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Sample records for repair responses histopathological

  1. Furcation Perforation: Periradicular Tissue Response to Biodentine as a Repair Material by Histopathologic and Indirect Immunofluorescence Analyses.

    Science.gov (United States)

    Silva, Lea Assed Bezerra; Pieroni, Karina Alessandra Michelão Grecca; Nelson-Filho, Paulo; Silva, Raquel Assed Bezerra; Hernandéz-Gatón, Patrícia; Lucisano, Marília Pacífico; Paula-Silva, Francisco Wanderley Garcia; de Queiroz, Alexandra Mussolino

    2017-07-01

    The purpose of this study was to evaluate the in vivo response of periradicular tissues after sealing of furcation perforations with Biodentine, mineral trioxide aggregate (MTA), and gutta-percha by means of histopathologic and indirect immunofluorescence analyses. Thirty teeth of 3 dogs were divided into 3 groups: Biodentine (n = 14 teeth), MTA (negative control, n = 10 teeth), and gutta-percha (positive control, n = 6 teeth). After endodontic treatment, perforations were made on the center of the pulp chamber floor and filled with the materials. After 120 days, the animals were killed, and blocks containing the teeth and periradicular tissues were processed histotechnically for histopathologic semiquantitative (new mineralized tissue formation and bone resorption at the perforation site) and quantitative (thickness and area of newly formed mineralized tissue and number of inflammatory cells) analyses and RUNX2 immunofluorescence assay. Data were analyzed by χ(2), Fisher exact test, Mann-Whitney test, one-way analysis of variance, Kruskal-Wallis test, and Dunn posttest (α = 0.05). MTA and Biodentine induced the formation of significantly more new mineralized tissue (P < .0001) than gutta-percha, which did not induce the formation of mineralized tissue in any case. Complete sealing of the perforations was more frequent with MTA, which formed mineralized tissue with greater thickness and area. Biodentine and MTA exhibited no bone resorption in the furcation region, fewer inflammatory cells, and greater RUNX2 immunostaining intensity than gutta-percha. Although MTA presented higher frequency of complete sealing and greater thickness and area of newly formed mineralized tissue, Biodentine also had good histopathologic results and can be considered as an adequate furcation perforation repair material. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  2. Histopathological Comparison of Mosquito Net with Polypropylene Mesh for Hernia Repair: An Experimental Study in Rats.

    Science.gov (United States)

    Sharma, Mukesh; Sharma, Deepti Bala; Chandrakar, Shiv Kumar; Sharma, Dhananjaya

    2015-12-01

    Use of mosquito net, in place of polypropylene mesh, had been reported for tension-free hernia repair, as a better cost-effective option. This experimental histopathological study was performed in rats to find out the tissue response and the foreign body reaction and its comparison between commercial polypropylene mesh and the sterilized mosquito net. This experimental study was conducted in the Department of Surgery, Government NSCB, Medical College, Jabalpur (Madhya Pradesh), India. It was carried out in 40 albino rats. A 1.5 × 0.5-cm hernial defect was created by excising full-thickness abdominal wall muscle. All rats underwent on-lay mesh repair of hernial defect (polypropylene mesh, n = 20; mosquito net, n = 20). Half of rats in each group were sacrificed on day 14, and the other half, on day 90. Sections of containing mesh were examined histopathologically for inflammatory infiltrate, giant cells, and collagen deposition. Mosquito net group showed significantly greater number of giant cells and inflammatory cells at 14 and 90 days (p  0.05 and p > 0.05, respectively). Results of mosquito net are comparable to conventional polypropylene mesh. In a setup, where cost-effectiveness is of primary importance, use of mosquito net for tension-free hernia repair can be an acceptable alternative as proven histologically, to commercially available polypropylene mesh.

  3. DNA repair responses in human skin cells

    Energy Technology Data Exchange (ETDEWEB)

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.

    1981-07-01

    Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

  4. 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

    The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair.......The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair....

  5. 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 locall...

  6. 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...... and mitochondrial DNA processes. The study population was 1089 long-lived and 736 middle-aged Danes. A self-contained set-based test of all SNPs displayed association with longevity (P-value=9.9 × 10-5), supporting that the overall pathway could affect longevity. Investigation of the nine sub-processes using...

  7. 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

    AIM: The aim of this study was to estimate the incidence of the post-implantation syndrome/systemic inflammatory response syndrome (SIRS) after endovascular aortic repair. METHODS: All patients, undergoing elective primary endovascular repair of an asymptomatic infrarenal abdominal aortic aneurysm...

  8. Immune Responses and Histopathological Changes in Rabbits Immunized with Inactivated SARS Coronavirus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To evaluate the immunogenicity of inactivated SARS coronavirus (SARS-CoV), three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant, adjuvant,and normal saline respectively. Eight batchs of serum were sampled from the auricular vein at day 7 to day 51, and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test. Antibody specificity was identified by proteinchip assay.Histopathological changes were detected by H&E staining. The results showed that, rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity, which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses. The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively. In the experimental group, no obvious histopathological changes was detected in the H&E stained slides of heart, spleen, kidney and testis samples, but the livers had slight histopathological changes, and the lungs presented remarkable histopathological changes. These findings are of importance for SARS-CoV inactivated vaccine development.

  9. 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...... 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...... 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....

  10. Proteomic and histopathological response in the gills of Poecilia reticulata exposed to glyphosate-based herbicide.

    Science.gov (United States)

    Rocha, Thiago Lopes; Santos, Ana Paula Rezende Dos; Yamada, Áureo Tatsumi; Soares, Célia Maria de Almeida; Borges, Clayton Luiz; Bailão, Alexandre Melo; Sabóia-Morais, Simone Maria Teixeira

    2015-07-01

    Glyphosate-based herbicides (GBH) are one of the most used herbicide nowadays, whilst there is growing concern over their impact on aquatic environment. Since data about the early proteomic response and toxic mechanisms of GBH in fish is very limited, the aim of this study was to investigate the early toxicity of GBH in the gills of guppies Poecilia reticulata using a proteomic approach associated with histopathological index. Median lethal concentration (LC50,96 h) was determined and LC50,96h values of guppies exposed to GBH were 3.6 ± 0.4 mg GLIL(-1). Using two-dimensional gel electrophoresis associated with mass spectrometry, 14 proteins regulated by GBH were identified, which are involved in different cell processes, as energy metabolism, regulation and maintenance of cytoskeleton, nucleic acid metabolism and stress response. Guppies exposed to GBH at 1.82 mg GLIL(-1) showed time-dependent histopathological response in different epithelial and muscle cell types. The histopathological indexes indicate that GBH cause regressive, vascular and progressive disorders in the gills of guppies. This study helped to unravel the molecular and tissue mechanisms associated with GBH toxicity, which are potential biomarkers for biomonitoring water pollution by herbicides.

  11. SIRT1 promotes DNA repair activity in response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae-Min; Lee, Kee-Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2006-07-01

    Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks.

  12. Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales

    Science.gov (United States)

    Siddiqui, Muhammed R S; Bhoday, Jemma; Battersby, Nicholas J; Chand, Manish; West, Nicholas P; Abulafi, Al-Mutaz; Tekkis, Paris P; Brown, Gina

    2016-01-01

    AIM To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer. METHODS A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included “tumour regression”, “mrTRG”, “poor response” and “colorectal cancers”. Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures. RESULTS Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR

  13. Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis.

    Science.gov (United States)

    McKenzie, E C; Eyrich, L V; Payton, M E; Valberg, S J

    2016-10-01

    A previous report suggests a substantial incidence of exertional rhabdomyolysis (ER) in Arabian horses performing endurance racing. This study compared formalin histopathology and clinical and metabolic responses to a standardised field exercise test (SET) between Arabians with and without ER. Arabian horses with (n = 10; age 15.4 ± 5.6 years) and without (n = 9; 12.9 ± 6.1 years) prior ER were stall-rested for 24-48 h, after which paired ER and control horses were fitted with a telemetric ECG and performed a 47 min submaximal SET. Plasma glucose, lactate, electrolyte and total protein concentrations and packed cell volume were measured before and immediately after exercise. Blood and percutaneous gluteal muscle samples were also obtained before and 3 h after exercise for measurement of plasma creatine kinase (CK) activity and muscle glycogen concentration, respectively. Histopathologic analysis of formalin-fixed pre-exercise muscle sections was performed. Data were analyzed by ANOVA and non-parametric tests (P exercise, and plasma CK increased similarly in ER and control Arabians. Muscle glycogen, heart rate, and remaining plasma variables did not differ between horses with ER and control horses. Horses with ER had more internalised nuclei in mature myofibers, more aggregates of cytoplasmic glycogen and desmin, and higher myopathic scores than control horses. Although many horses with ER had histopathologic evidence of chronic myopathy, muscle glycogen concentrations and metabolic exercise responses were normal. Results did not support a consistent metabolic myopathy or a glycogen storage disorder in Arabians with ER.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Systemic inflammatory responses during laparoscopic and open inguinal hernia repair: a randomised prospective study

    DEFF Research Database (Denmark)

    Jess, P; Schultz, Karen; Bendtzen, K

    2000-01-01

    To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed.......To see if the inflammatory responses during and after laparoscopic and open inguinal hernia repairs differed....

  16. Hepatic Histopathological Characteristics and Antioxidant Response of Phytoplanktivorous Silver Carp Intraperitoneally Injected with Extracted Microcystins

    Institute of Scientific and Technical Information of China (English)

    LI LI; PING XIE

    2009-01-01

    Objectives To investigate the hispathological characteristics and antioxidant responses in liver of silver carp after intraperitoneal administration of microcystins (MCs) for further understanding hepatic intoxication and antioxidation mechanism in fish. Methods Phytoplanktivorous silver carp was injected intraperitoneally (i.p.) with extracted hepatotoxic microcystins (mainly MC-RR and-LR) at a dose of 1000μg MC-LReq./kg body weight, and liver histopathological changes and antioxidant responses were studied at 1, 3, 12, 24, and 48 h, respectively, after injection. Results The damage to liver structure and the activities of hepatic antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and ghitathione peroxide (GPX) were increased in a time-dependent manner. Conclusion In terms of clinical and histological signs of intoxication and LD50 (i.p.) dose of MC-LR, silver carp appears rather resistant to MCs exposure than other fishes. Also, the significantly increased SOD activity in the liver of silver carp suggests a higher degree of response to MCs exposure than CAT and GPX.

  17. Sequestration and histopathology in Plasmodium chabaudi malaria are influenced by the immune response in an organ-specific manner.

    Science.gov (United States)

    Brugat, Thibaut; Cunningham, Deirdre; Sodenkamp, Jan; Coomes, Stephanie; Wilson, Mark; Spence, Philip J; Jarra, William; Thompson, Joanne; Scudamore, Cheryl; Langhorne, Jean

    2014-05-01

    Infection with the malaria parasite, Plasmodium, is associated with a strong inflammatory response and parasite cytoadhesion (sequestration) in several organs. Here, we have carried out a systematic study of sequestration and histopathology during infection of C57Bl/6 mice with Plasmodium chabaudi AS and determined the influence of the immune response. This parasite sequesters predominantly in liver and lung, but not in the brain, kidney or gut. Histopathological changes occur in multiple organs during the acute infection, but are not restricted to the organs where sequestration takes place. Adaptive immunity, and signalling through the IFNγ receptor increased sequestration and histopathology in the liver, but not in the lung, suggesting that there are differences in the adhesion molecules and/or parasite ligands utilized and mechanisms of pathogenesis in these two organs. Exacerbation of pro-inflammatory responses during infection by deletion of the il10 gene resultsin the aggravation of damage to lung and kidney irrespective of the degree of sequestration. The immune response therefore affected both sequestration and histopathology in an organ-specific manner. P.  chabaudi AS provides a good model to investigate the influence of the host response on the sequestration and specific organ pathology, which is applicable to human malaria.

  18. Histopathologic study on pulp response to single-bottle and self-etching adhesive systems.

    Science.gov (United States)

    Medina, Vicente O; Shinkai, Koichi; Shirono, Manabu; Tanaka, Norihiro; Katoh, Yoshiroh

    2002-01-01

    This study compared the pulp response to seven adhesive resins (three single-bottle and four self-etching primers) and their companion resin composite systems with a commercial calcium hydroxide material when applied to exposed monkey pulps. The control group was capped with Dycal (DY), while the experimental groups were capped with one of the following adhesive resin systems: AQ Bond (AQ), Single Bond (SB), Imperva Fluorobond (IF), One Step (OS), Prime&Bond NT (PBNT), Perme Bond F (PBF) and One-up Bond F (OBF). Histopathologic evaluation of pulp tissue disorganization, inflammatory cell infiltration, reparative dentin formation and bacterial penetration at the 3rd, 30th and 90th post-operative days was done using light microscopy. Data were analyzed using the Kruskal-Wallis test followed by the Least Significant Difference Test to determine differences between the control group and the experimental groups at each observation period. The correlation of inflammatory cell infiltration and bacterial presence was investigated by the Kendall correlation analysis. All tests were performed at a 95% level of confidence. The pulpal responses of groups DY, SB, OS, PBF and OBF were generally characterized by none-to-mild pulp tissue disorganization and inflammatory cell infiltration. Also, initiation of reparative dentin formation was found earlier in Group DY, resulting in more complete dentin bridges at the 30- and 90-day observation periods. Groups AQ, IF and PBNT had significantly more inflammatory cell infiltration and a lower incidence of reparative dentin formation than Group DY. A significant correlation was detected between inflammatory cell infiltration and the presence of bacteria. It is concluded that the pulp response to SB, OS, PBF and OBF is not significantly different from the calcium hydroxide preparation. However, calcium hydroxide capping resulted in a higher incidence and faster rate of reparative dentin formation.

  19. Biomarkers of adverse response to mercury: histopathology versus thioredoxin reductase activity.

    Science.gov (United States)

    Branco, Vasco; Ramos, Paula; Canário, João; Lu, Jun; Holmgren, Arne; Carvalho, Cristina

    2012-01-01

    Exposure to mercury is normally assessed by measuring its accumulation in hair, blood or urine. Currently, the biomarkers of effect that have been proposed for mercurials, such as coproporphyrines or oxidative stress markers, are not sensitive enough and lack specificity. Selenium and selenoproteins are important targets for mercury and thioredoxin reductase (TrxR) in particular was shown to be very sensitive to mercury compounds both in vitro and in vivo. In this study we looked into the relation between the inhibition of thioredoxin reductase (TrxR) activity and histopathological changes caused by exposure to mercurials. Juvenile zeabra-seabreams were exposed to Hg(2+) or MeHg for 28 days and histopathological changes were analyzed in the liver and kidney as well as TrxR activity. Both mercurials caused histopathological changes in liver and kidney, albeit Hg(2+) caused more extensive and severe lesions. Likewise, both mercurials decreased TrxR activity, being Hg(2+) a stronger inhibitor. Co-exposure to Hg(2+) and Se fully prevented TrxR inhibition in the liver and reduced the severity of lesions in the organ. These results show that upon exposure to mercurials, histopathological alterations correlate with the level of TrxR activity and point to the potential use of this enzyme as a biomarker of mercury toxicity.

  20. Histopathologic Responses of Dog’s Dental Pulp to Mineral Trioxide Aggregate, Bio Active Glass, Formocresol, Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Neda Ahmadi

    2007-01-01

    Full Text Available Introduction: Bio Active Glass (BAG is often used as a filler material for regeneration of dental bone defects. Mineral trioxide aggregate (MTA is used as retrofilling agent, repair of root resorption and pulpotomy agent in primary dentition. Formocresol (FC is old and standard fixation agent in pulpotomy procedures. Hydroxyapatite (HA is a biologic constitute. It is used in ridge augmentation, bony defect repair and pulpotomy agent in teeth. The purpose of this study was evaluation of histopathologicresponses of dog’s dental pulp to MTA, BAG, FC and HA after three months follow up.Materials and Methods: For this experimental prospective study forty-eight teeth were randomly selected in four dogs. Animals were anesthetized and pulpotomized. Three months later, animals were anesthetized and sacrificed. Then, teeth were extracted and histologic sections were prepared. Histologic sections were observed by an oral pathologist. The sections were observed from the viewof inflammation, hyperemia, necrosis, vitality, calcification and dentinal bridge. Relative frequency of histopathologic outcomes of dental pulp was analyzed and reported. Mean differences of fourgroups were analyzed by Kruskal-Wallis and Mann-Whitney tests.Results: Relative frequency of inflammation of FC, MTA, HA and BAG groups were 29.2, 25.9, 42.4 and 29.2 percent, respectively. Relative frequency of hyperemia of FC, MTA, HA and BAGgroups were 75.1, 63.6, 59.2, 81.6 and 62.5 percent, respectively. Relative frequency of necrosis of FC, MTA, HA and BAG groups were 29.2, 11.1, 12.1, 0 percent, respectively. Relative frequency ofcalcification of FC, MTA, HA and BAG groups were 75, 51.9, 69.7 and 54.8 percent, respectively. Relative frequency of dentinal bridge of FC, MTA, HA and BAG groups were 29.2, 70.4, 30.3 and 29.2 percent, respectively.Conclusion: Histopathologic reactions of dental pulp to four materials (MTA, HA, BAG, FC were different. Histopathologic outcomes of MTA was more

  1. Mean and maximum standardized uptake values in [{sup 18}F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Matthias; Dietlein, Markus; Kobe, Carsten; Eschner, Wolfgang; Schicha, Harald [University of Cologne, Department of Nuclear Medicine, Cologne (Germany); Bollschweiler, Elfriede; Moenig, Stefan P.; Vallboehmer, Daniel; Hoelscher, Arnulf [University of Cologne, Department of General-, Visceral and Cancer Surgery, Cologne (Germany)

    2009-05-15

    To evaluate the potential of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the assessment of histopathological response and survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer. In 2005 and 2006, 55 patients (43 men, 12 women; median age 60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21 (38%) were classified as histopathological responders (<10% vital residual tumour cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3-4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and average standardized uptake values (SUV) for correlation with histopathological response and survival. Histopathological responders had a slightly higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for responders and nonresponders) and the decrease was more prominent in responders. Except for SUVmax in patients with squamous cell carcinoma neither baseline nor preoperative SUV nor percent SUV reduction correlated significantly with histopathological response. Histopathological responders had a 2-year overall survival of 91 {+-} 9% and nonresponders a survival of 53 {+-} 10% (p = 0.007). Our study does not support recent reports that FDG-PET predicts histopathological response and survival in patients with locally advanced oesophageal cancer treated by neoadjuvant radiochemotherapy. (orig.)

  2. Histo-pathological study of pulp response to a composite resin restoration with two lining materials.

    Science.gov (United States)

    Aoki, S; Ishikawa, T

    1990-11-01

    This histopathological study investigated the pulp reaction to a restoration system employing a posterior composite resin with or without the pulp protection of visible light curing calcium hydroxide composition and alpha-TCP cement lining to dentin. Black's class V cavities were prepared in 120 adult dog teeth. They were then extracted for histological examination. As a result of this study, their lining materials were found to be effective in pulp protection. To understand the pathological finding, the pH values of "Fulfil", "Universal bond", "VLC Dycal" and "Vitacemen Type II" were measured. The pH levels of "Fulfil" and "Universal Bond" were mildly acidic (4.79-5.18) before polymerization, with no subsequent changes. "VLC Dycal" was initially a strongly alkaline (11.75) and remained this condition. "Vitacemen Type II" was initially acidic (3.78), but eventually reached the milder acidity of 5.12 after 24 hours.

  3. Active immunization against GnRH in ovine (Ovis aries: testicular morphometry, histopathology and endocrine responses in prepubertal ram lambs

    Directory of Open Access Journals (Sweden)

    Gutierrez-Reinoso MA

    2017-08-01

    Full Text Available The main objective of the present research was to assess the effects of an active immunization against GnRH on male reproductive function as an alternative to surgical sterilization evaluating testicular morphometry, histopathological alterations and plasma gonadotropin levels in prepubertal ram lambs. Dorper ram lambs (age= 2 months; control group, n= 5; treatment group, n=15 were immunised by using an anti-GnRH vaccine (two administrations spaced 15d developed by linking a GnRH homologous molecule to tetanus toxoid (clostridial toxoid with aluminum hydroxide as coadjuvant. To determine the effectiveness of the vaccination protocol, testicular morphometry was evaluated (length, width, mean volume and total volume together with histopathological alterations in testicular tissue samples (seminiferous tubule diameters, spermatogonia per testis and sperm presence and endocrine responses (ELISA from blood samples (FSH, LH, testosterone and cortisol plasma levels. Morphometric parameters (testicular length, width and volume were significantly reduced in vaccinated animals with respect to the control group (p0.05. In conclusion, prepubertal active immunization against GnRH led to marked differences on testes morphometry and activity in ovine species, however, it did not affect endocrine levels nor spermatogenesis in all individuals studied showing a partial vaccination effect in some of them. Thus, taking into account the heterogeneous dysfunctional responses obtained, different vaccination assays and strategies should be tested before active immunization against GnRH is considered as a viable alternative to conventional surgical sterilization.

  4. Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Riazy, Maziar; Kalloger, Steve E; Sheffield, Brandon S; Peixoto, Renata D; Li-Chang, Hector H; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-10-01

    Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective

  5. 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.

  6. 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.

  7. 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.

  8. Histopathological alterations, biochemical responses and acetylcholinesterase levels in Clarias gariepinus as biomarkers of exposure to organophosphates pesticides.

    Science.gov (United States)

    Doherty, V F; Ladipo, M K; Aneyo, I A; Adeola, A; Odulele, W Y

    2016-05-01

    Organophosphate pesticides, commonly used in large scale farming, have been found to be major contaminants in aquatic environment. Clarias gariepinus was exposed to acute and sublethal concentrations of phostoxin and DD Force to evaluate single and joint action toxicity of the organophosphates. Effects of phostoxin and DD force on antioxidant enzymes, fish organs and acetylcholinesterase levels in fingerlings and juveniles of C. gariepinus were also investigated. The lethal concentrations (96 h LC50) for phostoxin and DD Force were 0.631 and 1.759 mg/l, respectively. The results obtained from the bioassay showed that phostoxin was 2.8× more toxic than DD Force after exposure of C. gariepinus. Joint action toxicity evaluations of phostoxin and DD Force showed that the interaction between the chemicals was synergistic (RTU >1). The biochemical responses in the exposed fish differed significantly (P < 0.05) from the control fish. The result of acetylcholinesterase study revealed significant difference between acetylcholinesterase levels in the exposed fish and control, with reduction in the acetylcholineterase level in fish exposed to sublethal concentrations of phostoxin and DD Force. Haematological studies revealed an increase in WBC, RBC, PCV and platelets in the exposed fish. Histopathology of the gills showed shortened primary lamellae, loss of secondary lamellae and loss of ceratobrachial bones. In the acute toxicity studies, respiratory stress, erratic swimming and instant death of fish were observed in the exposed fish. This study reveals that changes in histopathology and acetylcholinesterase level are good biomarkers and can be successfully used to detect exposure to organophosphates pesticides in fish.

  9. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer.

    Science.gov (United States)

    Chuong, Michael D; Frakes, Jessica M; Figura, Nicholas; Hoffe, Sarah E; Shridhar, Ravi; Mellon, Eric A; Hodul, Pamela J; Malafa, Mokenge P; Springett, Gregory M; Centeno, Barbara A

    2016-04-01

    While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.

  10. 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.

  11. Antibiotic persistence: the role of spontaneous DNA repair response.

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    Debbia, E A; Roveta, S; Schito, A M; Gualco, L; Marchese, A

    2001-01-01

    Persisters are a small proportion of a bacterial population that exists in a physiological state permitting survival despite the lethal activity of antibiotics. To explain this phenomenon, it has been suggested that persisters are bacteria repairing spontaneous errors of DNA synthesis. To verify this assumption, Escherichia coli AB1157 and its lexA3 derivative were exposed to a dose 6x MIC of various antibiotics representative of different molecular mechanisms of action (ampicillin, ceftriaxone, meropenem, amikacin, ciprofloxacin). Bacterial cell counts, after 24 hr of exposure to the antimicrobials, revealed a reduction of about 90% of viable organisms in the lexA3 strains in comparison to the lexA+. In several cases, the number of colony-forming units decreased below the limit of assay. This behavior was noted with all antibiotics used, alone or in combination (amikacin plus ceftriaxone and amikacin plus ciprofloxacin). The same experiments were repeated using E. coli AB1157 cultured in the presence of mitomycin C (0.25x MIC), and the number of survivors exceeded by about 90% the values found in the nonexposed control. In contrast, in the sulA background, mitomycin C reacted synergically with all the antibiotics tested causing a strong reduction of the survivors in comparison with the control. The addition of chloramphenicol (0.125x MIC), on the contrary, caused a reduction of the number of survivors of about 90%. These findings indicate that, when DNA repair is active (a mechanism known to block cell division), the number of survivors is greater than that observed with lexA3. Thus, in addition to other possible explanations, persisters might be a fraction of bacteria that during antibiotic treatment are not growing because they are repairing spontaneous errors of DNA synthesis.

  12. Histopathological and expression profiling studies of early tumor responses to near-infrared PDT treatment in SCID mice

    Science.gov (United States)

    Starkey, Jean R.; Rebane, Aleksander; Drobizhev, Mikhail A.; Meng, Fanqin; Gong, Aijun; Elliott, Aleisha; McInnerney, Kate; Pascucci, Elizabeth; Spangler, Charles W.

    2008-02-01

    A novel class of porphyrin-based near-infrared photodynamic therapy (PDT) sensitizers is studied. We achieve regressions of human small cell lung cancer (NCI-H69), non-small cell lung cancer (A 459) and breast cancer (MDAMB- 231) xenografts in SCID mice at significant tissue depth by irradiation with an amplified femtosecond pulsed laser at 800 nm wavelength. Significant tumor regressions were observed during the first 10-14 days post treatment. Tumor histopathology was consistent with known PDT effects, while no significant changes were noted in irradiated normal tissues. In vivo imaging studies using intravenous injections of fluorescent dextran demonstrated an early loss of tumor blood flow. RNA was isolated from NCI-H69 PDT treated SCID mouse xenografts and paired untreated xenografts at 4 hours post laser irradiation. Similarly RNA was isolated from PDT treated and untreated Lewis lung carcinomas growing in C57/Bl6 mice. Expression profiling was carried out using Affymetrix TM human and mouse GeneChips®. Cluster analysis of microarray expression profiling results demonstrated reproducible increases in transcripts associated with apoptosis, stress, oxygen transport and gene regulation in the PDT treated NCI-H69 samples. In addition, PDT treated Lewis lung carcinomas showed reproducible increases in transcripts associated with immune response and lipid biosynthesis. PDT treated C57/Bl6 mice developed cytotoxic T cell activity towards this tumor, while untreated tumor bearing mice failed to do so.

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

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    Lehmann, A.R.; Arlett, C.F.; Broughton, B.C.; Harcourt, S.A.; Steingrimsdottir, H.; Stefanini, M.; Malcolm, A.; Taylor, R.; Natarajan, A.T.; Green, S.

    1988-11-01

    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.

  14. Treatment of Glucocorticoids Inhibited Early Immune Responses and Impaired Cardiac Repair in Adult Zebrafish.

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    Wei-Chang Huang

    Full Text Available Myocardial injury, such as myocardial infarction (MI, can lead to drastic heart damage. Zebrafish have the extraordinary ability to regenerate their heart after a severe injury. Upon ventricle resection, fibrin clots seal the wound and serve as a matrix for recruiting myeloid-derived phagocytes. Accumulated neutrophils and macrophages not only reduce the risk of infection but also secrete cytokines and growth factors to promote tissue repair. However, the underlying cellular and molecular mechanisms for how immune responses are regulated during the early stages of cardiac repair are still unclear. We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found that zebrafish treated with an anti-inflammatory glucocorticoid had significantly reduced heart regenerative capacities, consistent with findings in other higher vertebrates. Moreover, inhibiting the inflammatory response led to excessive collagen deposition. A microarray approach was used to assess the differential expression profiles between zebrafish hearts with normal or impaired healing. Combining cytokine profiling and immune-staining, our data revealed that impaired heart regeneration could be due to reduced phagocyte recruitment, leading to diminished angiogenesis and cell proliferation post-cardiac injury. Despite their robust regenerative ability, our study revealed that glucocorticoid treatment could effectively hinder cardiac repair in adult zebrafish by interfering with the inflammatory response. Our findings may help to clarify the initiation of cardiac repair, which could be used to develop a therapeutic intervention that may enhance cardiac repair in humans to compensate for the loss of cardiomyocytes after an MI.

  15. Dieldrin elicits a widespread DNA repair and antioxidative response in mouse brain.

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    Sava, Vasyl; Velasquez, Adriana; Song, Shijie; Sanchez-Ramos, Juan

    2007-01-01

    Dieldrin is an organochlorine pesticide that is toxic for monoaminergic neurons. This study was designed to test the hypothesis that a weak DNA repair response to dieldrin by nigrostriatal dopaminergic (DA) neurons results in depletion of striatal DA. The activity of the mammalian base excision repair enzyme oxyguanosine glycosylase was utilized as the index of DNA repair. Other measures of oxidative stress were also studied, including the regional distribution of lipid peroxidation and superoxide dismutase (SOD) activity. The effects of acute and slow infusion of dieldrin on striatal DA levels were biphasic with a transient initial depression followed by increases beyond normal steady-:state levels. Dieldrin administration caused a global oxidative stress evidenced by increased levels of lipid peroxidation in all brain regions, an effect consistent with its capacity to affect mitochondrial bioenergetics. Dieldrin also elicited strong antioxidative and DNA repair responses across the entire mouse brain. Although mitochondrial SOD was not as increased in midbrain as it was in other regions following a cumulative dose of 24 mg/kg, this response, along with the robust DNA repair response, appeared to be sufficient to protect potentially vulnerable DA neurons from cytotoxicity. However, the long-:term consequences of chronic low-:dose dieldrin exposure remain to be studied, especially in light of the concept of "slow excitotoxicity,'' which postulates that even a mild bioenergetic compromise can over time result in the demise of neurons.

  16. Inducible SOS Response System of DNA Repair and Mutagenesis in Escherichia coli

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    Celina Janion

    2008-01-01

    Full Text Available Chromosomal DNA is exposed to continuous damage and repair. Cells contain a number of proteins and specific DNA repair systems that help maintain its correct structure. The SOS response was the first DNA repair system described in Escherichia coli induced upon treatment of bacteria with DNA damaging agents arrest DNA replication and cell division. Induction of the SOS response involves more than forty independent SOS genes, most of which encode proteins engaged in protection, repair, replication, mutagenesis and metabolism of DNA. Under normal growth conditions the SOS genes are expressed at a basal level, which increases distinctly upon induction of the SOS response. The SOS-response has been found in many bacterial species (e.g., Salmonella typhimurium, Caulobacter crescentus, Mycobacterium tuberculosis, but not in eukaryotic cells. However, species from all kingdoms contain some SOS-like proteins taking part in DNA repair that exhibit amino acid homology and enzymatic activities related to those found in E. coli. but are not organized in an SOS system. This paper presents a brief up-to-date review describing the discovery of the SOS system, the physiology of SOS induction, methods for its determination, and the role of some SOS-induced genes.

  17. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

    Science.gov (United States)

    Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

    2011-10-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Early prediction of histopathological response of rectal tumors after one week of preoperative radiochemotherapy using 18 F-FDG PET-CT imaging. A prospective clinical study

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    Goldberg Natalia

    2012-08-01

    Full Text Available Abstract Background Preoperative radiochemotherapy (RCT is standard in locally advanced rectal cancer (LARC. Initial data suggest that the tumor’s metabolic response, i.e. reduction of its 18 F-FDG uptake compared with the baseline, observed after two weeks of RCT, may correlate with histopathological response. This prospective study evaluated the ability of a very early metabolic response, seen after only one week of RCT, to predict the histopathological response to treatment. Methods Twenty patients with LARC who received standard RCT regimen followed by radical surgery participated in this study. Maximum standardized uptake value (SUV-MAX, measured by PET-CT imaging at baseline and on day 8 of RCT, and the changes in FDG uptake (ΔSUV-MAX, were compared with the histopathological response at surgery. Response was classified by tumor regression grade (TRG and by achievement of pathological complete response (pCR. Results Absolute SUV-MAX values at both time points did not correlate with histopathological response. However, patients with pCR had a larger drop in SUV-MAX after one week of RCT (median: -35.31% vs −18.42%, p = 0.046. In contrast, TRG did not correlate with ΔSUV-MAX. The changes in FGD-uptake predicted accurately the achievement of pCR: only patients with a decrease of more than 32% in SUV-MAX had pCR while none of those whose tumors did not show any decrease in SUV-MAX had pCR. Conclusions A decrease in ΔSUV-MAX after only one week of RCT for LARC may be able to predict the achievement of pCR in the post-RCT surgical specimen. Validation in a larger independent cohort is planned.

  19. Nail histopathology.

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    Martin, B

    2013-09-01

    The structure of the nail unit is complex and many dermatologists and dermatopathologists have an incomplete understanding of it. Familiarity with the anatomy and histology of this unit, however, is a key factor in improving the diagnostic yield of nail biopsy. Inflammatory or infectious conditions that affect the nail can have a marked impact on a patient's quality of life. A wide-ranging variety of tumors can also develop in this region and they may be life-threatening or require surgery that will result in functional defects. The author reviews the anatomy and histology of the nail unit as well as the basic histopathologic findings in the most common conditions affecting the nails. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

  20. DNA damage response and repair data with pharmacological modulators of Tousled

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    Prakash Srinivasan Timiri Shanmugam

    2016-06-01

    Full Text Available Human Tousled kinase 1 (TLK1 plays an important role in chromatin remodeling, replication, and DNA damage response and repair. TLK1 activity is immediately, but transiently, downregulated after genotoxic insult, and its recovery is important for exit from checkpoint arrest and cell survival after radiation. The data in this article compliments research presented in the paper titled, “Tousled kinase activator, gallic acid, promotes DNA repair and suppresses radiation cytotoxicity in salivary gland cells” [1]. The identification of small molecule activators and inhibitors of TLK1 provided an opportunity to pharmacologically alter the protein׳s activity to elucidate its role in DNA damage response pathways. TLK1 effectors, gallic acid (GA and thioridazine (THD activate and inhibit the kinase, respectively, and the data report on the impact of these compounds and the significance of TLK1 to DNA break repair and the survival of human salivary acinar cells.

  1. Photo-biomodulatory response of low-power laser irradiation on burn tissue repair in mice.

    Science.gov (United States)

    Rathnakar, Bharath; Rao, Bola Sadashiva Satish; Prabhu, Vijendra; Chandra, Subhash; Rai, Sharada; Rao, Anuradha Calicut Kini; Sharma, Mrinalini; Gupta, Pradeep Kumar; Mahato, Krishna Kishore

    2016-12-01

    The present work reports the photo-biomodulatory effect of red (632.8 nm) and near infrared (785 and 830 nm) lasers on burn injury in Swiss albino mice. Animals were induced with a 15-mm full thickness burn injury and irradiated with various fluences (1, 2, 3, 4, and 6 J/cm(2)) of each laser wavelength under study having a constant fluence rate (8.49 mW/cm(2)). The size of the injury following treatment was monitored by capturing the wound images at regular time intervals until complete healing. Morphometric assessment indicated that the group treated with 3-J/cm(2) fluence of 830 nm had a profound effect on healing as compared to untreated controls and various fluences of other wavelengths under study. Histopathological assessment of wound repair on treatment with an optimum fluence (3 J/cm(2)) of 830 nm performed on days 2, 6, 12, and 18 post-wounding resulted in enhanced wound repair with migration of fibroblasts, deposition of collagen, and neovascularization as compared to untreated controls. The findings of the present study have clearly demonstrated that a single exposure of 3-J/cm(2) fluence at 830-nm enhanced burn wound healing progression in mice, which is equivalent to 5 % povidone iodine treatment (reference standard), applied on a daily basis till complete healing.

  2. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

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    Valentina Silvestrin

    2017-01-01

    Full Text Available After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid, the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol.

  3. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    Science.gov (United States)

    Silvestrin, Valentina; Bonvini, Stefano; Antonello, Michele; Grego, Franco; Vettor, Roberto

    2017-01-01

    After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol. PMID:28154580

  4. An Update on the Inflammatory Response after Endovascular Repair for Abdominal Aortic Aneurysm

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    Eleni Arnaoutoglou

    2015-01-01

    Full Text Available Postimplantation syndrome (PIS is the clinical and biochemical expression of an inflammatory response following endovascular repair of an aortic aneurysm (EVAR. The goal of this review is to provide an update on the inflammatory response after endovascular repair of abdominal aortic aneurysm, discussing its causes and effects on the clinical outcome of the patient. PIS concerns nearly one-third of patients after EVAR. It is generally a benign condition, although in some patients it may negatively affect outcome. The different definitions and conclusions drawn from several studies reveal that PIS needs to be redefined with standardized diagnostic criteria. The type of the endograft’s material seems to play a role in the inflammatory response. Future studies should focus on a better understanding of the underlying pathophysiology, predictors, and risk factors as well as determining whether effective preventive strategies are necessary.

  5. Petrolatum: Barrier repair and antimicrobial responses underlying this "inert" moisturizer.

    Science.gov (United States)

    Czarnowicki, Tali; Malajian, Dana; Khattri, Saakshi; Correa da Rosa, Joel; Dutt, Riana; Finney, Robert; Dhingra, Nikhil; Xiangyu, Peng; Xu, Hui; Estrada, Yeriel D; Zheng, Xiuzhong; Gilleaudeau, Patricia; Sullivan-Whalen, Mary; Suaréz-Fariñas, Mayte; Shemer, Avner; Krueger, James G; Guttman-Yassky, Emma

    2016-04-01

    Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed. We sought to define the cutaneous molecular and structural effects induced by petrolatum. Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only. Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human β-defensin 2 [DEFB4A]/FCH, 4.96; P petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects. Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Low velocity impact response and damage evolution in unreinforced resin systems and self-repairing polymer matrix composites

    Science.gov (United States)

    Motuku, Molefi

    The low velocity impact response and damage evolution in unreinforced polymer matrices, conventional polymer matrix composites, and self-repairing polymer matrix composites was investigated. The impact response study of unreinforced matrices and conventional laminates was undertaken because the failure initiation energies, threshold energy levels, failure characteristics and damage evolution in both the matrix material (unreinforced resin plaques) and the composite are intrinsic to proper design of a self-repairing composite. The self-repairing concept was investigated due to its attractive potential to alleviate damage problems in polymer matrix composites. Self-repairing composites, which fall under the category of passive smart polymer composites, have the potential to self repair both micro- and macro-damage resulting from impacts as well as non-impact loading. The self-repairing mechanism is achieved through the incorporation of hollow fibers in addition to the normal solid reinforcing fibers. The hollow fibers store the damage-repairing solution or chemicals that are released into the matrix or damaged zone upon fiber failure to repair and/or arrest damage progression. The room temperature low velocity impact response and damage evolution in DERAKANE 411-350 and 411-C50 vinyl ester unreinforced resin systems was investigated as a function of impact energy level, sample thickness, matrix material and catalyst system. The low velocity impact response of conventional and self-repairing glass reinforced polymer composites was investigated by addressing the fabrication and some of the parameters that influence their response to low velocity impact loading. Specific issues addressed by this study include developing a process to fabricate self-repairing laminates, processing quality; selection of storage material for the repairing solution; release and transportation of repairing solution; the effect of the number, type and spatial distribution of the repairing

  7. 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.

  8. Transcriptional Response of Yeast to Aflatoxin B1: Recombinational Repair Involving RAD51 and RAD1

    OpenAIRE

    2004-01-01

    The potent carcinogen aflatoxin B1 is a weak mutagen but a strong recombinagen in Saccharomyces cerevisiae. Aflatoxin B1 exposure greatly increases frequencies of both heteroallelic recombination and chromosomal translocations. We analyzed the gene expression pattern of diploid cells exposed to aflatoxin B1 using high-density oligonucleotide arrays comprising specific probes for all 6218 open reading frames. Among 183 responsive genes, 46 are involved in either DNA repair or in control of cel...

  9. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins.

    Science.gov (United States)

    Lisby, Michael; Barlow, Jacqueline H; Burgess, Rebecca C; Rothstein, Rodney

    2004-09-17

    DNA repair is an essential process for preserving genome integrity in all organisms. In eukaryotes, recombinational repair is choreographed by multiprotein complexes that are organized into centers (foci). Here, we analyze the cellular response to DNA double-strand breaks (DSBs) and replication stress in Saccharomyces cerevisiae. The Mre11 nuclease and the ATM-related Tel1 kinase are the first proteins detected at DSBs. Next, the Rfa1 single-strand DNA binding protein relocalizes to the break and recruits other key checkpoint proteins. Later and only in S and G2 phase, the homologous recombination machinery assembles at the site. Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse. The cellular response to DSBs and DNA replication stress is likely directed by the Mre11 complex detecting and processing DNA ends in conjunction with Sae2 and by RP-A recognizing single-stranded DNA and recruiting additional checkpoint and repair proteins.

  10. Response shift of the Western Ontario Rotator Cuff index in patients undergoing arthroscopic rotator cuff repair.

    Science.gov (United States)

    Hollman, Freek; Wessel, Ronald N; Wolterbeek, Nienke

    2016-12-01

    This study determined the response shift in patients undergoing rotator cuff repair using the Western Ontario Rotator Cuff index (WORC), a disease-specific quality of life questionnaire. We hypothesized there would be a response shift with a positive recalibration (overestimated their preoperative disability) on the WORC and increases over time. The study prospectively included 36 patients undergoing arthroscopic rotator cuff repair. At baseline, 3 months (T1), and 1 year (T2) after surgery the WORC, EuroQol (EQ)-5D-3L, and the patient's level of satisfaction after surgery were scored. To evaluate the response shift, patients also completed the WORC at 3 months (Pre-T1) and 1 year (Pre-T2) as how they perceived themselves to have been before surgery. The result on Pre-T1 and Pre-T2 results revealed that patients retrospectively rated their overall WORC score comparable with the baseline WORC score (Pre-T0; T0 = 40.5 ± 18.4, Pre-T1 = 45.0 ± 22.7, Pre-T2 = 34.3 ± 21.3). No response shift was observed on all domains except a negative recalibrated response shift for emotional disability on T1 (P = .04). No significant group-level response shift was observed using the WORC, except for the subdomain emotional disability at 3 months after arthroscopic rotator cuff repair. With the absence of any shift in patient's perception on the self-administered quality of life-related WORC questionnaire, this study suggests one could retrospectively reliably conduct group-level preoperative baseline information on quality of life up to 1 year after surgery. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  11. 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.

  12. 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

  13. 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

  14. Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response.

