects an enzyme activity for the incision step initiating this repair, while the gene hcr 42 affects a step subsequent to incision in the mechanism. In addition a third, independent repair system, termed ''germinative excision repair,'' is discovered and shown to be specific for excising only cyclobutane-type pyrimidine dimers but not ''spore photoproduct.'' This repair system is responsible for the observed high ultraviolet-resistance and temporary capacity for host cell reactivation on recently germinated spores of Bacillus subtilis HCR - strains

  20. Meniscal repair devices.

    Science.gov (United States)

    Barber, F A; Herbert, M A

    2000-09-01

    Meniscal repair devices not requiring accessory incisions are attractive. Many factors contribute to their clinical effectiveness including their biomechanical characteristics. This study compared several new meniscal repair devices with standard meniscal suture techniques. Using a porcine model, axis-of-insertion loads were applied to various meniscal sutures and repair devices. A single device or stitch was placed in a created meniscal tear and a load applied. Both loads and modes of failure were recorded. The load-to-failure data show stratification into 4 distinct statistical groups. Group A, 113 N for a double vertical stitch; group B, 80 N for a single vertical stitch; group C, 57 N for the BioStinger, 56 N for a horizontal mattress stitch, and 50 N for the T-Fix stitch; and group D, 33 N for the Meniscus Arrow (inserted by hand or gun), 32 N for the Clearfix screw, 31 N for the SDsorb staple, 30 N for the Mitek meniscal repair system, and 27 N for the Biomet staple. The failure mechanism varied. Sutures broke away from the knot. The Meniscus Arrow and BioStinger pulled through the inner rim with the crossbar intact. The Clearfix screw failed by multiple mechanisms, whereas 1 leg of the SDsorb staple always pulled out of the outer rim. The Mitek device usually failed by pullout from the inner rim. The Biomet staple always broke at the crosshead or just below it. Although the surgeon should be aware of the material properties of the repair technique chosen for a meniscal repair, this information is only an indication of device performance and may not correlate with clinical healing results.

  1. DNA repair and cancer

    International Nuclear Information System (INIS)

    Rathore, Shakuntla; Joshi, Pankaj Kumar; Gaur, Sudha

    2012-01-01

    DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecule that encode it's genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many one million individual molecular lesions per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions include potentially harmful mutation in cell's genome which affect the survival of it's daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. Inherited mutation that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary non polyposis colorectal cancer (HNPCC) is strongly associated with specific mutation in the DNA mismatch repair pathway. BRCA1, BRCA2 two famous mutation conferring a hugely increased risk of breast cancer on carrier, are both associated with a large number of DNA repair pathway, especially NHEJ and homologous recombination. Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatment attempt to localize the DNA damage to cells and tissue only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). (author)

  2. Collagenous colitis: histopathology and clinical course.

    Science.gov (United States)

    Goff, J S; Barnett, J L; Pelke, T; Appelman, H D

    1997-01-01

    Collagenous colitis is a chronic diarrheal disease characterized by a normal or near-normal mucosa endoscopically and microscopic inflammation in the lamina propria, surface epithelial injury and a thick subepithelial collagen layer. The symptoms of collagenous colitis vary in duration and intensity, and long periods of remission have been described, but long-term follow-up data are limited. Our goal was to determine the natural clinical history of collagenous colitis and to determine whether there was a relationship between histopathologic changes and course of disease. Cases were identified at the University of Michigan Hospitals using surgical pathology records before 1992. All charts, including medical records from other hospitals, were reviewed, and a telephone interview was conducted with each locatable patient (pt). Biopsy specimens were reviewed by two pathologists for degree of collagen layer thickness, epithelial damage, and inflammation. There were 31 patients (26 F, 5 M) with a mean age of 66 yr (range 33-83) and a mean duration of symptoms of 5.4 yr at the time of diagnosis. Of the 31 patients, 18 (56%) had some form of arthritis, and 22 (71%) were using NSAIDS regularly at the time of diagnosis. Follow-up interviews were conducted at least 2 yr after diagnosis (mean 3.5 yr, range 2-5 yr) with 27 of 31 patients (3 could not be located, 1 died). Two definable groups of patients were identified: (1) those with either spontaneous or treatment-related symptom resolution (63%), and (2) those with ongoing or intermittent symptoms requiring at least intermittent therapy (37%). There was no significant difference between the two groups with regard to sex, age, associated diseases, and use of medications. Patients with symptom resolution (mean duration 3.1 yr) had been treated with antidiarrheals (6), sulfasalazine (3), discontinuation of NSAIDS (3), reversal of jejunoilial bypass (1), or nothing (4). Those with ongoing symptoms experienced a wide range of

  3. Repair-misrepair model of cell survival

    International Nuclear Information System (INIS)

    Tobias, C.A.; Blakely, E.A.; Ngo, F.Q.H.

    1980-01-01

    During the last three years a new model, the repair-misrepair model (RMR) has been proposed, to interpret radiobiological experiments with heavy ions. In using the RMR model it became apparent that some of its features are suitable for handling the effects produced by a variety of environmental agents in addition to ionizing radiation. Two separate sequences of events are assumed to take place in an irradiated cell. The first sequence begins with an initial energy transfer consisting of ionizations and excitations, culminating via fast secondary physical and chemical processes in established macromolecular lesions in essential cell structures. The second sequence contains the responses of the cell to the lesions and consists of the processes of recognition and molecular repair. In normal cells there exists one repair process or at most a few enzymatic repair processes for each essential macromolecular lesion. The enzymatic repair processes may last for hours and minutes, and can be separated in time from the initial physicochemical and later genetic phases

  4. Histopathological diagnosis and outcome of paediatric nephrotic syndrome

    International Nuclear Information System (INIS)

    Ejaz, I; Khan, H.I.; Javaid, B.K.; Bhatti, M.T.; Rasool, G.

    2004-01-01

    Objective: To determine the histological picture and outcome of treatment in cases of childhood nephrotic syndrome who needed renal biopsy. Subjects and Methods: Children suffering from nephrotic syndrome who had atypical features at presentation were initially or late non-responders; frequent relapsers on > 1 mg kg/day and were steroid dependent or frequently relapsed on < 1 mg kg/day but developed steroid toxicity were included. Renal biopsy was performed in these patients. Treatment was administered according to the histopathology reports. Prednisolone 60 mg /m/sup 2//day followed after response by 40 mg /m/sup /2 on alternate days (AD) which was later tapered off. In minimal change nephrotic syndrome (MCNS) with frequent relapses cyclophosphamide, cyclosporine and levimisole were used. For steroid resistant focal segmental glomerulosclerosis (FSGS) intravenous pulses of methylprednisolone and cyclosporine were also given. These patients were followed to see the response of the therapy. Results: The commonest diagnosis was focal segmental glomerulosclerosis (FSGS) (42%) followed by minimal change disease (MCNS) (22%), membranoproliferative or mesangiocapillary glomerulonephritis (MPGN) (14%) and Mesangioproliferative glomerulonephritis (Mes PGN) (12%). There were 6% cases of membranous nephropathy and 4% of diffuse proliferative glomerulonephritis. On presentation, 40% had hematuria, 20% were found to be hypertensive, 12% patients had renal insufficiency and in 40% C3 level was low. Majority of the patients with MPGN and FSGS had atypical features whereas none of the patients with membranous nephropathy had any of these features. Thirty percent cases each of FSGS and MCNS were responders. Among non-responders there were 4 cases of FSGS and one of MPGN. Conclusion: FSGS was the commonest histology in cases of childhood nephrotic syndrome that needed renal biopsy. Highest frequency of atypical features was seen in MPGN and FSGS. (author)

  5. Histopathologic criteria to confirm white-nose syndrome in bats.

    Science.gov (United States)

    Meteyer, Carol Uphoff; Buckles, Elizabeth L; Blehert, David S; Hicks, Alan C; Green, D Earl; Shearn-Bochsler, Valerie; Thomas, Nancy J; Gargas, Andrea; Behr, Melissa J

    2009-07-01

    White-nose syndrome (WNS) is a cutaneous fungal disease of hibernating bats associated with a novel Geomyces sp. fungus. Currently, confirmation of WNS requires histopathologic examination. Invasion of living tissue distinguishes this fungal infection from those caused by conventional transmissible dermatophytes. Although fungal hyphae penetrate the connective tissue of glabrous skin and muzzle, there is typically no cellular inflammatory response in hibernating bats. Preferred tissue samples to diagnose this fungal infection are rostral muzzle with nose and wing membrane fixed in 10% neutral buffered formalin. To optimize detection, the muzzle is trimmed longitudinally, the wing membrane is rolled, and multiple cross-sections are embedded to increase the surface area examined. Periodic acid-Schiff stain is essential to discriminate the nonpigmented fungal hyphae and conidia. Fungal hyphae form cup-like epidermal erosions and ulcers in the wing membrane and pinna with involvement of underlying connective tissue. In addition, fungal hyphae are present in hair follicles and in sebaceous and apocrine glands of the muzzle with invasion of tissue surrounding adnexa. Fungal hyphae in tissues are branching and septate, but the diameter and shape of the hyphae may vary from parallel walls measuring 2 microm in diameter to irregular walls measuring 3-5 microm in diameter. When present on short aerial hyphae, curved conidia are approximately 2.5 microm wide and 7.5 microm in curved length. Conidia have a more deeply basophilic center, and one or both ends are usually blunt. Although WNS is a disease of hibernating bats, severe wing damage due to fungal hyphae may be seen in bats that have recently emerged from hibernation. These recently emerged bats also have a robust suppurative inflammatory response.

  6. Histopathologic criteria to confirm white-nose syndrome in bats

    Science.gov (United States)

    Meteyer, Carol U.; Buckles, Elizabeth L.; Blehert, David S.; Hicks, Alan C.; Green, David E.; Shearn-Bochsler, Valerie I.; Thomas, Nancy J.; Gargas, Andrea; Behr, Melissa

    2009-01-01

    White-nose syndrome (WNS) is a cutaneous fungal disease of hibernating bats associated with a novel Geomyces sp. fungus. Currently, confirmation of WNS requires histopathologic examination. Invasion of living tissue distinguishes this fungal infection from those caused by conventional transmissible dermatophytes. Although fungal hyphae penetrate the connective tissue of glabrous skin and muzzle, there is typically no cellular inflammatory response in hibernating bats. Preferred tissue samples to diagnose this fungal infection are rostral muzzle with nose and wing membrane fixed in 10% neutral buffered formalin. To optimize detection, the muzzle is trimmed longitudinally, the wing membrane is rolled, and multiple cross-sections are embedded to increase the surface area examined. Periodic acid-Schiff stain is essential to discriminate the nonpigmented fungal hyphae and conidia. Fungal hyphae form cup-like epidermal erosions and ulcers in the wing membrane and pinna with involvement of underlying connective tissue. In addition, fungal hyphae are present in hair follicles and in sebaceous and apocrine glands of the muzzle with invasion of tissue surrounding adnexa. Fungal hyphae in tissues are branching and septate, but the diameter and shape of the hyphae may vary from parallel walls measuring 2 ??m in diameter to irregular walls measuring 3-5 ??m in diameter. When present on short aerial hyphae, curved conidia are approximately 2.5 ??m wide and 7.5 ??m in curved length. Conidia have a more deeply basophilic center, and one or both ends are usually blunt. Although WNS is a disease of hibernating bats, severe wing damage due to fungal hyphae may be seen in bats that have recently emerged from hibernation. These recently emerged bats also have a robust suppurative inflammatory response.

  7. Biological radiolesions and repair

    International Nuclear Information System (INIS)

    Laskowski, W.

    1981-01-01

    In 7 chapters, the book answers the following questions: 1) What reactions are induced in biological matter by absorption of radiation energy. 2) In what parts of the cell do the radiation-induced reactions with detectable biological effects occur. 3) In which way are these cell components changed by different qualities of radiation. 4) What are the cell mechanisms by which radiation-induced changes can be repaired. 5) What is the importance of these repair processes for man, his life and evolution. At the end of each chapter, there is a bibliography of relevant publications in this field. (orig./MG) [de

  8. Repair of potentially lethal damage following irradiation with x rays or cyclotron neutrons: response of the EMT-6/UW tumor system treated under various growth conditions in vitro and in vivo

    International Nuclear Information System (INIS)

    Rasey, J.S.; Nelson, N.J.

    1981-01-01

    Postirradiation potentially lethal damage (PLD) repair was examined in the EMT-6/UW tumor system under a variety of in vitro and in vivo growth conditions. Following x irradiation, surviving fraction increased in fed and unfed plateau cultures if subculture and plating were delayed; in exponentially growing cultures if they were covered with depleted medium for the first 6 h postirradiation; and in tumors in vivo if excision for preparation of a cell suspension was delayed. Following irradiation with 21.5 meV (d + → Be) neutrons, PLD repair was measurable only in unfed plateau cultures when subculture was delayed and in exponentially growing cells exposed to depleted culture medium immediately after irradiation. In x-irradiated EMT-6/UW cells, the greatest repair capacity and the highest surviving fraction ratios were measured in unfed plateau cultures; the least repair was observed in exponentially growing cells exposed to depleted medium. Thus post-neutron repair was not limited to situations where the amount of repair of photon PLD is large. The demonstration of PLD repair in tumors irradiated in vivo with X rays and the absence of such repair after neutrons could have important implications in radiotherapy if this is a general phenomenon

  9. DNA Repair and Genome Maintenance in Bacillus subtilis

    Science.gov (United States)

    Lenhart, Justin S.; Schroeder, Jeremy W.; Walsh, Brian W.

    2012-01-01

    Summary: From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis. PMID:22933559

  10. Composite Repair System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — GTL has developed an innovative composite repair methodology known as the Composite Repair System (CRS). In this phase I effort, CRS is being developed for the...

  11. About the Collision Repair Campaign

    Science.gov (United States)

    EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.

  12. Vesicovaginal Fistula Repair During Pregnancy

    African Journals Online (AJOL)

    Vesicovaginal Fistula Repair During Pregnancy: A Case Report ... Abstract. We report a repair of Vesicovaginal fistula during pregnancy that was aimed at preventing another spontaneous ... practices that encourage teenage marriage and girl.

  13. Ship Repair Workflow Cost Model

    National Research Council Canada - National Science Library

    McDevitt, Mike

    2003-01-01

    The effects of intermittent work patterns and funding on the costs of ship repair and maintenance were modeled for the San Diego region in 2002 for Supervisor of Shipbuilding and Repair (SUPSHIP) San Diego...

  14. Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

    Science.gov (United States)

    Jacob, Tina Elizabeth; Malathi, N; Rajan, Sharada T; Augustine, Dominic; Manish, N; Patil, Shankargouda

    2016-01-01

    It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of

  15. Comprehensive Small Engine Repair.

    Science.gov (United States)

    Hires, Bill; And Others

    This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…

  16. Patent urachus repair - slideshow

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair - series—Normal anatomy URL of this ...

  17. Patent urachus repair

    Science.gov (United States)

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair URL of this page: //medlineplus.gov/ ...

  18. DNA Repair Systems

    Indian Academy of Sciences (India)

    Thanks to the pioneering research work of Lindahl, Sancar, Modrich and their colleagues, we now have an holistic awareness of how DNA damage occurs and how the damage is rectified in bacteria as well as in higher organisms including human beings. A comprehensive understanding of DNA repair has proven crucial ...

  19. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R [ORNL; Peter, William H [ORNL

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.

  20. Role of DNA repair in repair of cytogenetic damages. Slowly repaired DNA injuries involved in cytogenetic damages repair

    International Nuclear Information System (INIS)

    Zaichkina, S.I.; Rozanova, O.M.; Aptikaev, G.F.; Ganassi, E.Eh.

    1989-01-01

    Caffeine was used to study the kinetics of cytogenetic damages repair in Chinese hamster fibroblasts. Its half-time (90 min) was shown to correlate with that of repair of slowly repaired DNA damages. The caffeine-induced increase in the number of irreparable DNA damages, attributed to inhibition of double-strand break repair, is in a quantitative correlation with the effect of the cytogenetic damage modification

  1. Renal and hepatic histopathology of intraperitoneally administered ...

    African Journals Online (AJOL)

    user

    2016-10-12

    Oct 12, 2016 ... chlorine free tap water at 25°C and acclimated for two weeks in the laboratory ... The behavioural responses of the fish were noted, such as erratic swimming ..... controlling external fungal, bacterial and protozoan infections of ...

  2. Wellbore Seal Repair Using Nanocomposite Materials

    Energy Technology Data Exchange (ETDEWEB)

    Stormont, John [Univ. of New Mexico, Albuquerque, NM (United States)

    2016-08-31

    Nanocomposite wellbore repair materials have been developed, tested, and modeled through an integrated program of laboratory testing and numerical modeling. Numerous polymer-cement nanocomposites were synthesized as candidate wellbore repair materials using various combinations of base polymers and nanoparticles. Based on tests of bond strength to steel and cement, ductility, stability, flowability, and penetrability in opening of 50 microns and less, we identified Novolac epoxy reinforced with multi-walled carbon nanotubes and/or alumina nanoparticles to be a superior wellbore seal material compared to conventional microfine cements. A system was developed for testing damaged and repaired wellbore specimens comprised of a cement sheath cast on a steel casing. The system allows independent application of confining pressures and casing pressures while gas flow is measured through the specimens along the wellbore axis. Repair with the nanocomposite epoxy base material was successful in dramatically reducing the flow through flaws of various sizes and types, and restoring the specimen comparable to an intact condition. In contrast, repair of damaged specimens with microfine cement was less effective, and the repair degraded with application of stress. Post-test observations confirm the complete penetration and sealing of flaws using the nanocomposite epoxy base material. A number of modeling efforts have supported the material development and testing efforts. We have modeled the steel-repair material interface behavior in detail during slant shear tests, which we used to characterize bond strength of candidate repair materials. A numerical model of the laboratory testing of damaged wellbore specimens was developed. This investigation found that microannulus permeability can satisfactorily be described by a joint model. Finally, a wellbore model has been developed that can be used to evaluate the response of the wellbore system (casing, cement, and microannulus

  3. Periapical repair after root canal filling with different root canal sealers.

    Science.gov (United States)

    Tanomaru-Filho, Mário; Tanomaru, Juliane Maria Guerreiro; Leonardo, Mario Roberto; da Silva, Lea Assed Bezerra

    2009-01-01

    The aim of this study was to evaluate periapical repair after root canal filling with different endodontic sealers. Sixty-four root canals from dog s teeth were filled, divided into 4 groups (n=16). Root canals were instrumented with K-type files and irrigated with 1% sodium hypochlorite solution. Root canals were filled in the same session by active lateral condensation of the cones and sealers: Intrafill, AH Plus, Roeko Seal and Resilon/Epiphany System. After 90 days, the animals were euthanized and the tissues to be evaluated were processed and stained with hematoxylin and eosin. For histopathological analysis, the following parameters were evaluated: inflammatory process, mineralized tissue resorption, and apical mineralized tissue deposition. Histopathological analysis demonstrated that Intrafill had less favorable results in terms of apical and periapical repair, compared to the other sealers (p0.05). In conclusion, AH Plus and the materials Roeko Seal and Epiphany are good options for clinical use in Endodontics.