    Science.gov (United States)

    Liu, Qiang; Ma, Jian; Wang, Xue-Feng; Xiao, Fei; Li, Li-Jia; Zhang, Jiao-Er; Lin, Yue-Zhi; Du, Cheng; He, Xi-Jun; Wang, Xiaojun; Zhou, Jian-Hua

    2016-02-01

    The live equine infectious anemia virus (EIAV) vaccine strain EIAVDLV121 was developed by in vitro attenuation of a virulent strain, EIAVLN40, in the 1970s, and it has been demonstrated to induce protective immunity under laboratory and natural EIAV infection conditions. The detailed biological features of this attenuated virus remain to be further investigated. Experimental inoculation with EIAVDLV121 did not result in clinical symptoms even with immunosuppressive treatment in our previous studies. Here, we further investigated whether the replication of the vaccine strain EIAVDLV121 in experimentally infected horses causes histopathological lesions to develop in the targeted organs. Both the lungs and the spleen have been demonstrated to support EIAV replication. By evaluating the gross macroscopic and histological changes, we found that EIAVDLV121 did not cause detectable histopathological lesions and that it replicated several hundred times more slowly than its parental virulent strain, EIAVLN40, in tissues. Immunochemical assays of these tissues indicated that the primary target cells of EIAVDLV121 were monocytes/macrophages, but that EIAVLN40 also infected alveolar epithelial cells and vascular endothelial cells. In addition, both of these viral strains promoted the up- and down-regulation of the expression of various cytokines and chemokines, implicating the potential involvement of these cellular factors in the pathological outcomes of EIAV infection and host immune responses. Taken together, these results demonstrate that the EIAV vaccine strain does not cause obvious histopathological lesions or clinical symptoms and that it induces a unique cytokine response profile. These features are considered essential for EIAVDLV121 to function as an effective live vaccine. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Similarities and differences among eosinophilic esophagitis, proton-pump inhibitor-responsive esophageal eosinophilia, and reflux esophagitis: comparisons of clinical, endoscopic, and histopathological findings in Japanese patients.

    Science.gov (United States)

    Jiao, Dijin; Ishimura, Norihisa; Maruyama, Riruke; Ishikawa, Noriyoshi; Nagase, Mamiko; Oshima, Naoki; Aimi, Masahito; Okimoto, Eiko; Mikami, Hironobu; Izumi, Daisuke; Okada, Mayumi; Ishihara, Shunji; Kinoshita, Yoshikazu

    2017-02-01

    Esophageal eosinophilia is classified as either eosinophilic esophagitis (EoE) or proton-pump inhibitor-responsive esophageal eosinophilia (PPI-REE), depending on the response to PPI treatment. The aim of this study was to compare the clinical, endoscopic, and histopathological findings of EoE and PPI-REE in Japanese patients. In addition, the characteristics of these cases were compared with those of reflux esophagitis (RE) cases. Eleven patients diagnosed with EoE, 16 with PPI-REE, and 39 with RE, who were all consecutively examined from 2005 to 2015 at Shimane University Hospital, were enrolled. Clinical, endoscopic, and histopathological esophageal findings in these groups were retrospectively examined and compared. The differences in the clinical characteristics of EoE and PPI-REE were not remarkable, though patients with EoE and PPI-REE were younger, presented a higher prevalence of allergic comorbidities, and complained of symptoms of dysphagia more frequently than those with RE. The only noteworthy differences between EoE and PPI-REE were more frequent reports of asthma (36.4 vs. 2.6 %) and food allergy (27.3 vs. 0 %) by patients with EoE (P eosinophilia is difficult and requires further investigation.

  16. Prostaglandin E2 promotes intestinal repair through an adaptive cellular response of the epithelium.

    Science.gov (United States)

    Miyoshi, Hiroyuki; VanDussen, Kelli L; Malvin, Nicole P; Ryu, Stacy H; Wang, Yi; Sonnek, Naomi M; Lai, Chin-Wen; Stappenbeck, Thaddeus S

    2017-01-04

    Adaptive cellular responses are often required during wound repair. Following disruption of the intestinal epithelium, wound-associated epithelial (WAE) cells form the initial barrier over the wound. Our goal was to determine the critical factor that promotes WAE cell differentiation. Using an adaptation of our in vitro primary epithelial cell culture system, we found that prostaglandin E2 (PGE2) signaling through one of its receptors, Ptger4, was sufficient to drive a differentiation state morphologically and transcriptionally similar to in vivo WAE cells. WAE cell differentiation was a permanent state and dominant over enterocyte differentiation in plasticity experiments. WAE cell differentiation was triggered by nuclear β-catenin signaling independent of canonical Wnt signaling. Creation of WAE cells via the PGE2-Ptger4 pathway was required in vivo, as mice with loss of Ptger4 in the intestinal epithelium did not produce WAE cells and exhibited impaired wound repair. Our results demonstrate a mechanism by which WAE cells are formed by PGE2 and suggest a process of adaptive cellular reprogramming of the intestinal epithelium that occurs to ensure proper repair to injury. © 2016 The Authors.

  17. DNA Damage Response and DNA Repair in Skeletal Myocytes From a Mouse Model of Spinal Muscular Atrophy.

    Science.gov (United States)

    Fayzullina, Saniya; Martin, Lee J

    2016-09-01

    We studied DNA damage response (DDR) and DNA repair capacities of skeletal muscle cells from a mouse model of infantile spinal muscular atrophy (SMA) caused by loss-of-function mutation of survival of motor neuron (Smn). Primary myocyte cultures derived from skeletal muscle satellite cells of neonatal control and mutant SMN mice had similar myotube length, myonuclei, satellite cell marker Pax7 and differentiated myotube marker myosin, and acetylcholine receptor clustering. DNA damage was induced in differentiated skeletal myotubes by γ-irradiation, etoposide, and methyl methanesulfonate (MMS). Unexposed control and SMA myotubes had stable genome integrity. After γ-irradiation and etoposide, myotubes repaired most DNA damage equally. Control and mutant myotubes exposed to MMS exhibited equivalent DNA damage without repair. Control and SMA myotube nuclei contained DDR proteins phospho-p53 and phospho-H2AX foci that, with DNA damage, dispersed and then re-formed similarly after recovery. We conclude that mouse primary satellite cell-derived myotubes effectively respond to and repair DNA strand-breaks, while DNA alkylation repair is underrepresented. Morphological differentiation, genome stability, genome sensor, and DNA strand-break repair potential are preserved in mouse SMA myocytes; thus, reduced SMN does not interfere with myocyte differentiation, genome integrity, and DNA repair, and faulty DNA repair is unlikely pathogenic in SMA.

  18. Concordance between Responses to Questionnaire Scenarios and Actual Treatment to Repair or Replace Dental Restorations in the National Dental PBRN

    Science.gov (United States)

    Heaven, Tim J.; Gordan, Valeria V.; Litaker, Mark S.; Fellows, Jeffrey L.; Rindal, D. Brad; Gilbert, Gregg H.

    2015-01-01

    Objective To quantify the agreement between treatment recommended during hypothetical clinical scenarios and actual treatment provided in comparable clinical circumstances. Methods A total of 193 practitioners in the National Dental Practice-Based Research Network participated in both a questionnaire and a clinical study. The questionnaire included three hypothetical scenarios about treatment of existing restorations. Clinicians then participated in a clinical study about repair or replacement of existing restorations. We quantified the overall concordance between their questionnaire responses and what they did in actual clinical treatment. Results Practitioners who recommended repair (instead of replacement) of more scenario restorations also had higher repair percentages in clinical practice. Additionally, for each of the three hypothetical scenario restorations, practitioners who recommended repair had higher repair percentages in clinical practice. Conclusions The questionnaire scenarios were a valid measure of clinicians’ tendency to repair or replace restorations in actual clinical practice. Clinical implications Although there was substantial variation in practitioners’ tendency to repair or replace restorations, responses to questionnaire scenarios by individual practitioners were concordant with what they did in actual clinical practice. PMID:25998565

  19. 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

  20. Charpy Impact Response of the Cracked Aluminum Plates Repaired with FML Patches using the Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Faramarz Ashenai Ghasemi

    2016-09-01

    Full Text Available Here, the effect of fiber metal laminate (FMLs patches was studied for repairing of single-sided cracked aluminum plates experimentally to see their response to Charpy impact tests. The main desired parameters were composite patch lay-up, crack length, and crack angle each one in three levels. All experimental attempts generated and followed based on the design of experiments method by using of response surface methodology. The predicted energy absorption values obtained from the model were in good agreement with the experimental results. No matter the specimens were repaired or not, as the crack length was increased the energy absorption of the structure was decreased. The experimental results also showed that for lengthen cracks, increasing of the crack angle had more effect on energy absorption. Also it was observed that the patch lay-up effective on the impact response of the specimens. The more the metal layer was departed from the aluminum plate and the FML patches interfacial surface, the less energy was absorbed in the structure.

  1. Immunological and histopathological responses of the kidney of common carp (Cyprinus carpio L.) sublethally exposed to glyphosate.

    Science.gov (United States)

    Ma, Junguo; Bu, Yanzhen; Li, Xiaoyu

    2015-01-01

    Glyphosate is a broad-spectrum herbicide frequently used world widely in agricultural and non-agricultural areas to control unwanted plants. Health risk of chronic and subchronic exposure of glyphosate on animals and humans has received increasing attention in recent years. The aim of this study was to evaluate the effects of glyphosate on the immunoglobulin M (IgM), complement C3 (C3), and lysozyme (LYZ) in the kidney of common carp exposed to 52.08 or 104.15mgL(-1) of glyphosate for 168h. The results showed that the transcriptions of IgM, C3, or LYZ were altered due to glyphosate-exposure, for example, IgM and C3 initially increased at 24h later it decreased (except for a increase of C3 in higher dose group at 24h) while the expression of G-type LYZ were not affected at 24h, then increased at 72h, but decreased at the end of test, however C-type LYZ expression was initially up-regulated (24-72h) but down-regulated at the end of exposure (168h). However, glyphosate-exposure generally decreased the contents of IgM and C3 or inhibited LYZ activity in the kidney of common carp. In addition, glyphosate-exposure also caused remarkable histopathological damage, mainly including vacuolization of the renal parenchyma and intumescence of the renal tubule in fish kidney. The results of this study indicate that glyphosate causes immunotoxicity on common carp via suppressing the expressions of IgM, C3, and LYZ and also via damaging the fish kidney.

  2. 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.

  3. 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.

  4. Inhibition of non-homologous end joining repair impairs pancreatic cancer growth and enhances radiation response.

    Directory of Open Access Journals (Sweden)

    Ying-Hua Li

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is amongst the deadliest of human cancers, due to its late diagnosis as well as its intense resistance to currently available therapeutics. To identify mechanisms as to why PDAC are refractory to DNA damaging cytoxic chemotherapy and radiation, we performed a global interrogation of the DNA damage response of PDAC. We find that PDAC cells generally harbor high levels of spontaneous DNA damage. Inhibition of Non-Homologous End Joining (NHEJ repair either pharmacologically or by RNAi resulted in a further accumulation of DNA damage, inhibition of growth, and ultimately apoptosis even in the absence of exogenous DNA damaging agents. In response to radiation, PDAC cells rely on the NHEJ pathway to rapidly repair DNA double strand breaks. Mechanistically, when NHEJ is inhibited there is a compensatory increase in Homologous Recombination (HR. Despite this upregulation of HR, DNA damage persists and cells are significantly more sensitive to radiation. Together, these findings support the incorporation of NHEJ inhibition into PDAC therapeutic approaches, either alone, or in combination with DNA damaging therapies such as radiation.

  5. Precise temporal modulation in the response of the SOS DNA repair network in individual bacteria.

    Directory of Open Access Journals (Sweden)

    Nir Friedman

    2005-07-01

    Full Text Available The SOS genetic network is responsible for the repair/bypass of DNA damage in bacterial cells. While the initial stages of the response have been well characterized, less is known about the dynamics of the response after induction and its shutoff. To address this, we followed the response of the SOS network in living individual Escherichia coli cells. The promoter activity (PA of SOS genes was monitored using fluorescent protein-promoter fusions, with high temporal resolution, after ultraviolet irradiation activation. We find a temporal pattern of discrete activity peaks masked in studies of cell populations. The number of peaks increases, while their amplitude reaches saturation, as the damage level is increased. Peak timing is highly precise from cell to cell and is independent of the stage in the cell cycle at the time of damage. Evidence is presented for the involvement of the umuDC operon in maintaining the pattern of PA and its temporal precision, providing further evidence for the role UmuD cleavage plays in effecting a timed pause during the SOS response, as previously proposed. The modulations in PA we observe share many features in common with the oscillatory behavior recently observed in a mammalian DNA damage response. Our results, which reveal a hitherto unknown modulation of the SOS response, underscore the importance of carrying out dynamic measurements at the level of individual living cells in order to unravel how a natural genetic network operates at the systems level.

  6. Tai chi improves oxidative stress response and DNA damage/repair in young sedentary females.

    Science.gov (United States)

    Huang, Xing-Yu; Eungpinichpong, Wichai; Silsirivanit, Atit; Nakmareong, Saowanee; Wu, Xiu-Hua

    2014-06-01

    [Purpose] This study was to examine the effects of 12 weeks of Tai Chi (TC) exercise on antioxidant capacity, and DNA damage/repair in young females who did not perform regular physical exercise. [Subjects and Methods] Ten female students from a Chinese university voluntarily participated in this program. All of them practiced the 24-form simplified Tai Chi, 5 times weekly, for 12 weeks. Plasma levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), hydroxyl radical inhibiting capacity (OH·-IC), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 8-oxoguanine DNA glycosylase (OGG1) were measured at 0, 8, and 12 weeks. Heart rate (HR) was monitored during the last set of the training session at 4, 8, and 12 weeks. [Results] Plasma SOD and OH·-IC levels were increased at 8 and 12 weeks compared to the baseline (0 weeks). Gpx and GSH levels did not change significantly throughout the study period. The plasma MDA level was decreased significantly at 8 weeks but not at 12 weeks compared to the baseline value. While the plasma 8-OHdG level did not change throughout the study period, the plasma OGG1 level was significantly increased at 8 and 12 weeks compared to the baseline value. [Conclusion] TC practice for 12 weeks efficiently improved the oxidative stress response in young females who did not perform regular physical exercise. The TC exercise also increased the DNA repairing capacity.

  7. The clinical value of the systemic inflammatory response syndrome (SIRS) in abdominal aortic aneurysm repair.

    Science.gov (United States)

    Norwood, M G; Bown, M J; Lloyd, G; Bell, P R F; Sayers, R D

    2004-03-01

    The systemic inflammatory response syndrome (SIRS) is common after major surgery. We examine the dynamics of SIRS in AAA patients, and assess the impact of the number of SIRS criteria on patient outcome. Prospective study of 151 consecutive patients with AAA, undergoing repair electively, urgently or with rupture. SIRS scores and organ failure scores were recorded prospectively each day for all patients. Outcome measures included length of stay, evidence of organ failure and mortality. The majority of patients developed SIRS postoperatively. Elective patients with a cumulative SIRS score of > or =10 during postoperative days 1-4 were more likely to die, compared to patients with a SIRS score of SIRS late in the postoperative period (day 5-10) was associated with adverse outcome (death) in elective patients (p=0.01). The actual number of SIRS criteria present did not significantly correlate with either outcome or the incidence of organ failure. SIRS is common in patients undergoing AAA repair. The SIRS score provides useful information regarding a patient's physiological state. High SIRS scores, and the development of SIRS late in the postoperative period are associated with adverse outcome in elective patients, and can therefore be used as an indicator of potential problems.

  8. Functions of FUS/TLS From DNA Repair to Stress Response: Implications for ALS

    Directory of Open Access Journals (Sweden)

    Reddy Ranjith Kumar Sama

    2014-08-01

    Full Text Available Fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS is a multifunctional DNA-/RNA-binding protein that is involved in a variety of cellular functions including transcription, protein translation, RNA splicing, and transport. FUS was initially identified as a fusion oncoprotein, and thus, the early literature focused on the role of FUS in cancer. With the recent discoveries revealing the role of FUS in neurodegenerative diseases, namely amyotrophic lateral sclerosis and frontotemporal lobar degeneration, there has been a renewed interest in elucidating the normal functions of FUS. It is not clear which, if any, endogenous functions of FUS are involved in disease pathogenesis. Here, we review what is currently known regarding the normal functions of FUS with an emphasis on DNA damage repair, RNA processing, and cellular stress response. Further, we discuss how ALS-causing mutations can potentially alter the role of FUS in these pathways, thereby contributing to disease pathogenesis.

  9. Histopathological, immunohistochemical and ultraestructural evaluation of inflammatory response in Arius genus fish under experimental inoculation of BCG

    Directory of Open Access Journals (Sweden)

    Ricardo Yuji Sado

    2008-10-01

    Full Text Available The aim of this study was to evaluate the inflammatory response kinetics after experimental inoculation with BCG in the primitive Arius sp. fish. The BCG was applied through the intramuscular injection in the caudal peduncular region, and the samples were collected for the analyses at days 1, 3, 7, 14, 21, and 33 post-injection. Acute phase inflammatory infiltrate was characterized by the predominant mononuclear cells, intersticial edema, and muscular tissue necrosis. As the inflammatory response evolved, a large number of multinuclear giant cells were formed containing the BCG. These giant cells were positive for the S100 protein at the histochemical analysis, which demonstrate the macrofage activity, confirmed by the ultra-structural analysis showing the lack of the cytoplasmic membrane enveloping the many nuclei within the giant cell. These results led to the conclusion that Arius sp. fish injected with the BCG showed a difuse inflammatory response characterized by a large number of mononuclear cells, absence of granuloma formation, and predominant giant cells.Avaliou-se a cinética da resposta inflamatória induzida experimentalmente com BCG em peixes primitivos pertencentes ao gênero Arius. Os animais foram inoculados com BCG por via intramuscular na região do pedúnculo caudal, sendo realizada a coleta do material nos tempos experimentais de 1, 3, 7, 14, 21 e 33 dias pós-inoculação. A fase aguda da resposta inflamatória se mostrou na forma de infiltrado inflamatório composto predominantemente por células mononucleares, edema intersticial e necrose de tecido muscular. À medida que o processo se desenvolveu, houve formação e aumento no número de células gigantes multinucleadas envolvendo o inóculo. Essas células gigantes, ao exame imunohistoquímico, apresentaram positividade à proteína S100 indicando ação de células macrofágicas, além da ultraestrutura apontar a ausência de membrana citoplasmática entre os in

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

    African Journals Online (AJOL)

    user

    2016-10-12

    Oct 12, 2016 ... The biochemistry and histopathology of intraperitoneally administered potassium ... and necrosis of crops in birds. ..... The stressful behavior of respiratory impairment .... specific bile acid transport system) which is responsible.

  11. Feasibility of exercise stress echocardiography and myocardial response in patients with repaired congenital heart disease.

    Science.gov (United States)

    Hasan, Babar S; Lunze, Fatima I; Alvi, Najveen; Shafer, Keri M; Rhodes, Jonathan

    2017-06-01

    Exercise stress echocardiography (ESE) can unmask ventricular dysfunction in asymptomatic patients with congenital heart disease (CHD), but its acquisition and interpretation is often challenging, and the method has not been validated in CHD. This study aimed to evaluate the feasibility of ESE using Doppler imaging and to assess myocardial response to exercise in patients with biventricular (BiV) and univentricular (UniV) circulation after CHD repair. In this single-center prospective study, we recruited 55 participants (17 females), median age 14 years (8-22 years). Our analysis categorized participants in these three groups: with structurally normal hearts as controls (n=21), with BiV circulation (n=20) and with UniV circulation (n=14). We acquired ESE images of the systemic ventricle including pulsed-wave flow and spectral tissue Doppler imaging (TDI) of lateral free wall before and immediately after standard, symptom-limited exercise tests on an electronically braked cycle ergometer. During ESE we obtained inflow E-wave and TDI systolic (S') and early diastolic (E') velocities in 93% to 100% of participants at rest and in 90% to 100% of participants post exercise. Feasibility to obtain Doppler imaging parameter was the same across study groups. The myocardial response to exercise was increase in heart rate (HR), S' and inflow E-wave velocity in all participants. Patients with BiV circulation had preserved ventricular function at rest. While patients with UniV circulation had low S', E', and E-wave velocities at rest in comparison to controls and to BiV group (all Pincreases in HR, S' velocity and inflow E-wave velocity post exercise, with magnitudes of these increases higher in controls than in the BiV and UniV group. The S' and E' velocities were strongly associated with lower percent predicted peak oxygen consumption VO2 (rs=0.614 and rs=0.64, respectively, both Pexercise in patients after biventricular and univentricular CHD repair. Although patients with Bi

  12. 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.

  13. Loss of VHL in RCC reduces repair and alters cellular response to benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Marten eSchults

    2013-10-01

    Full Text Available Mutations of the von Hippel-Lindau (VHL tumor suppressor gene occur in the majority of sporadic renal-cell carcinomas (RCC. Loss of VHL function is associated with stabilization of hypoxia-inducible factor α (HIFα. We and others demonstrated that there is a two-way interaction between the aryl hydrocarbon receptor, which is an important mediator in the metabolic activation and detoxification of carcinogens, and the HIF1-pathway leading to an increased genetic instability when both pathways are simultaneously activated. The aim of this study was to investigate how environmental carcinogens, such as benzo[a]pyrene (BaP, which can be metabolically activated to BaP-7,8-diOH-9,10-epoxide (BPDE play a role in the etiology of renal-cell carcinomas (RCC. We exposed VHL deficient RCC4 cells, in which HIFα is stabilized regardless of oxygen tension, to 0.1µM BaP for 18 hours. The mutagenic BPDE-DNA adduct levels were increased in HIFα stabilized cells. Using qRT-PCR, we demonstrated that absence of VHL significantly induced the mRNA levels of AhR downstream target CYP1A1. Furthermore, HPLC analysis indicated that loss of VHL increased the concentration of BaP-7,8-dihydroxydiol, the pre-cursor metabolite of BPDE. Interestingly, the capacity to repair BPDE-DNA adducts in the HIFα stabilized RCC4 cells, was markedly reduced. Taken together, these data indicate that loss of VHL affects BaP-mediated genotoxic responses in renal-cell carcinoma and decreases repair capacity.

  14. 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.

  15. Erythropoietin responsive cardiomyogenic cells contribute to heart repair post myocardial infarction.

    Science.gov (United States)

    Zafiriou, Maria Patapia; Noack, Claudia; Unsöld, Bernhard; Didie, Michael; Pavlova, Elena; Fischer, Henrike J; Reichardt, Holger M; Bergmann, Martin W; El-Armouche, Ali; Zimmermann, Wolfram-Hubertus; Zelarayan, Laura Cecilia

    2014-09-01

    The role of erythropoietin (Epo) in myocardial repair after infarction remains inconclusive. We observed high Epo receptor (EPOR) expression in cardiac progenitor cells (CPCs). Therefore, we aimed to characterize these cells and elucidate their contribution to myocardial regeneration on Epo stimulation. High EPOR expression was detected during murine embryonic heart development followed by a marked decrease until adulthood. EPOR-positive cells in the adult heart were identified in a CPC-enriched cell population and showed coexpression of stem, mesenchymal, endothelial, and cardiomyogenic cell markers. We focused on the population coexpressing early (TBX5, NKX2.5) and definitive (myosin heavy chain [MHC], cardiac Troponin T [cTNT]) cardiomyocyte markers. Epo increased their proliferation and thus were designated as Epo-responsive MHC expressing cells (EMCs). In vitro, EMCs proliferated and partially differentiated toward cardiomyocyte-like cells. Repetitive Epo administration in mice with myocardial infarction (cumulative dose 4 IU/g) resulted in an increase in cardiac EMCs and cTNT-positive cells in the infarcted area. This was further accompanied by a significant preservation of cardiac function when compared with control mice. Our study characterized an EPO-responsive MHC-expressing cell population in the adult heart. Repetitive, moderate-dose Epo treatment enhanced the proliferation of EMCs resulting in preservation of post-ischemic cardiac function.

  16. A Histopathological Comparison of Pulpal Response to Chitra-CPC and Formocresol used as Pulpotomy Agents in Primary Teeth: A Clinical Trial

    Science.gov (United States)

    Thomas, Bijimol

    2012-01-01

    ABSTRACT Preventive measures have helped to minimize the occurrence of dental caries. However, premature loss of primary teeth on account of dental caries still remains a common problem among children. The pulpotomy technique has been the choice for treating vital primary and young permanent teeth with carious, mechanical and traumatic pulp exposures. The ideal pulpotomy medicament should be bioinductive or at least biocompatible, bactericidal and harmless to the pulp and surrounding structures. It should also promote healing of the radicular pulp and prevent bacterial microleakage with the least interference in the physiological process of root resorption. Since the best criteria for judging the effectiveness of a medicament when used for vital pulp therapy is the response that it produces in the pulp. The purpose of the present study was to evaluate and compare the response of human pulp tissue to recently developed Indian material, Sree Chitra-Calcium Phosphate Cement (Chitra-CPC) and formocresol, used as pulpotomy agent in deciduous teeth. Chitra-CPC has been compared with formocresol, taking into account that formocresol is still considered the gold standard in primary tooth pulpotomy. The study was conducted among 10 children in the age group of 8 to 12 years focusing on 20 noncarious primary canines indicated for serial extraction. Each patient received two different pulpotomy procedures—one in each of the primary canines using formocresol and the other with Chitra-CPC as pulpotomy agents. After 70 days, the teeth were extracted and subjected to histological examination. The results did not reveal statistically significant difference between the two groups. But Chitra-CPC gave more favorable results, in respect of pulpal inflammation, dentin bridge formation, quality of dentin bridge and connective tissue in dentin bridge. How to cite this article: Ratnakumari N, Thomas B. A Histopathological Comparison of Pulpal Response to Chitra- CPC and Formocresol

  17. Histopathologic Responses of the Dental Pulp to Calcium-Enriched Mixture (CEM) and Mineral Trioxide Aggregate (MTA) in Diabetic and Non-Diabetic Rats.

    Science.gov (United States)

    Madani, Zahra Sadat; Haddadi, Azam; Mesgarani, Abbas; Seyedmajidi, Maryam; Mostafazadeh, Amrollah; Bijani, Ali; Ashraphpour, Manouchehr

    2014-01-01

    Diabetes mellitus is a chronic disease which affects the healing ability of the pulp and periodontium. The aim of the present study was to assess the histopathologic response of dental pulp to pulp capping using MTA or CEM cement in diabetic rats. Thirty two Wistar male rats aged between 8 and 10 weeks (weight: 200-250g) were divided into two groups of diabetic (n=16) and healthy (n=16) animals and then subdivided into MTA and CEM subgroups. In each group, 10 MTA treated, 10 CEM treated and 12 intact (without any intervention) teeth were analyzed. Intact teeth were considered as a baseline inflammation control. Then, class I cavity was made in the maxillary first molars teeth with pinpoint pulpal exposure. Either MTA or CEM cement was then placed over exposed pulp as pulp capping agent and the cavities were restored using resin- modified glass ionomer cement. Both teeth of rats in subgroups remained intact without any intervention. After four weeks, the rats were sacrificed and the teeth were subjected to histological evaluation in terms of inflammation intensity, dentin bridge formation and dentin bridge continuity. The CEM cement treated diabetic rats exhibited a significant higher inflammatory response when compared to healthy control group (P=0.004) whereas, MTA treated diabetic rats did not exhibit a significant higher inflammatory response in comparison to healthy controls. There was no significant difference between MTA and CEM cement in the induction of dentin bridge formation in diabetic and healthy controls. This preliminary study suggests that MTA is a superior dental material than CEM cement for pulp therapy in subjects with diabetes.

  18. A Histopathological Comparison of Pulpal Response to Chitra-CPC and Formocresol used as Pulpotomy Agents in Primary Teeth: A Clinical Trial.

    Science.gov (United States)

    Ratnakumari, N; Thomas, Bijimol

    2012-01-01

    Preventive measures have helped to minimize the occurrence of dental caries. However, premature loss of primary teeth on account of dental caries still remains a common problem among children. The pulpotomy technique has been the choice for treating vital primary and young permanent teeth with carious, mechanical and traumatic pulp exposures. The ideal pulpotomy medicament should be bioinductive or at least biocompatible, bactericidal and harmless to the pulp and surrounding structures. It should also promote healing of the radicular pulp and prevent bacterial microleakage with the least interference in the physiological process of root resorption. Since the best criteria for judging the effectiveness of a medicament when used for vital pulp therapy is the response that it produces in the pulp. The purpose of the present study was to evaluate and compare the response of human pulp tissue to recently developed Indian material, Sree Chitra-Calcium Phosphate Cement (Chitra-CPC) and formocresol, used as pulpotomy agent in deciduous teeth. Chitra-CPC has been compared with formocresol, taking into account that formocresol is still considered the gold standard in primary tooth pulpotomy. The study was conducted among 10 children in the age group of 8 to 12 years focusing on 20 noncarious primary canines indicated for serial extraction. Each patient received two different pulpotomy procedures-one in each of the primary canines using formocresol and the other with Chitra-CPC as pulpotomy agents. After 70 days, the teeth were extracted and subjected to histological examination. The results did not reveal statistically significant difference between the two groups. But Chitra-CPC gave more favorable results, in respect of pulpal inflammation, dentin bridge formation, quality of dentin bridge and connective tissue in dentin bridge. How to cite this article: Ratnakumari N, Thomas B. A Histopathological Comparison of Pulpal Response to Chitra- CPC and Formocresol used as

  19. Protein expression of DNA damage repair proteins dictates response to topoisomerase and PARP inhibitors in triple-negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Julie L Boerner

    Full Text Available Patients with metastatic triple-negative breast cancer (TNBC have a poor prognosis. New approaches for the treatment of TNBC are needed to improve patient survival. The concept of synthetic lethality, brought about by inactivating complementary DNA repair pathways, has been proposed as a promising therapeutic option for these tumors. The TNBC tumor type has been associated with BRCA mutations, and inhibitors of Poly (ADP-ribose polymerase (PARP, a family of proteins that facilitates DNA repair, have been shown to effectively kill BRCA defective tumors by preventing cells from repairing DNA damage, leading to a loss of cell viability and clonogenic survival. Here we present preclinical efficacy results of combining the PARP inhibitor, ABT-888, with CPT-11, a topoisomerase I inhibitor. CPT-11 binds to topoisomerase I at the replication fork, creating a bulky adduct that is recognized as damaged DNA. When DNA damage was stimulated with CPT-11, protein expression of the nucleotide excision repair enzyme ERCC1 inversely correlated with cell viability, but not clonogenic survival. However, 4 out of the 6 TNBC cells were synergistically responsive by cell viability and 5 out of the 6 TNBC cells were synergistically responsive by clonogenic survival to the combination of ABT-888 and CPT-11. In vivo, the BRCA mutant cell line MX-1 treated with CPT-11 alone demonstrated significant decreased tumor growth; this decrease was enhanced further with the addition of ABT-888. Decrease in tumor growth correlated with an increase in double strand DNA breaks as measured by γ-H2AX phosphorylation. In summary, inhibiting two arms of the DNA repair pathway simultaneously in TNBC cell lines, independent of BRCA mutation status, resulted in un-repairable DNA damage and subsequent cell death.

  20. Flexural Fatigue Response of Repaired S2-Glass/Vinyl Ester Composites

    Science.gov (United States)

    2009-08-01

    vacuum-assisted resin transfer molding ( VARTM ) (2), performance evaluations have assumed increasing importance due to the lack of historical databases on...composites produced affordably, including VARTM and those that possess thick sections. There is a need to standardize repair strategies for affordably...produced composites. This report presents preliminary work on VARTM -produced laminates subjected to idealized damage and repaired through different

  1. 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.

  2. Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Joellen M Schildkraut

    Full Text Available BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS, a population-based, case-control study. METHODS/PRINCIPAL FINDINGS: The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio(per allele = 0.66; 95% credible interval (CI = 0.44-1.00 and rs6005835 (median OR(per allele = 0.69; 95% CI = 0.53-0.91 in CHEK2, rs2078486 (median OR(per allele = 1.65; 95% CI = 1.21-2.25 and rs12951053 (median OR(per allele = 1.65; 95% CI = 1.20-2.26 in TP53, rs411697 (median OR (rare homozygote = 0.53; 95% CI = 0.35 - 0.79 in BACH1 and rs10131 (median OR( rare homozygote = not estimable in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. CONCLUSIONS/SIGNIFICANCE: Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.

  3. Base excision repair pathway: PARP1 genotypes as modulators of therapy response in cervical cancer patients.

    Science.gov (United States)

    Nogueira, Augusto; Assis, Joana; Faustino, Ilda; Pereira, Deolinda; Catarino, Raquel; Medeiros, Rui

    2017-02-01

    Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association between PARP1 Val762Ala polymorphism (rs1136410) and cancer therapy response. The purpose of our study was to determine whether PARP1 Val762Ala polymorphism have prognostic value in patients with cervical cancer. Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. The PARP1 Val762Ala genetic variants were analyzed by allelic discrimination by real-time PCR. We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test, p = 0.008 and p = 0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32-10.38; p = 0.013 and for DFS: HR, 3.97; 95%CI, 1.59-9.93; p = 0.003). This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.

  4. Inhibition of CRMP2 phosphorylation repairs CNS by regulating neurotrophic and inhibitory responses.

    Science.gov (United States)

    Nagai, Jun; Owada, Kazuki; Kitamura, Yoshiteru; Goshima, Yoshio; Ohshima, Toshio

    2016-03-01

    , and suppressed scarring were also observed by inhibiting CRMP2 phosphorylation. Therefore, inhibition of CRMP2 phosphorylation demonstrates the unique potential to repair SCI by both enhancing sensitivity to BDNF and reducing inhibitory responses.

  5. 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.

  6. The interplay among chromatin dynamics, cell cycle checkpoints and repair mechanisms modulates the cellular response to DNA damage.

    Science.gov (United States)

    Lazzaro, Federico; Giannattasio, Michele; Muzi-Falconi, Marco; Plevani, Paolo

    2007-06-01

    Cells are continuously under the assault of endogenous and exogenous genotoxic stress that challenges the integrity of DNA. To cope with such a formidable task cells have evolved surveillance mechanisms, known as checkpoints, and a variety of DNA repair systems responding to different types of DNA lesions. These lesions occur in the context of the chromatin structure and, as expected for all DNA transactions, the cellular response to DNA damage is going to be influenced by the chromatin enviroment. In this review, we will discuss recent studies implicating chromatin remodelling factors and histone modifications in the response to DNA double-strand breaks (DSBs) and in checkpoint activation in response to UV lesions.

  7. 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.

  8. DNA damage induction and/or repair as mammalian cell biomarker for the prediction of cellular radiation response

    Science.gov (United States)

    Baumstark-Khan, C.

    DNA damage and its repair processes are key factors in cancer induction and also in the treatment of malignancies. Cancer prevention during extended space missions becomes a topic of great importance for space radiobiology. The knowledge of individual responsiveness would allow the protection strategy to be tailored optimally in each case. Radiobiological analysis of cultured cells derived from tissue explants from individuals has shown that measurement of the surviving fraction after 2 Gy (SF2) may be used to predict the individual responsiveness. However, clonogenic assays are timeconsuming, thus alternative assays for the determination of radiore-sponse are being sought. For that reason CHO cell strains having different repair capacities were used for examining whether DNA strand break repair is a suitable experimental design to allow predictive statements. Cellular survival (CFA assay) and DNA strand breaks (total DNA strand breaks: FADU technique; DSBs: non-denaturing elution) were determined in parallel immediately after irradiation as well as after a 24 hour recovery period according to dose. There were no correlations between the dose-response curves of the initial level of DNA strand breaks and parameters that describe clonogenic survival curves (SF2). A good correlation exists between intrinsic cellular radioresistance and the extent of residual DNA strand breaks.

  9. FDG-PET/CT for the early prediction of histopathological complete response to neoadjuvant chemotherapy in breast cancer patients: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Buchbender, Christian [Univ Dusseldorf, Medical Faculty, Dept. of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Univ Duisburg-Essen, Medical Faculty, Dept. of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kuemmel, Sherko; Hoffmann, Oliver [Univ Duisburg-Essen, Medical Faculty, Dept. of Gynecology and Obstetrics, Essen (Germany)], E-mail: heusner@med.uni-duesselfdorf.de [and others

    2012-07-15

    Background. Up to about one-quarter of patients treated with neoadjuvant chemotherapy do not adequately respond to the given treatment. By a differentiation between responders and non-responders ineffective toxic therapies can be prevented. Purpose. To retrospectively test if FDG-PET/CT is able to early differentiate between breast cancer lesions with pathological complete response (pCR) and lesions without pathological complete response (npCR) after two cycles of neoadjuvant chemotherapy (NACT). Material and Methods. In this retrospective study 26 breast cancer patients (mean age, 46.9 years {+-} 9.9 years) underwent a pre-therapeutic FDG-PET/CT scan and a subsequent FDG-PET/CT after the second cycle of NACT. Histopathology of resected specimen served as the reference standard. Maximum standardized uptake values (SUVmax) of cancer lesions before and after the second cycle of NACT were measured. Two evaluation algorithms were used: (a) pCR: Sinn Score 3 and 4, npCR: Sinn Score 0-2; (b) pCR: Sinn Score 4, npCR: Sinn Score 0-3. The absolute and relative decline of the SUVmax ({Delta}SUVmax, {Delta}SUVmax(%))was calculated. Differences of the SUVmax as well as of the SUVmax decline between pCR lesions and npCR lesions were tested for statistical significance P < 0.05. To identify the optimal cut-off value of {Delta}SUVmax(%) to differentiate between pCR lesions and npCR lesions a receiver-operating curve (ROC) analysis was performed. Results. Using evaluation algorithm A the {Delta}SUVmax was 13.5 (pCR group) and 3.9 (npCR group) (P = 0.006); the {Delta}SUVmax(%) was 79% and 47%, respectively (P 0.001). On ROC analysis an optimal cut-off {Delta}SUVmax(%) of 66% was found. Using evaluation algorithm B the {Delta}SUVmax was 17.5 (pCR group) and 4.9 (npCR group) (P = 0.013); the {Delta}SUVmax(%) was 89% and 51%, respectively (P = 0.003). On ROC analysis an optimal cut-off {Delta}SUVmax(%) of 88% was found. Conclusion. FDG-PET/CT may be able to early differentiate between

  10. 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.

  11. 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

    , hepatic and supramammary). Histopathological examination and bacterial culture of tissues each revealed that six of the 16 cattle were infected, whereas repeated culture of rectal contents revealed only five infected animals. Except for the hepatic lymph node of a single animal, culture-positive tissues...

  12. Fluorogenic Real-Time Reporters of DNA Repair by MGMT, a Clinical Predictor of Antitumor Drug Response.

    Directory of Open Access Journals (Sweden)

    Andrew A Beharry

    Full Text Available Common alkylating antitumor drugs, such as temozolomide, trigger their cytotoxicity by methylating the O6-position of guanosine in DNA. However, the therapeutic effect of these drugs is dampened by elevated levels of the DNA repair enzyme, O6-methylguanine DNA methyltransferase (MGMT, which directly reverses this alkylation. As a result, assessing MGMT levels in patient samples provides an important predictor of therapeutic response; however, current methods available to measure this protein are indirect, complex and slow. Here we describe the design and synthesis of fluorescent chemosensors that report directly on MGMT activity in a single step within minutes. The chemosensors incorporate a fluorophore and quencher pair, which become separated by the MGMT dealkylation reaction, yielding light-up responses of up to 55-fold, directly reflecting repair activity. Experiments show that the best-performing probe retains near-native activity at mid-nanomolar concentrations. A nuclease-protected probe, NR-1, was prepared and tested in tumor cell lysates, demonstrating an ability to evaluate relative levels of MGMT repair activity in twenty minutes. In addition, a probe was employed to evaluate inhibitors of MGMT, suggesting utility for discovering new inhibitors in a high-throughput manner. Probe designs such as that of NR-1 may prove valuable to clinicians in selection of patients for alkylating drug therapies and in assessing resistance that arises during treatment.

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

    Science.gov (United States)

    Ganesan, Shanthi; Keating, Aileen F

    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 6μM) for 24 or 48h. Cell viability was reduced (Padduct was detected after 24h of 6μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48h 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.

  14. Chronic stress impairs the local immune response during cutaneous repair in gilthead sea bream (Sparus aurata, L.).

    Science.gov (United States)

    Mateus, Ana Patrícia; Anjos, Liliana; Cardoso, João R; Power, Deborah M

    2017-07-01

    Scale removal in fish triggers a damage-repair program to re-establish the lost epidermis and scale and an associated local immune response. In mammals, chronic stress is known to delay wound healing and to modulate the cutaneous stress axis, but this is unstudied in teleost fish the most successful extant vertebrates. The present study was designed to test the hypothesis that chronic stress impairs cutaneous repair in teleost fish as a consequence of suppression of the immune response. The hypothesis was tested by removing the scales and damaging the skin on one side of the body of fish previously exposed for 4 weeks to a chronic crowding stress and then evaluating cutaneous repair for 1 week. Scale removal caused the loss of the epidermis although at 3days it was re-established. At this stage the basement membrane was significantly thicker (p=0.038) and the hypodermis was significantly thinner (p=0.016) in the regenerating skin of stressed fish relative to the control fish. At 3days, stressed fish also had a significantly lower plasma osmolality (p=0.015) than control fish indicative of reduced barrier function. Chronic stress caused a significant down-regulation of the glucocorticoid receptor (gr) in skin before damage (time 0, p=0.005) and of star at 3 and 7days (p<0.05) after regeneration relative to control fish. In regenerating skin key transcripts of cutaneous repair, pcna, colivα1 and mmp9, and the inflammatory response, tgfβ1, csf-1r, mpo and crtac2, were down-regulated (p<0.05) by chronic stress. Irrespective of chronic stress and in contrast to intact skin many hyper pigmented masses, putative melanomacrophages, infiltrated the epidermis of regenerating skin. This study reveals that chronic stress suppresses the local immune response to scale removal and impairs the expression of key transcripts of wound healing. Elements of the stress axis were identified and modulated by chronic stress during cutaneous repair in gilthead seabream skin. Copyright

  15. 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.

  16. 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

    Directory of Open Access Journals (Sweden)

    Mulder-Stapel Adri

    2001-07-01

    Full Text Available Abstract Background 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. Patients and methods 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. Results 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 Conclusions 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.

  17. 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.

  18. 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.

  19. Artefacts in histopathology.

    Science.gov (United States)

    Chatterjee, Shailja

    2014-09-01

    Histopathology is the science of slide analysis for the diagnostic and research purposes. However, sometimes the presence of certain artefacts in a microscopic section can result in misinterpretations leading to diagnostic pitfalls that can result in increased patient morbidity. This article reviews the common artefacts encountered during slide examination alongside the remedial measures which can be undertaken to differentiate between an artefact and tissue constituent.

  20. Artefacts in histopathology

    Directory of Open Access Journals (Sweden)

    Shailja Chatterjee

    2014-01-01

    Full Text Available Histopathology is the science of slide analysis for the diagnostic and research purposes. However, sometimes the presence of certain artefacts in a microscopic section can result in misinterpretations leading to diagnostic pitfalls that can result in increased patient morbidity. This article reviews the common artefacts encountered during slide examination alongside the remedial measures which can be undertaken to differentiate between an artefact and tissue constituent.

  1. Dose response and adaptive response of non-homologous end joining repair genes and proteins in resting human peripheral blood mononuclear cells exposed to γ radiation.

    Science.gov (United States)

    Shelke, Shridevi; Das, Birajalaxmi

    2015-05-01

    Ionising radiation induces single-strand breaks, double-strand breaks (DSB) and base damages in human cell. DSBs are the most deleterious and if not repaired may lead to genomic instability and cell death. DSB can be repaired through non-homologous end joining (NHEJ) pathway in resting lymphocytes. In this study, NHEJ genes and proteins were studied in irradiated human peripheral blood mononuclear cells (PBMC) at resting stage. Dose-response, time point kinetics and adaptive-response studies were conducted in irradiated PBMC at various end points such as DNA damage quantitation, transcription and protein expression profile. Venous blood samples were collected from 20 random, normal and healthy donors with written informed consent. PBMC was separated and irradiated with various doses between 0.1 and 2.0 Gy ((60)CO-γ source) for dose-response study. Repair kinetics of DNA damage and time point changes in expression of genes and proteins were studied in post-irradiated PBMC at 2.0 Gy at various time points up to 240 min. Adaptive-response study was conducted with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4-h incubation. Our results revealed that Ku70, Ku80, XLF and Ligase IV were significantly upregulated (P Adaptive-response study showed significantly increased expression of the proteins involved in NHEJ, suggesting their role in adaptive response in human PBMC at G0/G1, which has important implications to human health. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Correlation of histopathology, urinary biomarkers, and gene expression responses following hexachloro-1:3-butadiene-induced acute nephrotoxicity in male Hanover Wistar rats: a 28-day time course study.

    Science.gov (United States)

    Maguire, David P; Turton, John A; Scudamore, Cheryl L; Swain, Aubrey J; McClure, Fiona J; Smyth, Rosemary; Pereira, Ines B; Munday, Michael R; York, Malcolm J

    2013-07-01

    Hexachloro-1:3-butadiene (HCBD) causes segment-specific injury to the proximal renal tubule. A time course study of traditional and more recently proposed urinary biomarkers was performed in male Hanover Wistar rats receiving a single intraperitoneal (ip) injection of 45 mg/kg HCBD. Animals were killed on days 1, 2, 3, 4, 5, 6, 7, 10, 14, and 28 postdosing and the temporal response of renal biomarkers was characterized using kidney histopathology, urinary and serum biochemistry, and gene expression. Histopathologic evidence of tubular degeneration was seen from day 1 until day 3 postdosing and correlated with increased urinary levels of α-glutathione S-transferase (α-GST), albumin, glucose, and kidney injury molecule-1 (KIM-1), and increased gene expression of KIM-1, NAD(P)H dehydrogenase, quinone 1, and heme oxygenase (decycling) 1. Histopathologic evidence of tubular regeneration was seen from day 2 postdosing and correlated with raised levels of urinary KIM-1 and osteopontin and increased gene expression of KIM-1 and annexin A7. Traditional renal biomarkers generally demonstrated low sensitivity. It is concluded that in rat proximal tubular injury, measurement of a range of renal biomarkers, in conjunction with gene expression analysis, provides an understanding of the extent of degenerative changes induced in the kidney and the process of regeneration.

  3. Alarm signal transduction and DNA repair in the adaptive response induced by X-rays in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wojewodzka, M.; Kruszewski, M.; Szumiel, I.; Wojcik, A. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); Staffer, C. [Universitatklinikum, Essen (Germany); Gasinska, A. [Radiotherapy Clinic Oncology Center, Cracow (Poland)

    1995-12-31

    Irradiation of human lymphocytes (1 cGy, 37 deg C) evoked a 30% decrease in the frequency of micronuclei upon subsequent X-irradiation (1.5 Gy). The response was reflected both by a reduction in the formation of micronuclei frequency and in an increase in the DNA repair rate measured by the comet assay directly after the challenge dose. The calcium antagonist, TMB-8, and staurosporine, an inhibitor of protein kinases, prevented the development of the adaptive response measured by the appearance of micronuclei. Psi-tectorigenin, an inhibitor of phosphatidylinositol turnover, did not modify the adaptive response. The induction of adaptation as not accompanied by altered progression through the cell cycle, or changes in chromatin condensation as determined by flow cytometry (DNA content and 90 deg side scatter, respectively). (author). 24 refs, 8 figs.

  4. Histopathology of chromoblastomycosis.

    Science.gov (United States)

    Uribe, F; Zuluaga, A I; Leon, W; Restrepo, A

    1989-01-01

    A study aimed at determining the histopathologic appearance of chromoblastomycotic lesions was undertaken. Biopsies from 26 patients with the disease were examined. It was found that 23 cases (88.46%) exhibited the organized mixed mycotic granuloma - OMMA -, a granuloma modified by the presence polymorphonuclear neutrophils - PMN's. An equal proportion of cases exhibited pseudoepitheliomatous hyperplasia, with the epithelium playing an important role in the transepidermic elimination of the fungus. Healing of the lesions took place by fibrosis which was observed in 21 (80.77%) patients; this type of reaction was more common in the deeper areas of the dermis.

  5. Abdominal adiposity is the main determinant of the C-reactive response to injury in subjects undergoing inguinal hernia repair

    Directory of Open Access Journals (Sweden)

    Irkulla Sashidhar

    2013-02-01

    Full Text Available Abstract Background Obesity and serum C-reactive protein (CRP (a sensitive marker of inflammatory activity are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery. Methods 102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP. Results Age and waist:hip ratio (WHR were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91 p = 0.0014 and 1.15(1.00-1.31 p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response. Conclusion Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for

  6. 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.

  7. Response of the oxygen pulse during exercise in children with atrial repair for transposition of the great arteries

    Directory of Open Access Journals (Sweden)

    Buys R

    2012-11-01

    Full Text Available Roselien Buys,1,2,* Kimberly Dockx,1,* Marc Gewillig,3 Tony Reybrouck1,21Department of Rehabilitation Sciences, 2Department of Cardiovascular Rehabilitation, University of Leuven, Leuven, Belgium; 3Department of Pediatric Cardiology, University Hospital Gasthuisberg, Leuven, Belgium*These authors contributed equally to this paperBackground: The oxygen pulse equals stroke volume times arterial–venous oxygen difference and is calculated by dividing oxygen uptake (VO2 by heart rate (HR. In children with a Senning repair for the transposition of the great arteries (TGA, the response of both HR and VO2 to exercise is impaired. Our aim was to assess the oxygen pulse response during exercise in patients who underwent a Senning operation, comparing it with healthy controls.Methods: Twenty-one children with a Senning repair (mean age 12.5 ± 1.7 years and a control group of 31 healthy children (mean age 13.2 ± 2.0 years performed a graded maximal exercise test on a treadmill, during which HR and VO2 were measured. Oxygen pulse was calculated by dividing VO2 by HR. Right ventricular function was quantitatively assessed by cardiac ultrasound.Results: Senning patients had a lower peak oxygen pulse than the control (P = 0.0024 (8.45 ± 1.90 mL • beats-1 versus 11.7 ± 3.93 mL • beats-1, as with the peak VO2 (P < 0.001 (35.8 ± 5.67 mL • min-1 • kg-1 versus 46.6 ± 8.02 mL • min-1 • kg-1 and peak HR (171 ± 14 beats • min-1 versus 188 ± 11 beats • min-1. During submaximal exercise, oxygen pulse and VO2 were also significantly lower in Senning patients when compared to the control group (P = 0.027. In seven Senning patients (33%, the oxygen pulse did not increase any further after the first exercise levels. These patients had lower right ventricular function compared to the control group (P = 0.04.Conclusion: Children with a Senning repair for TGA have a reduced peak VO2, peak HR, and peak oxygen pulse. Their oxygen pulse starts off at a

  8. 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

    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......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...... in both groups, with the CRP increase being significantly greater in the OR group. The other markers did not increase significantly. CONCLUSION: The acute phase response was more pronounced after OR, even when this was done under local anesthesia. Both techniques seemed rather atraumatic....

  9. 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.

  10. THE HISTOPATHOLOGY OF PSORIASIS

    Directory of Open Access Journals (Sweden)

    C. Mignogna

    2011-09-01

    Full Text Available Psoriasis is a common, chronic, relapsing, papulo-squamous dermatitis, with overlying silvery scales. The scalp, sacral region, and extensor surfaces of extremity are commonly involved, even if flexural and intertriginous areas may be affected in the so-called “inverse psoriasis”. Involvement of nails is frequent. Oral lesions (geographic stomatitis and/or glossitis are commonly described. 5-8% of psoriatic patients develop arthritis. Interphalangeal joints are characteristically involved, but large joints are also affected. From a histological point of view, psoriasis is a dynamic dermatosis that changes during the evolution of an individual lesion; we can classify it in an early stage, advanced stage, and later lesions. Lesions are usually diagnostic only in early stages or near the margin of advancing plaques. Munro microabscesses and Kogoj micropustoles are diagnostic clues of psoriasis, but they aren’t always present. All other features can be found in numerous eczematous dermatitis. Key words: Psoriasis, histopathology, immunohistochemistry

  11. Regulated expression of the Saccharomyces cerevisiae DNA repair gene RAD7 in response to DNA damage and during sporulation.

    Science.gov (United States)

    Jones, J S; Prakash, L; Prakash, S

    1990-06-11

    The RAD7 gene of Saccharomyces cerevisiae affects the proficiency of excision repair of DNA damaged by UV light. Here, we report our studies on the regulation of the RAD7 gene in response to UV irradiation and during sporulation. RAD7 transcript levels increased 6-fold within 40 min of exposure of cells to 37 J/m2 of UV light. Higher UV doses also elicited rapid increases in the level of RAD7 mRNA. RAD7 mRNA levels increased in sporulating MATa/MAT alpha diploid cells, but not in the asporogenous MATa/MATa strain exposed to sporulation conditions. The increase in RAD7 mRNA level in MATa/MAT alpha cells was 15-fold after 6 h and 9-fold after 7 h in sporulation medium; thereafter, RAD7 mRNA levels declined. Periodic transcription of RAD7 during sporulation suggests a role for RAD7 in this process.

  12. 7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of development. This study investigated DMBA-induced DNA double strand break (DSB) formation with subsequent activation of the ovarian DNA repair response in models of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344 (F344) rat ovaries were cultured for 4 days followed by single exposures of vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 μM DMBA at the start of culture for 2 days. Total RNA or protein was isolated, followed by qPCR or Western blotting to quantify mRNA or protein level, respectively. γH2AX and phosphorylated ATM were localized and quantified using immunofluorescence staining. DMBA exposure increased caspase 3 and γH2AX protein. Additionally, DMBA (12.5 nM and 1 μM) increased levels of mRNA encoding Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern (75 nM d4; 12.5 nM d8), while pATM was localized in large primary and secondary follicles and increased after 8 days of 75 nM DMBA exposure compared to both control and 12.5 nM DMBA. These findings support that, despite some concentration effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are induced as a potential mechanism to prevent follicle loss. - Highlights: • DMBA exposure increases ovarian caspase-3 protein expression. • DMBA exposure increases the γH2AX protein in oocytes. • DMBA exposure activates a DNA repair response in the ovary.

  13. Optimality in DNA repair.

    Science.gov (United States)

    Richard, Morgiane; Fryett, Matthew; Miller, Samantha; Booth, Ian; Grebogi, Celso; Moura, Alessandro

    2012-01-07

    DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge.

  14. Toxicologic and histopathologic response of the terrestrial salamander Plethodon cinereus to soil exposures of 1,3,5-trinitrohexahydro-1,3,5-triazine.

    Science.gov (United States)

    Johnson, M S; Paulus, H I; Salice, C J; Checkai, R T; Simini, M

    2004-11-01

    Red-backed salamanders (Plethodon cinereus) were exposed to four different concentrations of 1,3,5-trinitrohexahydro-1,3,5-triazine (RDX) in soil under controlled laboratory conditions for 28 days. Wild-caught P. cinereus (N = 20/treatment) were exposed to target concentrations of 5,000, 1000, 100, 10, and 0 mg RDX/kg soil (dry wt) using a microcosm design. Animals were fed 5 to 10 uncontaminated mutant Drosophila flies every 3 days and monitored daily. Animals were weighed 1 day before being placed in treatment and weekly thereafter. RDX concentrations in soil were analytically determined after the compound was added and mixed at the beginning, the midpoint, and the end of exposure. RDX soil concentrations were relatively stable throughout the exposure period. Signs of overt toxicity were observed primarily in the highest exposure group. Salamanders exposed to 5,000 mg RDX/kg soil exhibited signs of neuromuscular effects (lethargy, gaping, hypersensitivity, tremors) and exhibited significant weight loss. A single moribund animal from this group lost >20% of its original body weight and was killed. Animals in this exposure group also lost weight relative to animals in other treatments. Histopathologic evaluations, including an evaluation of melanomacrophage parameters, indicated no strong treatment-related findings. This study provided information regarding the effects from subchronic dermal exposure of a terrestrial amphibian species to RDX in soil and provides a microcosm approach to the evaluation of toxicity of contaminants in soil to a terrestrial vertebrate.

  15. Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO₃-Induced DNA Damage.

    Science.gov (United States)

    Spassova, Maria A; Miller, David J; Nikolov, Alexander S

    2015-01-01

    We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS) can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemical KBrO3 which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG). The single strand breaks (SSB) that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibits KBrO3-caused oxidative damage. Our modeling revealed that sustained exposure to KBrO3 can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical's toxicity dose dependence based on the dose-response of early genotoxic events.

  16. Collagen birefringence in skin repair in response to red polarized-laser therapy

    Science.gov (United States)

    da Silva, Daniela d. F. T.; Vidal, Benedicto d. C.; Zezell, Denise M.; Zorn, Telma M. T.; Núñez, Silvia C.; Ribeiro, Martha S.

    2006-03-01

    We use the optical path difference (OPD) technique to quantify the organization of collagen fibers during skin repair of full-thickness burns following low-intensity polarized laser therapy with two different polarization incidence vectors. Three burns are cryogenerated on the back of rats. Lesion L|| is irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction. Lesion L⊥ is irradiated using the electric field vector of the polarized laser radiation aligned perpendicularly to the aforementioned orientation. Lesion C is untreated. A healthy area labeled H is also evaluated. The tissue samples are collected and processed for polarized light microscopy. The overall finding is that the OPD for collagen fibers depends on the electric field vector of the incident polarized laser radiation. No significant differences in OPDs are observed between L|| and H in the center, sides, and edges of the lesion. Lesions irradiated using the electric field vector of the polarized laser radiation aligned in parallel with the rat's occipital-caudal direction show higher birefringence, indicating that collagen bundles in these lesions are more organized.

  17. [Relationship between aortic arch shape and blood pressure response after coarctation repair].

    Science.gov (United States)

    Ou, P; Mousseaux, E; Auriacombe, L; Pédroni, E; Balleux, F; Sidi, D; Bonnet, D

    2005-01-01

    The mechanisms of secondary hypertension after repair of coarctation of the aorta are not well understood. Abnormalities of the architecture of the aortic arch and their consequences on blood pressure have not been studied. In order to study the relationship between abnormalities or aortic arch architecture and resting blood pressure ninety-four patients without re-coarctation were followed up prospectively from 1997 to 2004 (mean age 16.9 +/- 8.1 years; mean weight 57.5 +/- 18.3 Kg; interval since surgery 16.3 +/- 5.4 years). All underwent MRI angiography of the thoracic aorta which enabled the abnormalities to be classified in 3 groups: gothic arch, crenellated arch and roman arch. Twenty-four patients (25.5%) were hypertensive and 70 (74.4%) normotensive. There were 40 gothic arches (42.5%). 14 crenellated arches (15%) and 40 roman arches (42.5%). Gothic arches were more commonly observed in the hypertensive patients (18/40, [45%, 95% CI 31-62]) than the crenellated arches (4/14, [28.5%, 95% CI 7-48]) or the roman arches (2/40, [5%, 95% CI 2-12]). Only the gothic arch was independently correlated with hypertension on multivariate analysis. The authors conclude that gothic deformation of the aortic arch is an independent predictive factor of hypertension in patients operated for coarctation with an excellent result on the isthmic region. Patients with a gothic appearance of their aortic arch should be followed up closely.

  18. [Histopathological meniscus diagnostic].

    Science.gov (United States)

    Fisseler-Eckhoff, A; Müller, K-M

    2009-06-01

    Menisci fulfill many functions within the complex biomechanics of the knee joint. In the case of meniscus lesions, sparing arthroscopic resections and operative refixation are the treatments of choice. With regard to diagnostics, this means that in general terms, the histopathologic diagnostics are carried out on detached meniscus fragments of between 5 mm and 2 cm in size. An experienced pathologist's knowledge of physiologically possible cellular and fibrous histological meniscus damage, as opposed to nonphysiological change regarded as normal with respect to age, is essential during a diagnostic meniscus evaluation. The clinician expects clear statements from the pathologist regarding the severity of previous or secondary degenerative meniscus damage, the age and type of traumatic tears, and appraisal of the relationship between trauma and meniscus damage from an insurance point of view. Close cooperation between the clinician and the pathologist allows for fast and unambiguous correlation of anamnesis, the clinical picture, and morphological reporting so that cases involving insurance problems - which are numerous, often long-term, and often unsatisfactory - can be clarified quickly.

  19. Proliferation rate but not mismatch repair affects the long-term response of colon carcinoma cells to 5FU treatment.

    Science.gov (United States)

    Choudhary, B; Hanski, M L; Zeitz, M; Hanski, C

    2012-07-01

    The role of mismatch repair (MMR) in the response of colon carcinoma cells to 5-fluorouracil (5FU) is not well understood. In most of the in vitro studies only short-term response was investigated. We focussed here on the influence of MMR status on the mechanism of the short- and long-term response to clinically relevant 5FU concentrations by using isogenic or semiisogenic cell line pairs expressing/nonexpressing the hMLH1 protein, an important component of the MMR system. We show that the lower survival of MMR-proficient than of MMR-deficient cells in the clonogenic survival assay is due to a more frequent early cell arrest and to subsequent senescence. By contrast, the long-term cell growth after treatment, which is also affected by long-term arrest and senescence, is independent from the MMR status. The overall effect on the long-term cell growth is a cumulative result of cell proliferation rate-dependent growth inhibition, apoptosis and necrotic cell death. The main long-term cytotoxic effect of 5FU is the inhibition of growth while apoptosis and the necrotic cell death are minor contributions.

  20. 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.

  1. 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...

  2. Response properties of whisker-associated primary afferent neurons following infraorbital nerve transection with microsurgical repair in adult rats.

    Science.gov (United States)

    Xiao, Bo; Zanoun, Rami R; Carvell, George E; Simons, Daniel J; Washington, Kia M

    2016-03-01

    The rodent whisker/trigeminal system, characterized by high spatial and temporal resolution, provides an experimental model for developing new therapies for improving sensory functions of damaged peripheral nerves. Here, we use controlled whisker stimulation and single-unit recordings of trigeminal ganglion cells to examine in detail the nature and time course of functional recovery of mechanoreceptive afferents following nerve transection with microsurgical repair of the infraorbital nerve (ION) branch of the trigeminal nerve in adult rats. Response measures include rapid vs. slow adaptation, firing rate, interspike intervals, latency, and angular (directional) tuning. Whisker-evoked responses, readily observable by 3 wk post-transection, recover progressively for at least the next 5 wk. All cells in transected animals, as in control cases, responded to deflections of single whiskers only, but topography within the ganglion was clearly disrupted. The time course and extent of recovery of quantitative response measures were receptor dependent. Cells displaying slowly adapting (SA) properties recovered more quickly than rapidly adapting (RA) populations, and for some response measures-notably evoked firing rates-closely approached or attained control levels by 8 wk post-transection. Angular tuning of RA cells was slightly better than control units, whereas SA tuning did not differ from control values. Nerve conduction times and refractory periods, examined separately using electrical stimulation of the ION, were slower than normal in all transected animals and poorly reflected recovery of whisker-evoked response latencies and interspike intervals. Results underscore the need for multiple therapeutic strategies that target different aspects of functional restitution following peripheral nerve injury. Copyright © 2016 the American Physiological Society.

  3. Clinical and histopathological study of palmoplantar keratoderma

    Directory of Open Access Journals (Sweden)

    Mahajan P

    1994-01-01

    Full Text Available Study of palmo-plantar keratoderma in eighty-two cases showed that twenty different diseases, both hereditary and acquired were responsible for palmoplantar keratoderma. Maximum number of cases were of hereditary variety of palmoplantar keratoderma (Unna-Thost syndrome (28.05%. Whereas psoriasis was the leading cause among the acquired conditions (17.07%. Two histopathological types of Unna-Thost syndrome and their correlation with clinical features are reported.

  4. Comparative histopathology of vitiligo and contact depigmentation

    Directory of Open Access Journals (Sweden)

    Mittal R

    1992-01-01

    Full Text Available Fifteen cases of vitiligo and 12 cases of contact depigmentation were compared histopathologically. Incontinence of melanin in dermis was seen in 33% cases of contact depigmentation and 6.6% cases of vitiligo. Mononuclear infiltrate was more in contact depigmentation and had lichenoid character at places. Vasculitis with perivascular mononuclear infiltrate was seen in all cases of contact depigmentation. It is proposed that chemicals responsible for contact destruction of melanocytes.

  5. CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas.

    Science.gov (United States)

    Paz, Maria F; Yaya-Tur, Ricard; Rojas-Marcos, Iñigo; Reynes, Gaspar; Pollan, Marina; Aguirre-Cruz, Lucinda; García-Lopez, Jose Luis; Piquer, Jose; Safont, María-Jose; Balaña, Carmen; Sanchez-Cespedes, Montserrat; García-Villanueva, Mercedes; Arribas, Leoncio; Esteller, Manel

    2004-08-01

    The DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents, and its loss in cancer cells is associated with hypermethylation of the MGMT CpG island. Thus, methylation of MGMT has been correlated with the clinical response to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in primary gliomas. Here, we investigate whether the presence of MGMT methylation in gliomas is also a good predictor of response to another emergent alkylating agent, temozolomide. Using a methylation-specific PCR approach, we assessed the methylation status of the CpG island of MGMT in 92 glioma patients who received temozolomide as first-line chemotherapy or as treatment for relapses. Methylation of the MGMT promoter positively correlated with the clinical response in the glioma patients receiving temozolomide as first-line chemotherapy (n = 40). Eight of 12 patients with MGMT-methylated tumors (66.7%) had a partial or complete response, compared with 7 of 28 patients with unmethylated tumors (25.0%; P = 0.030). We also found a positive association between MGMT methylation and clinical response in those patients receiving BCNU (n = 35, P = 0.041) or procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (n = 17, P = 0.043) as first-line chemotherapy. Overall, if we analyze the clinical response of all of the first-line chemotherapy treatments with temozolomide, BCNU, and procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea as a group in relation to the MGMT methylation status, MGMT hypermethylation was strongly associated with the presence of partial or complete clinical response (P < 0.001). Finally, the MGMT methylation status determined in the initial glioma tumor did not correlate with the clinical response to temozolomide when this drug was administered as treatment for relapses (P = 0.729). MGMT methylation predicts the clinical response of primary gliomas to first-line chemotherapy with the alkylating agent

  6. In vivo and in vitro cellular response to PEG-based hydrogels for wound repair

    Science.gov (United States)

    Waldeck, Heather

    Biomaterials are continuously being explored as a means to support, improve, or influence wound healing processes. Understanding the determining factors controlling the host response to biomaterials is crucial in developing strategies to employ materials for biomedical uses. In order to evaluate the host response to poly(ethylene glycol) (PEG)-based hydrogels, both in vivo and in vitro studies were performed to determine its efficacy as a dermal wound treatment and to investigate the mechanisms controlling cell-material interaction, respectively. The results of an in vivo study using a full thickness wound in a rat model demonstrated that both soluble and immobilized bioactive factors could be incorporated into a PEG-based semi-interpenetrating network (sIPN) to enhance the rate and the quality of dermal wound healing. To gain a better understanding of the results observed in vivo, in vitro studies were then conducted to examine the dynamics and mechanisms of the cell-material interaction. Degradation of the sIPN was explored as an influential factor in both mediating cellular response and controlling solute transport from the material. As degradation through gelatin dissolution could be influenced by simple alterations to the material formulation, these results provide facile guidelines to control the delivery of high molecular weight compounds. Further investigation of the cellular response to PEG-based biomaterials focused on key factors influencing cell-material interaction. Specifically, the role of the beta1 integrin subunit and several serum proteins (TGF-aalpha, IL-1beta and PDGF-BB) in mediating cellular response was explored. As cell-material interactions are based on commonly occurring interfaces between cells and molecules of the native extracellular environment, these studies provided insight into the mechanisms controlling the observed cellular response. Finally, the inflammatory response of primary monocytes to biomaterials was examined. Monocytes

  7. Impaired Cytogenetic Damage Repair and Cell Cycle Regulation in Response to Ionizing Radiation in Human Fibroblast Cells with Individual Knock-down of 25 Genes

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish; Jeevarajan, Antony; Pierson, Duane; Wu, Honglu

    2008-01-01

    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 demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

  8. Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide.

    Science.gov (United States)

    McFaline-Figueroa, José L; Braun, Christian J; Stanciu, Monica; Nagel, Zachary D; Mazzucato, Patrizia; Sangaraju, Dewakar; Cerniauskas, Edvinas; Barford, Kelly; Vargas, Amanda; Chen, Yimin; Tretyakova, Natalia; Lees, Jacqueline A; Hemann, Michael T; White, Forest M; Samson, Leona D

    2015-08-01

    Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity. RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases provided an unexpectedly strong mechanism of temozolomide resistance. In a mouse xenograft model of human GBM, small changes in MSH2 were sufficient to suppress temozolomide-induced tumor regression. Using The Cancer Genome Atlas to analyze mRNA expression patterns in tumors from temozolomide-treated GBM patients, we found that MSH2 transcripts in primary GBM could predict patient responses to initial temozolomide therapy. In recurrent disease, the absence of microsatellite instability (the standard marker for MMR deficiency) suggests a lack of involvement of MMR in the resistant phenotype of recurrent disease. However, more recent studies reveal that decreased MMR protein levels occur often in recurrent GBM. In accordance with our findings, these reported decreases may constitute a mechanism by which GBM evades temozolomide sensitivity while maintaining microsatellite stability. Overall, our results highlight the powerful effects of MSH2 attenuation as a potent mediator of temozolomide resistance and argue that MMR activity offers a predictive marker for initial therapeutic response to temozolomide treatment.

  9. Repair of DNA Alkylation Damage by the Escherichia coli Adaptive Response Protein AlkB as Studied by ESI-TOF Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Deyu Li

    2010-01-01

    Full Text Available DNA alkylation can cause mutations, epigenetic changes, and even cell death. All living organisms have evolved enzymatic and non-enzymatic strategies for repairing such alkylation damage. AlkB, one of the Escherichia coli adaptive response proteins, uses an α-ketoglutarate/Fe(II-dependent mechanism that, by chemical oxidation, removes a variety of alkyl lesions from DNA, thus affording protection of the genome against alkylation. In an effort to understand the range of acceptable substrates for AlkB, the enzyme was incubated with chemically synthesized oligonucleotides containing alkyl lesions, and the reaction products were analyzed by electrospray ionization time-of-flight (ESI-TOF mass spectrometry. Consistent with the literature, but studied comparatively here for the first time, it was found that 1-methyladenine, 1,N 6-ethenoadenine, 3-methylcytosine, and 3-ethylcytosine were completely transformed by AlkB, while 1-methylguanine and 3-methylthymine were partially repaired. The repair intermediates (epoxide and possibly glycol of 3,N 4-ethenocytosine are reported for the first time. It is also demonstrated that O 6-methylguanine and 5-methylcytosine are refractory to AlkB, lending support to the hypothesis that AlkB repairs only alkyl lesions attached to the nitrogen atoms of the nucleobase. ESI-TOF mass spectrometry is shown to be a sensitive and efficient tool for probing the comparative substrate specificities of DNA repair proteins in vitro.

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

    Science.gov (United States)

    Cheng, Chia-Chi; Yu, Chih-peng; Wu, Jiunn-Hong; Hsu, Keng-Tsan; Ke, Ying-Tsu

    2014-02-01

    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.

  11. Neuroendocrine and behavioral response to social rupture and repair in preschoolers with autism spectrum disorders interacting with mother and father.

    Science.gov (United States)

    Ostfeld-Etzion, Sharon; Golan, Ofer; Hirschler-Guttenberg, Yael; Zagoory-Sharon, Orna; Feldman, Ruth

    2015-01-01

    Preschoolers with autism spectrum disorder (ASD) exhibit difficulties in handling social stress and utilizing efficient emotion regulation (ER) strategies to manage high arousal. While researchers called to assess ER in ASD, few studies utilized direct observations. We tested children's behavioral and cortisol response to maternal and paternal unavailability and hypothesized that children with ASD will employ less complex ER strategies and their parents would show increased regulation facilitation effort to accommodate their child's difficulties. Forty preschoolers with ASD were matched with 40 typically developing (TD) preschoolers. Children were seen twice for identical battery with mother or father in the face-to-face-still-face paradigm, a three-episode paradigm where parent-child play (free play (FP)) is interrupted by elimination of communication (still face (SF)) followed by resuming play (reunion (RE)). Micro-coding of parent and child's social behavior and ER strategies was conducted. Parent and child's cortisol was assessed at baseline, following stress, and at recovery. Children with ASD exhibited the typical SF effect, indexed by an increase in negative affect and decrease in positive communications, but employed more simple regulatory behavior (self-soothing, proximity-seeking) and less complex strategies involving attention redirection and substitutive play. Their parents used more regulation-facilitation behavior, both simple and complex. All children showed initial cortisol response to novelty, which declined over time. However, maternal presence suppressed initial cortisol response in children with ASD. Children with ASD form typical expectations of parental availability and their parents increase effort to help repair social rupture. Among children with ASD, maternal presence and regulation facilitation provide social buffering for the child's HPA stress response in a manner similar to mammalian neonates. Results highlight the importance of

  12. 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.

  13. Tendon repair

    Science.gov (United States)

    Repair of tendon ... Tendon repair can be performed using: Local anesthesia (the immediate area of the surgery is pain-free) ... a cut on the skin over the injured tendon. The damaged or torn ends of the tendon ...

  14. 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

    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...

  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. Radiological Features and Postoperative Histopathologic Diagnosis ...

    African Journals Online (AJOL)

    Radiological Features and Postoperative Histopathologic Diagnosis of Intracranial Masses at Tikur Anbessa ... East and Central African Journal of Surgery ... features and postoperative histopathology diagnosis of intracranial mass lesions.

  17. Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients.

    Science.gov (United States)

    Scartozzi, Mario; Franciosi, Vittorio; Campanini, Nicoletta; Benedetti, Giovanni; Barbieri, Fausto; Rossi, Giulio; Berardi, Rossana; Camisa, Roberta; Silva, Rosa Rita; Santinelli, Alfredo; Ardizzoni, Andrea; Crinò, Lucio; Rindi, Guido; Cascinu, Stefano

    2006-07-01

    Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunohistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in > or = 50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in > 50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.

  18. Metonymic objects, cultural practices and narrative repair: Sri Lankan responses to the Indian Ocean tsunami.

    Science.gov (United States)

    Cassim, Shemana; Stolte, Ottilie; Hodgetts, Darrin

    2015-07-01

    The 2004 Indian Ocean tsunami resulted in a tragic loss of life and immense suffering. This article explores the ways in which a group of people from Sri Lanka worked to address the disruption to their life narratives caused by the loss of loved ones. We go beyond a focus on 'talk' in narrative research in health psychology to explore the importance of material objects in sustaining continued bonds with the deceased. This article provides an alternative to the tendency in mainstream psychology to pathologise grief and highlights the importance of culturally patterned responses to disaster. © The Author(s) 2013.

  19. 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.

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

    Science.gov (United States)

    Van Meter, Michael; Simon, Matthew; Tombline, Gregory; May, Alfred; Morello, Timothy D; Hubbard, Basil P; Bredbenner, Katie; Park, Rosa; Sinclair, David A; Bohr, Vilhelm A; Gorbunova, Vera; Seluanov, Andrei

    2016-09-06

    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.

  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. [Inflammatory process, histopathological aspects].

    Science.gov (United States)

    Diébold, J

    1995-01-01

    Inflammation occurs only in conjunctive tissue and is the result of a close cooperation of various cells: blood platelets, endothelial cells, leucocytes, mast cells, fibroblasts. Successive phases can be recognized, the first is characterized by vascular phenomenons defining the acute phase. The second by cellular reactions defining the chronic or granulomatous phase. Various morphological patterns can be recognized in acute or chronic inflammation. In addition, hypersensitivity is responsible of peculiar morphology of the inflammatory response. After tissue necrosis, tissular debris should be eliminated by detersion. Then, a granulation tissue develops representing the first step of the healing, which will not be described here.

  3. Porous alumina, zirconia and alumina/zirconia for bone repair: fabrication, mechanical and in vitro biological response.

    Science.gov (United States)

    Hadjicharalambous, Chrystalleni; Buyakov, Ales; Buyakova, Svetlana; Kulkov, Sergey; Chatzinikolaidou, Maria

    2015-04-23

    Zirconia (ZrO2) and alumina (Al2O3) based ceramics are widely used for load-bearing applications in bone repair due to their excellent mechanical properties and biocompatibility. They are often regarded as bioinert since no direct bone-material interface is created unless a porous structure intercedes, leading to better bone bonding. In this regard, investigating interactions between cells and porous ceramics is of great interest. In the present study, we report on the successful fabrication of sintered alumina A-61, zirconia Z-50 and zirconia/alumina composite ZA-60 ceramics with medium porosities of 61, 50 and 60%, respectively, indicating a bimodal pore size distribution and good interconnectivity. They exhibit elastic moduli of 3-10 GPa and compressive strength values of 60-240 MPa, similar to those of human cortical bone.We performed in vitro cell-material investigations comparing the adhesion, proliferation and differentiation of mouse pre-osteoblasts MC3T3-E1 on the three porous materials. While all three ceramics demonstrate a strong cell attachment, better cell spreading is observed on zirconia-containing substrates. Significantly higher cell growth was quantified on the latter ceramics, revealing an increased alkaline phosphatase activity, higher collagen production and increased calcium biomineralization compared to A-61. Hence, these porous zirconia-containing ceramics elicit superior biological responses over porous alumina of similar porosity, promoting enhanced biological interaction, with potential use as non-degradable bone grafts or as implant coatings.

  4. Preparation, characterization, in vitro bioactivity, and cellular responses to a polyetheretherketone bioactive composite containing nanocalcium silicate for bone repair.

    Science.gov (United States)

    Ma, Rui; Tang, Songchao; Tan, Honglue; Qian, Jun; Lin, Wentao; Wang, Yugang; Liu, Changsheng; Wei, Jie; Tang, Tingting

    2014-08-13

    In this study, a nanocalcium silicate (n-CS)/polyetheretherketone (PEEK) bioactive composite was prepared using a process of compounding and injection-molding. The mechanical properties, hydrophilicity, and in vitro bioactivity of the composite, as well as the cellular responses of MC3T3-E1 cells (attachment, proliferation, spreading, and differentiation) to the composite, were investigated. The results showed that the mechanical properties and hydrophilicity of the composites were significantly improved by the addition of n-CS to PEEK. In addition, an apatite-layer formed on the composite surface after immersion in simulated body fluid (SBF) for 7 days. In cell culture tests, the results revealed that the n-CS/PEEK composite significantly promoted cell attachment, proliferation, and spreading compared with PEEK or ultrahigh molecular weight polyethylene (UHMWPE). Moreover, cells grown on the composite exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes than cells grown on PEEK or UHMWPE. These results indicated that the incorporation of n-CS to PEEK could greatly improve the bioactivity and biocompatibility of the composite. Thus, the n-CS/PEEK composite may be a promising bone repair material for use in orthopedic clinics.

  5. Defective DNA single-strand break repair is responsible for senescence and neoplastic escape of epithelial cells.

    Science.gov (United States)

    Nassour, Joe; Martien, Sébastien; Martin, Nathalie; Deruy, Emeric; Tomellini, Elisa; Malaquin, Nicolas; Bouali, Fatima; Sabatier, Laure; Wernert, Nicolas; Pinte, Sébastien; Gilson, Eric; Pourtier, Albin; Pluquet, Olivier; Abbadie, Corinne

    2016-01-29

    The main characteristic of senescence is its stability which relies on the persistence of DNA damage. We show that unlike fibroblasts, senescent epithelial cells do not activate an ATM-or ATR-dependent DNA damage response (DDR), but accumulate oxidative-stress-induced DNA single-strand breaks (SSBs). These breaks remain unrepaired because of a decrease in PARP1 expression and activity. This leads to the formation of abnormally large and persistent XRCC1 foci that engage a signalling cascade involving the p38MAPK and leading to p16 upregulation and cell cycle arrest. Importantly, the default in SSB repair also leads to the emergence of post-senescent transformed and mutated precancerous cells. In human-aged skin, XRCC1 foci accumulate in the epidermal cells in correlation with a decline of PARP1, whereas DDR foci accumulate mainly in dermal fibroblasts. These findings point SSBs as a DNA damage encountered by epithelial cells with aging which could fuel the very first steps of carcinogenesis.

  6. Human longevity and variation in DNA damage response and repair: study of the contribution of sub-processes using competitive gene-set analysis.

    Science.gov (United States)

    Debrabant, Birgit; Soerensen, Mette; Flachsbart, Friederike; Dato, Serena; Mengel-From, Jonas; Stevnsner, Tinna; Bohr, Vilhelm A; Kruse, Torben A; Schreiber, Stefan; Nebel, Almut; Christensen, Kaare; Tan, Qihua; Christiansen, Lene

    2014-09-01

    DNA-damage response and repair are crucial to maintain genetic stability, and are consequently considered central to aging and longevity. Here, we investigate whether this pathway overall associates to longevity, and whether specific sub-processes are more strongly associated with longevity than 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 and mitochondrial DNA processes. The study population was 1089 long-lived and 736 middle-aged Danes. A self-contained set-based test of all SNPs displayed association with longevity (P-value=9.9 × 10(-5)), supporting that the overall pathway could affect longevity. Investigation of the nine sub-processes using the competitive gene-set analysis by Wang et al indicated that BER, HRR and RECQ associated stronger with longevity than the respective remaining genes of the pathway (P-values=0.004-0.048). For HRR and RECQ, only one gene contributed to the significance, whereas for BER several genes contributed. These associations did, however, generally not pass correction for multiple testing. Still, these findings indicate that, of the entire pathway, variation in BER might influence longevity the most. These modest sized P-values were not replicated in a German sample. This might, though, be due to differences 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.

  7. Modeling nucleotide excision repair and its impact on UV-induced mutagenesis during SOS-response in bacterial cells.

    Science.gov (United States)

    Bugay, Aleksandr N; Krasavin, Evgeny A; Parkhomenko, Aleksandr Yu; Vasilyeva, Maria A

    2015-01-01

    A model of the UV-induced mutation process in Escherichia coli bacteria has been developed taking into account the whole sequence of molecular events starting from initial photo-damage and finishing with the fixation of point mutations. The wild-type phenotype bacterial cells are compared with UV-sensitive repair-deficient mutant cells. Attention is mainly paid to excision repair system functioning as regards induced mutagenesis.

  8. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  9. Swept-source optical coherence tomography of lower limb wound healing with histopathological correlation

    Science.gov (United States)

    Barui, Ananya; Banerjee, Provas; Patra, Rusha; Das, Raunak Kumar; Dhara, Santanu; Dutta, Pranab K.; Chatterjee, Jyotirmoy

    2011-02-01

    Direct noninvasive visualization of wound bed with depth information is important to understand the tissue repair. We correlate skin swept-source-optical coherence tomography (OCT) with histopathological and immunohistochemical evaluation on traumatic lower limb wounds under honey dressing to compare and assess the tissue repair features acquired noninvasively and invasively. Analysis of optical biopsy identifies an uppermost brighter band for stratum corneum with region specific thickness (p technology.

  10. 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

  11. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2016-12-01

    technologies not presented in this SAP may also be explored in this study. The assay results from the most recent tumor biopsy will be used for each...integrity in pre-treatment biopsies with response to a PARPi in a prospective single-agent PARPi phase 2 clinical trial in recurrent ovarian...large number of DNA repair genes on small core biopsy specimens iv) begun accessioning samples from the phase 2 rucaparib trial (Ariel 2, NCT01891344

  12. 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

  13. Diverse Responses to UV-B Radiation and Repair Mechanisms of Bacteria Isolated from High-Altitude Aquatic Environments▿

    Science.gov (United States)

    Fernández Zenoff, V.; Siñeriz, F.; Farías, M. E.

    2006-01-01

    Acinetobacter johnsonii A2 isolated from the natural community of Laguna Azul (Andean Mountains at 4,560 m above sea level), Serratia marcescens MF42, Pseudomonas sp. strain MF8 isolated from the planktonic community, and Cytophaga sp. strain MF7 isolated from the benthic community from Laguna Pozuelos (Andean Puna at 3,600 m above sea level) were subjected to UV-B (3,931 J m−2) irradiation. In addition, a marine Pseudomonas putida strain, 2IDINH, and a second Acinetobacter johnsonii strain, ATCC 17909, were used as external controls. Resistance to UV-B and kinetic rates of light-dependent (UV-A [315 to 400 nm] and cool white light [400 to 700 nm]) and -independent reactivation following exposure were determined by measuring the survival (expressed as CFU) and accumulation of cyclobutane pyrimidine dimers (CPD). Significant differences in survival after UV-B irradiation were observed: Acinetobacter johnsonii A2, 48%; Acinetobacter johnsonii ATCC 17909, 20%; Pseudomonas sp. strain MF8, 40%; marine Pseudomonas putida strain 2IDINH, 12%; Cytophaga sp. strain MF7, 20%; and Serratia marcescens, 21%. Most bacteria exhibited little DNA damage (between 40 and 80 CPD/Mb), except for the benthic isolate Cytophaga sp. strain MF7 (400 CPD/Mb) and Acinetobacter johnsonii ATCC 17909 (160 CPD/Mb). The recovery strategies through dark and light repair were different in all strains. The most efficient in recovering were both Acinetobacter johnsonii A2 and Cytophaga sp. strain MF7; Serratia marcescens MF42 showed intermediate recovery, and in both Pseudomonas strains, recovery was essentially zero. The UV-B responses and recovery abilities of the different bacteria were consistent with the irradiation levels in their native environment. PMID:17056692

  14. 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.