  4. Cleft lip and palate repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002979.htm Cleft lip and palate repair To use the sharing features on this ... Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty Patient Instructions Cleft lip and palate repair - discharge Images Cleft lip repair - series References ...

  5. DNA repair in human cells

    International Nuclear Information System (INIS)

    Regan, J.D.; Carrier, W.L.; Kusano, I.; Furuno-Fukushi, I.; Dunn, W.C. Jr.; Francis, A.A.; Lee, W.H.

    1982-01-01

    Our primary objective is to elucidate the molecular events in human cells when cellular macromolecules such as DNA are damaged by radiation or chemical agents. We study and characterize (i) the sequence of DNA repair events, (ii) the various modalities of repair, (iii) the genetic inhibition of repair due to mutation, (iv) the physiological inhibition of repair due to mutation, (v) the physiological inhibition of repair due to biochemical inhibitors, and (vi) the genetic basis of repair. Our ultimate goals are to (i) isolate and analyze the repair component of the mutagenic and/or carcinogenic event in human cells, and (ii) elucidate the magnitude and significance of this repair component as it impinges on the practical problems of human irradiation or exposure to actual or potential chemical mutagens and carcinogens. The significance of these studies lies in (i) the ubiquitousness of repair (most organisms, including man, have several complex repair systems), (ii) the belief that mutagenic and carcinogenic events may arise only from residual (nonrepaired) lesions or that error-prone repair systems may be the major induction mechanisms of the mutagenic or carcinogenic event, and (iii) the clear association of repair defects and highly carcinogenic disease states in man [xeroderma pigmentosum (XP)

  6. The journey of DNA repair.

    Science.gov (United States)

    Saini, Natalie

    2015-12-01

    21 years ago, the DNA Repair Enzyme was declared "Molecule of the Year". Today, we are celebrating another "year of repair", with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.

  7. Histopathological analysis of hysterectomy specimens: one year study

    Directory of Open Access Journals (Sweden)

    R Baral

    2017-03-01

    Full Text Available Backgound: The uterus is prone to develop several non-neoplastic and neoplastic conditions during the life time of a woman. The aim of this study is to study the histopathological features of varied uterine lesions, their profile and distribution of different lesions in relation of age.Materials and Methods: This is a histopathological database analysis of hysterectomy specimen of one year 2011/12 in Patan Hospital. The variables studied were age and histopathological diagnosis. SPSS version 16 was used as an analytical tool.Results: A total of 3576 histopathology samples were received in this period. There were 1173 gynaecology samples during this period out of which 22% (261 cases were that of hysterectomy. Histopathology diagnosis showed Leiomyoma in 48.6% (127 cases, Adenomyosis was seen in 10.3% (27 cases, Endometrioid Adenocarcinoma was seen in 1.14% (3 cases.Conclusion: A large number of hysterectomy specimens had no significant findings. However, adenomyosis, leiomyomya and adenocarcinoma are also found which may be the cause of abnormal uterine bleeding. 

  8. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

    1982-01-01

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  9. Wound repair and regeneration: Mechanisms, signaling, and translation

    Science.gov (United States)

    Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

    2015-01-01

    The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

  10. Neoadjuvant radiation in primary extremity liposarcoma: correlation of MRI features with histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Wortman, Jeremy R. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston, MA (United States); Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston, MA (United States); Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Boston, MA (United States); Tirumani, Harika [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Boston, MA (United States); University of Arkansas Medical Sciences, Department of Radiology, Little Rock, AR (United States); Hornick, Jason L. [Harvard Medical School, Department of Pathology, Brigham and Women' s Hospital, Boston, MA (United States)

    2016-05-15

    To evaluate MRI features of response of primary extremity liposarcoma (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation. In this IRB-approved study including 125 patients with extremity LPS treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18 patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by two radiologists by consensus. Histopathology of the surgical specimens was reviewed by a pathologist with expertise in sarcomas. In the pleomorphic LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component; and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis. In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in enhancing component, and 5/13 increased in internal fat following RT. Histopathology showed ≥50 % residual tumour in 1/5 pleomorphic LPS and 2/13 myxoid LPS. Hyalinization/necrosis of ≥75 % was noted in 4/5 pleomorphic LPS and 11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13 myxoid LPS. While pleomorphic LPS showed an increase in size, peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an increase in internal fat. (orig.)

  11. Repair mechanisms and exposure standards

    International Nuclear Information System (INIS)

    Mills, W.A.

    1978-01-01

    The following topics are discussed; public policy for setting radiation standards; use of linear, nonthreshold theory in setting radiation standards; dose-rate dependence; occupational exposure to radiation; radon inhalation from radium in the soil in the vicinity of the phosphate industry; relation of repair mechanisms for cell survival to cancer induction; application of information on genetic repair to humans and to cancer induction; importance of repair processes in radiation protection standards; corrective factors for repair processes; relation of repair processes to age, sex, and other factors; and population distribution in radiosensitivity

  12. Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    BACKGROUND: A retrospective investigation of 53 consecutively treated patients with operable lobular carcinoma of the breast, with a median follow-up of 6.6 years, was performed to examine the prognostic value of quantitative histopathologic parameters.METHODS: The measurements were performed...... of disease, vv(nuc), MI, and NI were of significant independent, prognostic value. On the basis of the multivariate analyses, a prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed.CONCLUSION: Quantitative histopathologic variables are of value...... for objective grading of malignancy in lobular carcinomas. The new parameter--estimates of the mean nuclear volume--is highly reproducible and suitable for routine use. However, larger and prospective studies are needed to establish the true value of the quantitative histopathologic variables in the clinical...

  13. Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    BACKGROUND: A retrospective investigation of 53 consecutively treated patients with operable lobular carcinoma of the breast, with a median follow-up of 6.6 years, was performed to examine the prognostic value of quantitative histopathologic parameters. METHODS: The measurements were performed...... of disease, vv(nuc), MI, and NI were of significant independent, prognostic value. On the basis of the multivariate analyses, a prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed. CONCLUSION: Quantitative histopathologic variables are of value...... for objective grading of malignancy in lobular carcinomas. The new parameter--estimates of the mean nuclear volume--is highly reproducible and suitable for routine use. However, larger and prospective studies are needed to establish the true value of the quantitative histopathologic variables in the clinical...

  14. Reference values for blood pressure response to cycle ergometry in the first two decades of life: comparison with patients with a repaired coarctation of the aorta.

    Science.gov (United States)

    Kaafarani, Mirna; Schroer, Christian; Takken, Tim

    2017-12-01

    Hemodynamic responses to exercise are used as markers of diagnosis for cardiac diseases, systolic blood pressure (SBP) especially. However, the reference values for SBP in children at peak exertion level are outdated. This study aimed to establish current reference values for SBP, rate pressure product (RPP), and circulatory power (CircP). Data from children who previously underwent cardiopulmonary exercise testing were categorized as healthy (N = 184; age 12.6 ± 2.9 years), and CoA patients (N = 25; age 13.0 ± 3.2 years). With the Lambda-Mu-Sigma (LMS) method, percentile curves were made for SBP, CircP, and RPP in function of peak work rate (Wpeak). Data of CoA patients were used to validate the reference values. Wpeak was the best predictor of peak SBP during exercise. The prediction equations for SBP, CircP and RPP were: (0.2853 x Wpeak) + 111.46; (10.56 x Wpeak) + 2550.2 and (61.879 x Wpeak) + 19.887, respectively. CoA patients showed significantly increased values for peak SBP (Z-score 1.063 ± 1.347). This study provides reference values for SBP, RPP, and CircP at peak exercise. These values can be used for objective evaluation of participants 6-18 years of age in a Dutch population.

  15. Determination of the adaptive response induced In vivo by gamma radiation and its relation with the sensibility to the damage induction in the DNA and with the repairing capacity; Determinacion de la respuesta adaptativa inducida In vivo por radiacion gamma y su relacion con la sensibilidad a la induccion de dano en el ADN y con la capacidad de reparacion

    Energy Technology Data Exchange (ETDEWEB)

    Mendiola C, M T

    2002-07-01

    The kinetics of damage induction and repair at different doses as well as the adaptive response induced by gamma ray exposure were determined in murine leukocytes in vivo. The damage-repair kinetics were established after the exposure to 0.5, 1.0 or 2.0 Gy in a {sup 137}Cs source. Peripheral blood samples were obtained from the tails of mice, the percentage of damaged cells and the DNA migration in each one were analyzed by the single cell gel electrophoresis (SCG) technique or comet assay. Results indicated that there was an induction of approximately 75% comets with the doses of 1.0 and 2.0 Gy, which was considerably reduced to 22% and 42% respectively during the first 15 minutes. This evidences the presence of a rapid repair process and suggests that leucocytes are genetically well prepared to repair this kind of damage. After 15 minutes, a second increase in the percentage of damaged cells that was proportional to dose occurred, which seems to represent the breaks produced during the repair of other kind of lesions. After that a second reduction was observed, reaching values near to the basal ones, except with the dose of 2.0 Gy. The kinetics obtained with the dose of 0.5 Gy was similar to that established with 1.0 Gy, but in this case the initial damage was 50 % lower. Besides, the adaptive response was observed after the exposure of the mice to an adaptive dose of 0.01 Gy and to a challenge dose of 1.0 Gy 60 minutes later. The pretreatment reduced the percentage of damaged cells caused by the challenge dose to one third approximately, and also diminished this parameter produced during the late repair process. This indicates that the early adaptive response is caused, instead of by an increment in repair, by the induction of a process that protects DNA from damage induction by radiation, i.e synthesis of substances that increase the scavenging of free radicals. (Author)

  16. Generating region proposals for histopathological whole slide image retrieval.

    Science.gov (United States)

    Ma, Yibing; Jiang, Zhiguo; Zhang, Haopeng; Xie, Fengying; Zheng, Yushan; Shi, Huaqiang; Zhao, Yu; Shi, Jun

    2018-06-01

    Content-based image retrieval is an effective method for histopathological image analysis. However, given a database of huge whole slide images (WSIs), acquiring appropriate region-of-interests (ROIs) for training is significant and difficult. Moreover, histopathological images can only be annotated by pathologists, resulting in the lack of labeling information. Therefore, it is an important and challenging task to generate ROIs from WSI and retrieve image with few labels. This paper presents a novel unsupervised region proposing method for histopathological WSI based on Selective Search. Specifically, the WSI is over-segmented into regions which are hierarchically merged until the WSI becomes a single region. Nucleus-oriented similarity measures for region mergence and Nucleus-Cytoplasm color space for histopathological image are specially defined to generate accurate region proposals. Additionally, we propose a new semi-supervised hashing method for image retrieval. The semantic features of images are extracted with Latent Dirichlet Allocation and transformed into binary hashing codes with Supervised Hashing. The methods are tested on a large-scale multi-class database of breast histopathological WSIs. The results demonstrate that for one WSI, our region proposing method can generate 7.3 thousand contoured regions which fit well with 95.8% of the ROIs annotated by pathologists. The proposed hashing method can retrieve a query image among 136 thousand images in 0.29 s and reach precision of 91% with only 10% of images labeled. The unsupervised region proposing method can generate regions as predictions of lesions in histopathological WSI. The region proposals can also serve as the training samples to train machine-learning models for image retrieval. The proposed hashing method can achieve fast and precise image retrieval with small amount of labels. Furthermore, the proposed methods can be potentially applied in online computer-aided-diagnosis systems. Copyright

  17. Breast ultrasonographic and histopathological characteristics without any mammographic abnormalities

    International Nuclear Information System (INIS)

    Tamaki, Kentaro; Kamada, Yoshihiko; Uehara, Kano; Tamaki, Nobumitsu; Ishida, Takanori; Miyashita, Minoru; Amari, Masakazu; Ohuchi, Noriaki; Sasano, Hironobu

    2012-01-01

    We evaluated ultrasonographic findings and the corresponding histopathological characteristics of breast cancer patients with Breast Imaging Reporting and Data System (BI-RADS) category 1 mammogram. We retrospectively reviewed the ultrasonographic findings and the corresponding histopathological features of 45 breast cancer patients with BI-RADS category 1 mammogram and 537 controls with mammographic abnormalities. We evaluated the ultrasonographic findings including mass shape, periphery, internal and posterior echo pattern, interruption of mammary borders and the distribution of low-echoic lesions, and the corresponding histopathological characteristics including histological classification, hormone receptor and human epidermal growth factor receptor 2 status of invasive ductal carcinoma and ductal carcinoma in situ, histological grade, mitotic counts and lymphovascular invasion in individual cases of BI-RADS category 1 mammograms and compared with those of the control group. The ultrasonographic characteristics of the BI-RADS category 1 group were characterized by a higher ratio of round shape (P<0.001), non-spiculated periphery (P=0.021), non-interruption of mammary borders (P<0.001) and non-attenuation (P=0.011) compared with the control group. A total of 52.6% of low-echoic lesions were associated with spotted distribution in the BI-RADS 1 group, whereas 25.8% of low-echoic lesions were associated with spotted distribution in the control group (P=0.012). As for histopathological characteristics, there was a statistically higher ratio of triple-negative subtype (P=0.021), and this particular tendency was detected in histological grade 3 in the BI-RADS category 1 group (P=0.094). We evaluated ultrasonographic findings and the corresponding histopathological characteristics for BI-RADS category 1 mammograms and noted significant differences among these findings in this study. Evaluation of these ultrasonographic and histopathological characteristics may provide

  18. Delay in the histopathologic diagnosis of mycosis fungoides

    DEFF Research Database (Denmark)

    Guldhammer Skov, Anne; Gniadecki, Robert

    2015-01-01

    The diagnosis of mycosis fungoides (MF) is difficult in early stages and is based on a combination of clinical findings and histopathologic criteria. The aim of this study was to assess the diagnostic delay in MF and to investigate the rationale for multiple biopsies in a single-centre, retrospec......The diagnosis of mycosis fungoides (MF) is difficult in early stages and is based on a combination of clinical findings and histopathologic criteria. The aim of this study was to assess the diagnostic delay in MF and to investigate the rationale for multiple biopsies in a single...

  19. Diffusion, Perfusion, and Histopathologic Characteristics of Desmoplastic Infantile Ganglioglioma.

    Science.gov (United States)

    Ho, Chang Y; Gener, Melissa; Bonnin, Jose; Kralik, Stephen F

    2016-07-01

    We present a case series of a rare tumor, the desmoplastic infantile ganglioglioma (DIG) with MRI diffusion and perfusion imaging quantification as well as histopathologic characterization. Four cases with pathologically-proven DIG had diffusion weighted imaging (DWI) and two of the four had dynamic susceptibility contrast imaging. All four tumors demonstrate DWI findings compatible with low-grade pediatric tumors. For the two cases with perfusion imaging, a higher relative cerebral blood volume was associated with higher proliferation index on histopathology for one of the cases. Our results are discussed in conjunction with a literature review.

  20. Histopathological alterations in neonate after in utero irradiation of rats

    International Nuclear Information System (INIS)

    Abdel Gawad, I.I.

    2000-01-01

    Series of experiments were performed to study the histopathological changes induced in embryonic tissue during various stages of gestation in female rats after gamma irradiation. Pregnant rats were exposed to doses 0.5, 1,2 and 3 Gy on 9 th 12 th and 15 th days of gestation. Histopathological changes were detected in tissues of neonates, namely, liver ileum, kidney, brain, spleen, suprarenal, thymus, lungs and heart. These tissues showed variable degrees of radiation induced tissue changes. For quantifying these changes arbitrary scores were formulated to assess the type and severity of changes observed tissues of thirty six neonates randomly selected after radiation exposure of pregnant animals as scheduled

  1. Histopathological and biochemical evidence of hepatopancreatic toxicity caused by cadmium in white shrimp, Palaemonetes argentinus.

    Science.gov (United States)

    Chiodi Boudet, L N; Polizzi, P; Romero, M B; Robles, A; Marcovecchio, J E; Gerpe, M S

    2015-03-01

    Cadmium (Cd) is one of the most common pollutants in the environment and induces a range of tissue changes or damages and organ dysfunction. The histopathological effects of Cd and lipid peroxidation (LPO) on hepatopancreas of the freshwater shrimp, Palaemonetes argentinus, were studied. Shrimp were obtained from two lagoons with contrasting environmental quality, De los Padres (LP, impacted site) and Nahuel Rucá (NR, reference site), and were exposed to 3.06 and 12.24µgCdL(-1) for 3, 7, 10 and 15 days. The health status of both populations was also evaluated by histological analysis of control individuals. After exposure, shrimp were transferred to clean water for 28 days to evaluate the recuperation capacity of hepatopancreas. Control shrimp from NR exhibited a normal hepatopancreas structure; unlike control shrimp from LP which showed several alterations. These results were attributed to the different environmental quality of lagoons. The exposure to Cd resulted in several alterations in the histological structure of the hepatopancreas of both populations. The observed alterations included haemocytic and connective infiltrations in the intertubular space, erosioned microvilli, ripple of basal lamina, atrophied epithelium and necrosis, however, the latter was only observed in shrimp from LP. The exposure also caused an increase of LPO levels in both populations. P. argentinus was able to repair the hepatopancreas structure from the damage caused by Cd, evidenced by the histopathological results and LPO levels. Obtained results are indicating that the histological analysis of the hepatopancreas proved to be a highly sensitive method for evaluating water quality, in both environmental and laboratory conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Handbook of Equipment Repair.