  15. [Histopathologic study of chronic sinusitis].

    Science.gov (United States)

    Wayoff, M; Parache, R M; Bodelet, B; Gazel, P

    1983-01-01

    The conventional histopathology of the sinus is a criterium for the therapeutic indication, since it is possible to distinguish between granulomatous chronic sinusitis, chronic sinusitis with oedema and nasal polyposis. Each one of these clinical pictures has his own etiology and requires a specific therapeutic approach.

  16. 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

  17. Histopathological spectrum of Psoriasiform dermatitis

    Directory of Open Access Journals (Sweden)

    PL Jayalakshmy

    2016-09-01

    Full Text Available Background: Psoriasiform dermatitis is a frequently encountered terminology in a wide variety of inflammatory dermatoses. It often poses challenges to both dermatologists and pathologists alike. Clinical features when considered alone may not be reliable, as they vary with both disease duration and treatment. On the contrary, histopathological material constitutes definite hard evidence, which can be preserved and will continue to be available for future review. The objective of the study is to study the histopathological findings in Psoriasiform dermatitis.Materials and Methods: This is a retrospective study in a tertiary care centre in Kerala, South India. All cases diagnosed as Psoriasis or mentioned as one of the differential diagnosis were included. The material included 66 skin biopsies. Patients with a previous diagnosis of the same were excluded from the study.Results: The lesions comprised 9% of the total number of skin biopsies. The age distribution pattern revealed that the highest percentage was in the 41-60 year age group (50% with a male preponderance of 65%. Psoriasis was the most common lesion (60.60% and Lichen simplex chronicus was the second most common lesion (10.60 %, encountered in the study.Conclusion: Some of the histopathological features are specific and characteristic for each entity like Psoriasis, Pityriasis rubra pilaris, Pityriasis rosea and Inflammatory linear verrucous epidermal nevus whereas some overlap in lesions like Prurigo nodularis, Lichen simplex chronicus and Allergic contact dermatitis. Hence, combination of proper clinical observation and histopathological study will give a conclusive diagnosis.

  18. 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 repla

  19. In vivo induction of antioxidant response and oxidative stress associated with genotoxicity and histopathological alteration in two commercial fish species due to heavy metals exposure in northern India (Kali) river.

    Science.gov (United States)

    Fatima, Mahino; Usmani, Nazura; Firdaus, Fakiha; Zafeer, Mohammad Faraz; Ahmad, Shafeeque; Akhtar, Kafil; Dawar Husain, S M; Ahmad, Mir Hilal; Anis, Ehraz; Mobarak Hossain, M

    2015-01-01

    Heavy metals can significantly bioaccumulate in fish tissues. The step wise mechanism of heavy metal toxicities on fish health is still limited. The present study assessed the tissue-specific antioxidant response and oxidative stress biomarkers of commercially important fish species namely, Channa striatus and Heteropneustes fossilis inhabiting Kali River of northern India where heavy-metal load is beyond the World Health Organisation - maximum permissible limits. Heavy metals chromium (Cr), nickel (Ni), lead (Pb) and cadmium (Cd) were elevated in both fish species compared to recommended values of the Federal Environmental Protection Agency (FEPA), 1999 for edible fishes. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CATA) activities in all tissues (brachial, neural, renal and hepatic) were altered. Cellular lipid and protein compromisation in both fishes induced by heavy metals was determined by lipid peroxidation (LPO) and protein carbonylation (PC) assays. Micronucleus (MN) test of erythrocytes and comet assay of liver cells confirmed genotoxicity. Histopathology of the liver, kidney and brain of affected fishes was distorted significantly with its reference fishes thereby affecting the quality and quantity of these fish stocks. This raises a serious concern as these fishes are consumed by the local population which would ultimately affect human health.

  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. Histopathological examination of Acanthamoeba sclerokeratitis

    Directory of Open Access Journals (Sweden)

    Kato K

    2014-01-01

    Full Text Available Kumiko Kato,1 Koji Hirano,2 Tetsuro Nagasaka,3 Koichi Matsunaga,1 Yuko Takashima,1 Mineo Kondo1 1Department of Ophthalmology, Mie University School of Medicine, Tsu, Japan; 2Department of Ophthalmology, Fujita Health University, Nagoya, Japan; 3Department of Medical Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya, Japan Purpose: To report the histopathological findings in a case of severe Acanthamoeba sclerokeratitis (ASK. Patient and methods: A 46-year-old patient was referred to the Department of Ophthalmology of Mie University Hospital because of a severe corneal ulcer of the right eye of 6 months' duration. Our initial examination showed a ring-shaped corneal opacity with extensive epithelial defects and nodular scleritis. Cysts of Acanthamoeba were identified in cultures from corneal scrapings, and he was diagnosed with ASK. He was started on antiamoebic treatment, including topical micafungin and chlorhexidine. The corneal ulcer was debrided several times. One month later, he developed necrotizing scleritis, and the cornea suddenly perforated. The eye was enucleated because of severe pain and prepared for histopathological examination. Results: The histopathological examination showed an infiltration of polymorphonuclear leukocytes throughout the corneal stroma and also in the limbal area of the sclera, forming an abscess. Granulation tissue was observed in the anterior sclera close to the ciliary body, but the posterior regions of the eye were not affected by inflammation or tissue destruction. The cysts of Acanthamoeba were observed only in the cornea. Conclusion: Histopathological examination of an eye with severe ASK showed that the inflammation and tissue granulation were present only in the anterior part of eye, and the posterior segment was not affected. Because the inflammation and tissue destruction were confined to the anterior segment, enucleation might not have been necessary if the severe pain was

  2. Comprehensive SNP scan of DNA repair and DNA damage response genes reveal multiple susceptibility loci conferring risk to tobacco associated leukoplakia and oral cancer.

    Science.gov (United States)

    Mondal, Pinaki; Datta, Sayantan; Maiti, Guru Prasad; Baral, Aradhita; Jha, Ganga Nath; Panda, Chinmay Kumar; Chowdhury, Shantanu; Ghosh, Saurabh; Roy, Bidyut; Roychoudhury, Susanta

    2013-01-01

    Polymorphic variants of DNA repair and damage response genes play major role in carcinogenesis. These variants are suspected as predisposition factors to Oral Squamous Cell Carcinoma (OSCC). For identification of susceptible variants affecting OSCC development in Indian population, the "maximally informative" method of SNP selection from HapMap data to non-HapMap populations was applied. Three hundred twenty-five SNPs from 11 key genes involved in double strand break repair, mismatch repair and DNA damage response pathways were genotyped on a total of 373 OSCC, 253 leukoplakia and 535 unrelated control individuals. The significantly associated SNPs were validated in an additional cohort of 144 OSCC patients and 160 controls. The rs12515548 of MSH3 showed significant association with OSCC both in the discovery and validation phases (discovery P-value: 1.43E-05, replication P-value: 4.84E-03). Two SNPs (rs12360870 of MRE11A, P-value: 2.37E-07 and rs7003908 of PRKDC, P-value: 7.99E-05) were found to be significantly associated only with leukoplakia. Stratification of subjects based on amount of tobacco consumption identified SNPs that were associated with either high or low tobacco exposed group. The study reveals a synergism between associated SNPs and lifestyle factors in predisposition to OSCC and leukoplakia.

  3. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-­‐13-­‐1-­‐0485 TITLE: Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor...UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Mayo Clinic and Foundation AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT...Biomarkers That Predict Response to PARP Inhibitors and Platinum.” Over the past 12 months we have i) completed validation of the immunohistochemical

  4. Immunopathology and histopathology of experimental chlamydial salpingitis.

    Science.gov (United States)

    Patton, D L

    1985-01-01

    Experimental infection of fallopian tubes was produced in four sexually mature pig-tailed monkeys (Macaca nemestrina) by intratubal inoculation with serovar E or F Chlamydia trachomatis. Infection was confirmed by reisolation of the organism from both the endosalpinx and the endocervix. An antibody response to the infecting strain of C. trachomatis was demonstrated in monkey sera and in cervical secretions by the microimmunofluorescence test. A cellular immune response to C. trachomatis was shown by the in vitro lymphocyte transformation assay. Histopathologic examination of the endosalpinx following infection showed epithelial degeneration and deciliation of ciliated cells. Lymphocytic infiltration into both submucosa and mucosa was present at day 7 and approximated areas of epithelial cell degeneration. Two control monkeys remained unresponsive throughout the study. These results indicate that the pig-tailed macaque should be a suitable model for further studies of the pathogenesis of, immune responses to, and therapy for acute C. trachomatis salpingitis.

  5. Arterial Stiffness Alterations and Inflammatory Response Following Endovascular Aortic Repair: Based on a Presentation at the 2013 VEITH Symposium, November 19-23, 2013 (New York, NY, USA).

    Science.gov (United States)

    Moulakakis, Konstantinos G; Mylonas, Spyridon N; Kakisis, John; Kadoglou, Nikolaos P E; Papadakis, Ioannis; Sfyroeras, George S; Antonopoulos, Constantine C N; Mantas, George; Ikonomidis, Ignatios; Liapis, Christos D

    2015-04-01

    Endovascular abdominal aortic aneurysm repair (EVAR) and thoracic aortic aneurysm repair (TEVAR) have been widely incorporated into clinical practice. However, changes in arterial stiffness and post-implantation syndrome after aortic endografting remain important issues under investigation. The aneurysm sac wall motion after successful EVAR and TEVAR reflects complex interactions between all the components of the excluded aneurysm, including true compliance of the aneurysm wall itself, intra-aneurysm sac pressure, remodeling of the thrombus, and mechanical characteristics of the endograft. Experimental and clinical studies have shown that aortic endografting results in increased arterial stiffness in animal models. It can be assumed that the alterations of aortic mechanical properties can have a direct impact on heart output. The long-term impact of these mechanical changes on cardiovascular outcomes and the potential effects of different endografts on hemodynamics are important issues under investigation. Post-implantation syndrome (PIS) is a systemic inflammatory response frequently observed after endovascular treatment of aortic pathologies. The main features of PIS include fever, leukocytosis, elevated C-reactive protein levels, and coagulation disturbances. Endograft design appears to influence this inflammatory response following aortic endografting; woven polyester endografts have been shown to be associated with greater inflammatory response compared to PTFE stent grafts. The purpose of this paper is to review the literature to elucidate arterial stiffness alterations and inflammatory response after EVAR and TEVAR and the impact of endograft design on aortic stiffness and the post-inflammatory response.

  6. 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

    IP to chromatin and subsequent end resection during DNA DSB repair. Our data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins. Consequently, depletion of CHD1 specifically affects HR-mediated DNA repair but not non......-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......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...

  7. Molecular constituents of the extracellular matrix in rat liver mounting a hepatic progenitor cell response for tissue repair

    DEFF Research Database (Denmark)

    Vestentoft, Peter Siig; Jelnes, Peter; Andersen, Jesper Bøje

    2013-01-01

    Tissue repair in the adult mammalian liver occurs in two distinct processes, referred to as the first and second tiers of defense. We undertook to characterize the changes in molecular constituents of the extracellular matrix when hepatic progenitor cells (HPCs) respond in a second tier of defense...

  8. Pityriasis rosea: A histopathologic study

    Directory of Open Access Journals (Sweden)

    Prasad D

    2000-01-01

    Full Text Available The histopathologic features of pityriasis rosea (PR have been considered by many authors to be compatible with those of dermatitis, but it is not surprising that histological difference may exist between PR and dermatitis. fifty patients of pityriasis rosea were included in this study. We studied the 50 biopsies including 9 biopsies from herald patches. The characteristic features were; absence or decrease of the granular cell layer, extravasation of red blood cells in papillary dermis and partly into the epidermis, dyskeratosis, liquefaction of basal cells, homogenization of papillary collagen, intraepidermal vesicles in apparently dry skin. In addition of these features, we observed prominent delling of epidermis and a typical spongiotic pattern not reported earlier. The biopsies from herald patches showed minor differences from the secondary lesions. We also compared the histopathological features of recent lesions with older lesions.

  9. Associations of polymorphisms in DNA repair genes and MDR1 gene with chemotherapy response and survival of non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yan Du

    Full Text Available OBJECTIVES: We aimed to determine the associations of genetic polymorphisms of excision repair cross-complementation group 1 (ERCC1 rs11615, xeroderma pigmentosum group D (XPD/ERCC2 rs13181, X-ray repair cross complementing group 1 (XRCC1 rs25487, XRCC3 rs1799794, and breast cancer susceptibility gene 1 (BRCA1 rs1799966 from the DNA repair pathway and multiple drug resistance 1 (MDR1/ABCB1 rs1045642 with response to chemotherapy and survival of non-small cell lung cancer (NSCLC in a Chinese population. MATERIALS AND METHODS: A total of 352 NSCLC patients were enrolled to evaluate the associations of the six SNPs with response to chemotherapy and overall survival. Logistic regressions were applied to test the associations of genetic polymorphisms with response to chemotherapy in 161 advanced NSCLC patients. Overall survival was analyzed in 161 advanced and 156 early stage NSCLC patients using the Kaplan-Meier method with log-rank test, respectively. Multivariate Cox proportional hazards model was performed to determine the factors independently associated with NSCLC prognosis. RESULTS: BRCA1 rs1799966 minor allele C (TC+CC vs. TT, OR = 0.402, 95% CI = 0.204-0.794, p = 0.008 and MDR1/ABCB1 rs1045642 minor allele A (GA +AA vs. GG, OR = 0.478, 95% CI = 0.244-0.934, p = 0.030 were associated with a better response to chemotherapy in advanced NSCLC patients. Survival analyses indicated that BRCA1 rs1799966 TC+CC genotypes were associated with a decreased risk of death (HR = 0.617, 95% CI = 0.402-0.948, p = 0.028 in advanced NSCLC patients, and the association was still significant after the adjustment for covariates. Multivariate Cox regression analysis showed that ERCC1 rs11615 AA genotype (P = 0.020 and smoking (p = 0.037 were associated with increased risks of death in early stage NSCLC patients after surgery. CONCLUSIONS: Polymorphisms of genes in DNA repair pathway and MDR1 could contribute to chemotherapy response and survival of patients with

  10. 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.

  11. 42 CFR 493.1219 - Condition: Histopathology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Histopathology. 493.1219 Section 493....1219 Condition: Histopathology. If the laboratory provides services in the subspecialty of Histopathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, §...

  12. Hypospadias repair

    Science.gov (United States)

    ... the problem. If the repair is not done, problems may occur later on such as: Difficulty controlling and directing urine stream A curve in the penis during erection Decreased fertility Embarrassment about appearance of penis Surgery ...

  13. Stimulation of DNA repair and increased light output in response to UV irradiation in Escherichia coli expressing lux genes.

    Science.gov (United States)

    Cutter, Kerry L; Alloush, Habib M; Salisbury, Vyv C

    2007-01-01

    It has previously been suggested that the evolutionary drive of bacterial bioluminescence is a mechanism of DNA repair. By assessing the UV sensitivity of Escherichia coli, it is shown that the survival of UV-irradiated E. coli constitutively expressing luxABCDE in the dark is significantly better than either a strain with no lux gene expression or the same strain expressing only luciferase (luxAB) genes. This shows that UV resistance is dependent on light output, and not merely on luciferase production. Also, bacterial survival was found to be dependent on the conditions following UV irradiation, as bioluminescence-mediated repair was not as efficient as repair in visible light. Moreover, photon emission revealed a dose-dependent increase in light output per cell after UV exposure, suggesting that increased lux gene expression correlates with UV-induced DNA damage. This phenomenon has been previously documented in organisms where the lux genes are under their natural luxR regulation but has not previously been demonstrated under the regulation of a constitutive promoter.

  14. Lower nasopharyngeal epithelial cell repair and diminished innate inflammation responses contribute to the onset of acute otitis media in otitis-prone children.

    Science.gov (United States)

    Verhoeven, David; Nesselbush, Monica; Pichichero, Michael E

    2013-08-01

    About 30 % of young children experience excessive, frequent episodes of middle ear infection and are classified as acute otitis media prone (OP). Streptococcus pneumoniae (Spn) is a predominant otopathogen in OP and non-OP (NOP) children. The pathogenesis of middle ear infection involves otopathogen nasopharyngeal (NP) colonization followed by an upper respiratory viral infection that modifies the NP environment to allow a sufficient inoculum of bacteria to reflux via the Eustachian tube into the middle ear space. Here, we analyzed the NP mucosal repair response between age-matched stringently defined OP (sOP) and NOP children who progressed to middle ear infection caused by Spn. We found lower epidermal growth factor, epidermal growth factor receptor, and angiogenin cytokine concentrations in nasal washes of sOP compared with NOP children. Despite higher expression of TLR2/4 transcript expression in nasal epithelium and in polymorphonuclear cells present in nasal secretions in sOP children, sOP children had lower expression of proinflammatory cytokines such as IL-6 and IL-8 in the NP. Chemotaxis-associated cytokine expression at onset of AOM in sOP children was also lower compared with NOP children, possibly indicating a lower capacity to signal the innate immune system. We conclude that lower epithelial cell repair responses during viral infection in the NP combined with diminished innate inflammatory responses potentiate Spn pathogenesis in the sOP child.

  15. 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.

  16. Radio-adaptive response of base excision repair genes and proteins in human peripheral blood mononuclear cells exposed to gamma radiation.

    Science.gov (United States)

    Toprani, Sneh M; Das, Birajalaxmi

    2015-09-01

    Radio-adaptive response is a mechanism whereby a low-dose exposure (priming dose) induces resistance to a higher dose (challenging dose) thus significantly reducing its detrimental effects. Radiation-induced DNA damage gets repaired through various DNA repair pathways in human cells depending upon the type of lesion. The base excision repair (BER) pathway repairs radiation-induced base damage, abasic sites and single-strand breaks in cellular DNA. In the present study, an attempt has been made to investigate the involvement of BER genes and proteins in the radio-adaptive response in human resting peripheral blood mononuclear cells (PBMC). Venous blood samples were collected from 20 randomly selected healthy male individuals with written informed consent. PBMC were isolated and irradiated at a priming dose of 0.1 Gy followed 4h later with a challenging dose of 2.0 Gy (primed cells). Quantitation of DNA damage was done using the alkaline comet assay immediately and expression profile of BER genes and proteins were studied 30 min after the challenging dose using real-time quantitative polymerase chain reaction and western blot, respectively. The overall result showed significant (P ≤ 0.05) reduction of DNA damage in terms of percentage of DNA in tail (%T) with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4 h. Twelve individuals showed significant (P ≤ 0.05) reduction in %T whereas eight individuals showed marginal reduction in DNA damage that was not statistically significant. However, at the transcriptional level, BER genes such as APE1, FEN1 and LIGASE1 showed significant (P ≤ 0.05) up-regulation in both groups. Significant (P ≤ 0.05) up-regulation was also observed at the protein level for OGG1, APE1, MBD4, FEN1 and LIGASE1 in primed cells. Up-regulation of some BER genes and proteins such as APE1, FEN1 and LIGASE1 in primed cells of resting PBMC is suggestive of active involvement of the BER pathway in radio-adaptive response.

  17. 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.

  18. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

    Directory of Open Access Journals (Sweden)

    Rudge Marilza VC

    2011-08-01

    Full Text Available Abstract Objective To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation. Research design and methods One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH, gestational DM (GDM or overt DM (DM. Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin. Results Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a "post-mortem" phenomenon. Conclusion Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.

  19. Femoral hernia repair

    Science.gov (United States)

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  20. Undescended testicle repair

    Science.gov (United States)

    Orchidopexy; Inguinal orchidopexy; Orchiopexy; Repair of undescended testicle; Cryptorchidism repair ... first year of life without treatment. Undescended testicle repair surgery is recommended for patients whose testicles do ...

  1. 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 applications: A picture for the next 20 years. Journal of the european ceramic society, 29(7):1245-55. 4. dorozhkin, s.V. 2007. Bioceramics based on calcium orthophosphates (review). Glass and ceramics, 64(11):442-7. 5. schilling A... requirements for bone repair and replacement due to some characteristics such as: • Lack of collagen fibres2-4 • Very brittle, therefore not prone for use in load-bearing circumstances • General bioactivity needs improvement • Most applications...

  2. Repair and reconstruction of common bile duct by poly(lactide stent

    Directory of Open Access Journals (Sweden)

    Xiaoyi Xu

    2010-01-01

    Full Text Available To investigate the effect of repair of bioabsorbable poly(lactide (PLA biliary stent in common bile duct (CBD transection injury in canine prior to the clinical application. Circular tubing CBD stent was prepared by melt extraction technique using PLA. A transection incision was made on CBD of the normal canine, and then closed the incision with laser welding followed the implantation of PLA tubular stent into it. The stent was obtained to determine degradation of PLA in vivo at postoperative week 1, 4, and 12, respectively. The changes of outer diameter and burst pressure of CBD were investigated. Furthermore, serum liver enzyme values and CBD histopathological analysis were examined in the animals. The results noted that the polymer stent exhibited the same biomedical functions as T tubes and no significant tissue response. Therefore, biodegradable PLA stent matches the requirements in repair and reconstruction of CBD to support the duct, guide bile drainage and reduce T-tube-related complications.

  3. Histopathology of black gill disease caused by Fusarium solani ( Martius ) infection in the Kuruma prawn Penaeus japonicus Bate

    Institute of Scientific and Technical Information of China (English)

    B.Z.BIAN; S.EGUSA

    1986-01-01

    A histopathological description is given of the black gill disease in Kururna prawn Penaeus japomicns. The inflammatory responses of P. japonicu against Fusarium solaniare haemocytic infiltration, haemocytic encapsulation,

  4. 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...

  5. 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.

  6. Intestinal obstruction repair

    Science.gov (United States)

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  7. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  8. [Histopathological evaluation of the meniscus].

    Science.gov (United States)

    Fisseler-Eckhoff, A; Müller, K-M

    2011-05-01

    Menisci fulfill many functions within the complex biomechanics of the knee joint. In the case of meniscus lesions, sparing arthroscopic resection and surgical refixation are the treatments of choice. In terms of diagnosis, this means in general that histopathologic diagnostics are carried out on detached meniscus fragments of between 5 mm and 2 cm in size. A good knowledge of physiologically possible cellular and fibrous histological meniscus damage, as opposed to nonphysiological change regarded as normal with respect to age, is essential for diagnostic meniscus evaluation. The clinician expects clear statements from the pathologist regarding the severity of previous or secondary degenerative meniscus damage, the age and type of traumatic tears, and an appraisal of the relationship between trauma and meniscus damage from an insurance point of view. Close cooperation between the clinician and the pathologist allows for a fast and unambiguous correlation of anamnesis, the clinical picture, and morphological reporting such that problematic insurance cases can be clarified quickly.

  9. p53 isoform Δ113p53/Δ133p53 promotes DNA double-strand break repair to protect cell from death and senescence in response to DNA damage.

    Science.gov (United States)

    Gong, Lu; Gong, Hongjian; Pan, Xiao; Chang, Changqing; Ou, Zhao; Ye, Shengfan; Yin, Le; Yang, Lina; Tao, Ting; Zhang, Zhenhai; Liu, Cong; Lane, David P; Peng, Jinrong; Chen, Jun

    2015-03-01

    The inhibitory role of p53 in DNA double-strand break (DSB) repair seems contradictory to its tumor-suppressing property. The p53 isoform Δ113p53/Δ133p53 is a p53 target gene that antagonizes p53 apoptotic activity. However, information on its functions in DNA damage repair is lacking. Here we report that Δ113p53 expression is strongly induced by γ-irradiation, but not by UV-irradiation or heat shock treatment. Strikingly, Δ113p53 promotes DNA DSB repair pathways, including homologous recombination, non-homologous end joining and single-strand annealing. To study the biological significance of Δ113p53 in promoting DNA DSB repair, we generated a zebrafish Δ113p53(M/M) mutant via the transcription activator-like effector nuclease technique and found that the mutant is more sensitive to γ-irradiation. The human ortholog, Δ133p53, is also only induced by γ-irradiation and functions to promote DNA DSB repair. Δ133p53-knockdown cells were arrested at the G2 phase at the later stage in response to γ-irradiation due to a high level of unrepaired DNA DSBs, which finally led to cell senescence. Furthermore, Δ113p53/Δ133p53 promotes DNA DSB repair via upregulating the transcription of repair genes rad51, lig4 and rad52 by binding to a novel type of p53-responsive element in their promoters. Our results demonstrate that Δ113p53/Δ133p53 is an evolutionally conserved pro-survival factor for DNA damage stress by preventing apoptosis and promoting DNA DSB repair to inhibit cell senescence. Our data also suggest that the induction of Δ133p53 expression in normal cells or tissues provides an important tolerance marker for cancer patients to radiotherapy.

  10. 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…

  11. Mitotic regulator Nlp interacts with XPA/ERCC1 complexes and regulates nucleotide excision repair (NER) in response to UV radiation.

    Science.gov (United States)

    Ma, Xiao-Juan; Shang, Li; Zhang, Wei-Min; Wang, Ming-Rong; Zhan, Qi-Min

    2016-04-10

    Cellular response to DNA damage, including ionizing radiation (IR) and UV radiation, is critical for the maintenance of genomic fidelity. Defects of DNA repair often result in genomic instability and malignant cell transformation. Centrosomal protein Nlp (ninein-like protein) has been characterized as an important cell cycle regulator that is required for proper mitotic progression. In this study, we demonstrate that Nlp is able to improve nucleotide excision repair (NER) activity and protects cells against UV radiation. Upon exposure of cells to UVC, Nlp is translocated into the nucleus. The C-terminus (1030-1382) of Nlp is necessary and sufficient for its nuclear import. Upon UVC radiation, Nlp interacts with XPA and ERCC1, and enhances their association. Interestingly, down-regulated expression of Nlp is found to be associated with human skin cancers, indicating that dysregulated Nlp might be related to the development of human skin cancers. Taken together, this study identifies mitotic protein Nlp as a new and important member of NER pathway and thus provides novel insights into understanding of regulatory machinery involved in NER.

  12. Adaptive response in mouse bone-marrow stromal cells exposed to 900-MHz radiofrequency fields: Gamma-radiation-induced DNA strand breaks and repair.

    Science.gov (United States)

    Ji, Yongxin; He, Qina; Sun, Yulong; Tong, Jian; Cao, Yi

    2016-01-01

    The aim of this study was to examine whether radiofrequency field (RF) preexposure induced adaptive responses (AR) in mouse bone-marrow stromal cells (BMSC) and the mechanisms underlying the observed findings. Cells were preexposed to 900-MHz radiofrequency fields (RF) at 120 μW/cm(2) power intensity for 4 h/d for 5 d. Some cells were subjected to 1.5 Gy γ-radiation (GR) 4 h following the last RF exposure. The intensity of strand breaks in the DNA was assessed immediately at 4 h. Subsequently, some BMSC were examined at 30, 60, 90, or 120 min utilizing the alkaline comet assay and γ-H2AX foci technique. Data showed no significant differences in number and intensity of strand breaks in DNA between RF-exposed and control cells. A significant increase in number and intensity of DNA strand breaks was noted in cells exposed to GR exposure alone. RF followed by GR exposure significantly decreased number of strand breaks and resulted in faster kinetics of repair of DNA strand breaks compared to GR alone. Thus, data suggest that RF preexposure protected cells from damage induced by GR. Evidence indicates that in RF-mediated AR more rapid repair kinetics occurs under conditions of GR-induced damage, which may be attributed to diminished DNA strand breakage.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Transcript levels of the Saccharomyes cerevisiae DNA repair gene RAD23 increase in response to UV light and in meiosis but remain constant in the mitotic cell cycle.

    Science.gov (United States)

    Madura, K; Prakash, S

    1990-08-25

    The RAD23 gene of Saccharomyces cerevisiae is required for excision-repair of UV damaged DNA. In this paper, we determine the location of the RAD23 gene in a cloned DNA fragment, identify the 1.6 kb RAD23 transcript, and examine RAD23 transcript levels in UV damaged cells, during the mitotic cell cycle, and in meiosis. The RAD23 mRNA levels are elevated 5-fold between 30 to 60 min after 37 J/m2 of UV light. RAD23 mRNA levels rise over 6-fold during meiosis at a stage coincident with high levels of genetic recombination. This response is specific to sporulation competent MATa/MAT alpha diploid cells, and is not observed in asporogenous MATa/MATa diploids. RAD23 mRNA levels, however, remain constant during the mitotic cell cycle.

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

    Science.gov (United States)

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

    2012-04-01

    Cellular responses to DNA double-strand breaks (DSBs) are linked in mammals and yeasts to the phosphorylated histones H2AX (γH2AX) 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 γH2AX deficiency in Arabidopsis thaliana plants challenged with DSBs in terms of genotoxic sensitivity and E2F-mediated transcriptional responses. We further establish the existence, restrictive to the G1/S transition, of specific DSB-induced foci containing tobacco E2F transcription factors, in both A. thaliana roots and BY-2 tobacco cells. These E2F foci partially colocalize with γH2AX foci while their formation is ataxia telangiectasia mutated (ATM)-dependent, requires the E2F transactivation domain with its retinoblastoma-binding site and is optimal in the presence of functional H2AXs. Overall, our results unveil a new interplay between plant H2AX and E2F transcriptional activators during the DSB response.

  16. 42 CFR 493.1273 - Standard: Histopathology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Histopathology. 493.1273 Section 493.1273 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1273 Standard: Histopathology. (a) As specified in § 493.1256(e)(3), fluorescent...

  17. Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO3-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Maria A. Spassova

    2015-01-01

    Full Text Available We have developed a kinetic model to investigate how DNA repair processes and scavengers of reactive oxygen species (ROS can affect the dose-response shape of prooxidant induced DNA damage. We used as an example chemical KBrO3 which is activated by glutathione and forms reactive intermediates that directly interact with DNA to form 8-hydroxy-2-deoxyguanosine DNA adducts (8-OH-dG. The single strand breaks (SSB that can result from failed base excision repair of these adducts were considered as an effect downstream from 8-OH-dG. We previously demonstrated that, in the presence of effective base excision repair, 8-OH-dG can exhibit threshold-like dose-response dependence, while the downstream SSB can still exhibit a linear dose-response. Here we demonstrate that this result holds for a variety of conditions, including low levels of GSH, the presence of additional SSB repair mechanisms, or a scavenger. It has been shown that melatonin, a terminal scavenger, inhibits KBrO3-caused oxidative damage. Our modeling revealed that sustained exposure to KBrO3 can lead to fast scavenger exhaustion, in which case the dose-response shapes for both endpoints are not substantially affected. The results are important to consider when forming conclusions on a chemical’s toxicity dose dependence based on the dose-response of early genotoxic events.

  18. Sequence and stress-response analyses of the DNA mismatch repair gene hexA in Lactococcus lactis.

    Science.gov (United States)

    Ren, J; Park, J H; Dunn, N W; Kim, W S

    2001-10-01

    The DNA mismatch repair gene hexA was identified in Lactococcus lactis by PCR amplification by using a pair of primers homologous to the DNA-binding Dps protein. The gene in its entirety, including the regulatory regions, was sequenced, by using a strategy of chromosomal walking based on two PCR protocols. The open reading frame of 2526 bp was preceded by a strong ribosome-binding site (AGGAAG) and was followed by a potential transcription terminator (hairpin loop structure). The 5' terminus of the hexA mRNA was located 135 bp upstream of the start codon, and putative -10 and -35 regions were identified. The deduced amino acid sequence revealed two motifs, the ATP/GTP-binding site (P-loop) and the "MutS family signature". The hexA promoter was cloned into pMU1327, which contained a promoter-less CAT reporter gene, and the promoter activity was examined under oxidative-stress conditions. It appears that the promoter activity is down-shifted by H2O2 at 4 mM.

  19. 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...

  20. Arecoline, a major alkaloid of areca nut, inhibits p53, represses DNA repair, and triggers DNA damage response in human epithelial cells.

    Science.gov (United States)

    Tsai, Yi-Shan; Lee, Ka-Wo; Huang, Jau-Ling; Liu, Yu-Sen; Juo, Suh-Hang Hank; Kuo, Wen-Rei; Chang, Jan-Gowth; Lin, Chang-Shen; Jong, Yuh-Jyh

    2008-07-30

    The International Agency for Research on Cancer declared that areca nut was carcinogenic to human. Areca nut is the main component of betel quid (BQ), which is commonly consumed in Asia. Epidemiological studies have shown that BQ chewing is a predominant risk factor for oral and pharyngeal cancers. It has been known that areca nut is genotoxic to human epithelial cells. However, the molecular and cellular mechanisms underlying areca nut-associated genotoxicity are not fully understood. Here we showed that arecoline, a major alkaloid of areca nut, might contribute to oral carcinogenesis through inhibiting p53 and DNA repair. We found, on the biological aspect, that arecoline could induce gamma-H2AX phosphorylation, a sensitive DNA damage marker, in KB, HEp-2, and 293 cells, suggesting that DNA damages were elicited by arecoline. This phenomenon was supported by the observations of arecoline-induced hyperphosphorylation of ATM, Nbs1, Chk1/2, p53, and Cdc25C, as well as G2/M cell cycle arrest, indicating that a cellular DNA damage response was activated. To explore the possible mechanism accounting for arecoline-elicited DNA damages, we found that arecoline could inhibit p53 by its expression and transactivation function. As a result, the expression of p53-regulated p21(WAF1) and the p53-activated DNA repair were repressed by arecoline. Finally, we showed that p53 mRNA transcripts were frequently down-regulated in BQ-associated oral cancer, suggesting that arecoline-mediated p53 inhibition might play a role in BQ-associated tumorigenesis.

  1. 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.

  2. Impaired mechanical response of an EDMD mutation leads to motility phenotypes that are repaired by loss of prenylation.

    Science.gov (United States)

    Zuela, Noam; Zwerger, Monika; Levin, Tal; Medalia, Ohad; Gruenbaum, Yosef

    2016-05-01

    There are roughly 14 distinct heritable autosomal dominant diseases associated with mutations in lamins A/C, including Emery-Dreifuss muscular dystrophy (EDMD). The mechanical model proposes that the lamin mutations change the mechanical properties of muscle nuclei, leading to cell death and tissue deterioration. Here, we developed an experimental protocol that analyzes the effect of disease-linked lamin mutations on the response of nuclei to mechanical strain in living Caenorhabditis elegans We found that the EDMD mutation L535P disrupts the nuclear mechanical response specifically in muscle nuclei. Inhibiting lamin prenylation rescued the mechanical response of the EDMD nuclei, reversed the muscle phenotypes and led to normal motility. The LINC complex and emerin were also required to regulate the mechanical response of C. elegans nuclei. This study provides evidence to support the mechanical model and offers a potential future therapeutic approach towards curing EDMD.

  3. Minimally disruptive schedule repair for MCM missions

    Science.gov (United States)

    Molineaux, Matthew; Auslander, Bryan; Moore, Philip G.; Gupta, Kalyan M.

    2015-05-01

    Mine countermeasures (MCM) missions entail planning and operations in very dynamic and uncertain operating environments, which pose considerable risk to personnel and equipment. Frequent schedule repairs are needed that consider the latest operating conditions to keep mission on target. Presently no decision support tools are available for the challenging task of MCM mission rescheduling. To address this capability gap, we have developed the CARPE system to assist operation planners. CARPE constantly monitors the operational environment for changes and recommends alternative repaired schedules in response. It includes a novel schedule repair algorithm called Case-Based Local Schedule Repair (CLOSR) that automatically repairs broken schedules while satisfying the requirement of minimal operational disruption. It uses a case-based approach to represent repair strategies and apply them to new situations. Evaluation of CLOSR on simulated MCM operations demonstrates the effectiveness of case-based strategy. Schedule repairs are generated rapidly, ensure the elimination of all mines, and achieve required levels of clearance.

  4. 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...

  5. Chromatin structure and DNA damage repair

    Directory of Open Access Journals (Sweden)

    Dinant Christoffel

    2008-11-01

    Full Text Available Abstract The integrity of the genome is continuously challenged by both endogenous and exogenous DNA damaging agents. These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks, single strand breaks, oxidative lesions and pyrimidine dimers. The cell has evolved intricate DNA damage response mechanisms to counteract the genotoxic effects of these lesions. The two main features of the DNA damage response mechanisms are cell-cycle checkpoint activation and, at the heart of the response, DNA repair. For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis on the response to lesions resolved by nucleotide excision repair. We will discuss the role of histone modifications as well as their displacement or exchange in nucleotide excision repair and make a comparison with their requirement in transcription and double strand break repair.

  6. A new prognostic histopathologic classiifcation ofnasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hai-YunWang; Shie-LeeCheah; MingLee; LiGao; Hui-ZhongZhang; Jie-HuaHe; HaoJiang; Pei-QingMa; Xiao-DongZhu; LiangZeng; Chun-YanChen; Yih-LeongChang; GangChen; Ma-YanHuang; ShaFu; QiongShao; An-JiaHan; Hai-GangLi; Chun-KuiShao; Pei-YuHuang; Chao-NanQian; Tai-XiangLu; Ka-FaiTo; Jin-TianLi; WeiminYe; IngemarErnberg; HoKeungNg; JosephT.S.Wee; Yi-XinZeng; Hans-OlovAdami; AnthonyT.C.Chan1; Jian-YongShao; JacquelineS.G.Hwang; Hai-QiangMai; Yan-FenFeng; EllenT.Chang; Chen-PingWang; MichaelKoonMingKam

    2016-01-01

    Background:The current World Health Organization (WHO) classiifcation of nasopharyngeal carcinoma (NPC) con‑veys little prognostic information. This study aimed to propose an NPC histopathologic classiifcation that can poten‑tially be used to predict prognosis and treatment response. Methods:We initially developed a histopathologic classiifcation based on the morphologic traits and cell differentia‑tion of tumors of 2716 NPC patients who were identiifed at Sun Yat‑sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classiifcation was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The effcacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% conifdence intervals (CI) for overall survival (OS). Results:The 5‑year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid‑epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P<0.001). In mul‑tivariate models, patients with MSEC had a shorter OS than patients with EC (HR=1.44, 95% CI=1.27–1.62), SC (HR=2.00, 95% CI=1.76–2.28), or SCC (HR=4.23, 95% CI=3.34–5.38). Radiochemotherapy signiifcantly improved survival compared with radiotherapy alone for patients with EC (HR=0.67, 95% CI=0.56–0.80), MSEC (HR=0.58, 95% CI=0.49–0.75), and possibly for those with SCC (HR=0.63; 95% CI=0.40–0.98), but not for patients with SC (HR=0.97, 95% CI=0.74–1.28). Conclusions:The proposed classiifcation offers more information for the prediction of NPC prognosis compared with the WHO classiifcation and might be a valuable tool to guide treatment decisions for subtypes that are

  7. The 53BP1 homolog in C. elegans influences DNA repair and promotes apoptosis in response to ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Jin-Sun Ryu

    Full Text Available 53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs, as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.

  8. Histopathologic changes during mesenteric ischaemia and ...

    African Journals Online (AJOL)

    administration of drugs (ketamine, heparin) and for administra- tion of saline given to ... Table 1 Histopathologic scoring based on я modification of the Swerdlow .... cal and contractile activities of the canine small intestines. Am. J. Surg. 1976 ...

  9. Assessment of organosomatic indices and histopathological ...

    African Journals Online (AJOL)

    Assessment of organosomatic indices and histopathological changes in vital organs of ... of fish fed 0 and 20% BSSM inclusions showed no visible signs of damage. ... 20% in C. gariepinus' diet could cause adverse histological alterations.

  10. Breast Hemangioma: MR Appearance with Histopathological Correlation

    Directory of Open Access Journals (Sweden)

    Rasha Ameen

    2012-01-01

    Full Text Available Breast hemangioma is a rare tumor and when small, it may be difficult to diagnose using conventional imaging techniques. In this report the MR appearance is described with histopathological correlation.

  11. Eye muscle repair - discharge

    Science.gov (United States)

    ... Lazy eye repair - discharge; Strabismus repair - discharge; Extraocular muscle surgery - discharge ... You or your child had eye muscle repair surgery to correct eye muscle ... term for crossed eyes is strabismus. Children most often ...

  12. Ventral hernia repair

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007661.htm Ventral hernia repair To use the sharing features on this page, please enable JavaScript. Ventral hernia repair is surgery to repair a ventral hernia. ...

  13. 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 ...

  14. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

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

    2011-01-01

    : homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage......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...

  15. HIC1 (hypermethylated in cancer 1) SUMOylation is dispensable for DNA repair but is essential for the apoptotic DNA damage response (DDR) to irreparable DNA double-strand breaks (DSBs).

    Science.gov (United States)

    Paget, Sonia; Dubuissez, Marion; Dehennaut, Vanessa; Nassour, Joe; Harmon, Brennan T; Spruyt, Nathalie; Loison, Ingrid; Abbadie, Corinne; Rood, Brian R; Leprince, Dominique

    2017-01-10

    The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1. Furthermore, HIC1 SUMOylation is dispensable for DNA repair since the non-SUMOylatable E316A mutant is as efficient as wt HIC1 in Comet assays. Upon induction of irreparable DSBs, the ATM-mediated increase of HIC1 SUMOylation is independent of its effector kinase Chk2. Moreover, irreparable DSBs strongly increase both the interaction of HIC1 with MTA1 and MTA3 and their binding to the SIRT1 promoter. To characterize the molecular mechanisms sustained by this increased repression potential, we established global expression profiles of BJ-hTERT fibroblasts transfected with HIC1-siRNA or control siRNA and treated or not with etoposide. We identified 475 genes potentially repressed by HIC1 with cell death and cell cycle as the main cellular functions identified by pathway analysis. Among them, CXCL12, EPHA4, TGFβR3 and TRIB2, also known as MTA1 target-genes, were validated by qRT-PCR analyses. Thus, our data demonstrate that HIC1 SUMOylation is important for the transcriptional response to non-repairable DSBs but dispensable for DNA repair.

  16. 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

  17. 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...... to H2O2 were typically related to carbohydrate and energy metabolism, cysteine biosynthesis, and stress. In particular, increased cysteine synthase activity may accumulate a cysteine pool relevant for protein stability, enzyme catalysis and the disulfide-reducing pathway. The stress response further...... by refolding. The proteome analysis provides novel insight into resistance mechanisms in lactic acid bacteria against reactive oxygen species and constitutes a valuable starting point for improving industrial processes, food design or strain engineering preserving microorganism viability....

  18. Equine pastern vasculitis: a clinical and histopathological study.

    Science.gov (United States)

    Psalla, Dimitra; Rüfenacht, Silvia; Stoffel, Michael H; Chiers, Koen; Gaschen, Véronique; Doherr, Marcus G; Gerber, Vincent; Welle, Monika M

    2013-11-01

    Equine pastern vasculitis is clinically challenging and the underlying aetiopathogenesis is unclear. The aims of this retrospective study were to establish histopathological criteria for pastern vasculitis, to look for an underlying cause, to investigate whether the histopathological lesions are associated with a distinct clinical picture, to assess if and how the clinical picture varies, and to determine the treatment response. Skin biopsies and clinical data from 20 horses with a diagnosis of vasculitis of the distal extremities were investigated and histology was compared to biopsies from healthy horses. It was concluded that intramural inflammatory cells, leukocytoclasia with nuclear dust, thickening and oedema of the vessel walls, and microhaemorrhages are highly specific histological findings in equine pastern vasculitis. Based on the feedback from the clinicians, the lesions were mostly seen on the lateral and medial aspects of un-pigmented legs. Lesions in white skin were characterised by exudation and crusts, whereas those in pigmented skin were alopecic and characterised by scaling. The response to treatment was poor and the prognosis guarded. No association was found between any of the histopathological findings and a distinct clinical picture. An underlying cause of equine pastern vasculitis could not be identified. Considering the large number of confounding factors, the causative agents are difficult to identify, but may involve drugs or a hypersensitivity reactions to yet unknown antigens.

  19. Role of ubiquitination in meiotic recombination repair

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Programmed and unprogrammed double-strand breaks (DSBs) often arise from such physiological requirements as meiotic recombination, and exogenous insults, such as ionizing radiation (IR). Due to deleterious impacts on genome stability, DSBs must be appropriately processed and repaired in a regulatory manner. Recent investigations have indicated that ubiquitination is a critical factor in DNA damage response and meiotic recombination repair. This review summarizes the effects of proteins and complexes associated with ubiquitination with regard to homologous recombination (HR)-dependent DSB repair.

  20. Histopathological changes in relation to cadmium concentration in horse kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Elinder, C.G.; Jonsson, L.; Piscator, M.; Rahnster, B.

    1981-10-01

    Histopathological changes in kidney cortex, as observed by light microscopy, are related to cadmium concentration in kidney cortex from 69 normal Swedish horses. Cadmium concentrations in kidney ranged from 11 to 186 ..mu..g Cd/g wet wt with an average of 60 ..mu..g Cd/g, which is considerably higher than those normally found in humans. The microscopical changes were rated and related to cadmium concentrations in kidneys by dose-response curves. A relationship existed between frequency of morphological changes and cadmium concentration in the renal cortex. There was no obvious relationship between age and frequency of histopathological changes. This indicates that in horse kidneys morphological changes occur at cadmium concentrations which are lower than the tentative critical level for humans of 200 ..mu..g Cd/g. It is concluded that horses constitute a population at risk for environmental cadmium contamination.

  1. DNA Repair and Genome Maintenance in Bacillus subtilis

    OpenAIRE

    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 mutage...

  2. Histopathology of mallards dosed with lead and selected substitute shot

    Science.gov (United States)

    Locke, L.N.; Irby, H.D.; Bagley, G.E.

    1967-01-01

    The histopathological response of male game farm mallards fed lead, three types of plastic-coated lead, two lead-magnesium alloys, iron, copper, zinc-coated iron, and molybdenum-coated iron shot was studied. Mallards fed lead, plastic-coated lead, or lead-magnesium alloy shot developed a similar pathological response, including the formation of acid-fast intranuclear inclusion bodies in the kidneys. Birds fed iron or molybdenum-coated iron shot developed hemosiderosis of the liver. Two of four mallards fed zinc-coated iron shot also developed hemosiderosis of the liver. No lesions were found in mallards fed copper shot.

  3. 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.

  4. 低钾逆境下根结线虫感染所诱导的番茄根巨型细胞的组织病理学反应%Histopathological Response of Giant Cell Induced by Root-knot Nematode, Meloidogyne javanica, in Tomato Roots under Potassium Stress

    Institute of Scientific and Technical Information of China (English)

    袁林; 方文珍; 罗大民

    2008-01-01

    Comparison of histopathological response and quantitative measurement of giant cell(GC)induced by Meloidogyne javanica in tomato root were studied under potassium-deficient(0.2 mmol/L K+)and replete conditions(control,6.0 mmol/L K+).K+-deficient stress did not impede the formation and maintenance of GC.The mean number of GC per feeding site as well as the meall diameter of GC did not differ between the treatments.However,the thickness of cell wall including components resulted from the accumulated polysaccharide and the length of cell-wall ingrowth increased 5-25 d after inoculation in K+-deficient as compared with K+-replete conditions.An increase of cell-wall ingrowth suggested a kind of compensational response to the potassium stress.

  5. Altered cortical responsiveness to pain stimuli after high frequency electrical stimulation of the skin in patients with persistent pain after inguinal hernia repair.

    Directory of Open Access Journals (Sweden)

    Emanuel N van den Broeke

    Full Text Available BACKGROUND: High Frequency electrical Stimulation (HFS of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate whether this enhanced ERP N1 amplitude could be a potential marker for altered cortical sensory processing in patients with persistent pain after surgery. MATERIALS AND METHODS: Nineteen male patients; 9 with and 10 without persistent pain after inguinal hernia repair received HFS. Before, directly after and thirty minutes after HFS evoked potentials and the subjective pain intensity were measured in response to electric pain stimuli applied to the surrounding unconditioned skin. RESULTS: The results show that, thirty minutes after HFS, the ERP N1 amplitude observed at the conditioned arm was statistically significantly larger than the amplitude at the control arm across all patients. No statistically significant differences were observed regarding ERP N1 amplitude between patients with and without persistent pain. However, thirty minutes after HFS we did observe statistically significant differences of P2 amplitude at the conditioned arm between the two groups. The P2 amplitude decreased in comparison to baseline in the group of patients with pain. CONCLUSION: The ERP N1 effect, induced after HFS, was not different between patients with vs. without persistent pain. The decreasing P2 amplitude was not observed in the patients without pain and also not in the previous healthy volunteer study and thus might be a marker for altered cortical sensory processing in patients with persistent pain after surgery.

  6. Quality and safety aspects in histopathology laboratory.

    Science.gov (United States)

    Adyanthaya, Soniya; Jose, Maji

    2013-09-01

    Histopathology is an art of analyzing and interpreting the shapes, sizes and architectural patterns of cells and tissues within a given specific clinical background and a science by which the image is placed in the context of knowledge of pathobiology, to arrive at an accurate diagnosis. To function effectively and safely, all the procedures and activities of histopathology laboratory should be evaluated and monitored accurately. In histopathology laboratory, the concept of quality control is applicable to pre-analytical, analytical and post-analytical activities. Ensuring safety of working personnel as well as environment is also highly important. Safety issues that may come up in a histopathology lab are primarily those related to potentially hazardous chemicals, biohazardous materials, accidents linked to the equipment and instrumentation employed and general risks from electrical and fire hazards. This article discusses quality management system which can ensure quality performance in histopathology laboratory. The hazards in pathology laboratories and practical safety measures aimed at controlling the dangers are also discussed with the objective of promoting safety consciousness and the practice of laboratory safety.

  7. Microbiological and histopathological aspects of canine pyometra

    Science.gov (United States)

    Coggan, Jennifer Anne; Melville, Priscilla Anne; de Oliveira, Clair Motos; Faustino, Marcelo; Moreno, Andréa Micke; Benites, Nilson Roberti

    2008-01-01

    As pyometra is recognized as one of the main causes of disease and death in the bitch the purposes of this study were to evaluate microbiological and histopathological aspects of canine pyometra and to research the virulence factors of the E. coli isolates identifying possible risks to human health. The microbiological isolation from the intrauterine contents of 100 dogs with pyometra was carried out and the virulence factors in the E. coli strains were identified using PCR method. This study also consisted of the counting of microorganisms colonies forming units in samples of intrauterine content, tests of antimicrobial susceptibility of the E. coli isolates and the histological examination of the uterus. E. coli was the most prevalent microorganism isolated (76.6%) and 120 strains (79.5%) were positive for sfa, 86 (56.9%) were positive for cnf, 87 (57.6%) were positive for pap, 52 (34.4%) were positive for hly, 51 (33.8%) were positive for iuc and 5 (3.3%) were positive for afa genes. One observed more sensitivity of E. coli to norfloxacin, polimixin B, sulphazotrin, chloranfenicol and enrofloxacin. In 42% of the samples of uterine walls where microorganisms were isolated, the sizes of the areas of the inflammatory responses corresponded to 39–56%. Virulence factors were identified in 98.0% of the strains evaluated, demonstrating a high frequency of potentially pathogenic E. coli. It must be considered that dogs are animals that are living in close proximity to man for thousands of years and have an important role in the transmission of E. coli to other animals and to man. PMID:24031249

  8. 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.

  9. DNA repair. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    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. (HLW)

  10. Is routine histopathology of tonsil specimen necessary?

    Directory of Open Access Journals (Sweden)

    Agida S Adoga

    2011-01-01

    Full Text Available Background: Tonsillar diseases are common in paediatric and adult otolaryngological practice. These diseases require tonsillectomy. Specimens are subjected to histopathology routinely in my institution for fear of infections and tumour without consideration for risk factors. The financial burden is on the patients and waste of histopathologist′s man hour because other specimens are left un-attended. This study aims to find out the necessity of routine histopathology of tonsil specimens. Materials and Methods : A 2 year retrospective review of the histopathological results of two (paediatric and adult groups of 61 patients managed for tonsillar diseases at the ENT UNIT of Jos University Teaching Hospital from July 2005 to June, 2007. Data extracted included biodata, clinical features and histopathological diagnosis. Result : The 61 patients comprise 35 children and 26 adults. The youngest and oldest paediatric patients were 1 year and 3 months and 16 years respectively, a range of 1 year 3 months to 16 years. The youngest and oldest adults were 17 and 50 years with a range of 17-50 years. Groups mean ages were 5.1 and 28.5 years. The gender ratios were 1:2.7 and 1:1.9 respectively. One adult was HIV positive. The histopathological diagnosis were chronic nonspecific tonsillitis in 10(16.6%, follicular tonsillitis in 23(38.3%, chronic suppurative tonsillitis in 10(16.6%, lymphoid hyperplasia in 18(30.0% and lymphoma in 1(1.0% respectively. Conclusion : Histopathologic request for tonsillectomy specimens should be based on certain risk factors with consideration of the cost to patients and to spare the histopathologist′s man hour.

  11. Tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) by biocomputation.

    Science.gov (United States)

    Wang, Lin; Huang, Juxiang; Jiang, Minghu; Lin, Hong

    2012-06-01

    We constructed the low-expression tissue-specific transplantation antigen P35B (TSTA3) immune response-mediated metabolism coupling cell cycle to postreplication repair network in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) compared with high-expression (fold change ≥ 2) human hepatocellular carcinoma in GEO data set, by using integration of gene regulatory network inference method with gene ontology analysis of TSTA3-activated up- and downstream networks. Our results showed TSTA3 upstream-activated CCNB2, CKS1B, ELAVL3, GAS7, NQO1, NTN1, OCRL, PLA2G1B, REG3A, SSTR5, etc. and TSTA3 downstream-activated BAP1, BRCA1, CCL20, MCM2, MS4A2, NTN1, REG1A, TP53I11, VCAN, SLC16A3, etc. in no-tumor hepatitis/cirrhotic tissues. TSTA3-activated network enhanced the regulation of apoptosis, cyclin-dependent protein kinase activity, cell migration, insulin secretion, transcription, cell division, cell proliferation, DNA replication, postreplication repair, cell differentiation, T-cell homeostasis, neutrophil-mediated immunity, neutrophil chemotaxis, interleukin-8 production, inflammatory response, immune response, B-cell activation, humoral immune response, actin filament organization, xenobiotic metabolism, lipid metabolism, phospholipid metabolism, leukotriene biosynthesis, organismal lipid catabolism, phosphatidylcholine metabolism, arachidonic acid secretion, activation of phospholipase A2, deoxyribonucleotide biosynthesis, heterophilic cell adhesion, activation of MAPK activity, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, G-protein-coupled receptor protein signaling pathway, response to toxin, acute-phase response, DNA damage response, intercellular junction assembly, cell communication, and cell recognition, as a result of inducing immune response-mediated metabolism coupling cell cycle to postreplication repair in no-tumor hepatitis/cirrhotic tissues.

  12. 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.

  13. Mastitis, a Radiographic, Clinical, and Histopathologic Review.

    Science.gov (United States)

    Cheng, Lin; Reddy, Vijaya; Solmos, Gene; Watkins, Latanja; Cimbaluk, David; Bitterman, Pincas; Ghai, Ritu; Gattuso, Paolo

    2015-01-01

    Mastitis is a benign inflammatory process of the breast with heterogeneous histopathological findings, which clinically and radiographically may mimic a mammary carcinoma. We undertook a retrospective study on 37 cases of mastitis in our institution to correlate the radiographic imaging features and the clinical presentation with the histopathological findings. Histologically, there were 21 granulomatous, 7 fibrous, 3 plasma cell, 3 lupus, 2 lymphocytic, and 1 case of acute mastitis. Radiographically, 16/25 (64%) patients with ultrasound studies showed irregular hypoechoic masses suspicious for malignancy. Clinically, 38% of patients had an associated systemic disease. © 2015 Wiley Periodicals, Inc.

  14. Databases and Bioinformatics Tools for the Study of DNA Repair

    Directory of Open Access Journals (Sweden)

    Kaja Milanowska

    2011-01-01

    Full Text Available DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER and nucleotide excision repair (NER or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS. There are also other mechanisms of DNA repair such as homologous recombination repair (HRR, nonhomologous end-joining repair (NHEJ, or DNA damage response system (DDR. This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

  15. 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.

  16. Clinico- histopathological study of subacute cutaneous lupus erythematous

    Directory of Open Access Journals (Sweden)

    Mittal R

    2001-01-01

    Full Text Available Fourteen cases of sub acute cutaneous lupus erythematosus (SCLE were selected from Dermato- Venereology outpatients during the last 2½ years. Clinically all patients revealed photosensitivity and annular plaques either covered with peripheral collarette of scale or EM - like or DLE - like lesions. Systemic associations were arthralgia in 4, hypertension in I. rheumatoid arthritis in I and pulmonary tuberculosis in L Histopathologically epidermal atrophy, interface dermatitis, basal cell degeneration, colloid bodies and mononuclear infiltrate of dermis were salient features. Good response to 15 mg prednisolonc, medium potency topical steroids and sunscreens was seen in all cases.

  17. Histopathological effects of boldenone in cattle

    NARCIS (Netherlands)

    Groot, M.J.; Biolatti, B.

    2004-01-01

    Histopathology of male cattle previously found positive for béta-boldenone in urine in the Netherlands and in Italy was studied. The animals were derived from practice and several weeks had passed after the finding of béta-boldenone before the animals were examined. The animals consisted of 34 male

  18. Histopathology of fish: I. Techniques and principles

    Science.gov (United States)

    Wood, E.M.; Yasutake, W.T.

    1955-01-01

    The techniques of histopathology have been used for many years in the study of human and animal diseases. Until very recent times, however, histology has been applied to fish studies only very infrequently. This brief discussion is intended to acquaint the reader with the techniques and principles involved and to explain how histological studies may help to overcome fish diseases and nutritional problems.

  19. 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...

  20. Pectus excavatum repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002949.htm Pectus excavatum repair To use the sharing features on this page, please enable JavaScript. Pectus excavatum repair is surgery to correct pectus excavatum . This ...

  1. Histopathological Response in the Interaction between Cotinus coggygria and Verticillium dahliae%黄栌与大丽轮枝菌互作的组织病理学变化

    Institute of Scientific and Technical Information of China (English)

    鲍绍文; 陶万强; 田呈明

    2011-01-01

    Histopathological changes of Cotinus coggygria inoculated with Venicillium dahliae were observed by using paraffin sections and optical microscope photography. The results showed that the different parts of C. coggygria had different infection levels, with leaves the highest (18.83%), and branches the lowest (6. 72% ). After inoculation, the hyphae initially invaded the elongation zone and mature zone of roots, and then appeared in the intercelluar space cortex parenchyma cells within 1 - 3 cm of the root tip, and further went into vessels of the roots, then reached leaves through the vessels of stems and branches finally. V. dahliae mainly occurred in vessels of xylem in the form of hyphae, however it did not appear continuously. In order to prevent expansion of the pathogen after infected, wall of the vessel was thickened,inner diameter of the vessel was decreased by accumulating jelly and tylosis generated in the xylem, or even the vessel was totally blocked. When the C. coggygria was infected, the vessel walls, parenchyma cells and cortical cells were thickened, the inclusions of pith, resin canals and secretory cells nearby increased, the jelly appeared in the parenchyma cells and wood rays. Although parts of vessels were blocked with hyphae, jelly and tylosis to different extent, most of the vessels were healthy and were able to function water transport normally. The partial block of vessels sometime caused plants wilt, but the plant managed to maintain almost normal activities.%采用石蜡切片和光学显微摄像的方法,对黄栌接种大丽轮枝菌后的组织病理学变化进行系统观察.接种大丽轮枝菌后黄栌不同组织部位受侵染的程度不同,叶部最高(18.83%),而枝条最低(6.72%).菌丝首先由根的伸长区及成熟区侵入,而后出现在距根尖1~3 cm处的皮层薄壁细胞的间隙,接着进入根部的导管内,最终经茎部及枝条的导管到达叶部.大耐轮枝菌主要以菌丝形态存在于木

  2. When "Other" Initiate Repair.

    Science.gov (United States)

    Schegloff, Emanuel A.

    2000-01-01

    Elaborates on the locus of other-initiated repair, and reports on a number of environments in which others initiate repair turns later than the one directly following the trouble-source turn. Describes several ways that other initiation of repair, which occurs in next-turn position, may be delayed within that position. (Author/VWL)

  3. Selenium compounds activate ATM-dependent DNA damage responses via the mismatch repair protein hMLH1 in colorectal cancer cells

    Science.gov (United States)

    Epidemiological and animal studies indicate that selenium supplementation suppresses risk of colorectal and other cancers. The majority of colorectal cancers are characterized by a defective DNA mismatch repair (MMR) process. Here, we have employed the MMR-deficient HCT 116 colorectal cancer cells ...

  4. Histopathology of Lyme arthritis in LSH hamsters

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-05-01

    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.

  5. Histopathologic Approach to Oral Cavity Lesions

    Directory of Open Access Journals (Sweden)

    Cuyan Demirkesen

    2012-12-01

    Full Text Available Diseases of the oral cavity may be either a reflection of system or cutaneous diseases or can be seen as a primary oral lesion. These lesions are inflammatory reactions due to miscellaneous mechanisms, ulceration or erosion, reactive proliferative nodules, precancerous or neoplastic diseases. In this study, microscopic features of the most common diseases, together with their differential diagnosis are discussed. Some of the diseases of the oral cavity have overlapping histopathological findings. In these conditions, ancillary methods such as immunoflourescence or immunohistochemistry can be performed. Deep biopsies from representative areas are essential for proper histopathological diagnosis. Moreover, informing the pathologist about the exact anatomic localization of the biopsy, as well as the clinical findings of the lesion is crucial for a better approach.

  6. Lichen Planus-a Clinico-histopathological

    Directory of Open Access Journals (Sweden)

    Garg Vijay

    2000-01-01

    Full Text Available The clinico-histopathological features of 75 patients of lichen planus were studied. The male to female ratio was 1:13. The largest number of patients (30.6% fell into the 31-40 year age group. Two patients had systemic hypertension. There was no history of lichen planus in the family. All patients presented with severe itching within 1-2 months of onset. Papular lesions were seen in 72% and papules with plaques were seen 16%. Lower limbs were involved in 38% of cases. Mucosal involvement was seen in 24% in addition to skin involvement ; nail involvement hypertrophicus (17.3%. Lichen planopilaris and oral lichen planus were uncommon. Clinico-histopathological discrepancies were observed in 7 patients. Civatte bodies were seen in only 37% of cases.

  7. Phosphorylation: The Molecular Switch of Double-Strand Break Repair

    Directory of Open Access Journals (Sweden)

    K. C. Summers

    2011-01-01

    Full Text Available Repair of double-stranded breaks (DSBs is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ, homologous recombination (HR, or the inclusive DNA damage response (DDR. These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.

  8. 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.

  9. Histopathology of Conjunctivochalasis Compared to Normal Conjunctiva

    Science.gov (United States)

    Hashemian, Hesam; Mahbod, Mirgholamreza; Amoli, Fahimeh A.; Kiarudi, Mohammad Y.; Jabbarvand, Mahmoud; Kheirkhah, Ahmad

    2016-01-01

    Purpose: To evaluate the histopathologic changes in the conjunctiva of patients with conjunctivochalasis (CCh) compared to age-matched controls. Methods: This cross-sectional, controlled study included 27 eyes of 27 patients with CCh and 16 eyes of 16 age-matched controls. A biopsy of the bulbar conjunctiva was performed along the temporal lower lid margin before cataract surgery in both groups. Histopathologic evaluation of the specimens was done with light microscopy using staining with hematoxylin/eosin, periodic acid Schiff, and van Gieson elastic stain. Various histopathologic features of the conjunctival epithelium and stroma were compared between the two groups. Results: The mean age of patients was 62.4 ± 6.9 years in the CCh group and 65.1 ± 6.3 years in the control group (P = 0.54). No significant differences were noted between the two groups in terms of conjunctival epithelial changes including papillomatosis, epithelial clefts, epithelial goblet cells, or infiltration of inflammatory cells. Mean thickness of the conjunctival stroma was 0.21 ± 0.08 mm in the CCh group and 0.26 ± 0.21 mm in the control group (P = 0.10). For the conjunctival stroma, there were no significant differences between the two groups in terms of elastosis, fibrosis, lymphangiectasia, or infiltration of inflammatory cells. Conclusion: No noticeable differences were found in the histopathologic features by light microscopy between eyes with CCh and those of age-matched controls. Therefore, the primary pathology of CCh may not be within the conjunctiva itself. Instead, loose attachment of the conjunctiva to the underlying tissue may be the reason for the redundant folds in the bulbar conjunctiva. PMID:27994801

  10. Histopathological and immunohistochemical profile in anaplastic gangliogliomas.

    Science.gov (United States)

    Romero-Rojas, Alfredo E; Diaz-Perez, Julio A; Chinchilla-Olaya, Sandra I; Amaro, Deirdre; Lozano-Castillo, Alfonso; Restrepo-Escobar, Ligia I

    2013-01-01

    The anaplastic ganglioglioma (AG) is the high-grade counterpart of ganglioglioma, a rare mixed tumor composed of neuronal/ganglion and glial cells. We describe the histopathology and immunohistochemistry in 7 cases of AG and correlate them with the clinical and radiological features. Our AG patients correspond to 2.5% of the central nervous system tumor patients evaluated in our institution. The mean age at presentation was 25.7 years, with a male predominance. The most common clinical presentation was generalized tonic-clonic seizures (3/7 cases), in correlation with frequent cortical/subcortical location (6/7 cases). Histopathologically, all our cases showed high-grade features in glial (glial fibrillary acid protein-positive) and neuron-ganglion cells (synaptophysin, PGP-9.5, neurofilament, NSE and CD56-positive), as well as moderate cellularity, frequent mitotic figures and a Ki-67 labeling index >5%. All our patients had poor survival. We found that a typical histopathological and immunohistochemical profile is constant and can be useful in early diagnosis of these aggressive neoplasms. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  11. Histopathologic and immunohistochemical features of Hashimoto thyroiditis

    Directory of Open Access Journals (Sweden)

    H Kazem Amani

    2011-01-01

    Full Text Available Background: 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. Aim: 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. Materials and Methods: 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. Results: 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. Conclusions: Hashimoto thyroiditis differs both histopathologically and immunohistochemically from thyroid lymphoma. In suspicious cases, immunohistochemistry could be helpful in reaching a definitive diagnosis.

  12. [Joint endoprosthesis pathology. Histopathological diagnostics and classification].

    Science.gov (United States)

    Krenn, V; Morawietz, L; Jakobs, M; Kienapfel, H; Ascherl, R; Bause, L; Kuhn, H; Matziolis, G; Skutek, M; Gehrke, T

    2011-05-01

    Prosthesis durability has steadily increased with high 10-year rates of 88-95%. However, four pathogenetic groups of diseases can decrease prosthesis durability: (1) periprosthetic wear particle disease (aseptic loosening) (2) bacterial infection (septic loosening) (3) periprosthetic ossification, and (4) arthrofibrosis. The histopathological "extended consensus classification of periprosthetic membranes" includes four types of membranes, arthrofibrosis, and osseous diseases of endoprosthetics: The four types of neosynovia are: wear particle-induced type (type I), mean prosthesis durability (MPD) in years 12.0; infectious type (type II), MPD 2.5; combined type (type III) MPD 4.2; and indeterminate type (type IV), MPD 5.5. Arthrofibrosis can be determined in three grades: grade 1 needs clinical information to be differentiated from a type IV membrane, and grades 2 & 3 can be diagnosed histopathologically. Periprosthetic ossification, osteopenia-induced fractures, and aseptic osteonecrosis can be histopathologically diagnosed safely with clinical information. The extended consensus classification of periprosthetic membranes may be a diagnostic groundwork for a future national endoprosthesis register.

  13. 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.

  14. Immediate Learner Repair and Its Relationship with Learning Targeted Forms in Dyadic Interaction

    Science.gov (United States)

    Nassaji, Hossein

    2011-01-01

    This study investigated the relationship between immediate learner repair in response to interactional feedback and learning targeted forms. In particular, the study examined and compared the relationship between two major types of repair: learner-generated self-repair following elicitations and teacher-generated repair following recasts. It also…

  15. Preoperative and postoperative histopathological findings in patients with endometrial hyperplasia

    OpenAIRE

    Đorđević Biljana; Stanojević Zorica; Živković Vesna; Lalošević Dušan; Gligorijević Jasmina; Krstić Miljan

    2007-01-01

    Introduction. The aim of this study was to analyze and compare the histopathological findings in curettage and hysterectomy specimens, to evaluate the accuracy of histopathological diagnosis in curettage specimens, and to determine the frequency of coexisting endometrial carcinoma in patients with histopathological diagnosis of endometrial hyperplasia. Material and methods. Curettage and hysterectomy specimens of 135 female patients with initially diagnosed endometrial hyperplasia were retros...

  16. The effect of rotator cuff repair on early overhead shoulder function: a study in 1600 consecutive rotator cuff repairs.

    Science.gov (United States)

    Robinson, Hayden A; Lam, Patrick H; Walton, Judie R; Murrell, George A C

    2017-01-01

    Rotator cuff tears are often surgically repaired, generally with good results. However, repairs not infrequently retear, and how important repair integrity is with respect to early functional outcomes after rotator cuff repair is unclear. Thus, the purpose of this study was to determine the effect of a retear on overhead activities in a large cohort of patients after rotator cuff repair. This was a retrospective cohort study of prospectively collected data from 1600 consecutive rotator cuff repairs. Outcomes were based on patient responses to the L'Insalata Shoulder Questionnaire and findings on examination preoperatively and at 6 months of follow-up. Repair integrity was determined by ultrasound imaging at the 6-month follow-up visit. The 1600 patients (885 men, 715 women) were a mean age of 58 years. Postoperative ultrasound imaging found 13% (211 of 1600) of repairs had retorn. Significant improvements were seen irrespective of rotator cuff integrity in pain levels with overhead activity (P rotation strength (P rotator cuff repair integrity on shoulder function. Patients who had an arthroscopic rotator cuff repair reported significant improvements in overhead pain levels irrespective of the repair integrity at 6 months. Repair integrity influenced supraspinatus and external rotation power, where patients with intact repairs were stronger than those with a retear. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  17. Percutaneous mitral valve repair.

    Science.gov (United States)

    Gillinov, A Marc; Liddicoat, John R

    2006-01-01

    Surgical mitral valve repair is the procedure of choice to treat mitral regurgitation of all etiologies. Whereas annuloplasty is the cornerstone of mitral valve repair, a variety of other surgical techniques are utilized to correct dysfunction of the leaflets and subvalvular apparatus; in most cases, surgical repair entails application of multiple repair techniques in each patient. Preclinical studies and early human experience have demonstrated that some of these surgical repair techniques can be performed using percutaneous approaches. Specifically, there has been great progress in the development of novel technology to facilitate percutaneous annuloplasty and percutaneous edge-to-edge repair. The objectives of this report were to (1) discuss the surgical foundations for these percutaneous approaches; (2) review device design and experimental and clinical results of percutaneous valve repair; and (3) address future directions, including the key challenges of patient selection and clinical trial design.

  18. Comparison of two porcine-derived materials for repairing abdominal wall defects in rats.

    Directory of Open Access Journals (Sweden)

    Zhengni Liu

    Full Text Available OBJECTIVE: The purpose of this study was to compare the mechanical properties, host responses and incorporation of porcine small intestine submucosa (PSIS and porcine acellular dermal matrix (PADM in a rat model of abdominal wall defect repair. MATERIALS AND METHODS: Prior to implantation, PSIS and PADM were prepared and evaluated in terms of structure and mechanical properties. Full-thickness abdominal wall defects were created in 50 Sprague-Dawley rats, and were repaired using either PSIS or PADM. Rats were sacrificed 1, 2, 4, 8 and 12 weeks post-repair and examined for herniation, infection, adhesions, contraction, and changes in the thickness and strength of the tissues incorporated at the defect sites. Histopathology and immunohistochemistry were performed to analyze inflammatory responses, collagen deposition and vascularization. RESULTS: PADM showed more dense collagen deposition and stronger mechanical properties than PSIS prior to implantation (P<0.01. However, the mechanical properties observed after integration with the surrounding native tissues was similar for PADM and PSIS. Both PADM and PSIS showed significant contraction by week 12. However, PADM tissue induced less adhesion and increased in thickness more slowly, and showed less infiltration by foreign giant cells, polymorphonuclear cells, and mononuclear cells. Improved remodeling of host tissue was observed after PSIS implantation, which was apparent from the orientation of bands of fibrous connective tissue, intermixed with newly formed blood vessels by Week 12. CONCLUSION: PSIS showed weaker mechanical properties prior to implantation. However, after implantation PSIS induced more pronounced host responses and showed better incorporation into host tissues than PADM.

  19. Local Morphological Response of the Distal Femoral Articular–Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children

    Science.gov (United States)

    Hendrickson, Eli H.S.; Ekman, Stina; Carlson, Cathy S.; Dolvik, Nils I.

    2013-01-01

    Objective: Describe the local morphological response of the articular–epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Design: Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Results: Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Conclusions: Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular–epiphyseal cartilage complex of all species. PMID:26069670

  20. DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions.

    Science.gov (United States)

    Cristini, Agnese; Park, Joon-Hyung; Capranico, Giovanni; Legube, Gaëlle; Favre, Gilles; Sordet, Olivier

    2016-02-18

    Although defective repair of DNA double-strand breaks (DSBs) leads to neurodegenerative diseases, the processes underlying their production and signaling in non-replicating cells are largely unknown. Stabilized topoisomerase I cleavage complexes (Top1cc) by natural compounds or common DNA alterations are transcription-blocking lesions whose repair depends primarily on Top1 proteolysis and excision by tyrosyl-DNA phosphodiesterase-1 (TDP1). We previously reported that stabilized Top1cc produce transcription-dependent DSBs that activate ATM in neurons. Here, we use camptothecin (CPT)-treated serum-starved quiescent cells to induce transcription-blocking Top1cc and show that those DSBs are generated during Top1cc repair from Top1 peptide-linked DNA single-strand breaks generated after Top1 proteolysis and before excision by TDP1. Following DSB induction, ATM activates DNA-PK whose inhibition suppresses H2AX and H2A ubiquitination and the later assembly of activated ATM into nuclear foci. Inhibition of DNA-PK also reduces Top1 ubiquitination and proteolysis as well as resumption of RNA synthesis suggesting that DSB signaling further enhances Top1cc repair. Finally, we show that co-transcriptional DSBs kill quiescent cells. Together, these new findings reveal that DSB production and signaling by transcription-blocking Top1 lesions impact on non-replicating cell fate and provide insights on the molecular pathogenesis of neurodegenerative diseases such as SCAN1 and AT syndromes, which are caused by TDP1 and ATM deficiency, respectively.

  1. Calmodulin Mediates DNA Repair Pathways Involving H2AX in Response to Low-Dose Radiation Exposure of RAW 264.7 Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Smallwood, Heather S.; Lopez Ferrer, Daniel; Eberlein, P. Elis; Watson, David J.; Squier, Thomas C.

    2009-02-05

    Understanding the molecular mechanisms that modulate macrophage radioresistance is necessary for the development of effective radiation therapies, as tumor-associated macrophages promote both angiogenesis and matrix remodeling that, in turn, enhance metastasis. In this respect, we have identified a dose-dependent increase in the abundance of the calcium regulatory protein calmodulin (CaM) in RAW 264.7 macrophages upon irradiation. CaM overexpression results in increased macrophage survival following radiation exposure, acting to diminish the sensitivity to low-dose exposures. Increases in CaM abundance also result in an increase in the number of phosphorylated histone H2AX protein complexes associated with DNA repair following macrophage irradiation, with no change in the extent of double-stranded DNA damage. In comparison, when NFκB-dependent pathways are inhibited, through the expression of a dominant-negative IκB construct, there is no significant increase in phosphorylated H2AX upon irradiation. These results indicate that the molecular basis for the up-regulation of histone H2AX mediated DNA-repair pathways is not the result of nonspecific NFκB-dependent pathways or a specific threshold of DNA damage. Rather, increases in CaM abundance act to minimize the low-dose hypersensitivity to radiation to enhance macrophage radioresistance through processes that include the upregulation of DNA repair pathways involving histone protein H2AX phosphorylation.

  2. 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

  3. Gene expression profiles of human glioblastomas are associated with both tumor cytogenetics and histopathology.

    Science.gov (United States)

    Vital, Ana Luísa; Tabernero, Maria Dolores; Castrillo, Abel; Rebelo, Olinda; Tão, Hermínio; Gomes, Fernando; Nieto, Ana Belen; Resende Oliveira, Catarina; Lopes, Maria Celeste; Orfao, Alberto

    2010-09-01

    Despite the increasing knowledge about the genetic alterations and molecular pathways involved in gliomas, few studies have investigated the association between the gene expression profiles (GEP) and both cytogenetics and histopathology of gliomas. Here, we analyzed the GEP (U133Plus2.0 chip) of 40 gliomas (35 astrocytic tumors, 3 oligodendrogliomas, and 2 mixed tumors) and their association with tumor cytogenetics and histopathology. Unsupervised and supervised analyses showed significantly different GEP in low- vs high-grade gliomas, the most discriminating genes including genes involved in the regulation of cell proliferation, apoptosis, DNA repair, and signal transduction. In turn, among glioblastoma multiforme (GBM), 3 subgroups of tumors were identified according to their GEP, which were closely associated with the cytogenetic profile of their ancestral tumor cell clones: (i) EGFR amplification, (ii) isolated trisomy 7, and (iii) more complex karyotypes. In summary, our results show a clear association between the GEP of gliomas and tumor histopathology; additionally, among grade IV astrocytoma, GEP are significantly associated with the cytogenetic profile of the ancestral tumor cell clone. Further studies in larger series of patients are necessary to confirm our observations.

  4. 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.

  5. Role of Deubiquitinating Enzymes in DNA Repair

    OpenAIRE

    2016-01-01

    Both proteolytic and nonproteolytic functions of ubiquitination are essential regulatory mechanisms for promoting DNA repair and the DNA damage response in mammalian cells. Deubiquitinating enzymes (DUBs) have emerged as key players in the maintenance of genome stability. In this minireview, we discuss the recent findings on human DUBs that participate in genome maintenance, with a focus on the role of DUBs in the modulation of DNA repair and DNA damage signaling.

  6. Comparative histopathology of scabies versus nodular scabies

    Directory of Open Access Journals (Sweden)

    Mittal R

    1997-01-01

    Full Text Available Comparative histopathology was studied in 25 cases of scabies versus 25 cases of nodular scabies which were selected from Dermato-Venereology out patients. Salient differences observed were that in scabies lifting of stratum corneum at places was seen in all 100% cases, spongiosis in 100%, spongiotic vesicles in 28%, burrows in 56%, mite in 40% and vasculitis in 28% whereas in nodular scabies acanthosis was seen in 100%, pseudo epitheliomatous hyperplasia in 8%, burrows in 48%, mite in 24% and vasculitis in 84%. In nodular scabies, dermal infiltrate in 32% cases was arranged as lymphoid follicles with admixture of plasma cells and eosinophils.

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

    Science.gov (United States)

    Hatipoglu, Nuh; Bilgin, Gokhan

    2017-02-28

    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. Molecular and Histopathological Changes Associated with Keratoconus

    Science.gov (United States)

    Khaled, Mariam Lotfy; Helwa, Inas; Drewry, Michelle; Seremwe, Mutsa; Estes, Amy

    2017-01-01

    Keratoconus (KC) is a corneal thinning disorder that leads to loss of visual acuity through ectasia, opacity, and irregular astigmatism. It is one of the leading indicators for corneal transplantation in the Western countries. KC usually starts at puberty and progresses until the third or fourth decade; however its progression differs among patients. In the keratoconic cornea, all layers except the endothelium have been shown to have histopathological structural changes. Despite numerous studies in the last several decades, the mechanisms of KC development and progression remain unclear. Both genetic and environmental factors may contribute to the pathogenesis of KC. Many previous articles have reviewed the genetic aspects of KC, but in this review we summarize the histopathological features of different layers of cornea and discuss the differentially expressed proteins in the KC-affected cornea. This summary will help emphasize the major molecular defects in KC and identify additional research areas related to KC, potentially opening up possibilities for novel methods of KC prevention and therapeutic intervention. PMID:28251158

  9. Phyllodes tumor: diagnostic imaging and histopathology findings.

    Science.gov (United States)

    Venter, Alina Cristiana; Roşca, Elena; Daina, Lucia Georgeta; Muţiu, Gabriela; Pirte, Adriana Nicoleta; Rahotă, Daniela

    2015-01-01

    Phyllodes tumors are rare breast tumors, accounting for less than 1% of all primary tumors of the breast. Histologically, phyllodes tumors can be divided into benign (60%), borderline (20%) and malignant (20%). The mammography examination was performed by means of a digital mammography system Giotto 3D Images; the ultrasound examination was performed through a GE Logiq P6 device and histological confirmation was possible after surgery or following the histological biopsy. We grouped the nine patients who presented clinically palpable nodules into two groups, namely: the six patients presenting histological benign results into Group I, and Group II where we included those with borderline and malignant histological results. Mammography performed in 77.7% revealed a well-circumscribed round or oval opacity or with contour lobules. Ultrasound examination was performed in all patients. Mammography and ultrasound have limitation in differentiating between benign lesion and phyllodes tumor. In the nine analyzed cases, mammographic and ultrasound examinations did not allow the differentiation into the three groups of phyllodes tumor. Histopathological examination is considered the golden standard for their diagnosis. Correlations between mammographic and microscopic aspects were inconclusive for determining the degree of differentiation, ultrasound changes could be correlated with the histopathological aspects.

  10. Histopathological characterization of a Cameron lesion.

    Science.gov (United States)

    Katz, Jordan; Brar, Sonia; Sidhu, Jagmohan S

    2012-10-01

    Cameron lesions are linear erosions located at the neck of a hiatal hernia (HH) in patients with a large HH. The prevalence has been seen in up to 5% of patients with HH who undergo esophagogastroduodenoscopy, and they can be associated with overt gastrointestinal bleeding or anemia. These lesions occur due to vascular compression by the diaphragm in a large sliding HH. Histopathologic changes seen in the biopsy tissue of a Cameron lesion are due to ischemia, but this ischemia is reversible with treatment of HH. The existence of this entity and the histopathologic picture of a Cameron lesion is not well known to pathologists, and therefore, a microscopic picture of a Cameron lesion can be easily confused with ischemic gastritis. Ischemic gastritis is the result of atherosclerosis, usually seen in older people, unrelated to HH, and is not easily reversible. The authors received a gastric biopsy of a hiatal hernia without any associated clinical diagnosis of a Cameron lesion conveyed to the pathologist. This biopsy tissue showed ischemic changes in the gastric mucosa on microscopic examination. Diagnosis of ischemic gastritis was considered but ruled out after the case was discussed with the gastroenterologist. The correct diagnosis was made once the clinical diagnosis of HH with Cameron lesion (ie, a vertical red erosion) was made known to the pathologist. By reporting this case, the authors aim to increase awareness of Cameron lesion among pathologists so that they ask about the presence of a Cameron lesion before making the diagnosis of ischemic gastritis.

  11. Paederus fuscipes dermatitis. A histopathological study.

    Science.gov (United States)

    Borroni, G; Brazzelli, V; Rosso, R; Pavan, M

    1991-10-01

    Paederus fuscipes (PF) dermatitis is a self-healing blistering disorder of the skin caused by a small insect belonging to genus Paederus, family Staphylinidae, order Coleoptera. Crushing PF on the skin causes acute dermatitis within 24 hours, corresponding in shape and dimensions to the area affected by the substance released (pederin). The acute vesicular lesions become crusted and scaly within a few days and heal completely in 10-12 days, with a transitory postinflammatory hypercromic patch. Twenty consecutive cases of PF dermatitis at different stages were studied histologically by routine light microscopy. The pederin causes a spectrum of histopathologic changes ranging from acute epidermal necrosis and blistering in acute stages, to marked acanthosis with mitotic figures in the late stages. PF dermatitis is an entomological model of irritant contact dermatitis, having histopathologic features of intraepidermal and subepidermal blistering, epidermal necrosis and acantholysis. The presence of some acantholytic foci, relatively far from the foci of clinically involved skin, in four of the cases considered suggests a possible role of pederin in inducing acantholysis indirectly. Acantholysis is probably caused by the release of epidermal proteases.

  12. Metastatic pheochromocytoma: clinical, genetic, and histopathologic characteristics

    Science.gov (United States)

    Zelinka, Tomáš; Musil, Zdeněk; Dušková, Jaroslava; Burton, Deborah; Merino, Maria J; Milosevic, Dragana; Widimský, Jiří; Pacak, Karel

    2011-01-01

    Background Pheochromocytomas are tumors arising from chromaffin tissue located in the adrenal medulla associated with typical symptoms and signs which may occasionally develop metastases, which are defined as the presence of tumor cells at sites where these cells are not found. This retrospective analysis was focused on clinical, genetic, and histopathologic characteristics of primary metastatic versus primary benign pheochromocytomas. Materials and methods We identified 41 subjects with metastatic pheochromocytoma and 108 subjects with apparently benign pheochromocytoma. We assessed dimension and biochemical profile of the primary tumor, age at presentation, and time to develop metastases. Results Subjects with metastatic pheochromocytoma presented at a significantly younger age (41.4±14.7 vs. 50.2±13.7 years; Ppheochromocytomas. No significant differences were found in the incidence of genetic mutations in both groups of subjects (25.7 % in the metastatic group and 14.7 % in the benign group; P=0.13). From available histopathologic markers of potential malignancy, only necrosis occurred more frequently in subjects with metastatic pheochromocytoma (27.6 % vs. 0 %; Ppheochromocytoma and age of its first presentation are two independent risk factors associated with the development of metastatic disease. PMID:21692797

  13. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest.