    Science.gov (United States)

    1981-05-14

    state of leapin- fn’rw.rd. Tn recent years, many mechanical repair workers often write and ask us to reprint the book. In our consideration, however...ast 4iron 1. .-eat _--OSIS-RTS 5.5 . . 4-5 t4- cast -3.01 -6 ~.0 ’ ɘ.᝱ 5,,:e j?24 2 * 10- 5 aron C l 50 S lcon : Ielt rSSIS-RQTS-s;.4 u a 2.47 5at- .0

  3. Immobilization After Rotator Cuff Repair: What Evidence Do We Have Now?

    Science.gov (United States)

    Hsu, Jason E; Horneff, John G; Gee, Albert O

    2016-01-01

    Recurrent tears after rotator cuff repair are common. Postoperative rehabilitation after rotator cuff repair is a modifiable factor controlled by the surgeon that can affect re-tear rates. Some surgeons prefer early mobilization after rotator cuff repair, whereas others prefer a period of immobilization to protect the repair site. The tendon-healing process incorporates biochemical and biomechanical responses to mechanical loading. Healing can be optimized with controlled loading. Complete load removal and chronic overload can be deleterious to the process. Several randomized clinical studies have also characterized the role of postoperative mobilization after rotator cuff repair. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Impact of radiotherapy on PBMCs DNA repair capacity - Use of a multiplexed functional repair assay

    International Nuclear Information System (INIS)

    Sauvaigo, S.; Sarrazy, F.; Breton, J.; Caillat, S.; Chapuis, V.

    2012-01-01

    Radiation therapy is an essential part of cancer treatment as about 50% of patients will receive radiations at least once. Significant broad variation in radiosensitivity has been demonstrated in patients. About 5-10% of patients develop acute toxicity after radiotherapy. Therefore there is a need for the identification of markers able to predict the occurrence of adverse effects and thus adapt the radiotherapy regimen for radiosensitive patients. As a first step toward this goal, and considering the DNA repair defects associated with hypersensitivity radiation syndromes, we investigated the DNA repair phenotype of patients receiving radiotherapy. More precisely, we used a functional repair assay on support to follow the evolution of the glycosylases/AP endonuclease activities of PBMCs extracts of a series of patients during the time course of radiotherapy. For each patient, we collected one PBMCs sample before the first radiotherapy application (S1) and three samples after (S2 to S4) (one day and one week after application 1, and one at the end of the radiotherapy protocol). These four samples have been analysed for 11 donors. Clustering analyses of the results demonstrated a great heterogeneity of responses among the patients. Interestingly, this heterogeneity decreased between S1 and S4 where only 2 classes of patients remained if we except one patient that exhibited an atypical DNA repair phenotype. Furthermore, we showed that repair of several oxidized bases significantly increased between S1 and S3 or S4 (8oxoG, thymine glycol, A paired with 8oxoG), suggesting an adaptation of patients repair systems to the oxidative stress generated by the ionising radiations. Our preliminary results provided evidence that the DNA repair phenotype was impacted by the radiotherapy regimen. Further characterization of patients with known repair defects are needed to determine if atypical repair phenotypes could be associated with radiotherapy complications. Finally

  5. Repair of radiation injury by transplantation of hemopoietic tissue

    International Nuclear Information System (INIS)

    Smith, L.H.

    1978-01-01

    The following topics are discussed: endogenous repair of tissue by surviving cells; exogenous repair by transplantation of tissue from unirradiated donor; repair of hematopoietic tissue following sublethal exposure or exposure in the LD 1 to LD 100 range; early studies on regeneration of hematopoietic tissue in x-irradiated dogs by giving bone marrow; hypotheses as to how bone marrow injections result in regeneration of blood-forming tissue; effects of rat bone marrow transplants on survival of lethally irradiated mice; and effect of tissue transplants on dose-response curve

  6. PRP as an Adjunct to Rotator Cuff Tendon Repair.

    Science.gov (United States)

    Barber, F Alan

    2018-06-01

    Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair.

  7. DNA repair mechanism in radioresistant bacteria

    International Nuclear Information System (INIS)

    Kitayama, Shigeru

    1992-01-01

    Many radiation resistant bacteria have been isolated from various sources which are not in high background field. Since Deinococcus radiodurans had been isolated first in 1956, studies on the mechanism for radioresistance were carried out mostly using this bacterium. DNA in this bacterium isn't protected against injury induced by not only ionizing radiation but also ultraviolet light. Therefore, DNA damages induced by various treatments are efficiently and accurately repaired in this cells. Damages in base and/or sugar in DNA are removed by endonucleases which, if not all, are synthesized during postirradiation incubation. Following the endonucleolytic cleavage the strand scissions in DNA are seemed to be rejoined by a process common for the repair of strand scissions induced by such as ionizing radiations. Induce protein(s) is also involved in this rejoining process of strand scissions. DNA repair genes were classified into three phenotypic groups. (1)Genes which are responsible for the endonucleolytic activities. (2) Genes involved in the rejoining of DNA strand scissions. (3) Genes which participate in genetic recombination and repair. Three genes belong to (1) and (2) were cloned onto approximately 1 kbp DNA fragments which base sequences have been determined. (author)

  8. Repair of the spondylolysis in lumbar spine

    International Nuclear Information System (INIS)

    Matta Ibarra, Javier; Arrieta Maria, Victor; Torres Romero Fernando; Ramirez Cabrales, Vladimir

    2005-01-01

    The objective is to present the surgical experience in the repair of the spondylolysis in lumbar spine. Background: Spodylolysis is an important cause of low back pain in young adults and is responsible for high grade of incapacity. Classically, patients with surgical indications with Spondylolysis have been treated with vertebral arthrodesis arthrodesis, with the following functional lost of the intervened segment and biomechanical overload of the upper contiguous segment. There are not previous reports about repairing of lysis in national literature and international references in this technique are scarce. Materials and methods: Eight patients within 2002-2004 were operated, a direct repairing of the lyses by in situ, fusion and interfragmental osteosynthesis with AO 3.5 mm titanium cortical screws with autogenous bone grafts was achieved. The casuistic was analyzed depending on clinical presentation, consolidation, mobility and vitality of the disc in imaginology studies. Results: During the follow-up a firm fusion in all cases, mobility and vitality preservation of the L5-S1 intervertebral disc was detected. There was neither infection nor neurological deficit. Recommendations: Repairing of spondylolysis in lumbar column, in young symptomatic patients without or with mild lystesis (grade I) and without associated disc damage, is a safe surgical technique

  9. DNA repair mechanism in radioresistant bacteria

    International Nuclear Information System (INIS)

    Kitayama, Shigeru

    1992-01-01

    Many radiation resistant bacteria have been isolated from various sources which are not in high background field. Since Deinococcus radiodurans had been isolated first in 1956, the studies on the mechanism of radioresistance were mostly carried out using this bacterium. DNA in this bacterium isn't protected against injury induced by not only ionizing radiation but also ultraviolet light. Therefore, DNA damages induced by various treatments are efficiently and accurately repaired in this cells. Damages in base and/or sugar in DNA are removed by endonucleases which, if not all, are synthesized during postirradiation incubation. Following the endonucleolytic cleavage the strand scissions in DNA are seemed to be rejoined by a process common for the repair of strand scissions induced by such as ionizing radiations. Induce protein(s) is also involved in this rejoining process of strand scissions. DNA repair genes were classified into three phenotypic groups. (1) Genes which are responsible for the endonucleolytic activities. (2) Genes involved in the rejoining of DNA strand scissions. (3) Genes which participate in genetic recombination and repair. Three genes belong to (1) and (2) were cloned onto approximately 1 kbp DNA fragments which base sequences have been determined. (author)

  10. Biomaterials based strategies for rotator cuff repair.

    Science.gov (United States)

    Zhao, Song; Su, Wei; Shah, Vishva; Hobson, Divia; Yildirimer, Lara; Yeung, Kelvin W K; Zhao, Jinzhong; Cui, Wenguo; Zhao, Xin

    2017-09-01

    Tearing of the rotator cuff commonly occurs as among one of the most frequently experienced tendon disorders. While treatment typically involves surgical repair, failure rates to achieve or sustain healing range from 20 to 90%. The insufficient capacity to recover damaged tendon to heal to the bone, especially at the enthesis, is primarily responsible for the failure rates reported. Various types of biomaterials with special structures have been developed to improve tendon-bone healing and tendon regeneration, and have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects. In this review, we first give a brief introduction of the anatomy of the rotator cuff and then discuss various design strategies to augment rotator cuff repair. Furthermore, we highlight current biomaterials used for repair and their clinical applications as well as the limitations in the literature. We conclude this article with challenges and future directions in designing more advanced biomaterials for augmentation of rotator cuff repair. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Laser-activated protein bands for peripheral nerve repair

    Science.gov (United States)

    Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

    1996-01-01

    A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

  12. Phytochemical, toxicological and histo-pathological studies of some ...

    African Journals Online (AJOL)

    The plants therefore possess some important biological activities that could be harnessed and employed beneficially in the management of viral and bacterial infections. Keywords: Phytochemistry; toxicology; histo-pathology; rat; medicinal plants; Nigeria International Journal of Natural and Applied Sciences Vol. 2 (3) 2006: ...

  13. Oral submucous fibrosis: A clinico-histopathological study in Chennai

    Directory of Open Access Journals (Sweden)

    Kiran Kumar K

    2007-01-01

    Full Text Available Background: Oral submucous fibrosis (OSF is a precancerous condition associated with the use of areca nut in various forms. There are very few reports to correlate the clinical stage to histopathological grading in OSF. Materials and Methods: A hospital-based study was conducted on 75 OSF cases who visited our hospital in Chennai from 2000-2003. A detailed history of each patient was recorded along with a clinical examination. Biopsy was performed for histopathological correlation. Clinical stage of the disease in terms of the ability to open one′s mouth was correlated with histopathological grading. Results: The male to female ratio of OSF cases was 6:1. All forms of areca nut products were associated with OSF. Chewing of paanmasala was associated with early presentation of OSF as compared to chewing of the betel nut. Out of 57 cases, which were in clinical stage II, 91.2% had histological grading of I and II in equal proportions and 8.8% had histological grade III. Out of 13 cases that showed a clinical stage of III, 52% showed a histological grade of II, 40% grade III and 8% grade I. Conclusion: In the present study, there was no direct correlation between clinical stages and histopathological grading. The possibility of difference in the severity and extent of fibrosis in different regions of the oral mucosa and involved muscles were considered as contributory factors for this variation.

  14. Perceived and Real Histopathology Turnaround Time: A Teaching ...

    African Journals Online (AJOL)

    2018-03-05

    Mar 5, 2018 ... Background: This study aims to audit analytic turnaround time (TAT) in a histopathology ... TAT was 3.6 ± 2 days, with 86.7% of reports being ready within 5 working days. ... The size of the institution, extent of automation, and number of ... advocates at least 10% rescreening of cytology slides for audit ...

  15. Histopathological findings in Becker-type muscular dystrophy

    NARCIS (Netherlands)

    ten Houten, R.; de Visser, M.

    1984-01-01

    Muscle biopsy specimens from 14 patients with Becker-type muscular dystrophy were analyzed to investigate possible neurogenic factors underlying the histopathological changes. Group atrophy, pyknotic nuclear clumps, and angular small fibers were seen respectively in 71%, 85%, and 100% of the cases.

  16. The oral mucosa in leprosy: a clinical and histopathological study.

    Science.gov (United States)

    de Abreu, Marilda Aparecida Milanez Morgado; Michalany, Nilceo Schwery; Weckx, Luc Louis Maurice; Neto Pimentel, Dalva Regina; Hirata, Cleonice Hitomi Watashi; de Avelar Alchorne, Maurício Mota

    2006-01-01

    Multibacillary leprosy may involve the oral mucosa, with or without apparent lesions. There are few studies that deal with this issue in the era of multidrug therapy. To assess the frequency of oral mucosa involvement in multibacillary leprosy patients. A transversal study with twenty non-treated multibacillary leprosy patients. The patients were treated in Dracena, São Paulo, between 2000 and 2002. Clinical examination of the oral mucosa was carried out. All patients were submitted to jugal mucosa, soft palate and tongue biopsies, in altered or in pre-established sites. The cross-sections were stained by techniques of hematoxilin-eosin and Ziehl-Neelsen. Granuloma and alcohol-acid-resistant bacilli findings determined the specific histopathological involvement. The study involved 19 patients with an average of 2.5 years of disease progression. Specific histopathological involvement occurred in the tongue and soft palate of one lepromatous patient with an apparently normal oral mucosa. (1) Clinical alterations in the oral mucosa does not imply disease involvement, it is necessary to have histopathological confirmation. (2) Apparent specific clinical alterations are rare. (3) The clinically normal oral mucosa can show specific histopathological involvement.

  17. Histopathological effects of lethal and sub-lethal concentrations of ...

    African Journals Online (AJOL)

    The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

  18. A 2-decade review of histopathological pattern of endometrial ...

    African Journals Online (AJOL)

    Background: Endometrial biopsy is a commonly performed procedure with a wide range of possible histopathological diagnoses. Objective: To determine the clinical spectrum, frequency and age distribution of endometrial pathologies at the University of Maiduguri Teaching Hospital (UMTH), Maiduguri. Methods: This was a ...

  19. Histopathological patterns in paediatric idiopathic steroid resistant nephrotic syndrome

    International Nuclear Information System (INIS)

    Shah, S.S.H.; Akhtar, N.; Rehman, M.F.U.; Sunbleen, F.; Ahmed, T.

    2015-01-01

    Background: Steroid-resistant nephrotic syndrome (SRNS) is a common problem but difficult to treat for pediatric nephrologists. Due to paucity of studies done in few centres in southern Pakistan regarding the histopathological aspects in paediatric patients with SRNS, this study was conducted to determine the histopathological spectrum in children with SRNS at our centre. Method: This descriptive study has been conducted at the Nephrology department, The Children's Hospital Lahore from February 2014 to January 2015. Based upon history, physical examination and laboratory results, all patients diagnosed as idiopathic SRNS were included in the study and renal biopsy was done to determine the underlying pathology. Histopathology reports were retrieved and data analysis done using SPSS-20.0. Results: There were a total of 96 patients, 64 (66.7 percentage) males and 32 (33.3 percentage) females. The age range was from 0.80 to 15 years with mean age of presentation being 6.34+3.75 years. The most common histo-pathological pattern was mesangio-proliferative Glomerulonephritis found in 79 (82.3 percentage) cases followed by Focal segmental glomerulosclerosis (FSGS) in 9 (9.4 percentage) patients while Minimal change disease (MCD) was seen in 5 (5.2 percentage) subjects. Conclusion: Mesangioproliferative glomerulonephritis is the most common histological pattern seen in children presenting with idiopathic SRNS at our centre followed by FSGS and MCD. (author)

  20. Histopathological Patterns of Endometrial Lesions in Patients with ...

    African Journals Online (AJOL)

    Mubeen

    Background: Endometrial diseases ranked among the most common gynecological disorders that affect women globally. These diseases cut across all age groups and contribute significantly to increased maternal morbidity and mortality. Due to the wide range of histopathological patterns,the need for urgent diagnosis and ...

  1. Clinical, Radiological, Microbiological, and Histopathological Aspects of Acquired Dacryocystoceles

    Directory of Open Access Journals (Sweden)

    Selam Yekta Sendul

    2014-01-01

    Full Text Available Purpose. The aim of this study is to investigate the etiology and the clinical, microbiological, histopathological, and radiological findings of acquired dacryocystoceles. Methods. In this retrospective study, we reviewed the clinical records of 10 eyes of 8 patients with dacryocystoceles who underwent external dacryocystorhinostomy (DCR surgery. Etiology, presenting symptoms and radiological findings as well as microbiological and histopathological assessment results and outcome were analyzed. Results. The records of 8 patients with dacryocystoceles were included in this study. In the histopathological evaluations of the samples collected from the lacrimal sac wall, chronic inflammation was found in all biopsied samples and fibrosis was observed in two histopathological evaluations. Computerized tomography (CT imaging showed fluid collection separated from adjacent tissues by a thin rim, corresponding to dacryocystoceles in the sac. In the microbiological culture examination of samples collected from the fluid within the cyst, no bacterial growth in 5 eyes, gram-negative bacillus growth in 3 eyes, and gram-positive cocci growth in 2 eyes were found. Conclusions. Acquired dacryocystoceles were observed extremely rarely and a definite pathogenic agent could not be identified in any of the cases, either microbiologically or histologically, whereas chronic inflammation was detected in all cases in our study.

  2. Effect of Hedera helix on lung histopathology in chronic asthma.

    Science.gov (United States)

    Hocaoglu, Arzu Babayigit; Karaman, Ozkan; Erge, Duygu Olmez; Erbil, Guven; Yilmaz, Osman; Kivcak, Bijen; Bagriyanik, H Alper; Uzuner, Nevin

    2012-12-01

    Hedera helix is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c mice were divided into four groups; I (Placebo), II (Hedera helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet cell numbers and thicknesses of basement membrane were found significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II. Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane in the asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of basement membrane better than Hedera helix.

  3. Clinical and Histopathological Evaluation of Cutaneous Pythiosis in Donkeys (Equusasinus

    Directory of Open Access Journals (Sweden)

    José Alberto Cardona Álvarez

    2013-06-01

    Full Text Available The purpose of this study was to evaluate and characterize the clinical and histopathological aspects of cutaneous pythiosis in donkeys (Equus asinus in the Department of Cordoba, Colombia. A descriptive, non-probability study was conducted on domesticated animals. Nine donkeys clinically and histopathologically diagnosed with cutaneous pythiosis were analyzed. After describing the cases, a serious, crater-shaped granulomatous ulcer was observed, with necrotic tissue, a tumor appearance, abundant fibrinous-bloody exudation and yellowish-white caseous material known as kunkers. The lesions were found in the members, ventral abdomen and chest of the animals. Histopathologically, with the hematoxylin-eosin staining, severe pyogranulomatous dermatitis was observed, with abundant eosinophilic and neutrophilic inflammatory infiltrate; with the Grocott staining, hyphae with septa were found, partially branching into a right angle and brown in color. The definitive diagnosis of the disease was based on the clinical features, the differential diagnosis and the histopathological findings. The diagnosis of cutaneous pythiosis was conclusive. This study becomes the first report of this disease in donkeys (Equus asinus in the department of Córdoba and in Colombia.