    Science.gov (United States)

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

    2008-11-01

    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 regulating DSB repair and cell cycle progression. In this 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. Frequency of micronuclei (MN) formation and chromosome aberrations were measured to determine efficiency of cytogenetic repair, especially DSB repair. In response to IR, 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-induced biological consequences. Furthermore, eight non-DBS repair genes showed involvement in regulating DSB repair, indicating that

  14. Repairs of composite structures

    Science.gov (United States)

    Roh, Hee Seok

    Repair on damaged composite panels was conducted. To better understand adhesively bonded repair, the study investigates the effect of design parameters on the joint strength. The design parameters include bondline length, thickness of adherend and type of adhesive. Adhesives considered in this study were tested to measure their tensile material properties. Three types of adhesively bonded joints, single strap, double strap, and single lap joint were considered under changing bondline lengths, thickness of adherend and type of adhesive. Based on lessons learned from bonded joints, a one-sided patch repair method for composite structures was conducted. The composite patch was bonded to the damaged panel by either film adhesive FM-73M or paste adhesive EA-9394 and the residual strengths of the repaired specimens were compared under varying patch sizes. A new repair method using attachments has been suggested to enhance the residual strength. Results obtained through experiments were analyzed using finite element analysis to provide a better repair design and explain the experimental results. It was observed that the residual strength of the repaired specimen was affected by patch length. Method for rapid repairs of damaged composite structures was investigated. The damage was represented by a circular hole in a composite laminated plate. Pre-cured composite patches were bonded with a quick-curing commercial adhesive near (rather than over) the hole. Tensile tests were conducted on specimens repaired with various patch geometries. The test results showed that, among the methods investigated, the best repair method restored over 90% of the original strength of an undamaged panel. The interfacial stresses in the adhesive zone for different patches were calculated in order to understand the efficiencies of the designs of these patch repairs. It was found that the composite patch that yielded the best strength had the lowest interfacial peel stress between the patch and

  15. Macrophage diversity in renal injury and repair

    NARCIS (Netherlands)

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

    2008-01-01

    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 re

  16. Gallbladder polyps: ultrasonographic and histopathological findings correlation

    Directory of Open Access Journals (Sweden)

    F. Rodriguez

    2014-11-01

    Full Text Available Gallbladder polyp is an increasingly common diagnosis, primarily as an abdominal ultrasound finding requested by another cause. Studies report a prevalence between 4% and 5.6%. The importance of an accurate diagnosis is related to the possibility of developing a malignancy desease. The objectvie is to correlate ultrasound and histopathologic findings in gallbladder polyp patients operated at the Hospital San Juan de Dios de La Serena. We reviewed retrospectively the medical records of patients undergoing cholecystectomy for gallbladder polyp from January 2000 to December 2010. a total of 40 patients underwent cholecystectomy for gallbladder polyp. 16 only had its tab clinic with abdominal ultrasonography report and the pathology report. 13 of them (81% were female. The mean age was 46 + / - 12 years. The reason for the ultrasonography was in 9 patients (56% abdominal pain in 3 patients (19%, a finding in asymptomatic patients, in one patient (6% biliary colic, none had jaundice, and in 3 patients (19% the cause was different. According to Abdominal ultrasound, the number of polyps was 1.1 + / - 0.3 per patient, and the average size was 5.8 + / - 1.8 mm. Histopathological examination showed the presence of polyps colesterolínicos in 11 of the 16 patients (69%. In the series described the abdominal ultrasonography showed a PPV = 0.68 for the diagnosis of gallbladder polyp. According to the report histopathological cholesterolosis diagnosed chronic cholecystitis in six cases (37.5%, chronic cholecystitis in six cases (37.5%, cholesterolosis in three cases (18.75% and cholelithiasis in one case (6 , 25%. Not demonstrated the presence of adenomas or foci of carcinoma in situ. In conclusion the described series does not allow to extrapolated or compare conclusions with other national and international series due to the small number of patients studied. There is a substantial sub-register of the pathology because the majority of patients undergoing

  17. Histopathologic Outcomes of Robotic Radical Prostatectomy

    Directory of Open Access Journals (Sweden)

    Vipul R. Patel

    2006-01-01

    Full Text Available Robotically assisted laparoscopic radical prostatectomy is a minimally invasive alternative for the treatment of prostate cancer. We report the histopathologic and shortterm PSA outcomes of 500 robotic radical prostatectomies. Five hundred patients underwent robotic radical prostatectomy. The procedure was performed via a six trocar transperitoneal technique. Prostatectomy specimens were analyzed for TNM stage, Gleason’s grade, tumor location, volume, specimen weight, seminal vesicle involvement, and margin status. A positive margin was reported if cancer cells were found at the inked specimen margin. PSA data were collected every 3 months for the first year, then every 6 months for a year, then yearly. The average preoperative PSA was 6.9 (1–90 with Gleason’s score of 5 (2%, 6 (52%, 7 (40%, 8 (4%, and 9 (2%; postoperatively, histopathologic analysis showed Gleason's 6 (44%, 7 (42%, 8 (10%, and 9 (4%; 10, 5, 63, 15, 5, and 2% had pathologic stage T2a, T2b, T2c, T3a, T3b, and T4, respectively. Positive margin rate was 9.4% for the entire series. The positive margin rate per 100 cases was: 13% (1–100, 8% (101–200, 13% (201–300, 5% (301–400, and 8% (401–500. By stage, it was 2, 4, and 2.5% for T2a, T2b, T2c tumors; 23% (T3a, 46% (T3b, and 53% (T4a. For organ-confined disease (T2, the margin rate was 2.5% and it was 31% for nonorgan-confined disease. There were a total of 47 positive margins, 26 (56% posterolateral, 4 (8.5% apical, 4 (8.5% bladder neck, 2 (4% seminal vesicle, and 11 (23% multifocal. Ninety-five percent of patients (n = 500 have undetectable PSA (<0.1 at average follow-up of 9.7 months. Recurrence has only been seen with nonorgan-confined tumors. Of those patients with a minimum follow-up of 1 year (average 15.7 months, 95% have undetectable PSA (<0.1. Our initial experience with robotic radical prostatectomy is promising. Histopathologic outcomes are acceptable with a low overall, positive margin rate. Shortterm

  18. Workshop on DNA repair.

    NARCIS (Netherlands)

    A.R. Lehmann (Alan); J.H.J. Hoeijmakers (Jan); A.A. van Zeeland (Albert); C.M.P. Backendorf (Claude); B.A. Bridges; A. Collins; R.P.D. Fuchs; G.P. Margison; R. Montesano; E. Moustacchi; A.T. Natarajan; M. Radman; A. Sarasin; E. Seeberg; C.A. Smith; M. Stefanini (Miria); L.H. Thompson; G.P. van der Schans; C.A. Weber (Christine); M.Z. Zdzienika

    1992-01-01

    textabstractA workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991. The local organization of the meeting was done under the auspices of the Medical Genetic C

  19. Laparoscopic lumbar hernia repair.

    Science.gov (United States)

    Madan, Atul K; Ternovits, Craig A; Speck, Karen E; Pritchard, F Elizabeth; Tichansky, David S

    2006-04-01

    Lumbar hernias are rare clinical entities that often pose a challenge for repair. Because of the surrounding anatomy, adequate surgical herniorraphy is often difficult. Minimally invasive surgery has become an option for these hernias. Herein, we describe two patients with lumbar hernias (one with a recurrent traumatic hernia and one with an incisional hernia). Both of these hernias were successfully repaired laparoscopically.

  20. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  1. Histopathological study of feline eosinophilic dermatoses.

    Science.gov (United States)

    Fondati, A; Fondevila, D; Ferrer, L

    2001-12-01

    A retrospective study was conducted on skin specimens from 24 cats with eosinophilic granuloma complex. The specimens were stained with haematoxylin and eosin and Gallego's trichrome stain. In all specimens, flame figures and/or large foci of so-called "collagen degeneration" were detected and histopathological features were not predictive of the clinical picture. Use of the term eosinophilic dermatosis was advocated in diagnostic dermatopathology. On trichrome-stained sections, normally stained collagen fibres were identified in the middle of both flame figures and large foci of "collagen degeneration" and the debris surrounding collagen bundles showed the same tinctorial properties as eosinophil granules. Eosinophil degranulation around collagen bundles seemed to represent the major pathogenetic event in these lesions, analogous with human flame figures. The term flame figures might therefore be more accurately used to designate those foci of eosinophilic to partly basophilic debris commonly referred to as "collagen degeneration".

  2. Salivary Duct Cyst: Histo-pathologic Correlation

    Directory of Open Access Journals (Sweden)

    Divya Vinayachandran

    2013-01-01

    Full Text Available Non-neoplastic cysts of the salivary glands are uncommon and represent 2-5% of all salivary gland lesions. They are mainly mucoceles or salivary duct cysts. Unlike a mucocele, which is surrounded by granulation tissue, the salivary duct cyst is lined by epithelium. Salivary duct cysts are more common in the oral minor salivary glands and rarely occur in the major salivary glands, show a marked predilection for the superficial lobe of the parotid, and represent 10% of all salivary gland cysts. Neoplastic differentiation of the lining of the salivary duct cyst has been reported. We report a case of a salivary duct cyst of the left parotid gland, with a review of radiographic and histopathologic features.

  3. Ovarian fibroma--clinical and histopathological characteristics.

    Science.gov (United States)

    Sivanesaratnam, V; Dutta, R; Jayalakshmi, P

    1990-11-01

    Twenty-three cases of ovarian fibroma, comprising 3% of all benign tumors seen over a 20-year period, were analyzed. It was unilateral in all cases affecting more commonly the left ovary (70%). Whilst a majority of cases (77%) were encountered in the reproductive age group, the tumor was rare before the second decade. Only in 13% of cases was ascitis clinically detectable. This was not influenced by the size and weight (average of 9.3 x 10.8 x 11.1 cm and 959 g, respectively) of the tumors; a smooth-surfaced tumor was, however, associated with a greater amount of peritoneal fluid. Varying degrees of calcification in some tumors are detectable on ultrasonography and occasionally on abdominal radiography. The classical Meig's Syndrome was seldom encountered. The histopathological features, diagnostic problems and management are discussed.

  4. CT diagnosis of retinoblastoma with histopathologic correlations

    Energy Technology Data Exchange (ETDEWEB)

    Olivecrona, H. [Dept. of Radiology, King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Agerberg, P.A. [Dept. of Radiology, King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Huaman, A. [Dept. of Pathology, King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    1994-08-01

    The authors correlated the radiologic and histopathologic characteristics of 108 retinoblastomas in 98 patients. Calcifications were demonstrable by CT scans in 92.6% of the cases, whereas only 82% were evident upon routine histologic study. Cases of severe invasion of the optic nerve beyond the lamina cribrosa and up to the surgical margin of the nerve were detected by CT scans. Lesser degrees of invasion could not be determined by the same method. Orbital extension was also demonstrable, whereas invasion limited to the sclera was rarely accessible to CT diagnosis. Choroidal invasion was not detectable. Computerized tomography detected enlargement of the ipsilateral lacrimal gland in 17.5% of patients. This phenomenon correlates with invasion of the choroid and the optic nerve. (orig.)

  5. Histopathology of marine vibrio wound infections.

    Science.gov (United States)

    Beckman, E N; Leonard, G L; Castillo, L E; Genre, C F; Pankey, G A

    1981-12-01

    Although marine vibrio wound infections and septicemia are being reported with increasing frequency, description of the histopathologic changes has been scanty. The histologic alterations in three patients with primary marine vibrio wound infections are presented. The lesions are characterized by intense acute cellulitis of the subcutis with much tissue destruction and extension into the adjacent dermis. The superficial dermis is devitalized and lacks an inflammatory cellular infiltrate. Subepidermal noninflammatory bullae are formed. Many organisms are seen both within the areas of intense acute inflammation and in devitalized areas. Organisms and inflammation are especially oriented around vessels, with associated acute vasculitis. It is concluded that the morphologic picture in marine vibrio wound infections is nonspecific yet characteristic.

  6. Value of routine histopathological examination of appendices in Hong Kong.

    OpenAIRE

    Chan, W; Fu, K H

    1987-01-01

    A retrospective study of the histopathological findings of more than 11,443 appendices submitted as surgical specimens over 14 years was performed in this department. In most cases routine histopathological examination added little clinically important information to other clinical and operative gross findings, but a variety of interesting and uncommon lesions were identified. In 85 cases clinically important pathological findings were first discovered on routine histopathological examination...

  7. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  8. Expression of the Saccharomyces cerevisiae DNA repair gene RAD6 that encodes a ubiquitin conjugating enzyme, increases in response to DNA damage and in meiosis but remains constant during the mitotic cell cycle.

    Science.gov (United States)

    Madura, K; Prakash, S; Prakash, L

    1990-02-25

    The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating (E2) enzyme and is required for the repair of damaged DNA, mutagenesis, and sporulation. Here, we report our studies on the regulation of RAD6 gene expression after UV damage, during the mitotic cell cycle, in meiosis, and following heat shock and starvation. RAD6 mRNA levels became elevated in cells exposed to UV light, and at all UV doses the increase in mRNA levels was rapid and occurred within 30 min after exposure to UV. RAD6 mRNA levels also increased in sporulating MATa/MAT alpha cells, and the period of maximal accumulation of RAD6 mRNA during meiosis is coincident with the time during which recombination occurs. However, RAD6 mRNA levels showed no periodic fluctuation in the mitotic cell cycle, were not elevated upon heat shock, and fell in cells in the stationary phase of growth. These observations suggest that RAD6 activity is required throughout the cell cycle rather than being restricted to a specific stage, and that during meiosis, high levels of RAD6 activity may be needed at a stage coincident with genetic recombination. The observation that RAD6 transcription is not induced by heat and starvation, treatments that activate stress responses, suggests that the primary role of RAD6 is in the repair of damaged DNA rather than in adapting cells to stress situations.

  9. Histopathological and Serological Studies on Paratuberculosis in Cattle and Buffaloes

    Directory of Open Access Journals (Sweden)

    Arbab Sikandar*, AH Cheema1, M Younus2, A Aslam1, MA Zaman2 and T Rehman3

    2012-10-01

    Full Text Available Paratuberculosis (Johne’s diseases is responsible for massive economic losses to dairy industry, both in the industrially advanced as well as in the developing countries. To detect its occurrence in cattle and buffaloes locally, blood and tissue samples from clinically weak and grossly suspected slaughtered animals were collected from two abattoirs of Jhang, municipal area, Pakistan. Acid-fast smear staining, gross/histopathology and indirect ELISA were done for the detection of Mycobacterium avium subsp. paratuberculosis (MAP. Total 134 samples illustrating gross pathological lesions were collected, only 11.19% (cattle: 6.67%, buffaloes: 12.5% showed acid fast bacilli through smear staining and were taken as confirmed cases. Thickening of intestines alone was not a reliable indicator of Johne’s disease. Tissue sections from intestines and mesenteric lymph nodes from these acid fast positive animals were stained with hematoxylin & eosin (H&E and Ziehl Neelsen (ZN methods. Sum of (15/134 impression smear staining as well as (15/15 tissue sections of the intestines were found ZN positive, and only 6.7% of impression smears and 100% of tissue sections of mesenteric lymph nodes showed acid fast bacilli. Through ELISA, two cattle and five buffaloes (07/134 gave positive optical densities, while one cattle and seven buffaloes (08/134 were judged as doubtful. It is concluded that infection of MAP can be identified by histopathology and ELISA. The present study was the first record of paratuberculosis among the dairy animals slaughtered at Jhang abattoirs. The objective was to compare different methods for the diagnosis of Johne’s disease.

  10. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. [Los Alamos National Lab., NM (United States); Chen, D.S. [Rochester Univ., NY (United States). Dept. of Radiation Oncology

    1993-02-01

    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.

  11. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. (Los Alamos National Lab., NM (United States)); Chen, D.S. (Rochester Univ., NY (United States). Dept. of Radiation Oncology)

    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. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  13. 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.

  14. Salvage hypospadias repairs

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2008-01-01

    Full Text Available Aim: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. Methods: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. Results: The age of children ranged from 1.5-15 years (mean 4.5. Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50% with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. Conclusions: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.

  15. Repair and regeneration in endodontics.

    Science.gov (United States)

    Lin, L M; Rosenberg, P A

    2011-10-01

    The ideal objective of treatment of established diseases, including irreversible pulpitis and apical periodontitis, is to achieve wound healing. Wound healing can result in repair or regeneration. The ultimate goal of wound healing is to restore the original architecture and biological function of the injured tissue or organ. Although humans are equipped with powerful innate and adaptive immune defence mechanisms, many intrinsic and extrinsic factors can affect wound healing. Complete regeneration following injury in humans can occur only in the pre-natal foetus within 24 weeks of gestation. Post-natal wounds including irreversible pulpitis or apical periodontitis always heal by repair or by a combination of repair and regeneration. Somatic cells, such as fibroblasts, macrophages, cementoblasts and osteoblasts, in the pulp and periapical tissues have limited potential for regeneration following injury and lack of telomerase. Wound healing of irreversible pulpitis and apical periodontitis requires recruitment and differentiation of progenitor/stem cells into tissue-committed somatic cells. Stem cell differentiation is regulated by intrinsic factors and extrinsic micro-environmental cues. Functionality of stem cells appears to show an age-related decline because of the change in intrinsic properties and diminished signals within the extrinsic local and systemic environment that modulate the function of stem cells or their progeny. Infection induces an immuno-inflammatory response and tissue destruction, which hinders the potential of tissue regeneration. Therefore, prevention, early detection and treatment of inflammation/infection of pulpal and periapical disease can enhance regeneration and minimize the repair of pulpal and periapical tissues after endodontic therapy. © 2011 International Endodontic Journal.

  16. Schwann cells for spinal cord repair

    Directory of Open Access Journals (Sweden)

    Oudega M.

    2005-01-01

    Full Text Available The complex nature of spinal cord injury appears to demand a multifactorial repair strategy. One of the components that will likely be included is an implant that will fill the area of lost nervous tissue and provide a growth substrate for injured axons. Here we will discuss the role of Schwann cells (SCs in cell-based, surgical repair strategies of the injured adult spinal cord. We will review key studies that showed that intraspinal SC grafts limit injury-induced tissue loss and promote axonal regeneration and myelination, and that this response can be improved by adding neurotrophic factors or anti-inflammatory agents. These results will be compared with several other approaches to the repair of the spinal cord. A general concern with repair strategies is the limited functional recovery, which is in large part due to the failure of axons to grow across the scar tissue at the distal graft-spinal cord interface. Consequently, new synaptic connections with spinal neurons involved in motor function are not formed. We will highlight repair approaches that did result in growth across the scar and discuss the necessity for more studies involving larger, clinically relevant types of injuries, addressing this specific issue. Finally, this review will reflect on the prospect of SCs for repair strategies in the clinic.

  17. 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.

  18. Two Cases of Melasma with Unusual Histopathologic Findings

    Science.gov (United States)

    Kang, Won-Hyoung

    2006-01-01

    We reported two cases of clinically typical melasma presenting with unusual histopathologic findings. In one case, the epidermal melanocytes were markedly increased in number and protruded into the dermis, and in the other case, increased epidermal pigmentation as well as dermal melanocytosis were found. We suggested that the various treatment modalities of melasma should be applied depend on its histopathologic finding. PMID:16614533

  19. 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

  20. Histopathological changes observed in the heart and gizzard of ...

    African Journals Online (AJOL)

    Administrator

    2006-10-02

    Oct 2, 2006 ... 2Department of Pharmacology, FPGMI, Lahore, Pakistan. 3Department of ... histopathological studies and effects of different levels were studied in these tissues. Histopathological .... translocation of the pyloric adjacent to the isthmus of the stomach produ- ... Chromium also causes toxicological effects on ...

  1. Progress of peripheral nerve repair

    Institute of Scientific and Technical Information of China (English)

    陈峥嵘

    2002-01-01

    Study on repair of peripheral nerve injury has been proceeding over a long period of time. With the use of microsurgery technique since 1960s,the quality of nerve repair has been greatly improved. In the past 40 years, with the continuous increase of surgical repair methods, more progress has been made on the basic research of peripheral nerve repair.

  2. Choreography of oxidative damage repair in mammalian genomes.

    Science.gov (United States)

    Mitra, Sankar; Izumi, Tadahide; Boldogh, Istvan; Bhakat, Kishor K; Hill, Jeff W; Hazra, Tapas K

    2002-07-01

    The lesions induced by reactive oxygen species in both nuclear and mitochondrial genomes include altered bases, abasic (AP) sites, and single-strand breaks, all repaired primarily via the base excision repair (BER) pathway. Although the basic BER process (consisting of five sequential steps) could be reconstituted in vitro with only four enzymes, it is now evident that repair of oxidative damage, at least in mammalian cell nuclei, is more complex, and involves a number of additional proteins, including transcription- and replication-associated factors. These proteins may be required in sequential repair steps in concert with other cellular changes, starting with nuclear targeting of the early repair enzymes in response to oxidative stress, facilitation of lesion recognition, and access by chromatin unfolding via histone acetylation, and formation of metastable complexes of repair enzymes and other accessory proteins. Distinct, specific subclasses of protein complexes may be formed for repair of oxidative lesions in the nucleus in transcribed vs. nontranscribed sequences in chromatin, in quiescent vs. cycling cells, and in nascent vs. parental DNA strands in replicating cells. Characterizing the proteins for each repair subpathway, their signaling-dependent modifications and interactions in the nuclear as well as mitochondrial repair complexes, will be a major focus of future research in oxidative damage repair.

  3. Achilles tendon repair

    Science.gov (United States)

    Achilles tendon rupture-surgery; Percutaneous Achilles tendon rupture repair ... To fix your torn Achilles tendon, the surgeon will: Make a cut down the back of your heel Make several small cuts rather than one large cut ...

  4. Diaphragmatic hernia repair - slideshow

    Science.gov (United States)

    ... presentations/100014.htm Diaphragmatic hernia repair - series—Normal anatomy To use the sharing ... Overview The chest cavity includes the heart and lungs. The abdominal cavity includes the liver, the stomach, ...

  5. Eye muscle repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100062.htm Eye muscle repair - series—Normal anatomy To use the sharing ... the eyeball to the eye socket. The external muscles of the eye are found behind the conjunctiva. ...

  6. Tracheoesophageal fistula repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100103.htm Tracheoesophageal fistula repair - series—Normal anatomy To use the sharing ... Editorial team. Related MedlinePlus Health Topics Esophagus Disorders Fistulas Tracheal Disorders A.D.A.M., Inc. is ...

  7. Inguinal hernia repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100027.htm Inguinal hernia repair - series—Normal anatomy To use the sharing ... to slide 4 out of 4 Overview A hernia occurs when part of an organ protrudes through ...

  8. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created

  9. Pectus excavatum repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100035.htm Pectus excavatum repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Pectus excavatum is a deformity of the front of the ...

  10. Hiatal hernia repair - slideshow

    Science.gov (United States)

    ... presentations/100028.htm Hiatal hernia repair - series—Normal anatomy To use the sharing features on ... Overview The esophagus runs through the diaphragm to the stomach. It functions to carry food from the mouth ...

  11. Repairing ceramic insulating tiles

    Science.gov (United States)

    Dunn, B. R.; Laymance, E. L.

    1980-01-01

    Fused-silica tiles containing large voids or gauges are repaired without adhesives by plug insertion method. Tiles are useful in conduits for high-temperature gases, in furnaces, and in other applications involving heat insulation.

  12. Rotator cuff repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100229.htm Rotator cuff repair - series—Normal anatomy To use the sharing ... to slide 4 out of 4 Overview The rotator cuff is a group of muscles and tendons that ...

  13. Cleft lip repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100010.htm Cleft lip repair - series—Normal anatomy To use the sharing ... abnormal opening in the middle of the upper lip. A cleft palate is an opening in the roof of ...

  14. A brief history of the DNA repair field.

    Science.gov (United States)

    Friedberg, Errol C

    2008-01-01

    The history of the repair of damaged DNA can be traced to the mid-1930s. Since then multiple DNA repair mechanisms, as well as other biological responses to DNA damage, have been discovered and their regulation has been studied. This article briefly recounts the early history of this field.

  15. A brief history of the DNA repair field

    Institute of Scientific and Technical Information of China (English)

    Errol C Friedberg

    2008-01-01

    The history of the repair of damaged DNA can be traced to the mid-1930s. Since then multiple DNA repair mecha-nisms, as well as other biological responses to DNA damage, have been discovered and their regulation has been studied. This article briefly recounts the early history of this field.

  16. Early Metalinguistic Competence: Speech Monitoring and Repair Behavior.

    Science.gov (United States)

    Levy, Yonata

    1999-01-01

    Reviews study of toddlers' responses to specific and neutral requests for clarification, focusing on ability to locate linguistic errors that provoked clarification requests and their successes in repair. Argues that this behavior provides evidence for a speech monitor that detects errors and enables repair. Suggests that metalinguistic ability…

  17. Histopathological Characteristics of Atrophic Gastritisin Adult Population

    Institute of Scientific and Technical Information of China (English)

    Marija Milicevic; Snezana Bozanic; Nenad Solajic

    2015-01-01

    Introduction: Chronic gastritis is inflammation of the gastric mucosa. It can be non-atrophic and atrophic. Atrophy isdefined as the loss of appropriate glands. It is frequently located in antral mucosa as consequence of Helicobacter pylori infectionand it is associated with intestinal gastric cancer. Goal: Describe histopathological and demographic characteristics of atrophicgastritis. Matherial and methods: We assessed the pathological reports of 100 patients with atrophic gastritis whose characteristicswere evaluated by using a semiquantitative scale of Sidney system of classification of gastritis. To assess the significance betweenthe incidence of various parametres we used ;~2 test. Results: We found that the difference in frequency of atrophic gastritis betweenmen and women was not statistically significant. The difference in distribution is statistically significant in favor of the antrum.Among patients who have atrophy with Helicobacterpylori infection and intestinal metaplasia and those who do not have metaplasia,it was found that the difference is highly statistically significant. Conclusion: The most frequent localisation of atrophic gastritis isantral mucosa. There is no difference between men and women in frequency of atrophic gastritis, while the aging is related with moreoften occurrence of atrophic gastritis.

  18. Histopathology of human laser thermal angioplasty recanalization.

    Science.gov (United States)

    White, R A; White, G H; Vlasak, J; Fujitani, R; Kopchok, G E

    1988-01-01

    Laserprobe thermal-assisted balloon, angioplasty (LTBA) has demonstrated promising initial clinical results in recanalizing stenotic or occluded superficial femoral and popliteal arteries. Over the past year we have obtained six specimens of laserprobe thermal (LT) and LTBA treated total occlusions (avg. length 12 cm) for histopathologic examination from patients who were treated for limb salvage. Three tissue specimens were obtained acutely, and one was obtained at 6, 8, and 13 days, respectively, after laser angioplasty at the time of revision for complications or failed procedures. Serial histologic sections of the treated LT segments demonstrated recanalization of atherosclerotic lesions to approximately 60-70% of the probe diameter. The LT channels were lined by a thin layer of carbonized or coagulated tissue and several layers of cell necrosis. The histology of the thermal injury was similar regardless of whether it was produced by the heated metal cap or by free argon laser energy. Stellate balloon angioplasty fractures were frequently filled with thrombus. Analysis of these human LT and LTBA specimens revealed that the thermal device produces a confined injury through the path of least resistance. Balloon dilatation produces fragmented cracks in the vessel wall, which appear to be more thrombogenic than the carbonized LT surface. With improved guidance methods, LTBA shows potential for continuing development.

  19. 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.

  20. Oral mucocele: A clinical and histopathological study

    Directory of Open Access Journals (Sweden)

    Chandramani B More

    2014-01-01

    Objectives: To analyze the data between 2010 and 2011 of, clinically and histopathologically diagnosed 58 oral mucoceles for age, gender, type, site, color, cause, symptoms and dimension. Results: Oral mucoceles were highly prevalent in the age group of 15-24 years, were seen in 51.72% of males and 48.28% of females, with a ratio of 1.07:1. The extravasation type (84.48% was more common than the retention type (15.52%. The most common affected site was lower lip (36.20% followed by ventral surface of the tongue (25.86%. The lowest frequency was observed in floor of mouth, upper lip and palate. The maximum numbers of mucoceles were asymptomatic (58.62%, and the color of the overlying mucosa had color of adjacent normal mucosa (48.28%. It was also observed that most of the mucoceles had diameter ranging from 5 to 14 mm. The causative factors of the lesion were lip biting (22.41%, trauma (5.18% and numerous lesions (72.41%. Conclusion: Oral Mucoceles are frequently seen in an oral medicine service, mainly affecting young people and lower lip, measuring around 5 to 14 mm and the extravasation type being the most common.

  1. Diffuse panbronchiolitis with histopathological confirmation among Chinese

    Institute of Scientific and Technical Information of China (English)

    谢广顺; 李龙芸; 刘鸿瑞; 张伟宏; 朱元珏

    2004-01-01

    Background Diffuse panbronchiolitis (DPB) was originally and is still primarily reported in Japan, rarely in other countries. As macrolide therapy is effective for this disease with once dismal prognosis, familiarity with its clinical features is urgently needed, especially for clinicians outside Japan. The objectives of this study were to investigate the clinical features of DPB in a Chinese population and propose diagnostic procedures that will lead to increased awareness of this treatable disease among clinicians, ultimately allowing for more rapid diagnosis. Methods After a literature review, the clinical features of DPB were histopathologically confirmed in a series of 9 cases either by open lung biopsy or video-assisted thoracic surgical biopsy, resulting in the largest series of confirmed DPB cases in a non-Japanese population. Here, the cases are retrospectively described and diagnostic procedures are discussed.Conclusions Although its clinical features may vary with disease course and ethnic populations, most cases of DPB can be diagnosed or suggested according to clinical diagnostic criteria. However, underdiagnosis as a result of unfamiliarity with its clinical features and diagnostic criteria prevails. If difficulty in diagnosis arises, the diagnosis should be based on clinicopathological features and the exclusion of other diseases. Few cases can be confirmed by transbronchial biopsies; in these cases, either an open-lung biopsy or a video-assisted thoracic surgical lung biopsy should be recommended.

  2. [Histopathological differential diagnosis of primary liver tumors].

    Science.gov (United States)

    Honsová, E

    2014-03-01

    The most common primary hepatic malignancy is hepatocellular carcinoma, which constitutes 80-85% of all malignant epithelial neoplasms originating in the liver. The second most common primary hepatic malignancy is cholangiocellular carcinoma. In recent years, remarkable progress has been made in elucidating the molecular pathology of hepatic tumors. Advances in our understanding of molecular subtypes have led to a creation of a new classification system of hepatocellular adenomas, with important genotype-phenotype correlations and easy application to routine diagnostic practice. In the field of early hepatic neoplasia, a consensus on the definition of dysplastic nodules and early hepatocellular carcinoma has been reached. Immunohistochemical detection of glypican-3 and stromal invasion are used for the differential diagnosis. A lot of problems still exist in the category of mixed hepatocellular and cholangiocellular carcinoma. Although this category is recognized in the WHO classification, confusing terminology has been generated to describe tumors with morphological features of both HCC and CC. We further specify problems and pitfalls of the differential histopathological diagnosis of liver malignant tumors.

  3. Critical steps in tissue processing in histopathology.

    Science.gov (United States)

    Comanescu, Maria; Annaratone, Laura; D'Armento, Giuseppe; Cardos, Georgeta; Sapino, Anna; Bussolati, Gianni

    2012-04-01

    Histopathological diagnosis using Formalin-Fixed Paraffin Embedded (FFPE) tissues is essential for the prognostic and therapeutic management of cancer patients. Pathologists are being confronted with increasing demands, from both clinicians and patients, to provide immunophenotypic and gene expression data from FFPE tissues to allow the planning of personalized therapeutic regimens. Recent improvements in the protocols for pre-analysis processing of pathological tissues aim to better preserve cellular details and to conserve antigens and nucleic acid sequences. These developments have been recently patented. The international protocol for the transporting of surgical specimens from the surgical theatre to the pathology department is to immerse the specimen in formalin. The alternative method of sealing the specimens into bags under a vacuum and then cooling is a well-accepted and environmentally safe procedure that overcomes the many drawbacks linked to transfer in formalin. Importantly, RNA is notoriously poorly preserved in FFPE tissue. Due to this, successful procedures for the extraction of genetic information from archival tissues have been the object of several studies and patents. Novel molecular approaches for RT-qPCR and gene array analysis on FFPE tissues are presented here. Moreover, a major advance is reported in this study, the observation that tissue fixation in cold conditions allows a much better preservation of nucleic acid sequences.

  4. Postmenopausal osteoporosis - clinical, biological and histopathological aspects.

    Science.gov (United States)

    Pavel, Oana Roxana; Popescu, Mihaela; Novac, Liliana; Mogoantă, LaurenŢiu; Pavel, LaurenŢiu Petrişor; Vicaş, Răzvan Marius; Trăistaru, Magdalena Rodica

    2016-01-01

    Osteoporosis is one of the most common disorders in postmenopausal women, affecting the quality of life and increasing the risk for fractures in minor traumas. Changes in the bone microarchitecture causes static changes in the body and affects motility. In this study, we analyzed two groups of women, one with physiological menopause and one with surgically induced menopause. The diagnosis of osteoporosis was suspected based on the clinical symptoms and confirmed by assessing bone mineral density by the dual-energy X-ray absorptiometry (DEXA). Comparing some clinical and biological aspects there was noted that a much higher percentage of women with surgically induced menopause exhibited increases in body mass index, changes in serum lipids, cholesterol, triglycerides, blood glucose, serum calcium, magnesemia and osteocalcin. In contrast, no significant differences were observed in the histopathological aspects of bone tissue examined from these two groups. In all patients, there was identified a significant reduction in the number of osteocytes and osteoblasts, the expansion of haversian channels, reducing the number of trabecular bone in the cancellous bone with wide areola cavities often full of adipose tissue, non-homogenous demineralization of both the compact bone and the cancellous bone, atrophy and even absence of the endosteal, and the presence of multiple microfractures. Our study showed that early surgically induced menopause more intensely alters the lipid, carbohydrate and mineral metabolism, thus favoring the onset of osteoporosis.

  5. Urinary biomarkers in hexachloro-1:3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression.

    Science.gov (United States)

    Swain, Aubrey; Turton, John; Scudamore, Cheryl L; Pereira, Ines; Viswanathan, Neeti; Smyth, Rosemary; Munday, Michael; McClure, Fiona; Gandhi, Mitul; Sondh, Surjit; York, Malcolm

    2011-05-01

    Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms. In a second study, rats were treated with a single nephrotoxic dose of HCBD and the time course release of a range of traditional and newer urinary biomarkers was followed over a 25 day period. Urinary albumin (a marker of both proximal tubular function and glomerular integrity) and α-glutathione S-transferase (α-GST, a proximal tubular cell marker of cytoplasmic leakage) showed the largest fold change at 24 h (day 1) after dosing. Most other markers measured on either the MSD or RBM platforms peaked on day 1 or 2 post-dosing, whereas levels of kidney injury molecule-1 (KIM-1), a marker of tubular regeneration, peaked on day 3/4. Therefore, in rat proximal tubular nephrotoxicity, the measurement of urinary albumin, α-GST and KIM-1 is recommended as they potentially provide useful information about the function, degree of damage and repair of the proximal tubule. Gene expression data provided useful confirmatory information regarding exposure of the kidney and liver to HCBD, and the response of these tissues to HCBD in terms of metabolism, oxidative stress, inflammation, and regeneration and repair.

  6. Grey Repairable System Analysis

    Institute of Scientific and Technical Information of China (English)

    Renkuan Guo; Charles Ernie Love

    2006-01-01

    In this paper, we systematically discuss the basic concepts of grey theory, particularly the grey differential equation and its mathematical foundation, which is essentially unknown in the reliability engineering community. Accordingly,we propose a small-sample based approach to estimate repair improvement effects by partitioning system stopping times into intrinsic functioning times and repair improvement times. An industrial data set is used for illustrative purposes in a stepwise manner.

  7. 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.

  8. Media Matter: The Effect of Medium of Presentation on Student’s Recognition of Histopathology

    Science.gov (United States)

    Jong, Nynke De; Dalen, Jan Van

    2016-01-01

    Introduction Pathology teaching has undergone transformation with the introduction of virtual microscopy as a teaching and learning tool. Aim To assess if dental students can identify histopathology irrespective of the media of presentation and if the media affect student’s oral pathology case based learning scores. The perception of students towards “hybrid” approach in teaching and learning histopathology in oral pathology was also assessed. Materials and Methods A controlled experiment was conduc-ted on year 4 and year 5 dental student groups using a perfor-mance test and a questionnaire survey. Results A response rate of 81% was noted for the performance test as well as the questionnaire survey. Results show a significant effect of media on performance of students with virtual microscopy bringing out the best performance across all student groups in case based learning scenarios. The order of preference for media was found to be virtual microscopy followed by photomicrographs and light microscopy. However, 94% of students still prefer the present hybrid system for teaching and learning of oral pathology. Conclusion The study shows that identification of histo-pathology by students is dependent on media and the type of media has a significant effect on the performance. Virtual microscopy is strongly perceived as a useful tool for learning which thus brings out the best performance, however; the hybrid approach still remains the most preferred approach for histopathology learning. PMID:28208881

  9. Histopathologic Analysis of Palpebral Conjunctiva in Thyroid-Related Orbitopathy (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Kikkawa, Don O.

    2010-01-01

    Purpose: To examine the histopathology of palpebral conjunctiva in patients with thyroid-related orbitopathy. Based on previously published anecdotes, the hypothesis is that conjunctiva shows increased inflammation and fibrosis. Methods: This was a comparative case series. Superior palpebral conjunctiva was examined from two groups. The study group consisted of 20 patients undergoing thyroid-related upper eyelid retraction surgery. The control group consisted of 18 patients undergoing ptosis repair. Specimens were processed and stained using hematoxylin and eosin and trichrome. Histopathologic grading was performed using light microscopy. Main outcome measures were degree of inflammation and fibrosis, mast cell infiltration, and fibroblast count. Results: The two groups did not differ with regard to age or gender. Mean degree of inflammation was 1.4 (95% CI: 0.9, 1.9) for the control group and 1.7 (95% CI: 1.3, 2.1) for the study group. Relative intensity of blue from trichrome staining mean was 134.3 (95% CI: 130.3, 138.3) for the control group and 138.6 (95% CI: 133.7, 143.6) for the study group. The Mann-Whitney test showed no difference between groups in inflammation (P=.17), relative blue intensity (P=.11), degree of mast cell infiltration (P=.61), and fibroblast count (P=.45). Point estimates show a trend toward greater inflammation in the study group. Conclusions: While there is a trend toward higher inflammation in the study group, the superior palpebral conjunctiva of patients with thyroid-related orbitopathy is largely spared from autoimmune changes. This has implications in surgical approaches to eyelid retraction repair. PMID:21212848

  10. 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.

  11. Meta-analysis of estrogen response in MCF-7 distinguishes early target genes involved in signaling and cell proliferation from later target genes involved in cell cycle and DNA repair

    Directory of Open Access Journals (Sweden)

    Jagannathan Vidhya

    2011-08-01

    Full Text Available Abstract Background Many studies have been published outlining the global effects of 17β-estradiol (E2 on gene expression in human epithelial breast cancer derived MCF-7 cells. These studies show large variation in results, reporting between ~100 and ~1500 genes regulated by E2, with poor overlap. Results We performed a meta-analysis of these expression studies, using the Rank product method to obtain a more accurate and stable list of the differentially expressed genes, and of pathways regulated by E2. We analyzed 9 time-series data sets, concentrating on response at 3-4 hrs (early and at 24 hrs (late. We found >1000 statistically significant probe sets after correction for multiple testing at 3-4 hrs, and >2000 significant probe sets at 24 hrs. Differentially expressed genes were examined by pathway analysis. This revealed 15 early response pathways, mostly related to cell signaling and proliferation, and 20 late response pathways, mostly related to breast cancer, cell division, DNA repair and recombination. Conclusions Our results confirm that meta-analysis identified more differentially expressed genes than the individual studies, and that these genes act together in networks. These results provide new insight into E2 regulated mechanisms, especially in the context of breast cancer.

  12. Reporting tumor molecular heterogeneity in histopathological diagnosis.

    Directory of Open Access Journals (Sweden)

    Andrea Mafficini

    Full Text Available Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples.To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS in characterizing gastrointestinal cancer molecular heterogeneity.35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing.TM-NGS yielded overlapping results on matched fresh-frozen and formalin-fixed paraffin-embedded (FFPE tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57% tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis.TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy.

  13. Reporting Tumor Molecular Heterogeneity in Histopathological Diagnosis

    Science.gov (United States)

    Mafficini, Andrea; Amato, Eliana; Fassan, Matteo; Simbolo, Michele; Antonello, Davide; Vicentini, Caterina; Scardoni, Maria; Bersani, Samantha; Gottardi, Marisa; Rusev, Borislav; Malpeli, Giorgio; Corbo, Vincenzo; Barbi, Stefano; Sikora, Katarzyna O.; Lawlor, Rita T.; Tortora, Giampaolo; Scarpa, Aldo

    2014-01-01

    Background Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples. Aim To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular heterogeneity. Methods 35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing. Results TM-NGS yielded overlapping results on matched fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57%) tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis. Conclusions TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy. PMID:25127237

  14. Margins of oral leukoplakia: autofluorescence and histopathology.

    Science.gov (United States)

    Elvers, D; Braunschweig, T; Hilgers, R-D; Ghassemi, A; Möhlhenrich, S C; Hölzle, F; Gerressen, M; Modabber, A

    2015-02-01

    Autofluorescence devices are widely used to examine oral lesions. The aim of this study was to see whether there were any signs of dysplasia, parakeratosis, or mucosal inflammation in the borders of homogeneous oral leukoplakia using autofluorescence, and we also compared clinically visible extensions with those detected by autofluorescence. Twenty patients with 26 homogeneous areas of oral leukoplakia were included in the study. After the clinically visible extensions of the lesion had been marked, we took a photograph through the autofluorescence device, which showed both borders in one picture. We then used photo-editing software to measure the size of the area of leukoplakia together with the area with loss of autofluorescence. We took 3 punch biopsy specimens: one from the leukoplakia, one 2.5mm from its marked borders, and one from healthy mucosa. Seventy-eight biopsy specimens were examined by an experienced pathologist, and 95% CI calculated to assess the amount of parakeratosis. Spearman's rank correlation was used to assess the association with mucosal inflammation. Ten areas of leukoplakia were surrounded by normal green autofluorescence, and 16 were consistent with loss of autofluorescence with a mean size of 66%, which exceeded the clinically visible size of the area of leukoplakia. We calculated that there was a strong association between these entities and their surrounding areas, with loss of autofluorescence for parakeratosis. Some leukoplakias showed clinically invisible extensions during histopathological examination and autofluorescence. The technique described enables clinicians to measure the extent of these lesions beyond their visible margins. We found no dysplasia, which emphasises that autofluorescence detects non-dysplastic lesions caused by mucosal inflammation and parakeratosis.

  15. Oral mucocele: A clinical and histopathological study

    Science.gov (United States)

    More, Chandramani B; Bhavsar, Khushbu; Varma, Saurabh; Tailor, Mansi

    2014-01-01

    Background: Oral mucocele is the most common benign minor (accessory) salivary gland lesion, caused due to mechanical trauma to the excretory duct of the gland. Clinically they are characterized by single or multiple, soft, fluctuant nodule, ranging from the normal color of the oral mucosa to deep blue. It affects at any age and is equally present in both sexes with highest incidence in second decade of life. They are classified as extravasation or retention type. Objectives: To analyze the data between 2010 and 2011 of, clinically and histopathologically diagnosed 58 oral mucoceles for age, gender, type, site, color, cause, symptoms and dimension. Results: Oral mucoceles were highly prevalent in the age group of 15-24 years, were seen in 51.72% of males and 48.28% of females, with a ratio of 1.07:1. The extravasation type (84.48%) was more common than the retention type (15.52%). The most common affected site was lower lip (36.20%) followed by ventral surface of the tongue (25.86%). The lowest frequency was observed in floor of mouth, upper lip and palate. The maximum numbers of mucoceles were asymptomatic (58.62%), and the color of the overlying mucosa had color of adjacent normal mucosa (48.28%). It was also observed that most of the mucoceles had diameter ranging from 5 to 14 mm. The causative factors of the lesion were lip biting (22.41%), trauma (5.18%) and numerous lesions (72.41%). Conclusion: Oral Mucoceles are frequently seen in an oral medicine service, mainly affecting young people and lower lip, measuring around 5 to 14 mm and the extravasation type being the most common. PMID:25364184

  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. Strategies for Zonal Cartilage Repair using Hydrogels

    NARCIS (Netherlands)

    Klein, Travis J.; Rizzi, Simone C.; Reichert, Johannes C.; Georgi, Nicole; Malda, Jos; Schuurman, Wouter; Crawford, Ross W.; Hutmacher, Dietmar W.

    2009-01-01

    Articular cartilage is a highly hydrated tissue with depth-dependent cellular and matrix properties that provide low-friction load bearing in joints. However, the structure and function are frequently lost and there is insufficient repair response to regenerate high-quality cartilage. Several hydrog

  18. Performance and service life of repairs of concrete structures in The Netherlands

    NARCIS (Netherlands)

    Visser, J.H.M.; Zon, Q.F. van

    2012-01-01

    In 2010, an inventory to the performance of repairs in the Netherlands has been executed, in response to reported low performances of repairs in Europe. Extensive records were collected concerning, among other, the age of the repairs and their current conditions in a similar way as in the European i

  19. Correlation of Magnetic Resonance Imaging Tumor Volume with Histopathology

    Science.gov (United States)

    Turkbey, Baris; Mani, Haresh; Aras, Omer; Rastinehad, Ardeshir R.; Shah, Vijay; Bernardo, Marcelino; Pohida, Thomas; Daar, Dagane; Benjamin, Compton; McKinney, Yolanda L.; Linehan, W. Marston; Wood, Bradford J.; Merino, Maria J.; Choyke, Peter L.; Pinto, Peter A.

    2017-01-01

    Purpose The biology of prostate cancer may be influenced by the index lesion. The definition of index lesion volume is important for appropriate decision making, especially for image guided focal treatment. We determined the accuracy of magnetic resonance imaging for determining index tumor volume compared with volumes derived from histopathology. Materials and Methods We evaluated 135 patients (mean age 59.3 years) with a mean prostate specific antigen of 6.74 ng/dl who underwent multiparametric 3T endorectal coil magnetic resonance imaging of the prostate and subsequent radical prostatectomy. Index tumor volume was determined prospectively and independently by magnetic resonance imaging and histopathology. The ellipsoid formula was applied to determine histopathology tumor volume, whereas manual tumor segmentation was used to determine magnetic resonance tumor volume. Histopathology tumor volume was correlated with age and prostate specific antigen whereas magnetic resonance tumor volume involved Pearson correlation and linear regression methods. In addition, the predictive power of magnetic resonance tumor volume, prostate specific antigen and age for estimating histopathology tumor volume (greater than 0.5 cm3) was assessed by ROC analysis. The same analysis was also conducted for the 1.15 shrinkage factor corrected histopathology data set. Results There was a positive correlation between histopathology tumor volume and magnetic resonance tumor volume (Pearson coefficient 0.633, p <0.0001), but a weak correlation between prostate specific antigen and histopathology tumor volume (Pearson coefficient 0.237, p=0.003). On linear regression analysis histopathology tumor volume and magnetic resonance tumor volume were correlated (r2=0.401, p <0.00001). On ROC analysis AUC values for magnetic resonance tumor volume, prostate specific antigen and age in estimating tumors larger than 0.5 cm3 at histopathology were 0.949 (p <0.0000001), 0.685 (p=0.001) and 0.627 (p=0

  20. Magnetic resonance imaging and histopathology in the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Takatori, Yoshio; Kamogawa, Morihide; Nakamura, Toshitaka; Ninomiya, Setsuo; Kokubo, Takashi

    1989-05-01

    To correlate the magnetic resonance (MR) images with the histopathological findings in the femoral head, the histopathology of 24 femoral heads, 15 with osteonecrosis, five with osteoarthritis and four with other hip disorders were subjected to preoperative MR imaging which demonstrated low intensity areas due to long T1 relaxation time in the femoral head. The MR signal was low where fibrovascular tissue, disintegrated fibrovascular tissue, amorphous necrotic material, bone, or cartilagenous tissue occupied the medullary space. From this study, it seems possible to predict the histopathologic changes in the femoral head using MR images. (author).

  1. Uveodermatologic Syndrome in a Siberian Husky: Clinical and Histopathological Findings

    Directory of Open Access Journals (Sweden)

    Min-Hee Kang

    2014-01-01

    Full Text Available A 2-year-old, intact male Siberian Husky was presented with corneal opacity, eye lid swelling, depigmentation, alopecia and erythema predominantly on face. Bilateral uveitis preceded periocular and nasal planum depigmentation. Ancillary tests excluded other systemic diseases. Histopathology of the skin revealed lichenoid interface dermatitis with pigmentary incontinence. Diffuse pyogranulomatous inflammation of the globes was also noted. Based on the clinical signs and characteristic histopathological findings, the dog was diagnosed as uveodermatologic syndrome (UDS. Further treatment was not attempted in this case and the dog was euthanized. This case report describes typical clinical and histopathologic features of UDS in a Siberian Husky.

  2. Excision repair cross-complementation group 1 codon 118 polymorphism, micro ribonucleic acid and protein expression, clinical outcome of the advanced gastric cancer response to first-line FOLFOX-4 in Qinghai-Tibetan plateau population

    Directory of Open Access Journals (Sweden)

    Yu-Juan Qi

    2013-01-01

    Full Text Available Context: The excision repair cross-complementation group 1 (ERCC1 codon 118 C/T polymorphism has been associated with clinical outcome in cancer patients treated with platinum chemotherapy. Ethnic differences in the frequency of this polymorphism have been observed in Caucasian and African populations. Aim: The aim of this study was to evaluate the frequency and survival benefit of the ERCC1 codon 118 C/T polymorphism in a high-altitude population with advanced gastric cancer. Materials and Methods: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the frequency of ERCC1 118 codon C/T polymorphism in 206 advanced gastric cancer patients residing in the high-altitude Qinghai-Tibetan plateau. The influence of the ERCC1 codon 118 C/T polymorphism on its micro ribonucleic acid (mRNA and protein expression, clinicopathological features; response to the platinum-based combination chemotherapy, and the outcome was evaluated. Statistical Analysis: The Kaplan-Meier method was used for survival analysis. The correlation of ERCC1 codon 118 polymorphism with ERCC1 mRNA and protein expression, clinicopathological characteristics, and first-line oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX-4 response was determined by χ2 -test. Results and Conclusions: ERCC1 codon 118 C/T polymorphism was not associated with ERCC1 mRNA and protein expression, FOLFOX-4 response, and progression-free survival (PFS or overall survival (OS. High ERCC1 mRNA and protein expression levels were associated with significantly lower FOLFOX-4 responses, PFS, and OS. ERCC1 codon 118 C/T polymorphism is not an important prognostic marker for advanced gastric cancer. Determination of ERCC1 mRNA and protein levels may be beneficial in predicting the response and outcome of FOLFOX-4 therapy in gastric cancer.

  3. 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)

  4. TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

    Science.gov (United States)

    Du, Zhongkun; Zhang, Yan; Wang, Guowei; Peng, Jianbiao; Wang, Zunyao; Gao, Shixiang

    2016-02-01

    Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle.

  5. Preserved in vivo response to interferon-alpha in multiple sclerosis patients with neutralising antibodies against interferon-beta (REPAIR study)

    DEFF Research Database (Denmark)

    Magyari, Melinda; Bach Søndergaard, Helle; Sellebjerg, Finn;

    2013-01-01

    BACKGROUND: A major problem in the treatment of multiple sclerosis (MS) patients with interferon-beta (IFN-β) is the development of neutralising antibodies (NAbs). High levels of NAbs block the induction of IFN-β-inducible markers, including Myxovirus Resistance Protein A (encoded by the MX1 gene......-label phase II study in 10 patients with relapsing-remitting MS with persisting NAbs against IFN-β and absent in vivo mRNA MxA response. We used in vivo induction of MX1 mRNA and other IFN-inducible genes as measure of the biological response. The primary endpoint was the in vivo mRNA MX1 response after...... an injection of IFN-α compared with the response after an injection of IFN-β. RESULTS: In all 10 patients we found high MX1 expression after injection of IFN-α 6 MIU, indicating a preserved in vivo response to IFN-α. We measured the gene expression index of immune system genes in blood cells from the 10 NAb...

  6. Detecting and Correcting Speech Repairs

    CERN Document Server

    Heeman, P A; Heeman, Peter; Allen, James

    1994-01-01

    Interactive spoken dialog provides many new challenges for spoken language systems. One of the most critical is the prevalence of speech repairs. This paper presents an algorithm that detects and corrects speech repairs based on finding the repair pattern. The repair pattern is built by finding word matches and word replacements, and identifying fragments and editing terms. Rather than using a set of prebuilt templates, we build the pattern on the fly. In a fair test, our method, when combined with a statistical model to filter possible repairs, was successful at detecting and correcting 80\\% of the repairs, without using prosodic information or a parser.

  7. 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

  8. 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

  9. American tegumentary leishmaniasis: correlations among immunological, histopathological and clinical parameters*

    Science.gov (United States)

    Martins, Ana Luiza Grizzo Peres; Barreto, Jaison Antonio; Lauris, José Roberto Pereira; Martins, Ana Claudia Grizzo Peres

    2014-01-01

    BACKGROUND American tegumentary leishmaniasis has an annual incidence of 1 to 1.5 million cases. In some cases, the patient's immune response can eliminate the parasite, and the lesion spontaneously resolves. However, when this does not occur, patients develop the disseminated form of the disease. OBJECTIVE To investigate the association between clinical, laboratory and pathological findings in cases of American tegumentary leishmaniasis. METHODS A retrospective study of the medical records of 47 patients with American cutaneous leishmaniasis. Clinical, laboratory and epidemiological data were collected, and semi-quantitative histopathological analyses were performed using the Spearman correlation coefficient (p Montenegro reaction, degree of granulomatous transformation and epithelioid cell count; duration of disease, Montenegro reaction and number of lymphocytes; epithelial hyperplasia and edema, hemorrhaging, and epithelial aggression; number of plasmocytes and number of parasites. The main negative correlations found were as follows: age and serology; time and parasite load; epithelial hyperplasia and degree of granulomatous transformation. CONCLUSION The long duration of the disease could be explained by the fact that lesions were relatively asymptomatic, and therefore ignored by patients with low literacy levels. Individuals may have simply waited for spontaneous healing, which proved to be dependent on the activation of hypersensitivity mechanisms. PMID:24626648

  10. Mandibular condylar hyperplasia: clinical, histopathological, and treatment considerations.

    Science.gov (United States)

    Angiero, Francesca; Farronato, Giampietro; Benedicenti, Stefano; Vinci, Raffaele; Farronato, Davide; Magistro, Sarah; Stefani, Michele

    2009-01-01

    Condylar hyperplasia is a rare disorder characterized by an increased volume of the condyle, ramus, and mandibular body leading to facial asymmetry. We present three cases of condylar hyperplasia: two women and one man, age range 27 to 34. Clinically, all three patients showed a deviation of the mandible to the opposite side and a protruded position of the chin, hypertrophy of the lower border of the mandible, combined with an elongation of the mandibular ramus, open-bite on the deformed side, and cross-bite on the opposite side. In all three cases, scintigraphy showed an increased uptake. Radiography and CT scanning confirmed the clinical diagnosis and patients were subjected to surgery, comprising high condylectomy on the affected side with access in the pre-tragus area. The surgical piece sent to the Institute of Pathological Anatomy for histological examination revealed a nonuniform picture, in terms of both the depth of cartilage islands and the thickness of the fibrous layer covering the joint surface. Common to all three cases, however, was the apparent evolution of fibrous tissue to cartilage, and of this to compact bone tissue. At two-four years, all cases have maintained a good occlusal response. The asymmetric deformity of the mandible resulting from the rare condition of hemimandibular hyperplasia is presented and the clinical, histopathological and therapeutic aspects discussed.

  11. 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.

  12. Histopathological Study of Trabeculum after Excimer Laser Trabeculectomy ab Interno

    Institute of Scientific and Technical Information of China (English)

    Shengsong Huang; Minbin Yu; Guangqiang Feng; Ping Zhang; Changyu Qiu

    2001-01-01

    Purpose: To study the clinical manifestations and histopathologic changes of trabeculum after excimer laser trabeculectomy ab interno (ELT), and to investigate the mechanisms of ELT in reducing intraocular pressure. Methods : ELT was performed on ten rabbit eves and postoperative responses were documented. Comeoscleral tissue samples were harvested consecutively each week until the 5th postoperative week and these samples were examined under light and electrical microscopy. Results: Mild stimulation signs were present postoperatix'ely in nine of ten eyes, but no serious complications were experienced. Obvious inflammation was observed in one rabbit eye as a result of iris damage during the surgical manipulations. Local kactures on the trabecular meshwork and openings into Schlemm' s canal were detected in all tissue samples under light microscope. Mitochondria were found to be turgescent and dilated like vacuoles and endoplasmic reticula were found to be dilated under electrical microscope in the early postoperative period. Later, all trabecular cells returned normal and no fihroblast cells were ever detected. Conclusions: Permanent openings through trabecular meshwork into the inner wall of Schlemm's canal can be created with ELT. The outflow resistance of aqueous humor can be reduced with these openings and intraocular pressure can be controlled thereafter. Eye Science 2001; 17:11 ~ 15.

  13. [DNA homologous recombination repair in mammalian cells].

    Science.gov (United States)

    Popławski, Tomasz; Błasiak, Janusz

    2006-01-01

    DNA double-strand breaks (DSBs) are the most serious DNA damage. Due to a great variety of factors causing DSBs, the efficacy of their repair is crucial for the cell's functioning and prevents DNA fragmentation, chromosomal translocation and deletion. In mammalian cells DSBs can be repaired by non-homologous end joining (NHEJ), homologous recombination (HRR) and single strand annealing (SSA). HRR can be divided into the first and second phase. The first phase is initiated by sensor proteins belonging to the MRN complex, that activate the ATM protein which target HRR proteins to obtain the second response phase--repair. HRR is precise because it utilizes a non-damaged homologous DNA fragment as a template. The key players of HRR in mammalian cells are MRN, RPA, Rad51 and its paralogs, Rad52 and Rad54.

  14. Clinical neurophysiological correlates of histopathological abnormalities in epilepsy surgery

    NARCIS (Netherlands)

    Ferrier, C.H.

    2006-01-01

    In search for variables that determine outcome in patients with pharmacoresistant epilepsy who undergo epilepsy surgery, we identified specific combinations of clinical neurophysiological findings with their underlying histopathology. These findings may have important surgical consequences. In a

  15. Histopathologic approaches to detect changes indicative of immunotoxicity

    NARCIS (Netherlands)

    Kuper, C.F.; Harleman, J.H.; Richter-Reichelm, H.B.; Vos, J.G.

    2000-01-01

    Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunot

  16. Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair

    NARCIS (Netherlands)

    Caskey, Robert C.; Allukian, Myron; Lind, Robert C.; Herdrich, Benjamin J.; Xu, Junwang; Radu, Antoneta; Mitchell, Marc E.; Liechty, Kenneth W.

    2013-01-01

    Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decr

  17. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2015-10-01

    A pivotal phase II study demonstrated that ola - parib induces responses in BRCA1/2 mutation car- riers with progressive high-grade OC, with efficacy...change that realigns critical residues in the enzyme active site,38-40 producing an up to 500-fold increase in activ- ity.39,41,42 Once activated

  18. Altered cortical responsiveness to pain stimuli after high frequency electrical stimulation of the skin in patients with persistent pain after inguinal hernia repair

    NARCIS (Netherlands)

    Broeke, E.N. van den; Koeslag, L.; Arendsen, L.J.; Nienhuijs, S.W.; Rosman, C.; Rijn, C.M. van; Wilder-Smith, O.H.G.; Goor, H. van

    2013-01-01

    BACKGROUND: High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate w

  19. Altered Cortical Responsiveness to Pain Stimuli after High Frequency Electrical Stimulation of the Skin in Patients with Persistent Pain after Inguinal Hernia Repair

    NARCIS (Netherlands)

    Broeke, E.N. van den; Koeslag, L.; Arendsen, L.J.; Nienhuijs, S.W.; Rosman, C.; Rijn, C.M. van

    2013-01-01

    Background High Frequency electrical Stimulation (HFS) of the skin induces enhanced brain responsiveness expressed as enhanced Event-Related Potential (ERP) N1 amplitude to stimuli applied to the surrounding unconditioned skin in healthy volunteers. The aim of the present study was to investigate wh

  20. Temporomandibular joint disc; a proposed histopathological degeneration grading score system

    OpenAIRE

    2010-01-01

    Summary. Aims: The purpose of this study was to draw up a TMJ disc histopathological score that is a semiquantitative transcription of the entire spectrum of TMJ disc degenerative diseases related to changes in disc tissue, and then validate the proposed grading, in order to contribute to a standardized histopathological diagnosis. Methods: Sections from sixty two temporomandibular joint disc specimens affected by tissue degenerative changes and stained with Hematox...

  1. Cystic adenomatoid malformation in children: CT histopathological correlation.

    Science.gov (United States)

    Lanza, C; Bolli, V; Galeazzi, V; Fabrizzi, B; Fabrizzi, G

    2007-06-01

    This study was performed to assess the accuracy of computed tomography (CT) in classifying the various types of cystic adenomatoid malformation (CAM) of the lung, as described by Stocker et al., taking histopathology as the gold standard. We retrospectively reviewed six cases of histologically proven CAM. Chest radiography, chest CT and histopathology results were available for all patients. The CT images were reviewed blinded to the histological findings, and attention was paid to the number and size of cysts so as to classify the lesions into the three groups described by Stocker et al. The classification of lesions based on the CT images was then correlated to the histopathological findings. Areas with small-sized cysts (2 cm) were seen in three cases (50%) whereas in the remaining case, the diagnosis was mixed type I and type II CAM. In one patient with type I CAM, an area of low-density consolidation around the cysts was interpreted as CAM in a context of pulmonary sequestration. The CT classification based on Stocker et al.'s categories was in agreement with the histopathological findings in four cases, whereas in the remaining two cases, the lesions were classed as type I or II on CT and as mixed (type I and II) lesions at histopathology. In one case, the CT classification was correct, but the histopathology revealed the coexistence of pulmonary sequestration. In our study, there was concordance between CT and histopathology in 66.7% of cases, whereas in 33.3% histopathology revealed areas with mixed grade lesions. CT proved to be accurate in identifying and characterising CAM and provided important information on lesion site and extension.

  2. Groin hernia repair in young males: mesh or sutured repair?

    DEFF Research Database (Denmark)

    Bisgaard, T; Bay-Nielsen, M; Kehlet, H

    2010-01-01

    Large-scale data for the optimal inguinal hernia repair in younger men with an indirect hernia is not available. We analysed nationwide data for risk of reoperation in younger men after a primary repair using a Lichtenstein operation or a conventional non-mesh hernia repair....

  3. Clinical-histopathological concordance in head and neck lesions.

    Directory of Open Access Journals (Sweden)

    Sahily Espino Otero

    2009-03-01

    Full Text Available Background: Clinical-histopathological data contributes to a better diagnosis, assessment and treatment of head and neck lesions. Objective: To determine clinical-histopathological correlation of head and neck lesions. Methods: a descriptive, retrospective, observational study was developed in a series of cases (360 patients to determine the clinical diagnostic scope in relation to the histopathological techniques used in the Maxillary Surgery Service of “Gustavo Aldereguía Lima” hospital between June 2006 and 2007. Required data was taken from clinical histories and records from Pathological Anatomy, which were transferred to a form design for that purpose. Results: The age group of 0-19 years had the higher concordance among the studied groups (72,4%. 59, 7% of the studied cases had clinical-histopathological concordance, mainly in extra-oral lesions (60, 4% particularly in the vermilion border (82, 4 % and among the intra-oral the most common were those in the vestibular duct (100%. The most important lesions where clinical diagnosis did not coincide with histopathological diagnosis were fibroma with 23 in the intra-oral and warts and a total of 34 in extra-oral, followed by basal carcinomas. Conclusions: There is a significant correlation between clinical and histopathological diagnosis, suggesting high attention quality and correct application of the clinical method as central element in patients’ management.

  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 page, please enable JavaScript. Cleft lip and cleft palate repair is surgery to fix birth defects ...

  5. Abdominal aortic aneurysm repair - open

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007392.htm Abdominal aortic aneurysm repair - open To use the sharing features on this page, please enable JavaScript. Open abdominal aortic aneurysm repair is surgery to fix a widened part ...

  6. Low power laser stimulation of the bone consolidation in tibial fractures of rats: a radiologic and histopathological analysis.

    Science.gov (United States)

    Briteño-Vázquez, M; Santillán-Díaz, G; González-Pérez, M; Gallego-Izquierdo, T; Pecos-Martín, D; Plaza-Manzano, G; Romero-Franco, N

    2015-01-01

    The objective of this study is to analyze the effectiveness of low power laser irradiation in the bone consolidation of tibial fractures in rats. An experimental, comparative, prospective study with control group was designed. Twenty Wistar rats were grouped into control (n = 10) and experimental groups (n = 10). A tibial fracture, with a mechanical drill, was inflicted in all rats. The experimental group received ten days of low power arsenide-gallium laser irradiation of 850 nm (KLD, Sao Paulo, Brasil)-100 mW, 8 J/cm(2), 64 s. Before and after the laser treatment, a radiologic analysis was carried out in both groups, in which the rats were graded from 0 to IV according the Montoya scale of bone consolidation. Also, we histopathologically analyzed the bone to estimate the proliferation of fibroblasts, bone matrix, and angiogénesis with a microscopy, which were graded as I (thin layer of fibroblasts and osteoid matrix), II (thick layer of fibroblasts and osteoid matrix), or III (thick layer of fibroblasts and osteoid matrix and new blood vessels). Radiologic data showed that the experimental group had a higher bone consolidation of Montoya scale after ten days of laser irradiation compared to control group (P Histopathologic data showed more fibroblasts and angiogenesis presence in the group receiving laser irradiation, compared to control group (P low power laser radiation therapy may expedite the bone repair after tibial fractures in rats, according to radiologic and histopathologic analysis.

  7. The role of tendon and subacromial bursa in rotator cuff tear pain: a clinical and histopathological study.

    Science.gov (United States)

    Chillemi, Claudio; Petrozza, Vincenzo; Franceschini, Vincenzo; Garro, Luca; Pacchiarotti, Alberto; Porta, Natale; Cirenza, Mirko; Salate Santone, Francesco; Castagna, Alessandro

    2016-12-01

    To evaluate a possible association of shoulder pain with the clinical features and the histopathological changes occurring in the ruptured tendon and subacromial bursa of patients with rotator cuff tear. One hundred and eighty patients were clinically evaluated with the constant score and the visual analogue pain scale. Radiographs and MRI were performed. The chronology of the rupture, the muscle fatty degeneration according to Goutallier's scale and the tear size were evaluated. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed during arthroscopic rotator cuff tear repair and the specimens were histopathologically analysed. Clinically, the shoulder was more painful in females, in the presence of a chronic cuff lesion and a low Goutallier's grade (P rotator cuff tear. In particular, a greater association of pain was observed with the histopathological changes in the bursa compared with those in the rotator cuff. Considering that the bursa plays also an essential role during the healing process, this "new" role of the subacromial bursa as pain generator has important repercussions in both pharmacological and surgical treatments of rotator cuff tears. IV.

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

    Science.gov (United States)

    Meteyer, C.U.; Buckles, E.L.; Blehert, D.S.; Hicks, A.C.; Green, D.E.; Shearn-Bochsler, V.; Thomas, N.J.; Gargas, A.; Behr, M.J.

    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.

  9. 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

  10. Nanomaterials promise better bone repair

    OpenAIRE

    Qifei Wang; Jianhua Yan; Junlin Yang; Bingyun Li

    2016-01-01

    Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture rep...

  11. Laparoscopic repair of femoral hernia

    OpenAIRE

    Yang, Xue-Fei; Liu, Jia-Lin

    2016-01-01

    Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed effects. Femoral hernia could be repaired through the laparoscopic procedures for inguinal hernia. These procedures have clear anatomic view in the operation and preoperatively undiagnosed femoral hernia could be confirmed and treated. Lower recurrence ratio was reported in laparoscopic procedures compared with open procedures for repair of femoral hernia. The technical details of laparoscopic repair of femoral hernia, ...

  12. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Peter, William H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    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.

  13. Regenerative endodontics: regeneration or repair?

    Science.gov (United States)

    Simon, Stéphane R J; Tomson, Phillip L; Berdal, Ariane

    2014-04-01

    Recent advances in biotechnology and translational research have made it possible to provide treatment modalities that protect the vital pulp, allow manipulation of reactionary and reparative dentinogenesis, and, more recently, permit revascularization of an infected root canal space. These approaches are referred to as regenerative procedures. The method currently used to determine the origin of the tissue secreted during the repair/regeneration process is largely based on the identification of cellular markers (usually proteins) left by cells that were responsible for this tissue production. The presence of these proteins in conjunction with other indicators of cellular behavior (especially biomineralization) and analysis of the structure of the newly generated tissue allow conclusions to be made of how it was formed. Thus far, it has not been possible to truly establish the biological mechanism controlling tertiary dentinogenesis. This article considers current therapeutic techniques to treat the dentin-pulp complex and contextualize them in terms of reparative and regenerative processes. Although it may be considered a semantic argument rather than a biological one, the definitions of regeneration and repair are explored to clarify our position in this era of regenerative endodontics. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  14. Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma

    Science.gov (United States)

    2014-10-01

    DNA ligase IV, XRCC4 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC...nonhomologous end-joining (NHEJ) pathway (53BP1, Ku70, Ku80, DNA-PKcs, XRCC4, DNA ligase IV) as well as PARP1. This group of proteins was chosen based on our...recombination, nonhomologous end-joining (NHEJ), immunohistochemistry, poly(ADP-ribose) polymerase, Ku70, Ku80, PARP1, 53BP1, DNA-PK, Artemis, DNA ligase IV

  15. 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

  16. DNA repair mechanisms in eukaryotes: Special focus in Entamoeba histolytica and related protozoan parasites.

    Science.gov (United States)

    López-Camarillo, César; Lopez-Casamichana, Mavil; Weber, Christian; Guillen, Nancy; Orozco, Esther; Marchat, Laurence A

    2009-12-01

    Eukaryotic cell viability highly relies on genome stability and DNA integrity maintenance. The cellular response to DNA damage mainly consists of six biological conserved pathways known as homologous recombination repair (HRR), non-homologous end-joining (NHEJ), base excision repair (BER), mismatch repair (MMR), nucleotide excision repair (NER), and methyltransferase repair that operate in a concerted way to minimize genetic information loss due to a DNA lesion. Particularly, protozoan parasites survival depends on DNA repair mechanisms that constantly supervise chromosomes to correct damaged nucleotides generated by cytotoxic agents, host immune pressure or cellular processes. Here we reviewed the current knowledge about DNA repair mechanisms in the most relevant human protozoan pathogens. Additionally, we described the recent advances to understand DNA repair mechanisms in Entamoeba histolytica with special emphasis in the use of genomic approaches based on bioinformatic analysis of parasite genome sequence and microarrays technology.

  17. Pigmentation associated histopathological variations in sympathetic ophthalmia.

    Science.gov (United States)

    Marak, G E; Ikui, H

    1980-01-01

    The severity of inflammation in sympathetic ophthalmia is related to the degree of pigmentation, and the granulomatous response seems to be related to pigmentation. Eosinophilia is also associated with pigmentation, but this association appears to be fortuitous and is a result of the association of eosinophilia with severity of the inflammation. PMID:7387955

  18. Nanomaterials promise better bone repair

    Directory of Open Access Journals (Sweden)

    Qifei Wang

    2016-10-01

    Full Text Available Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture repair. Next, the review discusses the applications of nanomaterials for bone fracture repair, with a focus on the recent breakthroughs such as nanomaterials leading to precise immobilization of growth factors at the molecular level, promoting vascularization without the use of growth factors, and re-loading therapeutic agents after implantation. The review concludes with perspectives on challenges and future directions for developing nanomaterials for improved bone fracture repair.

  19. 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)

  20. Role of histopathology as an aid to prognosis in rhino-orbito-cerebral zygomycosis

    Directory of Open Access Journals (Sweden)

    Goel Ashina

    2010-04-01

    Full Text Available Rhino-orbito-cerebral zygomycosis is a rapidly progressive opportunistic fungal infection characterized by a set of clinical and radiological findings that help in prognostication. The present study is aimed to evaluate its histopathologic features as an aid to prognosis in order to guide the physician at the stage of tissue diagnosis to optimize surgery, chemotherapy and immunosuppression. The study comprises of a microscopic analysis of specific histopathologic variables on 33 cases of zygomycosis that were diagnosed and treated in a seven-year period. Fungal load in the tissue (graded as mild, moderate and marked, mean diameter of fungus, degree of neutrophilic and granulomatous response, tissue invasion and necrosis were graded and assessed for their prognostic significance. Seasonal variation, signs and symptoms, extent of involvement and laboratory parameters were also analyzed to examine the trend of occurrence of the disease and to associate these with patient′s outcome, which was categorized as either survived or expired. The follow-up ranged from 1 month to 7 years. Of all the histological variables, angioinvasion was directly related to the mortality rate. Diameter of the fungal hyphae and its intraorbital or intracranial invasion also proved to be significant indicators of poor prognosis. (P = 0.04 and 0.0037, respectively though angioinvasion was directly related to the mortality rate. Thus, histopathology could assist the clinician in assessing patient′s progress and thus optimize the treatment in such patients.

  1. 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.)

  2. Fine Needle Aspiration Cytology of Thyroid Nodules: Correlation with Surgical Histopathology Histopathology

    Directory of Open Access Journals (Sweden)

    Nargess Ghazaleh

    2008-01-01

    Full Text Available Objective: Approximately 7% of people have thyroid nodules. The most important consideration in evaluating patients with thyroid nodules is whether the nodule is malignant. Fine needle aspiration (FNA biopsy is the best, safest, and most cost-effective measure for distinguishing malignancy, thus preventing unnecessary surgeries. In this survey, adequacy of smears, cytologic findings, histologic findings, and their concordance, have been studied. Materials and Methods: FNA biopsy was performed in 200 patients with palpable thyroid nodules in 2004-2005. Cytologic findings and adequacy of specimens were recorded. Of the 200 patients, 39 had surgery; postoperative histological results were compared with FNA biopsy results.Results: Of FNA smears, 88% were adequate; of these adequate smears, 57.2% were benign, 34.2% were suspicious for malignancy, and 8.6% were reported as malignant. When results of surgical pathology were compared with FNA cytology results, all benign surgical specimens also had benign cytology results, and all malignant surgical specimens had malignant results on cytology evaluation. In nodules with suspicious cytology, histopathology showed that 50% were malignant and 50% were benign.Conclusions: FNA is a simple and cost-effective procedure for identifying benign and malignant nodules. The incidence of malignant pathology in nodules with suspicious cytology was higher than other studies.Turk Jem 2008; 12: 73-4

  3. Other-Repair in Japanese Conversations Between Nonnative and Native Speakers

    OpenAIRE

    Hosoda, Yuri

    2000-01-01

    Although a preference for self-repair over other-repair has been observed in both native speaker (NS) discourse (e.g., Schegloff, Jefferson, & Sacks, 1977) and nonnative speaker (NNS) discourse (e.g., Firth, 1996), researchers note that other-repair still often occurs, especially in interactions with NNSs (e.g., Varonis & Gass, 1983). The present study examines conditions under which other-repair occurs and the response to other-repair in natural NS/NNS conversations in Japanese. Analysis of ...

  4. Correlation between Histopathological and Endoscopic Findings of Stomach Growth.

    Science.gov (United States)

    Mahmuda, S; Bashar, M F; Yesmin, N; Khatun, M A

    2016-01-01

    This study was carried out in the Department of Pathology of Islami Bank Hospital, Barisal to correlate between histopathological and endoscopic diagnosis of suspected malignant gastric lesions. A total of sixty six endoscopic biopsies were studied retrospectively, during the period from February 2011 to January 2014. The biopsies were retrieved using video-endoscope. These were transferred to a bottle containing 10% neutral formalin, processed and stained routinely with Haematoxylin and Eosin. Out of 66(100%) gastric endoscopic biopsies, 29(44%) were malignant. The correlation of endoscopic and histopathological diagnosis of these gastric lesions was 44%. Endoscopic examination and biopsy is a convenient procedure for accurate objective assessment of patients with symptoms of gastrointestinal tract. Endoscopy is incomplete without biopsy and histopathology is the gold standard for the diagnosis of endoscopically detected lesions.

  5. Neuroradiology and histopathology in two cases of adult medulloblastoma.

    Science.gov (United States)

    Romero-Rojas, Alfredo E; Diaz-Perez, Julio A; Raju, Sharat; Lozano-Castillo, Alfonso

    2014-04-01

    Medulloblastoma (MB) is the most common central nervous system neoplasm in children and only rarely presents in the adult population. Recent molecular biology findings have characterized MB as a heterogeneous neoplasm distinguished by well-defined tumour subsets each with specific histologic and molecular features. Available immunohistochemical stains can now be used to differentiate the distinct molecular types of MB. This report analyzed the histopathologic and neuroradiologic features of two new cases of adult MB. Imaging studies in these patients revealed the morphological appearance of high-grade, well-circumscribed heterogeneous tumours with necrosis, located laterally within the posterior cranial fossa. Histopathology of resected samples demonstrated high-grade tumours (WHO grade IV) containing sheets of undifferentiated neural cells with high mitotic activity and evidence of necrosis. The histopathologic and molecular characteristics of these cases of MB are reviewed for potential applications in new molecular methods of imaging.

  6. Histopathological changes in tendinopathy--potential roles of BMPs?

    Science.gov (United States)

    Lui, Pauline Po Yee

    2013-12-01

    The pathogenesis of tendinopathy remains unclear. Chondro-osteogenic BMPs such as BMP-2, BMP-4 and BMP-7 have been reported in clinical samples and animal models of tendinopathy. As chondrocyte-like cells and ossified deposits have been observed in both clinical samples and animal models of failed tendon healing tendinopathy, chondro-osteogenic BMPs might contribute to tissue metaplasia and other histopathological changes in tendinopathy. In this review I have summarized the current evidence supporting the roles of chondro-osteogenic BMPs in the histopathological changes of tendinopathy. The potential targets, effects and sources of these BMPs are discussed. I have also provided directions for future studies about the potential roles of BMPs in the pathogenesis of tendinopathy. Better understanding of the roles of these BMPs in the histopathological changes of tendinopathy could provide new options for the prevention and treatment of this disabling tendon disorder.

  7. Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.

    Science.gov (United States)

    Brown, Jessica S; O'Carrigan, Brent; Jackson, Stephen P; Yap, Timothy A

    2017-01-01

    Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2-mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell-cycle checkpoint activation, trigger apoptosis, and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations.

  8. Histopathologic effects of formaldehyde exposure on rat kidney

    Directory of Open Access Journals (Sweden)

    M.J. Golalipour

    2007-01-01

    Full Text Available AbstractBackground and purpose: Formaldehyde is a chemical traditionally used for fixing the cadaver. It is vaporized during dissection and practical studying on cadaver. Studies show that this vapour can cause some clinical sympotms such as throat, eye, skin and nasal irritation.This study was designed to determine the histopathological changes of rat kidney tissue exposed to formaldehyde for 18 weeks.Materials and Methods: This study was performed on 28, 6-7 weeks postnatal albino Wistar rats. The rats were divided into 3 case groups (E1: 4hrs/d, 4d/w; E2: 2hrs/d, 4d/w; E3: 2hrs/d, 2d/w and one control group (C. The kidney specimens were sectioned and stained with H&E technique for histopathological study.Results: In all histopathology sections of groups E1, E2 and E3, the following similar changes were observed: Mild congestion in the glumeroles, focal congestion and vacuolar (hydropic degeneration of tubular cells only mild non-specific congestion in renal vessels. There were no evidences of fibrotic change or inflammatory cells infiltration among interstitial tissue. Also there were no abnormalities in the staining of nucleus and cytoplasm. In Control group (C, no histopathologic changes were observed.Conclusion: The results of this study showed that formaldehyde vapour with a concentrations used in our study, can not induce histopathologic changes which could be detectable by light microscope. Also, there is no direct relationship between the duration of exposure to formaldehyde vapour and the intensity of histopathologic changes in the kidney.

  9. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  10. 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...

  11. Repairing split ends: SIRT6, mono-ADP ribosylation and DNA repair

    Science.gov (United States)

    Van Meter, Michael; Mao, Zhiyong; Gorbunova, Vera; Seluanov, Andrei

    2011-01-01

    The sirtuin gene family comprises an evolutionarily ancient set of NAD+ dependent protein deacetylase and mono-ADP ribosyltransferase enzymes. Found in all domains of life, sirtuins regulate a diverse array of biological processes, including DNA repair, gene silencing, apoptosis and metabolism. Studies in multiple model organisms have indicated that sirtuins may also function to extend lifespan and attenuate age-related pathologies. To date, most of these studies have focused on the deacetylase activity of sirtuins, and relatively little is known about the other biochemical activity of sirtuins, mono-ADP ribosylation. We recently reported that the mammalian sirtuin, SIRT6, mono-ADP ribosylates PARP1 to promote DNA repair in response to oxidative stress. In this research perspective we review the role of SIRT6 in DNA repair and discuss the emerging implications for sirtuin directed mono-ADP ribosylation in aging and age-related diseases. PMID:21946623

  12. Nucleotide Excision Repair in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hannes Lans

    2011-01-01

    Full Text Available Nucleotide excision repair (NER plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vitro and live cell experiments, particularly using model systems such as bacteria, yeast, and mammalian cell cultures. In recent years, the versatility of the nematode C. elegans to study DNA damage response (DDR mechanisms including NER has become increasingly clear. In particular, C. elegans seems to be a convenient tool to study NER during the UV response in vivo, to analyze this process in the context of a developing and multicellular organism, and to perform genetic screening. Here, we will discuss current knowledge gained from the use of C. elegans to study NER and the response to UV-induced DNA damage.

  13. Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair.

    Science.gov (United States)

    Czornak, Kamila; Chughtai, Sanaullah; Chrzanowska, Krystyna H

    2008-01-01

    Genomes are subject to a number of exogenous or endogenous DNA-damaging agents that cause DNA double-strand breaks (DSBs). These critical DNA lesions can result in cell death or a wide variety of genetic alterations, including deletions, translocations, loss of heterozygosity, chromosome loss, or chromosome fusions, which enhance genome instability and can trigger carcinogenesis. The cells have developed an efficient mechanism to cope with DNA damages by evolving the DNA repair machinery. There are 2 major DSB repair mechanisms: nonhomologous end joining (NHEJ) and homologous recombination (HR). One element of the repair machinery is the MRN complex, consisting of MRE11, RAD50 and NBN (previously described as NBS1), which is involved in DNA replication, DNA repair, and signaling to the cell cycle checkpoints. A number of kinases, like ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia and Rad-3-related), and DNA PKcs (DNA protein kinase catalytic subunit), phosphorylate various protein targets in order to repair the damage. If the damage cannot be repaired, they direct the cell to apoptosis. The MRN complex as well as repair kinases are also involved in telomere maintenance and genome stability. The dysfunction of particular elements involved in the repair mechanisms leads to genome instability disorders, like ataxia telangiectasia (A-T), A-T-like disorder (ATLD) and Nijmegen breakage syndrome (NBS). The mutated genes responsible for these disorders code for proteins that play key roles in the process of DNA repair. Here we present a detailed review of current knowledge on the MRN complex, kinases engaged in DNA repair, and genome instability disorders.

  14. 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

  15. 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....

  16. Mitosis Detection for Invasive Breast Cancer Grading in Histopathological Images.

    Science.gov (United States)

    Paul, Angshuman; Mukherjee, Dipti Prasad

    2015-11-01

    Histopathological grading of cancer not only offers an insight to the patients' prognosis but also helps in making individual treatment plans. Mitosis counts in histopathological slides play a crucial role for invasive breast cancer grading using the Nottingham grading system. Pathologists perform this grading by manual examinations of a few thousand images for each patient. Hence, finding the mitotic figures from these images is a tedious job and also prone to observer variability due to variations in the appearances of the mitotic cells. We propose a fast and accurate approach for automatic mitosis detection from histopathological images. We employ area morphological scale space for cell segmentation. The scale space is constructed in a novel manner by restricting the scales with the maximization of relative-entropy between the cells and the background. This results in precise cell segmentation. The segmented cells are classified in mitotic and non-mitotic category using the random forest classifier. Experiments show at least 12% improvement in F1 score on more than 450 histopathological images at 40× magnification.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. Revised histopathological consensus classification of joint implant related pathology.