  4. Pericoronal radiolucencies with significant pathology: Clinico-histopathologic evaluation

    Directory of Open Access Journals (Sweden)

    Sanjeev Anand

    2015-04-01

    Full Text Available Background: The purpose of the study was to correlate the provisional diagnosis of pericoronal radiolucencies associated with impacted, embedded, or unerupted teeth with the histopathologic diagnosis, and also to emphasize the importance of early detection for better diagnosis and management. Methods: This is a retrospective study involving 18 cases of pericoronal radiolucencies associated with unerupted, embedded, or impacted teeth whose data during 1-year period were retrieved, and were reviewed for clinical, radiological, and histopathologic data. Also, comparison and correlation of clinico-histopathologic diagnosis was made. Results: Of the 18 cases, 11 were provisionally diagnosed as dentigerous cyst and the remaining were diagnosed as ameloblastoma, odontogenic keratocyst, adenomatoid odontogenic tumor, and calcifying epithelial odontogenic cyst. Histopathologic diagnosis of the 18 cases showed varied results, with only 10% correlating with the provisional diagnosis. Conclusion: Although many pathological processes may present radiographically as pericoronal radiolucencies associated with unerupted teeth, the most common is the dentigerous cyst. Hence, it is crucial for the clinician to fully investigate all teeth that fail to erupt at the expected time, and promptly initiate appropriate assessment and management of suspected cystic lesions.

  5. Histopathology of the organs of Broiler Chickens exposed to flames ...

    African Journals Online (AJOL)

    Histopathology of the organs of broiler chickens exposed to the flame and fumes of refined petroleum product kerosene at varying distances over a period of 16hrs daily for 56 days in a poultry house were evaluated. Kerosene burning was simulated in a designed burner. Kerosene flame in a designed burner was placed 4, ...

  6. Piroxicam-Induced Hepatic and Renal Histopathological Changes in ...

    African Journals Online (AJOL)

    Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Methods: Animals were classified into a control group and 4 treated groups. Piroxicam was injected ...

  7. Omitting histopathology in wrist ganglions. A risky proposition

    Science.gov (United States)

    Zubairi, Akbar J.; Kumar, Santosh; Mohib, Yasir; Rashid, Rizwan H.; Noordin, Shahryar

    2016-01-01

    Objectives: To identify incidence and utility of histopathology in wrist ganglions. Methods: A retrospective study of 112 patients operated for wrist swellings between January 2009 and March 2014 at Aga Khan University Hospital, Karachi, Pakistan, was conducted. Medical records were reviewed for demographics, history, location and associated symptoms, provisional diagnosis and operative details. Histopathology reports were reviewed to confirm the final diagnosis. Results: One hundred and twelve patients were included in the study (34 males and 78 females) with a mean age of 28 ± 12 years. Ninety-five percent of ganglia were dorsally located and 85% were solitary in nature. Histopathology reports confirmed 107 as ganglion cysts, whereas 3 had giant cell tumor of tendon sheath and 2 were reported to be tuberculous tenosynovitis. Conclusion: Although most of the time, the clinical diagnosis conforms to the final diagnosis, the possibility of an alternate diagnosis cannot be ignored (4% in this study). We suggest routine histopathological analysis so that such diagnoses are not missed. PMID:27464871

  8. Helicobacter pylori and histopathological changes of gastric mucosa ...

    African Journals Online (AJOL)

    Helicobacter pylori and histopathological changes of gastric mucosa in Uganda population with varying prevalence of stomach cancer. ... Results: The severity of gastritis correlated with the presence of H. pylori in Ganda and Nyarwanda but not in Nkole. Intestinal metaplasia (IM) was observed in Nyarwanda and Nkole and ...

  9. Histopathological Study of Placentae in Low Birth Weight Babies in ...

    African Journals Online (AJOL)

    Histopathological Study of Placentae in Low Birth Weight Babies in India. JS Nigam, V Misra, P Singh, PA Singh, S Chauhan, B Thakur. Abstract. Background: The antenatal health-care given to pregnant women has great influence on the rates of perinatal death and morbidity. Amongst the different causes of perinatal ...

  10. Non-technical skills in histopathology: definition and discussion.

    Science.gov (United States)

    Johnston, Peter W; Fioratou, Evie; Flin, Rhona

    2011-09-01

    Health care is a high-risk industry, with most documented adverse incidents being associated with 'human factors' including cognitive and social skills termed 'non-technical skills'. Non-technical skills complement the diagnostic and specialist skills and professional attributes required by medical practitioners, including histopathologists, and can enhance the quality of practice and delivery of health-care services and thus contribute to patient safety. This review aims to introduce histopathologists to non-technical skills and how these pertain to everyday histopathological practice. Drawing from other domains in medicine, specifically anaesthesia and surgery, a variety of non-technical skills are identified and described in the context of histopathology to illustrate the role each plays, often collectively, in daily practice. The generic non-technical skills are defined as situation awareness, decision-making, communication, teamwork, leadership, managing stress and coping with fatigue. Example scenarios from histopathology are presented and the contributions to outcomes made by non-technical skills are explained. Consideration of these specific non-technical skills as a component in histopathology training may benefit practitioners as well as assuring patient safety. © 2011 Blackwell Publishing Limited.

  11. Regularity of laboratory supplies and delivery of histopathology ...

    African Journals Online (AJOL)

    Give the high turnaround time in the histopathology service, a computerized laboratory logistics and inventory management systems (LMIS) should be established at the health settings in the country in order to ensure continuous availability of laboratory supplies and improve the turnaround time in laboratory services.

  12. Regularity of laboratory supplies and delivery of histopathology ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    2015-06-23

    Jun 23, 2015 ... inventory management systems (LMIS) should be established at the health settings in the country in order to ensure continuous availability of laboratory supplies and improve the turnaround time in laboratory services. KEY WORDS: Laboratory; Supplies; Histopathology; Services. To cite: Mutagubya J, ...

  13. Clinico-histopathologic types of maxillofacial malignancies with ...

    African Journals Online (AJOL)

    Clinico-histopathologic types of maxillofacial malignancies with emphasis on sarcomas: A 10-year review. ... Sarcomas peaked in the third decade with 70% occurring below the age of 40 years. The maxilla and the mandible were the most afflicted sites in the maxillofacial region accounting for 52%. The patients on average

  14. Role of Surgeons in Determining Outcome of Histopathology ...

    African Journals Online (AJOL)

    Conclusion: To ensure the quality of histopathological diagnosis with minimal turnaround time, the surgeon plays a vital role by ensuring adequate and prompt fixation of tissue biopsies, put in the right container and accompanied by well labeled request cards. Keywords: Formalin, fixative, outcome, pathologist, surgeon ...

  15. Concordance between clinical and histopathologic diagnoses of oral mucosal lesions.

    Science.gov (United States)

    Patel, Kush J; De Silva, Harsha L; Tong, Darryl C; Love, Robert M

    2011-01-01

    To study the epidemiology of oral soft tissue lesions in New Zealand from 2002 to 2006 and to determine the concordance between the clinical diagnosis and the definitive histopathologic diagnosis achieved by general dental practitioners and by specialists. The details from biopsy referrals and the corresponding histopathologic reports of oral soft tissue lesions were recorded into a statistical software package, and the concordance between the clinical diagnosis and histopathologic diagnosis was determined for all the lesions. Most biopsies were benign lesions, and both clinician groups achieved a high diagnostic concordance for these lesions. However, when considering all lesion types, the overall concordance for both groups was a moderate 50.6%, with little difference between specialists and general dental practitioners, although specialists were more accurate in diagnosing a malignant or premalignant lesion. The clinical and histopathologic concordance achieved by oral health practitioners in New Zealand appears to be moderate. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Fanconi anemia and DNA repair.

    Science.gov (United States)

    Grompe, M; D'Andrea, A

    2001-10-01

    Fanconi anemia (FA) is an autosomal recessive disorder caused by defects in at least eight distinct genes FANCA, B, C, D1, D2, E, F and G. The clinical phenotype of all FA complementation groups is similar and is characterized by progressive bone marrow failure, cancer proneness and typical birth defects. The principal cellular phenotype is hypersensitivity to DNA damage, particularly interstrand DNA crosslinks. The FA proteins constitute a multiprotein pathway whose precise biochemical function(s) remain unknown. Five of the FA proteins (FANCA, C, E, F and G) interact in a nuclear complex upstream of FANCD2. FANCB and FANCD1 have not yet been cloned, but it is likely that FANCB is part of the nuclear complex and that FANCD1 acts downstream of FANCD2. The FA nuclear complex regulates the mono-ubiquitination of FANCD2 in response to DNA damage, resulting in targeting of this protein into nuclear foci. These foci also contain BRCA1 and other DNA damage response proteins. In male meiosis, FANCD2 also co-localizes with BRCA1 at synaptonemal complexes. Together, these data suggest that the FA pathway functions primarily as a DNA damage response system, although its exact role (direct involvement in DNA repair versus indirect, facilitating role) has not yet been defined.

  17. Improving Aviation Depot Level Repairable (AVDLR) Inventory and Repair Management

    National Research Council Canada - National Science Library

    Baird, Dennis

    1997-01-01

    .... Additionally, research was conducted to document the management process for determining repair requirements at the Naval Inventory Control Point Philadelphia and how those requirements are accepted...

  18. The timing of spontaneous detection and repair of naming errors in aphasia.

    Science.gov (United States)

    Schuchard, Julia; Middleton, Erica L; Schwartz, Myrna F

    2017-08-01

    This study examined the timing of spontaneous self-monitoring in the naming responses of people with aphasia. Twelve people with aphasia completed a 615-item naming test twice, in separate sessions. Naming attempts were scored for accuracy and error type, and verbalizations indicating detection were coded as negation (e.g., "no, not that") or repair attempts (i.e., a changed naming attempt). Focusing on phonological and semantic errors, we measured the timing of the errors and of the utterances that provided evidence of detection. The effects of error type and detection response type on error-to-detection latencies were analyzed using mixed-effects regression modeling. We first asked whether phonological errors and semantic errors differed in the timing of the detection process or repair planning. Results suggested that the two error types primarily differed with respect to repair planning. Specifically, repair attempts for phonological errors were initiated more quickly than repair attempts for semantic errors. We next asked whether this difference between the error types could be attributed to the tendency for phonological errors to have a high degree of phonological similarity with the subsequent repair attempts, thereby speeding the programming of the repairs. Results showed that greater phonological similarity between the error and the repair was associated with faster repair times for both error types, providing evidence of error-to-repair priming in spontaneous self-monitoring. When controlling for phonological overlap, significant effects of error type and repair accuracy on repair times were also found. These effects indicated that correct repairs of phonological errors were initiated particularly quickly, whereas repairs of semantic errors were initiated relatively slowly, regardless of their accuracy. We discuss the implications of these findings for theoretical accounts of self-monitoring and the role of speech error repair in learning. Copyright

  19. Histopathological Analysis of 422 Nononcological Hysterectomies in a University Hospital

    Directory of Open Access Journals (Sweden)

    Seda Ates

    2016-04-01

    Full Text Available Aim: The aim of the study was to evaluate the surgical indications, routes of surgery and the correlation between preoperative diagnosis and histopathological examination of hysterectomy specimens. Material and Method: Medical records and histopathological findings were reviewed and analyzed retrospectively, in 422 consecutive women who underwent hysterectomy over a two-year period from 2011 to 2014. Those with confirmed malignancy before operation were excluded. Cohen kappa statistics were used to measure agreement between preoperative clinical and postoperative histopathological diagnosis which was found to be fair with %u043A value being 0.4. Results: The mean age of our patients was 51.5 ± 8 years. The abdominal route was used in 378 cases (85.5%, the vaginal route in 55 patients (12.4% and the laparoscopic-assisted vaginal hysterectomy in 9 cases (2%. Abnormal uterine bleeding (28.9 % was the most common indication for hysterectomy. The histopathology of the endometrium prior to hysterectomy was reported in 75% of the cases and the most common finding was a secretory or proliferative endometrium. Leiomyomatous uterus was the most frequently encountered pathology (43.7% followed by coexistence of leiomyoma and adenomyosis (17.4% in hysterectomy specimens. Hysterectomy specimens may be unremarkable histopathologically, most of which are vaginal hysterectomies done for uterine prolapsed (kappa=0,407. Discussion: The correlation between the preoperative clinical and the pathological diagnosis were poor in cases with abdominal pain, abnormal uterine bleeding and fibroids. But there was a high correlation in cases with adnexial mass.

  20. Pediatric medicolegal autopsy in France: A forensic histopathological approach.

    Science.gov (United States)

    Delteil, Clémence; Tuchtan, Lucile; Torrents, Julia; Capuani, Caroline; Piercecchi-Marti, Marie-Dominique

    2018-01-01

    The aim of postmortem medicolegal examination in pediatric death is primarily to establish the circumstances and causes of death and to exclude child abuse. In France, pediatric death is systematically documented by medicolegal or medical autopsy. In case of medicolegal autopsy, the complementary examinations, requested and financed by justice, are rarely limited to a histopathological examination. However in medical autopsies other tools are available to the pathologist as toxicology, biochemistry and molecular biology. The purpose of this article is to evaluate the efficacy of forensic histopathology in pediatric forensic autopsies. We analyze the main causes of pediatric death in a forensic context. Between 2004 and 2015, 157 infant deaths were identified in Marseille university hospital. The forensic histopathology and autopsy reports of all 157 cases were available for systematic review. Medical or surgical causes represented 41,3% of deaths in our center, accidental causes 8.1% and child abuse 28,8%. The definitive diagnosis was made at autopsy in 30% of cases and at histopathological examination in 70% highlighting that forensic histopathology is an indispensable tool in pediatric medicolegal autopsies. Significant histological abnormalities may be detected in selected organs such as the brain, lungs, heart, liver, adrenal glands and kidneys in spite of macroscopically normal appearances. This justifies systematic sampling of all organs. Despite the implementation of the French sudden infant death protocol which recommends medical autopsies, too many pediatric autopsies are carried out in a medicolegal context. 30% of the cases remain without diagnosis at the end of the autopsy and histological examination. This number could be reduced by the contribution of others laboratory investigation. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Verweij Wim

    2007-01-01

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

  2. When is cartilage repair successful?

    International Nuclear Information System (INIS)

    Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S.; Schreiner, M.M.

    2017-01-01

    Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [de

  3. A biomechanical evaluation of all-inside 2-stitch meniscal repair devices with matched inside-out suture repair.

    Science.gov (United States)

    Ramappa, Arun J; Chen, Alvin; Hertz, Benjamin; Wexler, Michael; Grimaldi Bournissaint, Leandro; DeAngelis, Joseph P; Nazarian, Ara

    2014-01-01

    Many all-inside suture-based devices are currently available, including the Meniscal Cinch, FasT-Fix, Ultra FasT-Fix, RapidLoc, MaxFire, and CrossFix System. These different devices have been compared in various configurations, but to our knowledge, the Sequent meniscal repair device, which applies running sutures, has not been compared with the Ultra FasT-Fix, nor has it been compared with its suture, No. 0 Hi-Fi, using an inside-out repair technique. To assess the quality of the meniscal repair, all new devices should be compared with the gold standard: the inside-out repair. To that end, this study aims to compare the biomechanical characteristics of running sutures delivered by the Sequent meniscal repair device with 2 vertical mattress sutures applied using the Ultra FasT-Fix device and with 2 vertical mattress sutures using an inside-out repair technique with No. 0 Hi-Fi suture. Controlled laboratory study. Paired (medial and lateral), fresh-frozen porcine menisci were randomly assigned to 1 of 3 groups: Sequent (n = 17), Ultra FasT-Fix (n = 19), and No. 0 Hi-Fi inside-out repair (n = 20). Bucket-handle tears were created in all menisci and were subjected to repair according to their grouping. Once repaired, the specimens were subjected to cyclic loading (100, 300, and 500 cycles), followed by loading to failure. The Sequent and Ultra FasT-Fix device repairs and the suture repair exhibited low initial displacements. The Sequent meniscal repair device demonstrated the lowest displacement in response to cyclic loading. No. 0 Hi-Fi suture yielded the highest load to failure. With the development of the next generation of all-inside meniscal repair devices, surgeons may use these findings to select the method best suited for their patients. The Sequent meniscal repair device displays the least amount of displacement during cyclic loading but has a similar failure load to other devices.

  4. DNA repair: Dynamic defenders against cancer and aging

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet

  5. Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Tobias Peikert

    2012-01-01

    Full Text Available Fibrosing mediastinitis (FM and IgG4-related disease (IgG4-RD are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases. We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted.

  6. THE STUDY OF CLINICAL VARIATIONS AND HISTOPATHOLOGICAL FINDINGS IN POLYMORPHOUS LIGHT ERUPTION

    Directory of Open Access Journals (Sweden)

    Banoth Mohan Lal

    2016-07-01

    Full Text Available BACKGROUND Epstein. S in 1942 described PMLE under the name of Prurigo aestivalis. He first hypothesised that PMLE represents a form of delayed-type hypersensitivity response to an endogenous, cutaneous UV-induced antigen, because of the hours or days delay between sun exposure and manifestation of symptoms, and the histological appearance of lesional skin. Firm evidence; however, has been lacking and the responsible allergen has not been identified. PMLE a specific entity encompassing six clinical manifestations: Small erythematous papulovesicles, eczematous lesions, large papules, oedematous plaques, prurigo nodules and erythema multiforme-like lesions. The histological features of PMLE are characteristic, but not pathognomonic and vary with the different clinical presentation. A sincere effort has been put in this study to understand the clinical and histopathological features of polymorphic light lesions. The study is intended to help the practising physicians and dermatologists to diagnose the pathology on time and intervene before it develops into complications. METHODS Material for the present study consisted of 100 cases of clinically diagnosed untreated cases of polymorphous light eruption, who were attending the skin and STD and Leprosy Department, Kakatiya Medical College, Warangal, during January 2014 to Dec 2014 were selected for this study. The patients were selected randomly irrespective of age, sex, socioeconomic status. RESULTS Histopathology showed perivascular lymphocytic infiltration in the dermis in majority of our cases (93.33% and clinicohistopathological correlation was observed in most cases; hence apart from clinical examination, histopathological examination plays an important role in diagnosing PMLE. CONCLUSION 56 percent of the patients complained pruritus followed by burning. The study was similar to other studies in comparison.

  7. Impact of occupational mechanical exposures on risk of lateral and medial inguinal hernia requiring surgical repair

    DEFF Research Database (Denmark)

    Vad, Marie Vestergaard; Frost, Poul; Bay-Nielsen, Morten

    2012-01-01

    We undertook a register-based cohort study to evaluate exposure-response relations between cumulative occupational mechanical exposures, and risk of lateral and medial inguinal hernia repair.......We undertook a register-based cohort study to evaluate exposure-response relations between cumulative occupational mechanical exposures, and risk of lateral and medial inguinal hernia repair....

  8. Engineered Heart Repair.

    Science.gov (United States)

    Fujita, B; Zimmermann, W-H

    2017-08-01

    There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  9. An integrated view of molecular changes, histopathology and outcomes in kidney transplants.

    Science.gov (United States)

    Halloran, P F; de Freitas, D G; Einecke, G; Famulski, K S; Hidalgo, L G; MengeL, M; Reeve, J; Sellares, J; Sis, B

    2010-10-01

    Data-driven approaches to deteriorating kidney transplants, incorporating histologic, molecular and HLA antibody findings, have created a new understanding of transplant pathology and why transplants fail. Transplant dysfunction is best understood in terms of three elements: diseases, the active injury-repair response and the cumulative burden of injury. Progression to failure is mainly attributable to antibody-mediated rejection, nonadherence and glomerular disease. Antibody-mediated rejection usually develops late due to de novo HLA antibodies, particularly anti-class II, and is often C4d negative. Pure treated T cell-mediated rejection does not predispose to graft loss because it responds well, even with endothelialitis, but it may indicate nonadherence. The cumulative burden of injury results in atrophy-fibrosis (nephron loss), arterial fibrous intimal thickening and arteriolar hyalinosis, but these are not progressive without ongoing disease/injury, and do not explain progression. Calcineurin inhibitor toxicity has been overestimated because burden-of-injury lesions invite this default diagnosis when diseases such as antibody-mediated rejection are missed. Disease/injury triggers a stereotyped active injury-repair response, including de-differentiation, cell cycling and apoptosis. The active injury-repair response is the strongest correlate of organ function and future progression to failure, but should always prompt a search for the initiating injury or disease.

  10. Laser-activated protein solder for peripheral nerve repair

    Science.gov (United States)

    Trickett, Rodney I.; Lauto, Antonio; Dawes, Judith M.; Owen, Earl R.

    1995-05-01

    A 100 micrometers core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the albumin based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 +/- 5 min. (n equals 20) compared to 23 +/- 9 min. (n equals 10) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 +/- 5 g, while microsutured nerves had a tensile strength of 40 +/- 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study is under way comparing laser solder repaired tibial nerves to conventional microsuture repair. At the time of submission 15 laser soldered nerves and 7 sutured nerves were characterized at 3 months and showed successful regeneration with compound muscle action potentials of 27 +/- 8 mV and 29 +/- 8 mW respectively. A faster, less damaging and long lasting laser based anastomotic technique is presented.

  11. Cellular responses to environmental DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

  12. Types of repair in radiosensitive organs of mice subjected to continuous γ-irradiation

    International Nuclear Information System (INIS)

    Li Yuanmin; Hu Fenghua; Gao Yabin

    1990-01-01

    LACA mice were whole-body irradiated with 1 Gy continuous γ-irradiation for 22 hours daily. Animals were divided into groups according to different cumulative doses of 10, 15, 20, 25 and 30 Gy, and were sacrificed at different intervals after the termination of irradiation when the above doses were reached. Radiosensitive organs were stduied by determination of quantitative indices and microscopic examination of histopathological sections. Three types of repair of radiation damages were found in radiosensitive organs, i.e. (1) full repair during irradiation in small intestines, (2) repair only after cessation of irradiation in hemopoietic and lymphoid tissues, and (3) continuing damage even after cessation of irradiation in testes

  13. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

    Directory of Open Access Journals (Sweden)

    Palittiya Sintusek

    Full Text Available Gastrointestinal (GI defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA. Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.

  14. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

    Science.gov (United States)

    Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H.; Morgan, Jennifer E.; Muntoni, Francesco; Zhou, Haiyan

    2016-01-01

    Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. PMID:27163330

  15. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  16. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    Seed, T.M.

    1994-01-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d -1 ). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

  17. Agreement Between Cytology and Histopathology for Regional Lymph Node Metastasis in Dogs With Melanocytic Neoplasms.

    Science.gov (United States)

    Grimes, Janet A; Matz, Brad M; Christopherson, Pete W; Koehler, Jey W; Cappelle, Kelsey K; Hlusko, Katelyn C; Smith, Annette

    2017-07-01

    Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κ w ) or kappa (κ) analysis (original cytology vs cytology review κ w = 0.24; original cytology vs original histopathology κ w = 0.007; original cytology vs histopathology review κ w = 0.23; cytology review vs original histopathology κ w = 0.008; cytology review vs histopathology review κ w = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.

  18. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Mapping of repair genes

    International Nuclear Information System (INIS)

    Hori, Tadaaki

    1985-01-01

    Chromosome mapping of repair genes involved in U.V. sensitivity is reported. Twenty-three of 25 hybrid cells were resistant to U.V. light. Survival curves of 2 U.V.-resistant cell strains, which possessed mouse chromosomes and human chromosome No.7 - 16, were similar to those of wild strain (L5178Y). On the other hand, survival curves of U.V.-sensitive hybrid cells was analogous to those of Q31. There was a definitive difference in the frequency of inducible chromosome aberrations between U.V. resistant and sensitive mouse-human hybrid cells. U.V.-resistant cell strains possessed the ability of excision repair. Analysis of karyotype in hybrid cells showed that the difference in U.V. sensitivity is dependent upon whether or not human chromosome No.13 is present. Synteny test on esterase D-determining locus confirmed that there is an agreement between the presence of chromosome No.13 and the presence of human esterase D activity. These results led to a conclusion that human genes which compensate recessive character of U.V.-sensitive mutant strain, Q31, with mouse-human hybrid cells are located on the locus of chromosome No.13. (Namekawa, K.)

  20. A lncRNA to repair DNA

    DEFF Research Database (Denmark)

    Lukas, Jiri; Altmeyer, Matthias

    2015-01-01

    Long non-coding RNAs (lncRNAs) have emerged as regulators of various biological processes, but to which extent lncRNAs play a role in genome integrity maintenance is not well understood. In this issue of EMBO Reports, Sharma et al [1] identify the DNA damage-induced lncRNA DDSR1 as an integral...... player of the DNA damage response (DDR). DDSR1 has both an early role by modulating repair pathway choices, and a later function when it regulates gene expression. Sharma et al [1] thus uncover a dual role for a hitherto uncharacterized lncRNA during the cellular response to DNA damage....

  1. Etiopathogenetic, clinical and histopathological aspects regarding the involvement of dental focal infection in premature births with fetal hypotrophy.

    Science.gov (United States)

    Rîcă, Gabriel Radu; Badi, Claudia Paula; Rîcă, Ana Maria; Sîrbu, Carmen Mirela; Rîcă, Nicolae

    2014-01-01

    The study conducted on a total of 1344 preterm births, of which 403 hypotrophic fetuses births (between 2010-2012 within the Maternal Clinics of Craiova, Romania), studied the involvement of dental inflammatory infections in the chorioamnionitis onset. The possibility of transferring germs, toxins and degraded materials into the blood flow, and them entering the chorioamniotic structures is quite a common issue. Subclinically often evolving chorioamniotic membrane and its existence is clearly established after birth by histopathological and bacteriological examinations, being partially responsible for the growth delay of the conception product. Our study revealed this fact, by using clinical examinations, ultrasound exams, bacteriological determinations of the amniotic fluid and the placenta, alongside the histopathological examinations. The chorioamnionitis inflammatory process is responsible for premature birth, through a high synthesis of interleukins (IL) and prostaglandins, causing uterine contractions. Our IL-6 dosage determinations show its growth that can be considered a prediction marker for preterm birth.

  2. Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

    Science.gov (United States)

    Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

    2017-03-01

    Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation.

  3. Regulation of nucleotide excision repair through ubiquitination

    Institute of Scientific and Technical Information of China (English)

    Jia Li; Audesh Bhat; Wei Xiao

    2011-01-01

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

  4. Functional Tricuspid Regurgitation and Ring Annuloplasty Repair

    Directory of Open Access Journals (Sweden)

    William B. Weir, MD

    2018-01-01

    Full Text Available Functional tricuspid regurgitation (TR primarily arises from asymmetric dilation of the tricuspid annulus in the setting of right ventricular dysfunction and enlargement in response to left-sided myocardial and valvular abnormalities. Even if the TR is not severe at the time of mitral valve surgery, it can worsen and even appear late after successful mitral valve surgery, which portends a poor prognosis. Despite data demonstrating inferior outcomes in the presence of residual TR, surgical repair for functional TR remains underused. Acceptance of TR, in the presence of tricuspid annular dilation, may be unacceptable. Surgical repair should consist of placement of a rigid or semirigid annular ring, which has been shown to provide superior durability as compared with suture and flexible band techniques. Finally, percutaneous annuloplasty for correction of functional TR may allow treatment of patients with recurrent TR at high risk of reoperation.

  5. Genotoxic and histopathological biomarkers for assessing the effects of magnetic exfoliated vermiculite and exfoliated vermiculite in Danio rerio

    International Nuclear Information System (INIS)

    Cáceres-Vélez, Paolin Rocio; Fascineli, Maria Luiza; Koppe Grisolia, Cesar; Oliveira Lima, Emília Celma de; Sousa, Marcelo Henrique; Morais, Paulo César de; Bentes de Azevedo, Ricardo

    2016-01-01

    Magnetic exfoliated vermiculite is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. It was developed primarily to mitigate pollution, but the possible adverse impacts of its application have not yet been evaluated. In this context, the acute toxicity of magnetic exfoliated vermiculite and exfoliated vermiculite was herein assessed by genotoxic and histopathological biomarkers in zebrafish (Danio rerio). DNA fragmentation was statistically significant for all groups exposed to the magnetic exfoliated vermiculite and for fish exposed to the highest concentration (200 mg/L) of exfoliated vermiculite, whereas the micronucleus frequency, nuclear abnormalities and histopathological alterations were not statistically significant for the fish exposed to these materials. In the intestinal lumen, epithelial cells and goblet cells, we found the presence of magnetic exfoliated vermiculite and exfoliated vermiculite, but no alterations or presence of the materials-test in the gills or liver were observed. Our findings suggest that the use of magnetic exfoliated vermiculite and exfoliated vermiculite during standard ecotoxicological assays caused DNA damage in D. rerio, whose alterations may be likely to be repaired, indicating that the magnetic nanoparticles have the ability to promote genotoxic damage, such as DNA fragmentation, but not mutagenic effects. - Highlights: • MEV is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. • The use of MEV and EV during standard ecotoxicological assays caused DNA fragmentation in zebrafish. • The magnetic nanoparticles showed ability to promote genotoxic damage, but did not induce micronucleus in peripheral erythrocytes at 96 h of exposure. • The tested concentrations of MEV and EV do not cause significant histopathological alterations in the gills, liver and intestine of zebrafish.

  6. Genotoxic and histopathological biomarkers for assessing the effects of magnetic exfoliated vermiculite and exfoliated vermiculite in Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Cáceres-Vélez, Paolin Rocio; Fascineli, Maria Luiza; Koppe Grisolia, Cesar [Department of Genetics and Morphology, Institute of Biological Sciences, Brasília University, Brasília (Brazil); Oliveira Lima, Emília Celma de [Chemistry Institute, Federal University of Goiás, Goiânia (Brazil); Sousa, Marcelo Henrique [Green Nanotechnology Group, Faculty of Ceilândia, Brasília University, Brasília (Brazil); Morais, Paulo César de [Physics Institute, Brasília University, Brasília (Brazil); Huazhong University of Science and Technology, School of Automation, Wuhan 430074 (China); Bentes de Azevedo, Ricardo, E-mail: razevedo@unb.br [Department of Genetics and Morphology, Institute of Biological Sciences, Brasília University, Brasília (Brazil)

    2016-05-01

    Magnetic exfoliated vermiculite is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. It was developed primarily to mitigate pollution, but the possible adverse impacts of its application have not yet been evaluated. In this context, the acute toxicity of magnetic exfoliated vermiculite and exfoliated vermiculite was herein assessed by genotoxic and histopathological biomarkers in zebrafish (Danio rerio). DNA fragmentation was statistically significant for all groups exposed to the magnetic exfoliated vermiculite and for fish exposed to the highest concentration (200 mg/L) of exfoliated vermiculite, whereas the micronucleus frequency, nuclear abnormalities and histopathological alterations were not statistically significant for the fish exposed to these materials. In the intestinal lumen, epithelial cells and goblet cells, we found the presence of magnetic exfoliated vermiculite and exfoliated vermiculite, but no alterations or presence of the materials-test in the gills or liver were observed. Our findings suggest that the use of magnetic exfoliated vermiculite and exfoliated vermiculite during standard ecotoxicological assays caused DNA damage in D. rerio, whose alterations may be likely to be repaired, indicating that the magnetic nanoparticles have the ability to promote genotoxic damage, such as DNA fragmentation, but not mutagenic effects. - Highlights: • MEV is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. • The use of MEV and EV during standard ecotoxicological assays caused DNA fragmentation in zebrafish. • The magnetic nanoparticles showed ability to promote genotoxic damage, but did not induce micronucleus in peripheral erythrocytes at 96 h of exposure. • The tested concentrations of MEV and EV do not cause significant histopathological alterations in the gills, liver and intestine of zebrafish.

  7. Histopathology confirms white-nose syndrome in bats in Europe.

    Science.gov (United States)

    Pikula, Jiri; Bandouchova, Hana; Novotny, Ladislav; Meteyer, Carol U; Zukal, Jan; Irwin, Nancy R; Zima, Jan; Martínková, Natália

    2012-01-01

    White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans.

  8. Histopathology confirms white-nose syndrome in bats in Europe

    Science.gov (United States)

    Pikula, J.; Bandouchova, H.; Novotny, L.; Meteyer, C.U.; Zukal, J.; Irwin, N.R.; Zima, J.; Martinkova, N.

    2012-01-01

    White-nose syndrome, associated with the fungal skin infection geomycosis, caused regional population collapse in bats in North America. Our results, based on histopathology, show the presence of white-nose syndrome in Europe. Dermatohistopathology on two bats (Myotis myotis) found dead in March 2010 with geomycosis in the Czech Republic had characteristics resembling Geomyces destructans infection in bats confirmed with white-nose syndrome in US hibernacula. In addition, a live M. myotis, biopsied for histopathology during hibernation in April 2011, had typical fungal infection with cupping erosion and invasion of muzzle skin diagnostic for white-nose syndrome and conidiospores identical to G. destructans that were genetically confirmed as G. destructans. ?? Wildlife Disease Association 2012.

  9. Subcutaneous mercury injection by a child: A histopathology case report

    Directory of Open Access Journals (Sweden)

    Deepti Sukheeja

    2014-01-01

    Full Text Available Intentional subcutaneous injection of mercury by mentally healthy children is rare. Usually, it is seen as a part of suicidal attempt in severely depressed patients or by athletes to enhance their performance. We report a case of a 15-year-old child, inspired by a movie, who deliberately self-injected mercury subcutaneously into his forearm that led to the formation of a non-healing ulcer. Histopathology of the biopsy confirmed the diagnosis. A surgical procedure was thereby performed to treat the ulcer and reduce the blood and urinary levels of mercury. However, the patient did not develop clinical signs of chronic poisoning, proving that subcutaneous mercury injection has a low risk of systemic toxicity, and that histopathology plays an important role in diagnosis.

  10. Histopathological effects of doxorubicin on pancreas in male albino rats

    Directory of Open Access Journals (Sweden)

    I.A. Ali

    2015-06-01

    Full Text Available The aim of this study was to investigate the histopathological side effects of doxorubicin on pancreas tissue in male albino rats Rattus norvegicus. This study were used 55 adult rats (2.5-3.5 month of age. The rats divided into two groups, the first group include (35 rats. The second group were (20 rats. Microscopial examination of pancreas lesion demonstrated oedema around the acini, swelling of the epithelial cells of acini, occurance of cystic fibrosis (mucoviscidosis at the concentration of (4,5 mg/kg of body weight ,occurrence of small islets that form of few cells and exocrine-endocrine transformation. There were thickness in the walls of blood vessels, thrombus, congestion of blood vessels, we conclude, that doxorubicin had histopathological effect on pancreas in sub-acute doses more than chronic doses.

  11. Histopathological, Histomorphometrical, and Radiographical Evaluation of Injectable Glass-Ceramic-Chitosan Nanocomposite in Bone Reconstruction of Rat

    Directory of Open Access Journals (Sweden)

    Maryam Seyedmajidi

    2015-01-01

    Full Text Available Background. Bone defects following tumor resection and osteolysis due to bone lesions, periodontal tissue disorders, and bone reconstruction are challenges that surgeons face. Gass-ceramic-chitosan nanocomposite contains chitosan, a derivative of crustaceans’ exoskeleton. Methods. Thirty-two 6–8-week-old male Wistar rats were chosen. One hole on each right and left tibia was made. The right tibia holes were filled with injectable glass-ceramic-chitosan nanocomposite, and the left tibia holes were left empty. After 7, 14, 28, and 60 days, histopathological, histomorphometrical, and radiographical assessments were performed. Results. Radiographic density on days 7 and 14 was significantly higher in the right tibias than in the left tibias. Trabecular bone thickness, which was higher in the right tibias, increased from day 7 to day 60 in both right and left tibias, although not significantly. Conclusions. Glass-ceramic-chitosan nanocomposite is suggested for use in bone repair in cases of bone loss. More histopathological, histomorphometrical, and radiographical assessments are also recommended.

  12. Handbook of adhesive bonded structural repair

    CERN Document Server

    Wegman, Raymond F

    1992-01-01

    Provides repair methods for adhesive bonded and composite structures; identifies suitable materials and equipment for repairs; describes damage evaluation criteria and techniques, and methods of inspection before and after repair.

  13. [Constitutional mismatch repair deficiency syndrome

    NARCIS (Netherlands)

    Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

    2015-01-01

    BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

  14. Clamp wins pipe repair prize

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2001-04-01

    This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.

  15. Nucleotide excision repair in yeast

    NARCIS (Netherlands)

    Eijk, Patrick van

    2012-01-01

    Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The

  16. My journey to DNA repair.

    Science.gov (United States)

    Lindahl, Tomas

    2013-02-01

    I completed my medical studies at the Karolinska Institute in Stockholm but have always been devoted to basic research. My longstanding interest is to understand fundamental DNA repair mechanisms in the fields of cancer therapy, inherited human genetic disorders and ancient DNA. I initially measured DNA decay, including rates of base loss and cytosine deamination. I have discovered several important DNA repair proteins and determined their mechanisms of action. The discovery of uracil-DNA glycosylase defined a new category of repair enzymes with each specialized for different types of DNA damage. The base excision repair pathway was first reconstituted with human proteins in my group. Cell-free analysis for mammalian nucleotide excision repair of DNA was also developed in my laboratory. I found multiple distinct DNA ligases in mammalian cells, and led the first genetic and biochemical work on DNA ligases I, III and IV. I discovered the mammalian exonucleases DNase III (TREX1) and IV (FEN1). Interestingly, expression of TREX1 was altered in some human autoimmune diseases. I also showed that the mutagenic DNA adduct O(6)-methylguanine (O(6)mG) is repaired without removing the guanine from DNA, identifying a surprising mechanism by which the methyl group is transferred to a residue in the repair protein itself. A further novel process of DNA repair discovered by my research group is the action of AlkB as an iron-dependent enzyme carrying out oxidative demethylation. Copyright © 2013. Production and hosting by Elsevier Ltd.

  17. The journey of DNA repair

    OpenAIRE

    Saini, Natalie

    2015-01-01

    21 years ago, the DNA Repair Enzyme was declared “Molecule of the Year”. Today, we are celebrating another “year of repair”, with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.

  18. Historical development of the renal histopathology services in Malaysia.

    Science.gov (United States)

    Looi, Lai-Meng; Cheah, Phaik-Leng

    2009-06-01

    Western-style medicine was introduced to Malaya by the Portuguese, Dutch and British between the 1500s and 1800s. Although the earliest pathology laboratories were developed within hospitals towards the end of the 19th Century, histopathology emerged much later than the biochemistry and bacteriology services. The University Departments of Pathology were the pioneers of the renal histopathology diagnostic services. The Department of Pathology, University of Malaya (UM) received its first renal biopsy on 19 May 1968. Hospital Universiti Kebangsaan Malaysia (HUKM) and Hospital Universiti Sains Malaysia (HUSM) started their services in 1979 and 1987 respectively. It is notable that the early services in these University centres caterred for both the university hospitals and the Ministry of Health (MOH) until the mid-1990s when MOH began to develop its own services, pivoted on renal pathologists trained through Fellowship programmes. Currently, key centres in the MOH are Kuala Lumpur Hospital, Sultanah Aminah Hospital Johor Bahru and Malacca Hospital. With the inclusion of renal biopsy interpretation in the Master of Pathology programmes, basic renal histopathology services became widely available throughout the country from 2000. This subsequently filtered out to the private sector as more histopathologists embraced private practice. There is now active continuing professional development in renal histopathology through clinicopathological dicussions, seminars and workshops. Renal research on amyloid nephropathy, minimal change disease, IgA nephropathy, fibrillary glomerulonephritis, lupus nephritis and microwave technology have provided an insight into the patterns of renal pathology and changing criteria for biopsy. More recently, there has been increasing involvement of renal teams in clinical trials, particularly for lupus nephritis and renal transplant modulation.

  19. Histopathology confirms White-Nose Syndrome in bats in Europe

    Czech Academy of Sciences Publication Activity Database

    Pikula, J.; Banďouchová, H.; Novotný, L.; Meteyer, C. U.; Zukal, Jan; Irwin, N. R.; Zima, Jan; Martínková, Natália

    2012-01-01

    Roč. 48, č. 1 (2012), s. 207-211 ISSN 0090-3558 R&D Projects: GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : Geomyces destructans * geomycosis * histopathology * Myotis myotis * whitenose syndrome Subject RIV: EG - Zoology Impact factor: 1.271, year: 2012 http://www.jwildlifedis.org/content/48/1/207.full.pdf

  20. Comparative histopathology of Pityriasis versicolor and Pityrosporum folliculitis

    Directory of Open Access Journals (Sweden)

    Mittal R

    1992-01-01

    Full Text Available Twenty five cases each of pityriasis versicolor (PV and pityrosporum folliculitis (PF were selected for this study. Histopathologically in PV, spores and hyphae in spaghetti and meatball appearance in stratum corneum, and perivascular mononuclear infiltrate were seen. In PF, spores were inside the dilated hair follicles filled with keratin, perifollicular and perivascular mononuclear infiltration were seen. Basket weave hyperkeratosis, edema and disruption of collagen were seen in 88% cases of PF and have not been reported earlier.

  1. DNA repair in neurons: So if they don't divide what's to repair?

    Energy Technology Data Exchange (ETDEWEB)

    Fishel, Melissa L. [Department of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States) and Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202 (United States) and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States)]. E-mail: mkelley@iupui.edu

    2007-01-03

    Neuronal DNA repair remains one of the most exciting areas for investigation, particularly as a means to compare the DNA repair response in mitotic (cancer) vs. post-mitotic (neuronal) cells. In addition, the role of DNA repair in neuronal cell survival and response to aging and environmental insults is of particular interest. DNA damage caused by reactive oxygen species (ROS) such as generated by mitochondrial respiration includes altered bases, abasic sites, and single- and double-strand breaks which can be prevented by the DNA base excision repair (BER) pathway. Oxidative stress accumulates in the DNA of the human brain over time especially in the mitochondrial DNA (mtDNA) and is proposed to play a critical role in aging and in the pathogenesis of several neurological disorders including Parkinson's disease, ALS, and Alzheimer's diseases. Because DNA damage accumulates in the mtDNA more than nuclear DNA, there is increased interest in DNA repair pathways and the consequence of DNA damage in the mitochondria of neurons. The type of damage that is most likely to occur in neuronal cells is oxidative DNA damage which is primarily removed by the BER pathway. Following the notion that the bulk of neuronal DNA damage is acquired by oxidative DNA damage and ROS, the BER pathway is a likely area of focus for neuronal studies of DNA repair. BER variations in brain aging and pathology in various brain regions and tissues are presented. Therefore, the BER pathway is discussed in greater detail in this review than other repair pathways. Other repair pathways including direct reversal, nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination and non-homologous end joining are also discussed. Finally, there is a growing interest in the role that DNA repair pathways play in the clinical arena as they relate to the neurotoxicity and neuropathy associated with cancer treatments. Among the numerous side effects of cancer treatments, major

  2. Procedures for maintenance and repairs

    International Nuclear Information System (INIS)

    Pickel, E.

    1981-01-01

    After a general review of the operation experience in the history of more than 12 operating years, the organization in the plant will be shown with special aspect to quality assurance, capacity of the workshops and connected groups as radiation protection, chemical laboratories etc. The number, time intervals and manpower effort for the repeating tests will be discussed. Reasons and examples for back-fitting activities in the plant are given. Besides special repair and maintenance procedures as repair of the steam generators, in-service inspection of the reactor pressure vessel, repair of a feed-water pipe and repair of the core structure in the pressure vessel, the general system to handle maintenance and repair-work in the KWO-plant will be shown. This includes also the detailed planning of the annual refueling and revision of the plant. (orig./RW)

  3. CT and MR findings in retinoblastoma : correlation with histopathologic examination

    International Nuclear Information System (INIS)

    Park, Son Won; Han, Moon Hee; Chi, Je G.; Yu, Young Suk; Kim, Yeon Mee; Chung, Jin Haeng; Yu, In Kyu; Chang, Kee Hyun; Yeon, Kyung Mo

    1997-01-01

    To evaluate histopathologic correlation of the component of the lesion on CT and MR of retinoblastomas. Gross pathologic findings of 24 enucleated eyeballs in 24 patients with retinoblastomas were compared with preoperative CT (n=19) and MR (n=5) findings. In eight eyeballs, in which there were findings other than mass, histopathologic findings were reviewed and correlated with image findings. Retinal detachment and subretinal hemorrhage which were not detected on CT were demonstrated in two of eight eyeballs on histopathologic examination. In one eyeball, retinal detachment and subretinal effusion were detected on both CT and in a pathologic specimen. In two eyeballs with peripheral heterogeneous MR enhancement of the masses, tumor necrosis and calcification were demonstrated in the central non-emhancing portion of the mass, In two eveballs, linear soft tissue along the retina apart from the main mass were revealed as tumor spread along the retinal surface. In one patient, retinal thickening on MR was presumed to be an MR artifact and no lesion was found in the gross specimen. On CT, retinal detachment and subretinal hemorrhage associated with retinoblastoma can mimic mass, and tumor spread along the retinal surface can be seen as a linear retinal lesion. On MR, tumor necrosis and calcification can be a cause of heterogeneous enhancement

  4. Graph run-length matrices for histopathological image segmentation.

    Science.gov (United States)

    Tosun, Akif Burak; Gunduz-Demir, Cigdem

    2011-03-01

    The histopathological examination of tissue specimens is essential for cancer diagnosis and grading. However, this examination is subject to a considerable amount of observer variability as it mainly relies on visual interpretation of pathologists. To alleviate this problem, it is very important to develop computational quantitative tools, for which image segmentation constitutes the core step. In this paper, we introduce an effective and robust algorithm for the segmentation of histopathological tissue images. This algorithm incorporates the background knowledge of the tissue organization into segmentation. For this purpose, it quantifies spatial relations of cytological tissue components by constructing a graph and uses this graph to define new texture features for image segmentation. This new texture definition makes use of the idea of gray-level run-length matrices. However, it considers the runs of cytological components on a graph to form a matrix, instead of considering the runs of pixel intensities. Working with colon tissue images, our experiments demonstrate that the texture features extracted from "graph run-length matrices" lead to high segmentation accuracies, also providing a reasonable number of segmented regions. Compared with four other segmentation algorithms, the results show that the proposed algorithm is more effective in histopathological image segmentation.

  5. Automated Segmentation of Nuclei in Breast Cancer Histopathology Images.

    Science.gov (United States)

    Paramanandam, Maqlin; O'Byrne, Michael; Ghosh, Bidisha; Mammen, Joy John; Manipadam, Marie Therese; Thamburaj, Robinson; Pakrashi, Vikram

    2016-01-01

    The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E) stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP) algorithm on a Markov Random Field (MRF). The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods-Wienert et al. (2012) and Veta et al. (2013), which were tested using their own datasets.

  6. Automated Segmentation of Nuclei in Breast Cancer Histopathology Images.

    Directory of Open Access Journals (Sweden)

    Maqlin Paramanandam

    Full Text Available The process of Nuclei detection in high-grade breast cancer images is quite challenging in the case of image processing techniques due to certain heterogeneous characteristics of cancer nuclei such as enlarged and irregularly shaped nuclei, highly coarse chromatin marginalized to the nuclei periphery and visible nucleoli. Recent reviews state that existing techniques show appreciable segmentation accuracy on breast histopathology images whose nuclei are dispersed and regular in texture and shape; however, typical cancer nuclei are often clustered and have irregular texture and shape properties. This paper proposes a novel segmentation algorithm for detecting individual nuclei from Hematoxylin and Eosin (H&E stained breast histopathology images. This detection framework estimates a nuclei saliency map using tensor voting followed by boundary extraction of the nuclei on the saliency map using a Loopy Back Propagation (LBP algorithm on a Markov Random Field (MRF. The method was tested on both whole-slide images and frames of breast cancer histopathology images. Experimental results demonstrate high segmentation performance with efficient precision, recall and dice-coefficient rates, upon testing high-grade breast cancer images containing several thousand nuclei. In addition to the optimal performance on the highly complex images presented in this paper, this method also gave appreciable results in comparison with two recently published methods-Wienert et al. (2012 and Veta et al. (2013, which were tested using their own datasets.

  7. Histopathological and cytological correlation of tumors of breast

    Directory of Open Access Journals (Sweden)

    Sushma Yalavarthi

    2014-01-01

    Full Text Available Background :0 With the advent of fine needle aspiration cytology (FNAC, the approach to diagnosis and management of breast lesions has been revolutionized. Its accuracy in many situations can approach that of histopathology in providing an unequivocal diagnosis. Aim :0 The aim of this study is to examine the cytological details in aspirated smears from lumps in the breast and to evaluate the role of FNAC in improving the quality of diagnosis by comparing with histopathological features. Materials and Methods: Over a period of 2 years, 334 aspirations, including 16 bilateral were performed. Suppurative and inflammatory lesions and gynecomastia were excluded from the total aspirates. A total of 56 cases were followed-up by histopathologic examination. Results: Cytohistologic correlation was 73.68%, 42.85%, 94.44% for fibroadenoma, fibrocystic disease and duct cell carcinoma respectively. False positives were observed in proliferative lesions. No false negative cases observed. The sensitivity of the fine needle aspiration (FNA procedure was 100%, specificity, 88.5% and the predictive value of a positive result was 84%. Conclusion: Proliferative lesions may be misinterpreted as malignancy in FNA without complete clinical and mammographic details.

  8. Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

    Science.gov (United States)

    Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

    2013-03-01

    Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

  9. Parallel multiple instance learning for extremely large histopathology image analysis.

    Science.gov (United States)

    Xu, Yan; Li, Yeshu; Shen, Zhengyang; Wu, Ziwei; Gao, Teng; Fan, Yubo; Lai, Maode; Chang, Eric I-Chao

    2017-08-03

    Histopathology images are critical for medical diagnosis, e.g., cancer and its treatment. A standard histopathology slice can be easily scanned at a high resolution of, say, 200,000×200,000 pixels. These high resolution images can make most existing imaging processing tools infeasible or less effective when operated on a single machine with limited memory, disk space and computing power. In this paper, we propose an algorithm tackling this new emerging "big data" problem utilizing parallel computing on High-Performance-Computing (HPC) clusters. Experimental results on a large-scale data set (1318 images at a scale of 10 billion pixels each) demonstrate the efficiency and effectiveness of the proposed algorithm for low-latency real-time applications. The framework proposed an effective and efficient system for extremely large histopathology image analysis. It is based on the multiple instance learning formulation for weakly-supervised learning for image classification, segmentation and clustering. When a max-margin concept is adopted for different clusters, we obtain further improvement in clustering performance.

  10. The Histopathology of IgG4-Related Disease.

    Science.gov (United States)

    Avincsal, Mehmet Ozgur; Zen, Yoh

    2017-01-01

    IgG4-related disease is a multi-organ immune-mediated chronic fibroinflammatory condition characterized by elevated serum IgG4 concentrations, tumefaction, and tissue infiltration by IgG4-positive plasma cells. The exact etiology of IgG4-related disease remains unclear with no known role of the IgG4 molecule itself being identified. Although the pancreas and salivary glands are the main organs affected, the involvement of other organs has also been reported. This multi-organ disease mimics a large number of malignant, infectious, and inflammatory disorders; therefore, a prompt differential diagnosis is important for selecting the right therapeutic strategy. Early steroid therapy assists in preventing tissue fibrosis, parenchymal extinction, and severe functional impairments in the affected organs. The definitive and prompt diagnosis of IgG4-related disease requires both histopathological confirmation and clinicopathological correlations. A histopathological examination is mandatory to exclude neoplastic or inflammatory conditions that mimic IgG4-related disease. The histological changes that occur are basically similar in any organ manifestation, with several site-specific findings being recognized. This chapter summarizes general rules for the pathological examination of IgG4-related disease, as well as the histopathological features and differential diagnoses of major organ manifestations.

  11. A histopathological outlook on nephrotic syndrome: A pediatric perspective

    Directory of Open Access Journals (Sweden)

    M K Arif

    2016-01-01

    Full Text Available The developing world is observing changing histopathological patterns of idiopathic nephrotic syndrome (INS. However, the true burden of non-minimal change disease (non-MCD presenting as INS remains unestimated owing to a paucity of data on renal biopsies. Data were collected from January 2006 to June 2014 on 75 children up to 16 years of age who underwent renal biopsies for INS. Mean age at biopsy was 11.2 ± 3.7 years. The male to female ratio was 1.5:1. A total of 25 (33.3% children were steroid sensitive, 36 (48% were steroid resistant, 10 (13.3% were steroid dependent and 4 (5.3% came with relapse of nephrotic syndrome (NS. Focal segmental glomerulosclerosis (FSGS was the most common histopathological subtype observed in 35 (46.8% children followed by membranous glomerulonephritis (MGN in 11 (14.7%, membranoproliferative glomerulonephritis (MPGN and mesangioproliferative glomerulonephritis (MSGN in 4 (5.3% each and IgA nephropathy in one (1.3%. MCD was the histological lesion in 19 (25.3% children. The histopathology established FSGS as the main underlying cause of steroid resistant NS. The study highlights the emergence of non-MCD as the common cause of INS in the pediatric population and signifies the importance of renal biopsies in children with INS.

  12. Histopathological diagnosis of eyelid tumors in Chiang Mai University Hospital.

    Science.gov (United States)

    Nithithanaphat, Chanut; Ausayakhun, Sakarin; Wiwatwongwana, Damrong; Mahanupab, Pongsak

    2014-10-01

    To report the histopathological diagnosis ofeyelid tumors and to study the prevalence of eyelid tumors in Chiang Mai University Hospital Chiang Mai, Thailand. A retrospective review of medical and pathological records ofpatients diagnosed as eyelid tumor that underwent histopathological biopsy between January 2007 and December 2013 in Chiang Mai University Hospital was done. Three hundred sixteen cases of eyelid tumors were reviewed. The mean age at diagnosis was 54.2 +/- 19.6 years (range 1 month-99 years), women were 59.5% (n = 188) and men 40.5% (n = 128). The tumor sites were left lower eyelid (27.5%), right upper eyelid (24.4%), right lower eyelid (21.2%), and left upper eyelid (18.7%). There were 204 (64.6%) benign tumors and 112 (35.4%) malignant tumors. Nevi were the most common in benign group (16.4%) and basal cell carcinoma was the most common eyelid malignancy (18.0%). The most common histopathological diagnosis for benign eyelid tumor was nevus, while the most common malignant eyelid tumor was basal cell carcinoma at Chiang Mai University Hospital.

  13. The Histopathological Spectrum of Pyogenic Granuloma: A Case Series

    Directory of Open Access Journals (Sweden)

    Vinay Marla

    2016-01-01

    Full Text Available Background. Pyogenic granuloma is a reactive tumor-like lesion commonly affecting the oral cavity. These lesions usually appear as localized solitary nodule with a sessile or pedunculated base and colour varying from red, purplish, or pink, depending on the vascularity of the lesion. Pyogenic granuloma shows predilection for gingiva and is usually slow growing, but at times it shows rapid growth. The natural course of this lesion can be categorized into three distinct phases, namely, (i cellular phase, (ii capillary phase/vascular phase, and (iii involutionary phase. Histopathologically, pyogenic granuloma is classified into lobular capillary hemangioma (LCH and non-lobular capillary hemangioma (non-LCH. Case Presentation. In this series, four cases (varied age groups and both genders of pyogenic granuloma showing varying histopathological presentation in relation to its clinical course have been described. The lesion in its early phase reveals diffuse endothelial cells, with few budding into capillaries. Among the capillary phase, the LCH type shows numerous blood vessels organized into lobular aggregates whereas the non-LCH type does not show any such organization and resembles granulation tissue. The involutionary phase shows healing of the lesion and is characterized by extensive fibrosis in the connective tissue. Conclusion. In conclusion, knowledge of the various histopathological presentation of this lesion is necessary for proper identification.

  14. CT imaging and histopathological features of renal epithelioid angiomyolipomas

    International Nuclear Information System (INIS)

    Cui, L.; Zhang, J.-G.; Hu, X.-Y.; Fang, X.-M.; Lerner, A.; Yao, X.-J.; Zhu, Z.-M.

    2012-01-01

    Aim: To describe computed tomography (CT) imaging and histopathological manifestations of renal epithelioid angiomyolipomas (EAMLs) for better understanding and cognition in the diagnosis of this new category of renal tumours. Materials and methods: Clinical data and CT images from 10 cases of EAML were retrospectively analysed. All patients underwent CT with and without contrast medium administration, with multiplanar reconstruction (MPR) when needed. Results: Plain CT manifestations of EAMLs were a higher density of mass (10–25 HU) than renal parenchyma, bulging contour of the involved kidney, absence of fat, distinct edges without a lobulate appearance. Contrast-enhanced CT features were markedly heterogeneous enhancement (from rapid wash-in to slow wash-out), large tumour size without lobular appearance, complete capsule with distinct margins and frequent mild necrotic areas. Histopathological features were epithelioid cells with eosinophilic cytoplasm, large and deeply stained nuclei, and dense arrangement of tumour cells with patchy necrosis; diffuse sheets of epithelioid cells were positive for HMB-45 (melanoma-associated antigen) and negative for epithelial membrane antigen (EMA) staining. Conclusion: Multiple specific CT features correlated well with the histopathology and may play an important role in the primary diagnosis of EAMLs.

  15. Constrained Deep Weak Supervision for Histopathology Image Segmentation.

    Science.gov (United States)

    Jia, Zhipeng; Huang, Xingyi; Chang, Eric I-Chao; Xu, Yan

    2017-11-01

    In this paper, we develop a new weakly supervised learning algorithm to learn to segment cancerous regions in histopathology images. This paper is under a multiple instance learning (MIL) framework with a new formulation, deep weak supervision (DWS); we also propose an effective way to introduce constraints to our neural networks to assist the learning process. The contributions of our algorithm are threefold: 1) we build an end-to-end learning system that segments cancerous regions with fully convolutional networks (FCNs) in which image-to-image weakly-supervised learning is performed; 2) we develop a DWS formulation to exploit multi-scale learning under weak supervision within FCNs; and 3) constraints about positive instances are introduced in our approach to effectively explore additional weakly supervised information that is easy to obtain and enjoy a significant boost to the learning process. The proposed algorithm, abbreviated as DWS-MIL, is easy to implement and can be trained efficiently. Our system demonstrates the state-of-the-art results on large-scale histopathology image data sets and can be applied to various applications in medical imaging beyond histopathology images, such as MRI, CT, and ultrasound images.

  16. Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

    International Nuclear Information System (INIS)

    Cakir, Banu; Kirbas, Ismail; Demirhan, Beyhan; Tarhan, Nefise Cagla; Bozkurt, Alper; Ozcay, Figen; Coskun, Mehmet

    2009-01-01

    Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

  17. Conjunctival tumors in children: histopathologic diagnosis in 165 cases

    Directory of Open Access Journals (Sweden)

    Martin A. Zimmermann-Paiz

    2015-12-01

    Full Text Available ABSTRACT Purpose: Conjunctival tissue tumors have a varied presentation, and few series studies on pediatric patients have been published. The objective of this paper is to report the histopathologic diagnoses (spanning over 1988-2013 of conjunctival tumors in children younger than 14 years. Methods: We conducted a retrospective, descriptive, and observational study by reviewing the database of all children in whom a conjunctival tumor was surgically removed at Hospital de Ojos y Oídos "Dr. Rodolfo Robles V.," Benemérito Comité Pro Ciegos y Sordos de Guatemala. The data pertaining to gender, age, and histopathologic diagnosis of all cases was collected. The same ocular pathologist made all diagnoses. Results: One hundred sixty-five cases were found, with a mean age of 7.88 years, being 91 (55.15% male subjects. Melanocytic lesions were the most common tumors found (30.91% of cases, with only one case (0.60% being malignant. Conclusions: Melanocytic lesions were the most common tumors found, and of all the cases, only one was malignant; this was in a patient with xeroderma pigmentosum. These findings are consistent with those reported in other studies regarding the frequencies of the histopathology of conjunctival tumors in the pediatric population.

  18. Combinations of resting RSA and RSA reactivity impact maladaptive mood repair and depression symptoms.

    Science.gov (United States)

    Yaroslavsky, Ilya; Bylsma, Lauren M; Rottenberg, Jonathan; Kovacs, Maria

    2013-10-01

    We examined whether the combined indices of respiratory sinus arrhythmia at rest (resting RSA) and in response to a sad film (RSA reactivity) predict effective and ineffective responses to reduce sadness (adaptive vs. maladaptive mood repair) in women with histories of juvenile-onset depression (n=74) and no history of major mental disorders (n=75). Structural equation models were used to estimate latent resting RSA, depression, and adaptive and maladaptive mood repair and to test the study hypotheses. Results indicated that combinations of resting RSA+RSA reactivity (RSA patterns) predicted maladaptive mood repair, which in turn, mediated the effects of RSA pattern on depression. Further, RSA patterns moderated the depressogenic effects of maladaptive mood repair. RSA patterns were unrelated to adaptive mood repair. Our findings suggest that mood repair is one mechanism through which physiological vulnerabilities adversely affect mental health. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Hesperidin as radioprotector against radiation-induced lung damage in rat: A histopathological study

    Directory of Open Access Journals (Sweden)

    Gholam Hassan Haddadi

    2017-01-01

    Full Text Available Reactive oxygen species (ROS are generated by ionizing radiation, and one of the organs commonly affected by ROS is the lung. Radiation-induced lung injury including pneumonia and lung fibrosis is a dose-limiting factor in radiotherapy (RT of patients with thorax irradiation. Administration of antioxidants has been proved to protect against ROS. The present study was aimed to assess the protective effect of hesperidin (HES against radiation-induced lung injury of male rats. Fifty rats were divided into three groups. G1: Received no HES and radiation (sham. G2: Underwent γ-irradiation to the thorax. G3: Received HES and underwent γ-irradiation. The rats were exposed to a single dose of 18 Gy using cobalt-60 unit and were administered HES (100 mg/kg for 7 days before irradiation. Histopathological analysis was performed 24 h and 8 weeks after RT. Histopathological results in 24 h showed radiation-induced inflammation and presence of more inflammatory cells as compared to G1 (P < 0.05. Administration of HES significantly decreased such an effect when compared to G2 (P < 0.05. Histopathological evaluation in 8 weeks showed a significant increase in mast cells, inflammation, inflammatory cells, alveolar thickness, vascular thickness, pulmonary edema, and fibrosis in G2 when compared to G1 (P < 0.05. HES significantly decreased inflammatory response, fibrosis, and mast cells when compared to G2 (P < 0.05. Administration of HES resulted in decreased radiation pneumonitis and radiation fibrosis in the lung tissue. Thus, the present study showed HES to be an efficient radioprotector against radiation-induced damage in the lung of tissue rats.

  20. Wound repair in Pocillopora

    Science.gov (United States)

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo

    2016-01-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  1. Repairing Nanoparticle Surface Defects.

    Science.gov (United States)

    Marino, Emanuele; Kodger, Thomas E; Crisp, Ryan W; Timmerman, Dolf; MacArthur, Katherine E; Heggen, Marc; Schall, Peter

    2017-10-23

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We utilized atomically thin semiconductor nanoplatelets as a convenient platform for studying, both microscopically and spectroscopically, the development of defects during ligand exchange with the conductive ligands Na 4 SnS 4 and (NH 4 ) 4 Sn 2 S 6 . These defects can be repaired via mild chemical or thermal routes, through the addition of L-type ligands or wet annealing, respectively. This results in a higher-quality, conductive, colloidally stable nanomaterial that may be used as the active film in optoelectronic devices. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  2. Reward optimization of a repairable system

    Energy Technology Data Exchange (ETDEWEB)

    Castro, I.T. [Departamento de Matematicas, Facultad de Veterinaria, Universidad de Extremadura, Avenida de la Universidad, s/n. 10071 Caceres (Spain)]. E-mail: inmatorres@unex.es; Perez-Ocon, R. [Departamento de Estadistica e Investigacion Operativa, Facultad de Ciencias, Universidad de Granada, Avenida de Severo Ochoa, s/n. 18071 Granada (Spain)]. E-mail: rperezo@ugr.es

    2006-03-15

    This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures.

  3. Reward optimization of a repairable system

    International Nuclear Information System (INIS)

    Castro, I.T.; Perez-Ocon, R.

    2006-01-01

    This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures

  4. DNA Base Excision Repair (BER) and Cancer Gene Therapy: Use of the Human N-mythlpurien DNA Glycosylase (MPG) to Sensitize Breast Cancer Cells to Low Dose Chemotherapy

    National Research Council Canada - National Science Library

    Harvey, Tia

    2003-01-01

    The DNA Base Excision Repair (PER) pathway is responsible for the repair of alkylation and oxidative DNA damage resulting in protection against the deleterious effects of endogenous and exogenous agents encountered on a daily basis...

  5. Residual stress by repair welds

    International Nuclear Information System (INIS)

    Mochizuki, Masahito; Toyoda, Masao

    2003-01-01

    Residual stress by repair welds is computed using the thermal elastic-plastic analysis with phase-transformation effect. Coupling phenomena of temperature, microstructure, and stress-strain fields are simulated in the finite-element analysis. Weld bond of a plate butt-welded joint is gouged and then deposited by weld metal in repair process. Heat source is synchronously moved with the deposition of the finite-element as the weld deposition. Microstructure is considered by using CCT diagram and the transformation behavior in the repair weld is also simulated. The effects of initial stress, heat input, and weld length on residual stress distribution are studied from the organic results of numerical analysis. Initial residual stress before repair weld has no influence on the residual stress after repair treatment near weld metal, because the initial stress near weld metal releases due to high temperature of repair weld and then stress by repair weld regenerates. Heat input has an effect for residual stress distribution, for not its magnitude but distribution zone. Weld length should be considered reducing the magnitude of residual stress in the edge of weld bead; short bead induces high tensile residual stress. (author)

  6. Repair during multifraction exposures: spheroids versus monolayers

    International Nuclear Information System (INIS)

    Durand, R.E.

    1984-01-01

    Many type of mammalian cells, when grown in culture as multicell spheroids, display an increased ability to accumulate and repair sublethal radiation damage which has been called the ''contact effect''. Since this effect has the potential to markedly modify the multifraction radiation response of cells in V79 spheroids relative to cells in monolayer cultures, an investigation was made of regimens ranging from 1 to 100 fractions. Effective dose rates were chosen near 1 Gy h -1 to inhibit cell progression and thus simplify analysis of the results. As expected, larger doses per fraction produced more net cell killing in both systems than lower doses per fraction. Additionally, less killing of spheroid cells was observed in all regimens, in accord with their greater potential for repair. However, when the data were expressed as isoeffect curves, the spheroid and monolayer curves converged as the number of fractions increased. Thus, quite similar inherent sensitivity and repair capabilities would be predicted for ultra-low doses per fraction. High precision techniques for defining survival after doses of radiation from 0.2 to 1 Gy were, however, still able to demonstrate a survival advantage for cells grown as spheroids. (author)

  7. Histopathological effects of nanosilver (Ag-NPs in liver after dermal exposure during wound healing

    Directory of Open Access Journals (Sweden)

    Mohammad Saeed Heydarnejad

    2014-04-01

    Full Text Available   Objective(s: With the advent of nanotechnology, significant progress has been made in the area of nanoscale materials such as nanosilver (Ag-Nps. These nanoparticles have a wide range of applications and been used for antimicrobial purposes for more than a century. However, little attention has been paid to the toxicity of nanosilver wound dressing. This study was designed to investigate the possible histopathological toxicity of Ag-NPs in liver of mice during wound healing.     Materials and Methods:   A group of 50 female BALB/c mice of about 8 weeks were randomly divided into two groups: Ag-NPs and control groups (n=25. After creating similar wound on the backs of all animals, the wound bed was treated in Ag-NPs group, with a volume of 50 microliters of the nanosilver solution (10ppm ,and in control group, with the same amount of distilled water. The experiment lasted for 14 days. Histopathaological samplings of liver were conducted on days 2, 7 and 14 of the experiment.   Results: Histopathological studies demonstrated time-dependent changes in mice liver treated with Ag-NPs compared to control group. Some changes include dilation in central venous, hyperemia, cell swelling, increase of Kupffer and inflammatory cells. Conclusion: This study suggests that use of nanosilver for wound healing may cause a mild toxicity, as indicated by time-dependent toxic responses in liver tissue. However, this issue will have to be considered more extensively in further studies.

  8. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma.

    Science.gov (United States)

    Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Kozanoglu, Ilknur; Yilmaz, Osman; Uzuner, Nevin; Karaman, Ozkan

    2011-08-01

    Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n=6), Group 2 (ovalbumin induced asthma only, n=10), Group 3 (ovalbumin induced asthma + MSCs, n=10), and Group 4 (MSCs only, n=10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Feline sporotrichosis: histopathological profile of cutaneous lesions and their correlation with clinical presentation.

    Science.gov (United States)

    Miranda, Luisa H M; Conceição-Silva, Fátima; Quintella, Leonardo P; Kuraiem, Bianca P; Pereira, Sandro A; Schubach, Tânia M P

    2013-07-01

    Cutaneous lesions of feline sporotrichosis show high fungal load and are associated with severe disease and elevated zoonotic potential. The present study describes the histopathology and fungal load of the lesions in different clinical presentations of feline sporotrichosis. Cats with sporotrichosis were separated into groups L1, L2 and L3 (lesions in one, two and three or more locations, respectively) and subjected to skin biopsies for histopathology. Eighty-six cats were included in the study. Lesions were suppurative granulomatous in 84 cases and poorly formed granulomas were predominant. The well-formed granulomas were associated with group L1. The high fungal load was predominant in group L3 and in poorly formed granuloma cases and did not occur in well-formed granulomas cases. The good general condition was associated with low fungal load. These findings suggest that the fungal load control in animals with more localized lesions and well-organized response is linked with the improvement in the outcome of infected cats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

    Science.gov (United States)

    Carmona-Fonseca, Jaime; Arango, Eliana; Maestre, Amanda

    2013-01-01

    Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive. PMID:23546807

  11. Protracted radiation-induced alterations in hematopoietic repair and recovery

    International Nuclear Information System (INIS)

    Seed, T.M.; Fritz, T.E.

    1997-01-01

    Pathologic predisposition of beagle dogs under chronic, low daily dose (7.5 cGy day -1 ) whole-body gamma irradiation has been studied relative to molecular repair and hematopoietic competency. Molecular repair, assessed by a microscopy-based unscheduled DNA synthesis (UDS) response, was measured within proliferative and nonproliferative marrow myeloid elements of dogs with markedly different hematopoietic capacities (low capacity, aplasia-prone [AA + ] versus high capacity, myeloproliferative disease-prone [MPD + ]) under protracted radiation stress. Results indicated that protracted exposure elicited a net increase in UDS-repair capacity that was largely independent of exposure duration. This enhanced capacity resulted from the increased strength of the UDS signal together with an expanded number of positively responding cells. The combined response was strong in primitive blasts and weak in more differentiated myelocytic cells. The UDS repair response of the MPD + dogs was significantly greater than that of the AA + animals and was clearly modified relative to the controls. These results suggest that both resiliency and pathologic potential of the hematopoietic system under protracted radiation stress is, in part, associated with an augmentable DNA repair within the more primitive myeloid marrow elements. (author)

  12. Monogenic diseases of DNA repair

    DEFF Research Database (Denmark)

    Keijzers, Guido; Bakula, Daniela; Scheibye-Knudsen, Morten

    2017-01-01

    Maintaining the stability of the genome is essential for all organisms, and it is not surprising that damage to DNA has been proposed as an explanation for multiple chronic diseases.1-5 Conserving a pristine genome is therefore of central importance to our health. To overcome the genotoxic stress...... of a growing number of human diseases. Notably, many of these monogenic DNA-repair disorders display features of accelerated aging, supporting the notion that genome maintenance is a key factor for organismal longevity. This review focuses on the physiological consequences of loss of DNA repair, particularly...... in the context of monogenic DNA-repair diseases....

  13. Repairing and Upgrading Your PC

    CERN Document Server

    Thompson, Robert

    2009-01-01

    Repairing and Upgrading Your PC delivers start-to-finish instructions, simple enough for even the most inexperienced PC owner, for troubleshooting, repairing, and upgrading your computer. Written by hardware experts Robert Bruce Thompson and Barbara Fritchman Thompson, this book covers it all: how to troubleshoot a troublesome PC, how to identify which components make sense for an upgrade, and how to tear it all down and put it back together. This book shows how to repair and upgrade all of your PC's essential components.

  14. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Science.gov (United States)

    2010-07-01

    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a... killing or growth inhibition of repair deficient bacteria in a set of repair proficient and deficient...

  15. Male infertility after mesh hernia repair: A prospective study.

    Science.gov (United States)

    Hallén, Magnus; Sandblom, Gabriel; Nordin, Pär; Gunnarsson, Ulf; Kvist, Ulrik; Westerdahl, Johan

    2011-02-01

    Several animal studies have raised concern about the risk for obstructive azoospermia owing to vasal fibrosis caused by the use of alloplastic mesh prosthesis in inguinal hernia repair. The aim of this study was to determine the prevalence of male infertility after bilateral mesh repair. In a prospective study, a questionnaire inquiring about involuntary childlessness, investigation for infertility and number of children was sent by mail to a group of 376 men aged 18-55 years, who had undergone bilateral mesh repair, identified in the Swedish Hernia Register (SHR). Questionnaires were also sent to 2 control groups, 1 consisting of 186 men from the SHR who had undergone bilateral repair without mesh, and 1 consisting of 383 men identified in the general population. The control group from the SHR was matched 2:1 for age and years elapsed since operation. The control group from the general population was matched 1:1 for age and marital status. The overall response rate was 525 of 945 (56%). Method of approach (anterior or posterior), type of mesh, and testicular status at the time of the repair had no significant impact on the answers to the questions. Nor did subgroup analysis of the men ≤40 years old reveal any significant differences. The results of this prospective study in men do not support the hypothesis that bilateral inguinal hernia repair with alloplastic mesh prosthesis causes male infertility at a significantly greater rate than those operated without mesh. Copyright © 2011 Mosby, Inc. All rights reserved.

  16. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  17. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  18. Augmented Versus Nonaugmented Repair of Acute Achilles Tendon Rupture: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Zhang, Yi-Jun; Zhang, Chi; Wang, Quan; Lin, Xiang-Jin

    2017-04-01

    Although simple end-to-end repair of the Achilles tendon is common, many augmented repair protocols have been implemented for acute Achilles tendon rupture. However, whether augmented repair is better than nonaugmented repair of an acute Achilles tendon rupture is still unknown. To conduct a meta-analysis to determine whether augmented surgical repair of an acute Achilles tendon rupture improved subjective patient satisfaction without an increase in rerupture rates. Secondary outcomes assessed included infections, ankle range of motion, calf muscle strength, and minor complications. Meta-analysis. A systematic literature search of peer-reviewed articles was conducted to identify all randomized controlled trials (RCTs) comparing augmented repair and nonaugmented repair for acute Achilles tendon rupture from January 1980 to August 2016 in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE. The keywords (Achilles tendon rupture) AND (surg* OR operat* OR repair* OR augment* OR non-augment* OR end-to-end OR sutur*) were combined, and results were limited to human RCTs and controlled clinical trials published in the English language. Four RCTs involving 169 participants were eligible for inclusion; 83 participants were treated with augmented repair and 86 were treated with nonaugmented repair. Augmented repair led to similar responses when compared with nonaugmented repair for acute Achilles tendon rupture (93% vs 90%, respectively; P = .53). The rerupture rates showed no significant difference for augmented versus nonaugmented repair (7.2% vs 9.3%, respectively; P = .69). No differences in superficial and deep infections occurred in augmented (7 infections) and nonaugmented (8 infections) repair groups during postoperative follow-up ( P = .89). The average incisional infection rate was 8.4% with augmented repair and 9.3% with nonaugmented repair. No significant differences in other complications were found between augmented (7.2%) and

  19. Upper Gastrointestinal Involvement in Crohn Disease: Histopathologic and Endoscopic Findings.

    Science.gov (United States)

    Diaz, Liege; Hernandez-Oquet, Rafael Enrique; Deshpande, Amar R; Moshiree, Baharak

    2015-11-01

    Studies describing the prevalence of upper gastrointestinal (GI) Crohn disease (CD) and its histopathologic changes have been inconsistent as a result of different definitions used for upper GI involvement, diverse populations, and varying indications for endoscopy. We reviewed the literature describing endoscopic findings and histologic lesions in gastric and duodenal mucosa of patients with established CD. PubMed, EMBASE, and the Cochrane Library were searched for gastroduodenal biopsy findings in patients with CD from 1970 to 2014. We included all retrospective and prospective studies in adults. We calculated the prevalence of the most common endoscopic and histopathological findings among patients with overall CD and upper GI CD. Of the 385 articles identified, 20 eligible studies were included. A total of 2511 patients had CD and 815 had upper GI CD. In the CD group, the most common histopathological finding was nonspecific gastric inflammation in 32% of patients, followed by gastric granuloma in 7.9%. Focal gastritis was prevalent in 30.9% of patients. In the upper GI CD group, gastric inflammation was present in 84% of patients, followed by duodenal inflammation in 28.2% and gastric granuloma in 23.2%. The most common gastric endoscopic finding in patients with CD was erythema in 5.9%, followed by erosions in 3.7%. Duodenal endoscopic findings included ulcers and erythema in 5.3% and 3.0% of patients, respectively. We found a prevalence of 34% for CD involving the upper GI tract across these 20 studies. Routine upper endoscopy with biopsies of the upper GI tract in the diagnostic workup of patients with CD can correctly classify the distribution and extent of the disease.

  20. Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Cakir, Banu [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: banutopcu@yahoo.com; Kirbas, Ismail [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: drismailk@yahoo.com; Demirhan, Beyhan [Baskent University Faculty of Medicine Department of Pathology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: beyhand@baskent-ank.edu.tr; Tarhan, Nefise Cagla [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: caglat@gmail.com; Bozkurt, Alper [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: abozkurt78@hotmail.com; Ozcay, Figen [Baskent University Faculty of Medicine Department of Pediatric Gastroenterology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: fozcay@baskent.edu.tr; Coskun, Mehmet [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: mcoskun@baskent-ank.edu.tr

    2009-11-15

    Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

  1. Construction of a series of congenic mice with recombinant chromosome 1 regions surrounding the genetic loci for resistance to intracellular parasites (Ity, Lsh, and Bcg), DNA repair responses (Rep-1), and the cytoskeletal protein villin (Vil).

    Science.gov (United States)

    Mock, B A; Holiday, D L; Cerretti, D P; Darnell, S C; O'Brien, A D; Potter, M

    1994-01-01

    The interval of mouse chromosome 1 extending from Idh-1 to Pep-3 harbors the natural resistance gene Ity/Lsh/Bcg; it controls the outcome of infection with Salmonella typhimurium, Leishmania donovani, and several Mycobacterium species. This region also contains a DNA repair gene, Rep-1, which determines the rapidity with which double-strand breaks in chromatin are repaired. BALB/cAnPt and DBA/2N mice differ in their phenotypic expression of these genes. To generate appropriate strains of mice for the study of these genes, a series of 10 C.D2 congenic strains recombinant across a 28-centimorgan interval of mouse chromosome 1 extending from Idh-1 to Pep-3 were derived from crosses of the C.D2-Idh-1 Pep-3 congenic strain back to BALB/cAn. Analyses of these recombinant strains will allow the correlation of biological-immunological phenotypes with defined genetic regions.

  2. Corneal graft reversal: Histopathologic report of two cases

    OpenAIRE

    Qahtani, Abdullah A.; Alkatan, Hind M.

    2014-01-01

    Graft reversal is a rare cause for failed PKP. In this case report we are presenting 2 graft failure cases in which the corneal grafts were reversed unintentionally. The onset of signs of graft failure, however was variable. We have included their clinical course and the histopathologic findings of the removed corneal grafts. A total of 6 cases including ours have been reported so far. The aim of this report is to attract the attention of corneal surgeons to an additional rare cause for faile...

  3. Corneal graft reversal: Histopathologic report of two cases.

    Science.gov (United States)

    Qahtani, Abdullah A; Alkatan, Hind M

    2014-10-01

    Graft reversal is a rare cause for failed PKP. In this case report we are presenting 2 graft failure cases in which the corneal grafts were reversed unintentionally. The onset of signs of graft failure, however was variable. We have included their clinical course and the histopathologic findings of the removed corneal grafts. A total of 6 cases including ours have been reported so far. The aim of this report is to attract the attention of corneal surgeons to an additional rare cause for failed penetrating keratoplasty (PKP) which is donor graft reversal.

  4. Prognostic, quantitative histopathologic variables in lobular carcinoma of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    BACKGROUND: A retrospective investigation of 53 consecutively treated patients with operable lobular carcinoma of the breast, with a median follow-up of 6.6 years, was performed to examine the prognostic value of quantitative histopathologic parameters. METHODS: The measurements were performed...... in routinely processed histologic sections using a simple, unbiased technique for the estimation of the three-dimensional mean nuclear volume (vv(nuc)). In addition, quantitative estimates were obtained of the mitotic index (MI), the nuclear index (NI), the nuclear volume fraction (Vv(nuc/tis)), and the mean...... management of patients with breast cancer....

  5. Peripheral ossifying fibroma of oral cavity: histopathologic differential diagnoses.

    Science.gov (United States)

    Shamim, Thorakkal

    2012-01-01

    Peripheral ossifying fibroma is a benign neoplasm that usuallydevelops from gingiva, presenting as an exophytic smooth surfaced pink or red nodular mass that is sessile or is less frequently seen on a pedicle. From the Indian perspective, it is usually noticed in 5th-6th decades of life with female predilection. Microscopically, the tumour shows stratified squamous epithelium and highly cellular fibrous stroma, sparse endothelial proliferation with fibroblasts and dystrophic calcifications. It has to be differentiated histopathologically from pyogenic granuloma, fibroma, peripheral giant cell granuloma, peripheral odontogenic fibroma and fibrous hyperplasia. A case of peripheral ossifying fibroma of maxillary gingiva in a 55-year-old Indian woman is reported.

  6. Thyroid cancers: a three year retrospective histopathological study

    International Nuclear Information System (INIS)

    Than-Than-Htwe; Maung-Ko

    2001-01-01

    A laboratory based retrospective study was done on thyroid tissue specimen that were received from the surgically removed thyroid swellings of various reasons. It was a three year study from 1996-1998 with a total number of cases as (n=1690). Cases were between the age range of 8-88 years including both sexes. A routine histopathological examination was done according to the standard WHO classification, using conventional methods and techniques of specimen sectioning and processing. Occurrence of thyroid cancer among total cases of thyroid dysfunction is highly significant (P 0.860). The results obtained were discussed. (author)

  7. Cytomegalovirus peritonitis after kidney transplantation diagnosed through histopathological examination.

    Science.gov (United States)

    Hotta, Kiyohiko; Fukasawa, Yuichiro; Wada, Yoshiki; Fukuzawa, Nobuyuki; Seki, Toshimori; Harada, Hiroshi

    2017-08-01

    Among organ transplant recipients, cytomegalovirus (CMV) commonly results in various types of infection such as pneumonitis, hepatitis, and enterocolitis. However, CMV peritonitis is very rare and difficult to diagnose owing to lack of visible clinical signs. We present a case of a 35-year-old female kidney recipient who developed abdominal pain and urinary retention caused by CMV peritonitis. To our knowledge, this is the first case report of CMV peritonitis after organ transplantation to be diagnosed through histopathological examination. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Innovative repair of subsidence damage

    International Nuclear Information System (INIS)

    Marino, G.G.

    1992-01-01

    In order to improve handling of subsidence damages the Illinois Mine Subsidence Insurance Fund supported the development of novel cost-effective methods of repair. The research in developing the repairs was directed towards the most common and costly damages that had been observed. As a result repair techniques were designed for structurally cracked foundations in the tension zone; structurally cracked foundations in the compression zone; and damaged or undamaged tilted foundations. When appropriate the postulated methods would result in: 1. significant cost savings (over conventional procedures); 2. a structural capacity greater than when the foundation was uncracked; and 3. an aesthetic appeal. All the postulated repair methodologies were laboratory and/or field tested. This paper will summarize the essentials of each technique developed and the test results

  9. Umbilical hernia repair - series (image)

    Science.gov (United States)

    ... treatment. The indications for umbilical hernia repair include: incarcerated (strangulated) umbilical hernia defects not spontaneously closed by 4 to 5 years of age children under 2 with very large defects unacceptable to ...

  10. Mammalian DNA Repair. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Richard D.

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  11. Canadian company innovates dam repair

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    Successful repair without any downtime, of the Sabana Yegua power and irrigation structure in the western Dominican Republic by Aquatic Sciences Ltd., a St. Catherine, Ontario-based underwater specialist company, is discussed. The structure was damaged by Hurricane George last when when rising water levels damaged a major valve in the control gate chamber. The repair strategy designed by Aquatic Sciences used a remotely operated vehicle with a mechanical arm for minor tasks which placed a specially-made plug into the inlet pipe. The work was completed in one week, saving the utility company a great deal of money by making it possible to make the repairs remotely in the gate chamber without having to drain the tunnel, as would have been necessary had the repair been completed manually. The remotely operated vehicles use a scanning sonar as well as light to find their way. They are particularly well adapted to work underwater under low-visibility conditions

  12. Betonreparationers holdbarhed (Durability of Concrete Repairs)

    DEFF Research Database (Denmark)

    Brimnes, Eydbjørn; Dali, Bogi í; Larsen, Erik Stoklund

    1999-01-01

    Concrete repairs on 11 pillars on bridges built in the sixties and repaired 8 to 9 years ago have been examined. Especially the chloride penetration in the repair concrete have been measured. Chloride penetration in the repair concrete is much lower than in the original concrete....

  13. 40 CFR 63.1005 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1005 Section 63.1005... Standards for Equipment Leaks-Control Level 1 § 63.1005 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected no later than 15 calendar days after it is detected, except as...

  14. 40 CFR 63.1024 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical, but not later than 15 calendar...

  15. 40 CFR 65.105 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Leak repair. 65.105 Section 65.105... FEDERAL AIR RULE Equipment Leaks § 65.105 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical but not later than 15 calendar days after it is...

  16. The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate

    International Nuclear Information System (INIS)

    Bajinskis, Ainars; Olsson, Gunilla; Harms-Ringdahl, Mats

    2012-01-01

    The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO 3 ). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure.

  17. Testing of self-repairing composite airplane components by use of CAI and the release of the repair chemicals from carefully inserted small tubes

    Science.gov (United States)

    Dry, Carolyn

    2007-04-01

    The research on self repair of airplane components, under an SBIR phase II with Wright Patterson Air Force Base, has investigated the attributes and best end use applications for such a technology. These attributes include issues related to manufacturability, cost, potential benefits such as weight reduction, and cost reduction. The goal of our research has been to develop self-repairing composites with unique strength for air vehicles. Our revolutionary approach involves the autonomous release of repair chemicals from within the composite matrix itself. The repair agents are contained in hollow, structural fibers that are embedded within the matrix. Under stress, the composite senses external environmental factors and reacts by releasing the repair agents from within the hollow vessels. This autonomous response occurs wherever and whenever cracking, debonding or other matrix damage transpires. Superior performance over the life of the composite is achieved through this self-repairing mechanism. The advantages to the military would be safely executed missions, fewer repairs and eventually lighter vehicles. In particular the research has addressed the issues by correlating the impact of the various factors, such as 1) delivery vessel placement, shape/size and effect on composite strength, chemicals released and their effect on the matrix, release trigger and efficacy and any impact on matrix properties 2) impact of composite processing methods that involve heat and pressure on the repair vessels. Our self repairing system can be processed at temperatures of 300-350F, repairs in less than 30 seconds and does not damage the composite by repair fiber insertion or chemical release. Scaling up and manufacture of components has revealed that anticipating potential problems allowed us to avoid those associated with processing temperatures and pressures. The presentation will focus on compression after impact testing and the placement of repair fibers/tubes into prepreg

  18. The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate

    Energy Technology Data Exchange (ETDEWEB)

    Bajinskis, Ainars, E-mail: ainars.bajinskis@gmt.su.se [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden); Olsson, Gunilla; Harms-Ringdahl, Mats [Centre for Radiation Protection Research, Department of Genetics, Microbiology and Toxicology, Stockholm University, S-10691 Stockholm (Sweden)

    2012-03-01

    The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO{sub 3}). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure.

  19. An animal model (guinea pig) of ocular siderosis: histopathology, pharmacology, and electrophysiology.

    Science.gov (United States)

    Mumcuoglu, Tarkan; Ozge, Gokhan; Soykut, Bugra; Erdem, Onur; Gunal, Armagan; Acikel, Cengizhan

    2015-03-01

    Ocular siderosis is a rare sight-threatening complication that occurs after a penetrating ocular injury by an iron-containing foreign body. The purposes of this study were to (i) investigate the histopathology, electrophysiology and iron levels/accumulation in ocular siderosis using an animal (Guinea pig) model and (ii) determine the appropriate timing for follow-up foreign body-removal surgery. Thirty guinea pigs were divided into five groups (n = 6 animals/group). On day-1, an iron body was inserted into the vitreous of the right eye of all animals; the left eyes were left undisturbed and were used as controls. At the end of each week during the 5-week study period, electroretinography (ERG) was performed on all animals in one of the five groups. Each animal in that group was sacrificed, after which both eyes were enucleated for histopathological and pharmacological evaluation of intraocular iron. Accumulated iron levels of study eyes were significantly higher than those of control eyes (135.13 and 13.55 μg/g, respectively, p < 0.01). In addition, there was a significant decrease in electrophysiological responses of study eyes. During the first week, iron levels were higher in study eyes than control eyes, but neither histological iron accumulation nor decreased electrophysiological responses could be detected. By the end of the second week, increased iron accumulation was observed histologically in intraocular tissues, along with signs of retinal toxicity, as verified by decreased electrophysiological responses. The present study indicates that the 14th day after a penetrating eye injury by an iron-containing intraocular foreign body represents a clinically critical threshold, after which structural damage to and functional alterations in ocular tissues occur.

  20. Deficiency of double-strand DNA break repair does not impair Mycobacterium tuberculosis virulence in multiple animal models of infection.

    Science.gov (United States)

    Heaton, Brook E; Barkan, Daniel; Bongiorno, Paola; Karakousis, Petros C; Glickman, Michael S

    2014-08-01

    Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. tuberculosis, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA breaks are the most cytotoxic form of DNA damage and must be repaired for chromosome replication to proceed. M. tuberculosis elaborates three genetically distinct DSB repair systems: homologous recombination (HR), nonhomologous end joining (NHEJ), and single-strand annealing (SSA). NHEJ, which repairs DSBs in quiescent cells, may be particularly relevant to M. tuberculosis latency. However, very little information is available about the phenotype of DSB repair-deficient M. tuberculosis in animal models of infection. Here we tested M. tuberculosis strains lacking NHEJ (a Δku ΔligD strain), HR (a ΔrecA strain), or both (a ΔrecA Δku strain) in C57BL/6J mice, C3HeB/FeJ mice, guinea pigs, and a mouse hollow-fiber model of infection. We found no difference in bacterial load, histopathology, or host mortality between wild-type and DSB repair mutant strains in any model of infection. These results suggest that the animal models tested do not inflict DSBs on the mycobacterial chromosome, that other repair pathways can compensate for the loss of NHEJ and HR, or that DSB repair is not required for M. tuberculosis pathogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.