    Science.gov (United States)

    Krenn, V; Morawietz, L; Perino, G; Kienapfel, H; Ascherl, R; Hassenpflug, G J; Thomsen, M; Thomas, P; Huber, M; Kendoff, D; Baumhoer, D; Krukemeyer, M G; Natu, S; Boettner, F; Zustin, J; Kölbel, B; Rüther, W; Kretzer, J P; Tiemann, A; Trampuz, A; Frommelt, L; Tichilow, R; Söder, S; Müller, S; Parvizi, J; Illgner, U; Gehrke, T

    2014-12-01

    This extended classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistologic changes in periprosthetic tissues. These changes may occur as a consequence of endoprosthetic replacement of large joints and may lead to a reduction in the prosthesis survival rate. We describe the established consensus classification of the periprosthetic membrane, in which aseptic and septic prosthetic loosening can be subdivided into four histological types, as well as histopathological criteria for additional significant pathologies including endoprosthetic-associated arthrofibrosis, particle-induced immunological, inflammatory and toxic mechanisms (adverse reactions), and bone tissue pathologies. These characteristic tissue alterations and their relationships are summarized in the extended classification. Since particle heterogeneity in periprosthetic tissue is high and particle identification is a necessary part of diagnosis, the identification of different types of particles is described in the histopathological particle algorithm. The morphological qualities of prosthetic material particles and the demarcation between abrasion and non-abrasion endogenous particles are also summarized. This feasible classification which is based on low cost standard tissue processing and examination and on well-defined diagnostic criteria is a solid platform for the histological diagnosis of implant associated pathologies providing a stable and reproducible tool for the surgical pathologist. Since this classification is suitable for standardized histopathological diagnostics, it might also provide a useful data set for joint arthroplasty registers, particularly for registers based on so-called routine data.

  2. 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.

  3. Laparoscopic Repair of Morgagni Hernia

    Directory of Open Access Journals (Sweden)

    ilker murat arer

    2015-03-01

    Full Text Available Morgagni hernia is a congenital herniation of abdominal contents into the thoracic cavity through a retrosternal diaphragmatic defect and make up about 1 % - 5 % of all types of congenital diaphragmatic hernias. Surgical repair of Morgagni hernias is usually indicated when patients are symptomatic and have a high risk of strangulation or incarceration of the contained viscera. 71-year-old male patient admitted to emergency department with a 2-day history of abdominal pain, vomiting and obstipation. Laparoscopic repair for Morgagni hernia was performed. Laparoscopic repair for Morgagni hernia with mesh repair is secure, satisfactory and easily performed. [Cukurova Med J 2015; 40(Suppl 1: 71-74

  4. Combinatorial Reliability and Repair

    Science.gov (United States)

    1992-07-01

    Press, Oxford, 1987. [2] G. Gordon and L. Traldi, Generalized activities and the Tutte polynomial , Discrete Math. 85 (1990), 167-176. [3] A. B. Huseby, A...particular, Satyanarayana and Tindell introduced a notion of (K,j)-domination in their study of a K-terminal version of the chromatic polynomial [6], and it...G)) graphs. He also intends to look into the properties of the polynomial that gives the expected number of needed repairs of a K-terminal network

  5. Mammalian mismatch repair

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Jiricny, Josef

    2012-01-01

    A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent...... advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication fidelity by removing misincorporated nucleotides from the nascent DNA strand. We also discuss the involvement of MMR proteins in two other processes: trinucleotide repeat expansion and antibody maturation...

  6. 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.

  7. The hamster (Mesocricetus auratus) as an experimental model of toxocariasis: histopathological, immunohistochemical, and immunoelectron microscopic findings.

    Science.gov (United States)

    da Silva, Ana Maria Gonçalves; Chieffi, Pedro Paulo; da Silva, Wellington Luiz Ferreira; Kanashiro, Edite Hatsumi Yamashiro; Rubinsky-Elefant, Guita; Cunha-Neto, Edécio; Mairena, Eliane Conti; De Brito, Thales

    2015-03-01

    Toxocariasis is a globally distributed parasitic infection caused by the larval stage of Toxocara spp. The typical natural hosts of the parasite are dogs and cats, but humans can be infected by the larval stage of the parasite after ingesting embryonated eggs in soil or from contaminated hands or fomites. The migrating larvae are not adapted to complete their life cycle within accidental or paratenic hosts like humans and laboratory animals, respectively, but they are capable of invading viscera or other tissues where they may survive and induce disease. In order to characterize hamsters (Mesocricetus auratus) as a model for Toxocara canis infection, histopathological and immunohistochemistry procedures were used to detect pathological lesions and the distribution of toxocaral antigens in the liver, lungs, and kidneys of experimentally infected animals. We also attempted to characterize the immunological parameters of the inflammatory response and correlate them with the histopathological findings. In the kidney, a correlation between glomerular changes and antigen deposits was evaluated using immunoelectron microscopy. The hamster is an adequate model of experimental toxocariasis for short-term investigations and has a good immunological and pathological response to the infection. Lung and liver manifestations of toxocariasis in hamsters approximated those in humans and other experimental animal models. A mixed Th2 immunological response to T. canis infection was predominant. The hamster model displayed a progressive rise of anti-toxocaral antibodies with the formation of immune complexes. Circulating antigens, immunoglobulin, and complement deposits were detected in the kidney without the development of a definite immune complex nephropathy.

  8. Hematopoietic tissue repair under chronic low daily dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1994-12-01

    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{minus}26.3 cGy d{sup {minus}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 & 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.

  9. 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

  10. 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

  11. 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.

  12. Vitamin B12 deficiency and gastric histopathology in older patients

    Institute of Scientific and Technical Information of China (English)

    KR Dholakia; TS Dharmarajan; D Yadav; S Oiseth; EP Norkus; CS Pitchumoni

    2005-01-01

    AIM: To compare upper gastric endoscopic and histopathologic findings in older adults in the presence and absence of B12 deficiency.METHODS: A prospective analysis of upper gastric endoscopic and gastric histopathologic findings from 30 newly identified B12-deficient patients (11 males,19 females) and 16 controls with normal B12 status (6males, 10 females) was performed. For all subjects, the indication for upper endoscopy and gastric biopsy were unrelated to B12 status. A single pathologist, blinded to B12 status, processed and interpreted the biopsy samples. Endoscopic and histopathologic findings were correlated with age, gender, hematocrit (Hct), MCV and B12 status.RESULTS: The B12-deficient group had significantly lower mean serum B12 levels compared to the controls (P<0.00005) while their mean Hct, MCV and serum albumin levels were similar. Iron deficiency (ferritinbased) was present in 21% of B12-deficient patients and intrinsic factor antibodies were present in29% (5/17) of B12-deficient patients. The endoscopic findings revealed significantly different rates of gastritis and atrophy between the B12-deficient and control groups (P= 0.017).B12-deficient patients had significantly less superficial gastritis (62% vs 94%) and significantly more atrophic gastritis (28% vs 0%) as compared to the controls (P= 0.039). Intestinal metaplasia was similar in both groups. Helicobacter pyloriinfection rates were similar in the B12-deficient patients and controls (40% vs31%).CONCLUSION: Significantly different endoscopic findings and types of gastritis could often be observed in the presence and absence of B12 deficiency. Atrophy,based on endoscopy, and atrophic gastritis, based on histopathology, suggest the presence of B12 deficiency.Gastric histopathology is not influenced by the age,gender, Hct or MCV of the patients.

  13. 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.

  14. DNA replication, repair, and repair tests. [Rat; human leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lambert, B.

    1980-09-01

    The rate of inhibition and recovery of DNA synthesis can be used in a rapid assay system to detect genotoxic potentials of chemicals. Also, the observation that an agent stimulates DNA repair in a test system indicates its ability to cause damage in DNA. Different experimental approaches to the study of repair synthesis are discussed.

  15. Biologics for tendon repair.

    Science.gov (United States)

    Docheva, Denitsa; Müller, Sebastian A; Majewski, Martin; Evans, Christopher H

    2015-04-01

    Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

  16. Kvitebjoern gas pipeline repair - baptism of remote pipeline repair system

    Energy Technology Data Exchange (ETDEWEB)

    Gjertveit, Erling

    2010-07-01

    On the 1st of November 2007, severe anchor damage was discovered on the 30 inch Kvitebjoern gas export pipeline. The damage constituted a localised dent and a 17deg buckle, but no leakage. Statoil has invested in building an effective repair contingency structure for the large pipeline network on the Norwegian Continental shelf, with particular focus on the large gas export pipelines. The repair method for the Kvitebjoern pipeline was remotely operated using two Morgrip couplings and a spool. The installation used the purpose built Pipeline Repair System stored at Killingoey and couplings produced and tested back in 2005. This presentation will cover the initial damage investigations, the temporary operational phase, the repair preparations, the actual repair and lessons learned. (Author)

  17. 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.

  18. 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.

  19. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    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 DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of 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. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  20. Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

    2008-01-01

    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 DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of 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. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

  1. 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.

  2. Pain following the repair of an abdominal hernia

    DEFF Research Database (Denmark)

    Hansen, Mark Berner; Andersen, Kenneth Geving; Crawford, Michael Edward

    2010-01-01

    Pain and other types of discomfort are frequent symptoms following the repair of an abdominal hernia. After 1 year, the incidence of light to moderate pain following inguinal hernia repair is as high as 10% and 2% for severe disabling chronic pain. Postoperative chronic pain not only affects......, psychosocial characteristics, and surgical procedures) related to the postoperative pain conditions. Furthermore, the mechanisms for both acute and chronic pain are presented. We focus on inguinal hernia repair, which is the most frequent type of abdominal hernia surgery that leads to chronic pain. Finally...... the individual patient, but may also have a great impact on relatives and society, and may be a cause of concern for the responsible surgeon. This paper provides an overview of the anatomy, surgical procedures, and disposing factors (age, gender, ethnicity, genotype, previous hernia repair, pain prior to surgery...

  3. Role of poly(ADP-ribosepolymerase 2 in DNA repair

    Directory of Open Access Journals (Sweden)

    Lavrik O. I.

    2012-06-01

    Full Text Available Poly(ADP-ribosylation is a posttranslational protein modification significant for the genomic stability and cell survival in response to DNA damage. Poly(ADP-ribosylation is catalyzed by poly(ADP-ribosepolymerases (PARPs, which use NAD+ as a substrate, synthesize polymer of (ADP-ribose (PAR covalently attached to nuclear proteins including PARP themselves. PARPs constitute a large family of proteins, in which PARP1 is the most abundant and best-characterized member. In spite of growing body of PARPs’ role in cellular processes, PARP2, the closest homolog of PARP1, still remains poorly characterized at the level of its contribution to different pathways of DNA repair. An overview summarizes in vivo and in vitro data on PARP2 implication in specialized DNA repair processes, base excision repair and double strand break repair.

  4. Electronic Pathways in Photoactivated Repair of UV Mutated DNA

    Science.gov (United States)

    Bohr, Henrik; Jalkanen, K. J.; Bary Malik, F.

    An investigation of the physics, underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism, is presented in this study. Electronic pathways, starting from the initial damage to the final repair process, are presented. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of a dimer. The negative-ion of the cofactor riboflavin, FADH-, formed by the exposure of the photolyase protein to visible light, interacts with the hole-excited electronic orbital of the thymine dimer inducing a photon-less Auger transition, which restores the two thymines to the ground state, thereby detaching the lesion and repairing the DNA. Density functional theoretical calculations supporting the theory are presented. The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process. Recent experimental data are compatible with this theory.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Histopathological and biomechanical evaluation of tenocyte seeded allografts on rat Achilles tendon regeneration.

    Science.gov (United States)

    Güngörmüş, Cansın; Kolankaya, Dürdane; Aydin, Erkin

    2015-05-01

    Tendon injuries in humans as well as in animals' veterinary medicine are problematic because tendon has poor regenerative capacity and complete regeneration of the ruptured tendon is never achieved. In the last decade there has been an increasing need of treatment methods with different approaches. The aim of the current study was to improve the regeneration process of rat Achilles tendon with tenocyte seeded decellularized tendon matrices. For this purpose, Achilles tendons were harvested, decellularized and seeded as a mixture of three consecutive passages of tenocytes at a density of 1 × 10(6) cells/ml. Specifically, cells with different passage numbers were compared with respect to growth characteristics, cellular senescence and collagen/tenocyte marker production before seeding process. The viability of reseeded tendon constructs was followed postoperatively up to 6 months in rat Achilles tendon by histopathological and biomechanical analysis. Our results suggests that tenocyte seeded decellularized tendon matrix can significantly improve the histological and biomechanical properties of tendon repair tissue without causing adverse immune reactions. To the best of our knowledge, this is the first long-term study in the literature which was accomplished to prove the use of decellularized matrix in a clinically relevant model of rat Achilles tendon and the method suggested herein might have important implications for translation into the clinic.

  11. 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

    2013-01-01

    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. PMID:23827087

  12. Rethinking transcription coupled DNA repair.

    Science.gov (United States)

    Kamarthapu, Venu; Nudler, Evgeny

    2015-04-01

    Nucleotide excision repair (NER) is an evolutionarily conserved, multistep process that can detect a wide variety of DNA lesions. Transcription coupled repair (TCR) is a subpathway of NER that repairs the transcribed DNA strand faster than the rest of the genome. RNA polymerase (RNAP) stalled at DNA lesions mediates the recruitment of NER enzymes to the damage site. In this review we focus on a newly identified bacterial TCR pathway in which the NER enzyme UvrD, in conjunction with NusA, plays a major role in initiating the repair process. We discuss the tradeoff between the new and conventional models of TCR, how and when each pathway operates to repair DNA damage, and the necessity of pervasive transcription in maintaining genome integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Parametric studies on self-repairing approaches for resin infused composites subjected to low velocity impact

    Science.gov (United States)

    Motuku, M.; Vaidya, U. K.; Janowski, G. M.

    1999-10-01

    Low velocity impact response of glass reinforced polymer composites, which have the potential to self-repair both micro- and macro-damage, has been investigated. This class of material falls under the category of passive smart polymer composites. The self-repairing mechanism is achieved through the incorporation of hollow fibers in addition to the normal solid reinforcing fibers. The hollow fibers store the damage-repairing solution or chemicals that are released into the matrix or damaged zone upon fiber failure. Plain-weave S-2 glass fabric reinforcement, vinyl ester 411-C50 and EPON-862 epoxy resin systems were considered for this study. Different tubing materials were investigated for potential use as storage materials for the repairing chemicals instead of the actual hollow repair fibers and included borosilicate glass micro-capillary pipets, flint glass pasteur pipets, copper tubing and aluminum tubing. composite panels were fabricated by using a vacuum assisted resin transfer molding process. The present investigation addressed fabrication of self-repairing composite panels and some of the parameters that influence the response of self-repairing composites to impact loading. Specific issues addressed by this study include: the processing quality; the selection of storage material for the repairing solution; release and transportation of the repairing solution; the effect of the number, type and spatial distribution of the repairing tubes, specimen thickness, matrix material and impact energy level.

  14. 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.

  15. 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.

  16. Groin hernia repair

    DEFF Research Database (Denmark)

    Kehlet, Henrik; Aasvang, Eske

    2005-01-01

    The choice of anesthesia for groin hernia repair is between general, regional (epidural or spinal), and local anesthesia. Existing data from large consecutive patient series and randomized studies have shown local anesthesia to be the method of choice because it can be performed by the surgeon......, does not necessarily require an attending anesthesiologist, translates into the shortest recovery (bypassing the postanesthesia care unit), has the lowest cost, and has the lowest postoperative morbidity regarding risk of urinary retention. Spinal anesthesia has no documented benefits for this small...... scientific data to support the choice of anesthesia, large epidemiologic and nationwide information from databases show an undesirable high (about 10-20%) use of spinal anesthesia and low (about 10%) use of local infiltration anesthesia. Surgeons and anesthesiologists should therefore adjust their anesthesia...

  17. Prophylactic effect of vitamin E against hepatotoxicity, nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

    Directory of Open Access Journals (Sweden)

    Nahla S. EL-SHENAWY

    2009-06-01

    Full Text Available Considering that the involvement of reactive oxygen species (ROS has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E (100 mg/kg body weight on mice (25–30 mg treated with diazinon (32.5 or 16.25 mg/kg body weight organophosphate insecticide for 14 days. Subchronic DZN exposure and the protective effects of vitamins E (vitE were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase (ALT, aspartate aminotaransferase (AST, alkaline phosphatise (ALP, and some parameters of kidney function (urea and creatinine in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon (DZNH decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examined for histopathological changes. The high dose of diazinon decreased body weight significantly. Moreover, there was a statistically significant decrease in haemoglobin (Hb, red blood cell (RBC and hematocrit (Hct in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE + DZN-treated groups. According to the present study, we conclude that vitE can reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function [Current Zoology 55(3:219–226, 2009].

  18. Prophylactic effect of vitamin E against hepatotoxicity,nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

    Institute of Scientific and Technical Information of China (English)

    Nahla S.EL-SHENAWY; Rasha A.AL-EISA; Fawzia EL-SALMY; Omema SALAH

    2009-01-01

    Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E (100 mg/kg body weight) on mice (25-30 mg) treated with diazinon (32.5 or 16.25 mg/kg body weight) organophosphate insecticide for 14 days. Subchronic DZN exposure and the protective effects of vitamins E (vitE) were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase (ALT), aspartate aminotaransferase (AST), alkaline phosphatise (ALP), and some parameters of kidney function (urea and creatinine) in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon (DZNH) decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significantly. Moreover, there was a statistically significant decrease in haemoglobin (Hb), red blood cell (RBC) and hematocrit (Hct) in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received ritE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in ritE + DZN-treated groups. According to the present study, we conclude that vitE can reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function.

  19. 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.

  20. Review of Histopathological and Molecular Prognostic Features in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    John Schofield

    2011-06-01

    Full Text Available Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.

  1. 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.

  2. Review of Histopathological and Molecular Prognostic Features in Colorectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marzouk, Ola; Schofield, John, E-mail: john.schofield@nhs.net [Department of Cellular Pathology, Maidstone Hospital, Hermitage Lane, Maidstone, Kent ME16 9QQ (United Kingdom)

    2011-06-23

    Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.

  3. Giant solitary trichoepithelioma with desmoplasia on histopathology: An unusual finding

    Directory of Open Access Journals (Sweden)

    Sundeep Chowdhry

    2016-10-01

    Full Text Available Trichoepithelioma is a well-recognized hamartoma of hair germ clinically presenting as solitary or multiple papules. Uncommonly, it may present as a large solitary lesion, termed as giant solitary trichoepithelioma (GST. A 50-year old man presented with a large, pedunculated mass over the root of nose obstructing visual field. It was excised and sent for histopathological examination. H&E staining revealed in addition to characteristic features of trichoepithelioma, a desmoplastic hypocellular stroma. After taking into account the clinical and histopathological features, a diagnosis of GST was made. This case is the first case to the best of authors’ knowledge describing desmoplastic stroma in a case of GST. It is also noteworthy because it reports the largest GST described so far over the nose.

  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...... 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...

  5. A statistical model for characterization of histopathology images

    Science.gov (United States)

    Álvarez, Pablo; Castro, Guatizalema; Corredor, Germán.; Romero, Eduardo

    2015-01-01

    Accessing information of interest in collections of histopathology images is a challenging task. To address such issue, previous works have designed searching strategies based on the use of keywords and low-level features. However, those methods have demonstrated to not be enough or practical for this purpose. Alternative low-level features such as cell area, distance among cells and cell density are directly associated to simple histological concepts and could serve as good descriptors for this purpose. In this paper, a statistical model is adapted to represent the distribution of the areas occupied by cells for its use in whole histopathology image characterization. This novel descriptor facilitates the design of metrics based on distribution parameters and also provides new elements for a better image understanding. The proposed model was validated using image processing and statistical techniques. Results showed low error rates, demonstrating the accuracy of the model.

  6. 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.

  7. Primary adenocarcinoma of ureter: A rare histopathological variant

    Directory of Open Access Journals (Sweden)

    Prekshi Chaudhary

    2016-01-01

    Full Text Available Primary carcinoma of ureter is an uncommon malignancy. Of which, mostly are transitional cell carcinomas followed by squamous cell carcinomas and adenocarcinomas being the rarest histopathology encountered. We report a case of adenocarcinoma ureter in a middle-aged male along with its clinical scenario. A 62-year-old male, presented with complaints of lower urinary tract symptoms. Computerized tomography urogram showed a soft tissue lesion at the right ureterovesical junction. Cystoscopic biopsy reported villous adenoma. Diethylene triamine pentaacetic acid scan reported nonfunctioning right kidney. He underwent laparoscopic right nephroureterectomy, and histopathology reported adenocarcinoma of the right lower third of ureter, with positive distal and close radial margins. The patient received external beam radiation to the postoperative bed and lymph nodes, and he is disease-free till date.

  8. Basic Histopathological Methods and Breast Lesion Types for Research.

    Science.gov (United States)

    Ouyang, Nengtai; Wang, Lin

    2016-01-01

    The in situ observation on the tissues, such as histopathology, immunohistochemistry (IHC), immunofluorescence (IF), and in situ hybridization (ISH), is one of the most important methods in the biomedical scientific research. In this chapter we introduce the most often used methods-hematoxylin and eosin (H&E) and double IF staining. H&E staining is used for general morphology by which the different pathological types of breast lesions are identified. The double IF staining is often used to study the protein-protein interaction on tissues for signaling mechanisms. This chapter also includes the histopathology of primary or simplified breast lesion types that is essential for applying the above methods and the reclassification of breast cancers by molecular markers.

  9. [Histopathologic diagnostics in endoprosthetics: periprosthetic neosynovialitis, hypersensitivity reaction, and arthrofibrosis].

    Science.gov (United States)

    Krenn, V; Otto, M; Morawietz, L; Hopf, T; Jakobs, M; Klauser, W; Schwantes, B; Gehrke, T

    2009-06-01

    The durability of endoprosthetic implants of the large joints has increased over the last decades. North American studies have shown a 10-year durability of 94% for prosthetic hip implants, and European studies have shown 10-year durabilities of 88-95%. Pathologists differentiate three etiological disease patterns for the"pathology of endoprosthetics" that lead to reduction of implant durability: 1) periprosthetic particle disease (aseptic loosening), 2) infection, and 3) arthrofibrosis. Four types of neosynovitis/periprosthetic membrane have been determined in a consensus classification: particle-induced type (type I), with a mean prosthesis durability (MPD) of 12 years; infectious type (type II), MPD 2.5 years; combined type (type III), MPD 4.2 years; and indeterminate type (type IV), MPD 5.5 years. There are three histopathologic degrees of arthrofibrosis; grade 1 always needs clinical information for diagnosis, whereas grades 2 and 3 are distinct histopathologic entities.

  10. [Histopathology of strobilocercosis found in the livers of white mouse.].

    Science.gov (United States)

    Aydin, Nasuhi Engin; Miman, Ozlem; Gül, Mehmet; Daldal, Nilgün

    2010-01-01

    The adult form of Taenia taeniaeformis is found in the intestine of the cat and cheetah. The larva form is called Strobilocercus fasciolaris and is found in rodents such as mice and rats. Our objective was to draw attention to that rare zoonosis, since it has already been reported in the literature as strobilocercosis in humans. During an experimental animal study conducted at Inonu University, some unexpected cystic formations were found in the livers of nine 6-8-month-old healthy white mice, which affected the conducted study negatively. These cystic formations were examined histopathologically. Prepared sections were stained with haemotoxylin eosin, periodic acid-Schiff and Masson trichrome stains, and examined by light microscopy. Strobilocercus fasciolaris larvae that curled towards cyst cavity and their hooks were seen. Plasma cells, macrophage, focus of eosinophilic infiltration and fibroblastic connective tissue were simultaneous found. In this paper, histopathological changes in intermediate hosts caused by Strobilocercus fasciolaris and other cestod larvae have been discussed.

  11. Pediatric Gastrointestinal Diseases in Nigeria: Histopathologic Analysis of 74 Cases

    OpenAIRE

    Abudu; Emmanuel Kunle; Oyebadeyo; Tope Yinka; Inyang-Etoh; Emmanuel Columba

    2013-01-01

    BACKGROUND: Children are vulnerable to a vast number of diseases including gastrointestinal disorders, which may be associated with life threatening complications that sometimes result in mortality especially if left untreated. OBJECTIVE: To establish the age and sex distribution of children in the study population as well as the histopathological characteristics of gastrointestinal diseases that occurred in those children who were aged 14years and below in Sagamu, Southwestern Nigeria. MATER...

  12. 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.

  13. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    OpenAIRE

    Mujeeburahiman Thottathil; Ashish Verma; Nischith D′souza; Altaf Khan

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too.

  14. Histopathological analysis of 177 cases with operated intracranial meningioma

    Directory of Open Access Journals (Sweden)

    Guner Menekse

    2013-02-01

    Full Text Available Purpose: Aim of this study is to evaluate histopathologic properties of patients with intracranial meningioma who were operated due to intracranial mass. Method: 177 cases diagnosed with intracranial meningioma were retrospectively examined in our clinic between the years of 2007-2012 and their age, sex, tumor localization, and histopathologic properties were analyzed. Results: 74.6% of 177 intracranial meningioma cases were females, 25.4% were males and the ratio of Male/Female was found 3.4/10. The age interval of the cases was between 12-105 years old. It was most frequently seen at the interval of 51-60. In histopathologic examination, 163 cases (92.1% were noted as WHO Grade I, 11 cases (6.2% were WHO Grade II, and 3 cases (1.7% were WHO Grade III. While meningotelial transitional, and psammomatous type was the most frequently seen in WHO Grade I, atypical meningioma was only dominant in Grade II. In WHO Grade II and III cases, dominance of the male sex was present. While 88.1% of the cases had supratentorial localization, 11.9% had infratentorial localization, 1 case had lateral ventricle localization. In 7 cases (3.9% of the series, multiple meningiomas were determined. Conclusion: In a series of 177 cases, intracranial meningiomas were seen between 51-60 years old and its most frequent localization was convexity. While Grade I cases were seen in the female sex, dominance of the male sex was present in Grade II and III cases. Additionally, all of multiple meningiomas detected were female cases. Meningotelial meningiomas constitute the most commonly seen subtype among Grade I cases. Key Words: Intracranial meningioma, histopathological classification, clinical study [Cukurova Med J 2013; 38(1.000: 41-59

  15. Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis

    Science.gov (United States)

    2016-05-09

    coverage. Mass spectral data was proc- essed using Thermo Proteome Discoverer 1.4. These peak lists were searched by Sequest against a rat database...of average linkage. Random forest classifier . Random forest analysis was used to identify the top genes that contribute most to the classifier per...both the Bioplex and the microar- ray data were used to build the classifier . Histopathology was used to categorize the animals as true positives or

  16. Morphometry in pathology: another look at diagnostic histopathology.

    Science.gov (United States)

    Collan, Y

    1984-11-01

    Histopathology is crucial for diagnostic and therapeutic decisions in many disease states. The created classifications, however, have not always allowed explicit recognition of diagnostic categories. So, considerable intra- and interobserver variations are possible under diagnostic circumstances. Better reproducibility can be reached by applying other than traditional methods. These include morphometry as well as special stains, electron microscopy and immunohistochemistry. Morphometry is basic in that in detects structural and morphological aberrations in samples prepared by other methods and without doubt brings the element of accuracy to support the diagnostic decision. Morphometric approach includes item classification and grading, point counting and intersection counting methods, and the use of various semiautomatic or automatic instruments. In statistical morphometry morphometrical parameters are collected from several disease cases. Such data reinforced with prognostic follow-ups are the basis for disease classification. Diagnostic morphometry, on the other hand, tries to study the sample of one individual and give relevant data for diagnostic decisions. Morphometric methods allow estimation of the limits of possible performance in histopathology, estimation of human performance in the diagnostic process and estimation of the influence of interfering human factors. Diagnostic decisions as well as decisions linked with therapy are basically probabilistic. Also the data collected by diagnostic morphometry should be linked with probabilistic estimates of the prognostic relevance of the findings. Education of histopathology should be developed to meet these demands, both at elementary medical level and at postgraduate medical level. Education of morphometry can be incorporated into the medical curricula as shown by the experience at the University of Kuopio where aspects of morphometry are taught during histopathology course and special postgraduate courses have

  17. Intravascular papillary endothelial hyperplasia: An unusual histopathological entity.

    Science.gov (United States)

    Mahapatra, Qury S; Sahai, Kavita; Malik, Ajay; Mani, N S

    2015-01-01

    Intravascular papillary endothelial hyperplasia (Masson's tumor) is a benign lesion of the skin and subcutaneous tissue consisting of a reactive proliferation of endothelial cells with papillary formations related to a thrombus. It poses a diagnostic challenge as the clinical signs and symptoms are nonspecific and may mimic a soft tissue sarcoma. The diagnosis is based on histopathology. Here we report two cases of Masson's hemangioma occurring on the upper lip and on the left hand.

  18. Intravascular papillary endothelial hyperplasia: An unusual histopathological entity

    Directory of Open Access Journals (Sweden)

    Qury S Mahapatra

    2015-01-01

    Full Text Available Intravascular papillary endothelial hyperplasia (Masson′s tumor is a benign lesion of the skin and subcutaneous tissue consisting of a reactive proliferation of endothelial cells with papillary formations related to a thrombus. It poses a diagnostic challenge as the clinical signs and symptoms are nonspecific and may mimic a soft tissue sarcoma. The diagnosis is based on histopathology. Here we report two cases of Masson′s hemangioma occurring on the upper lip and on the left hand.

  19. Effect of Hedera helix on lung histopathology in chronic asthma.

    Directory of Open Access Journals (Sweden)

    Arzu Babayigit Hocaoglu

    2012-12-01

    Full Text Available 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.

  20. The relation between dermoscopy and histopathology of basal cell carcinoma*

    Science.gov (United States)

    Emiroglu, Nazan; Cengiz, Fatma Pelin; Kemeriz, Funda

    2015-01-01

    BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. PMID:26131865

  1. A Histopathological Study of the so-called Buruli ulcer

    OpenAIRE

    山下, 裕人; 千馬, 正敬; 板倉, 英世

    1980-01-01

    A histopathological study of the so-called "Buruli ulcer" was reported. The patient was a 10-year-old African boy in Kenya suffering from ulcer formation. The ulcer was 10cm in diameter and located over the left hip. It was undermined and covered by overhanged epithelia at the ulcer edge. There was edema or lytic change in the dermis which formed gaps between the epidermis and dermis in adjacent regions. Microscopically, inflammatory cells infiltration, granulation tissue, fibrosis, and sever...

  2. A histopathological and electron microscopical observation of urticaria pigmentosa

    Directory of Open Access Journals (Sweden)

    Ke-jian Zhu

    1990-01-01

    Full Text Available In a case of urticaria pigmentosa, histopathological and electron microscopical observation of skin lesions before and after dermatographism were compared. The results showed that the shape, membranes, nuclei and granules of mast cells in the lesions before and after dermatographism are different. The prognosis, the clinical significance of dermato-graphism test and the pattern of degranulation in urticaria pigmentosa are discussed.

  3. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    Science.gov (United States)

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-11-14

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.

  4. 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.

  5. 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.

  6. Histopathological audit of 373 nononcological hysterectomies in a teaching hospital.

    Science.gov (United States)

    Tiwana, Kanwardeep Kaur; Nibhoria, Sarita; Monga, Tanvi; Phutela, Richa

    2014-01-01

    Hysterectomy, the most common gynecological surgery, provides a definitive cure to various diseases like DUB (dysfunctional uterine bleeding), leiomyoma, adenomyosis, chronic pelvic pain, prolapse, and malignancy. However, with advent of effective medical and conservative treatment modalities for nononcological causes it is now posing question mark on justification of hysterectomy. Therefore, an audit is required to assess the correlation between preoperative diagnosis and histopathological examination of specimen for justification of the procedure. In this study over period of one year (April 2013 to March 2014) 373 hysterectomies specimens were received in the department of pathology for nononcological causes. The age of patients ranged from 22 to 85 years with mean 45 ± 9.2 years. All cases were divided into five categories on the basis of age and audit was done. In this study the most common finding was leiomyoma (43.7%) followed by adenomyosis (19.3%). Almost 50% of hysterectomies causes were justified as preoperative diagnosis matched with histopathology. Cohen kappa statistics were used to measure agreement between preoperative and postoperative histopathological diagnosis which was found to be fair with κ value being 0.36. This study highlights that regular audit of surgeries can help improve quality of health care services and provide safe conservative option to patients.

  7. Weakly supervised histopathology cancer image segmentation and classification.

    Science.gov (United States)

    Xu, Yan; Zhu, Jun-Yan; Chang, Eric I-Chao; Lai, Maode; Tu, Zhuowen

    2014-04-01

    Labeling a histopathology image as having cancerous regions or not is a critical task in cancer diagnosis; it is also clinically important to segment the cancer tissues and cluster them into various classes. Existing supervised approaches for image classification and segmentation require detailed manual annotations for the cancer pixels, which are time-consuming to obtain. In this paper, we propose a new learning method, multiple clustered instance learning (MCIL) (along the line of weakly supervised learning) for histopathology image segmentation. The proposed MCIL method simultaneously performs image-level classification (cancer vs. non-cancer image), medical image segmentation (cancer vs. non-cancer tissue), and patch-level clustering (different classes). We embed the clustering concept into the multiple instance learning (MIL) setting and derive a principled solution to performing the above three tasks in an integrated framework. In addition, we introduce contextual constraints as a prior for MCIL, which further reduces the ambiguity in MIL. Experimental results on histopathology colon cancer images and cytology images demonstrate the great advantage of MCIL over the competing methods.

  8. Histopathology of fathead minnow (Pimephales promelas) exposed to hydroxylated fullerenes.

    Science.gov (United States)

    Jovanović, Boris; Whitley, Elizabeth M; Palić, Dušan

    2014-11-01

    Hydroxylated fullerenes are reported to be very strong antioxidants, acting to quench reactive oxygen species, thus having strong potential for important and widespread applications in innovative therapies for a variety of disease processes. However, their potential for toxicological side effects is still largely controversial and unknown. Effects of hydroxylated fullerenes C60(OH)24 on the fathead minnow (Pimephales promelas) were investigated microscopically after a 72-hour (acute) exposure by intraperitoneal injection of 20 ppm of hydroxylated fullerenes per gram of body mass. Cumulative, semi-quantitative histopathologic evaluation of brain, liver, anterior kidney, posterior kidney, skin, coelom, gills and the vestibuloauditory system revealed significant differences between control and hydroxylated fullerene-treated fish. Fullerene-treated fish had much higher cumulative histopathology scores. Histopathologic changes included loss of cellularity in the interstitium of the kidney, a primary site of haematopoiesis in fish, and loss of intracytoplasmic glycogen in liver. In the coelom, variable numbers of leukocytes, including many macrophages and fewer heterophils and rodlet cells, were admixed with the nanomaterial. These findings raise concern about in vivo administration of hydroxylated fullerenes in experimental drugs and procedures in human medicine, and should be investigated in more detail.

  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. 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.

  11. Histopathological Audit of 373 Nononcological Hysterectomies in a Teaching Hospital

    Directory of Open Access Journals (Sweden)

    Kanwardeep Kaur Tiwana

    2014-01-01

    Full Text Available Hysterectomy, the most common gynecological surgery, provides a definitive cure to various diseases like DUB (dysfunctional uterine bleeding, leiomyoma, adenomyosis, chronic pelvic pain, prolapse, and malignancy. However, with advent of effective medical and conservative treatment modalities for nononcological causes it is now posing question mark on justification of hysterectomy. Therefore, an audit is required to assess the correlation between preoperative diagnosis and histopathological examination of specimen for justification of the procedure. In this study over period of one year (April 2013 to March 2014 373 hysterectomies specimens were received in the department of pathology for nononcological causes. The age of patients ranged from 22 to 85 years with mean 45±9.2 years. All cases were divided into five categories on the basis of age and audit was done. In this study the most common finding was leiomyoma (43.7% followed by adenomyosis (19.3%. Almost 50% of hysterectomies causes were justified as preoperative diagnosis matched with histopathology. Cohen kappa statistics were used to measure agreement between preoperative and postoperative histopathological diagnosis which was found to be fair with κ value being 0.36. This study highlights that regular audit of surgeries can help improve quality of health care services and provide safe conservative option to patients.

  12. Histopathological Image Classification Using Discriminative Feature-Oriented Dictionary Learning.

    Science.gov (United States)

    Vu, Tiep Huu; Mousavi, Hojjat Seyed; Monga, Vishal; Rao, Ganesh; Rao, U K Arvind

    2016-03-01

    In histopathological image analysis, feature extraction for classification is a challenging task due to the diversity of histology features suitable for each problem as well as presence of rich geometrical structures. In this paper, we propose an automatic feature discovery framework via learning class-specific dictionaries and present a low-complexity method for classification and disease grading in histopathology. Essentially, our Discriminative Feature-oriented Dictionary Learning (DFDL) method learns class-specific dictionaries such that under a sparsity constraint, the learned dictionaries allow representing a new image sample parsimoniously via the dictionary corresponding to the class identity of the sample. At the same time, the dictionary is designed to be poorly capable of representing samples from other classes. Experiments on three challenging real-world image databases: 1) histopathological images of intraductal breast lesions, 2) mammalian kidney, lung and spleen images provided by the Animal Diagnostics Lab (ADL) at Pennsylvania State University, and 3) brain tumor images from The Cancer Genome Atlas (TCGA) database, reveal the merits of our proposal over state-of-the-art alternatives. Moreover, we demonstrate that DFDL exhibits a more graceful decay in classification accuracy against the number of training images which is highly desirable in practice where generous training is often not available.

  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. Acute phenanthrene toxicity to juvenile diploid and triploid African catfish (Clarias gariepinus): Molecular, biochemical, and histopathological alterations.

    Science.gov (United States)

    Karami, Ali; Romano, Nicholas; Hamzah, Hazilawati; Simpson, Stuart L; Yap, Chee Kong

    2016-05-01

    Information on the biological responses of polyploid animals towards environmental contaminants is scarce. This study aimed to compare reproductive axis-related gene expressions in the brain, plasma biochemical responses, and the liver and gill histopathological alterations in diploid and triploid full-sibling juvenile African catfish (Clarias gariepinus). Fish were exposed for 96 h to one of the two waterborne phenanthrene (Phe) concentrations [mean measured (SD): 6.2 (2.4) and 76 (4.2) μg/L]. In triploids, exposure to 76 μg/L Phe increased mRNA level of fushi tarazu-factor 1 (ftz-f1). Expression of tryptophan hydroxylase2 (tph2) was also elevated in both ploidies following the exposure to 76 μg/L Phe compared to the solvent control. In triploids, 76 μg/L Phe increased plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels compared to the other Phe-exposed group. It also elevated lactate and glucose contents relative to the other groups. In diploids, however, biochemical biomarkers did not change. Phenanthrene exposures elevated glycogen contents and the prevalence of histopathological lesions in the liver and gills of both ploidies. This study showed substantial differences between diploids and triploids on biochemical and molecular biomarker responses, but similar histopathological alterations following acute Phe exposures.

  15. How to repair an episiotomy.

    Science.gov (United States)

    Steen, Mary; Cummins, Bernie

    2016-02-17

    Rationale and key points Skilful repair of an episiotomy is an important aspect of maternal health care. It is essential that midwives and doctors have the knowledge and skills to undertake this procedure in a safe and effective manner. ▶ An episiotomy should be repaired promptly to reduce blood loss and prevent infection. ▶ Repair of an episiotomy is undertaken in three stages: repair of the vaginal mucosa, repair of the muscle layer and repair of the skin layer. ▶ Adequate pain relief should be provided before suturing. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. Why a rectal examination is recommended before and following repair of an episiotomy. 2. What you would do to improve your suturing skills. 3. The factors that may prevent or delay an episiotomy from healing. Subscribers can upload their reflective accounts at rcni.com/portfolio .

  16. DNA repair in Chromobacterium violaceum.

    Science.gov (United States)

    Duarte, Fábio Teixeira; Carvalho, Fabíola Marques de; Bezerra e Silva, Uaska; Scortecci, Kátia Castanho; Blaha, Carlos Alfredo Galindo; Agnez-Lima, Lucymara Fassarella; Batistuzzo de Medeiros, Silvia Regina

    2004-03-31

    Chromobacterium violaceum is a Gram-negative beta-proteobacterium that inhabits a variety of ecosystems in tropical and subtropical regions, including the water and banks of the Negro River in the Brazilian Amazon. This bacterium has been the subject of extensive study over the last three decades, due to its biotechnological properties, including the characteristic violacein pigment, which has antimicrobial and anti-tumoral activities. C. violaceum promotes the solubilization of gold in a mercury-free process, and has been used in the synthesis of homopolyesters suitable for the production of biodegradable polymers. The complete genome sequence of this organism has been completed by the Brazilian National Genome Project Consortium. The aim of our group was to study the DNA repair genes in this organism, due to their importance in the maintenance of genomic integrity. We identified DNA repair genes involved in different pathways in C. violaceum through a similarity search against known sequences deposited in databases. The phylogenetic analyses were done using programs of the PHILYP package. This analysis revealed various metabolic pathways, including photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, recombinational repair, and the SOS system. The similarity between the C. violaceum sequences and those of Neisserie miningitidis and Ralstonia solanacearum was greater than that between the C. violaceum and Escherichia coli sequences. The peculiarities found in the C. violaceum genome were the absence of LexA, some horizontal transfer events and a large number of repair genes involved with alkyl and oxidative DNA damage.

  17. Relationships between chromatin remodeling and DNA damage repair induced by 8-methoxypsoralen and UVA in yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Lavínia Almeida Cruz

    2012-01-01

    Full Text Available Eukaryotic cells have developed mechanisms to prevent genomic instability, such as DNA damage detection and repair, control of cell cycle progression and cell death induction. The bifunctional compound furocumarin 8-methoxy-psoralen (8-MOP is widely used in the treatment of various inflammatory skin diseases. In this review, we summarize recent data about the role of chromatin remodeling in the repair of DNA damage induced by treatment with 8-methoxypsoralen plus UVA (8-MOP+UVA, focusing on repair proteins in budding yeast Saccharomyces cerevisiae, an established model system for studying DNA repair pathways. The interstrand crosslinks (ICL formed by the 8-MOP+UVA treatment are detrimental lesions that can block transcription and replication, leading to cell death if not repaired. Current data show the involvement of different pathways in ICL processing, such as nucleotide excision repair (NER, base excision repair (BER, translesion repair (TLS and double-strand break repair. 8-MOP+UVA treatment in yeast enhances the expression of genes involved in the DNA damage response, double strand break repair by homologous replication, as well as genes related to cell cycle regulation. Moreover, alterations in the expression of subtelomeric genes and genes related to chromatin remodeling are consistent with structural modifications of chromatin relevant to DNA repair. Taken together, these findings indicate a specific profile in 8-MOP+UVA responses related to chromatin remodeling and DNA repair.

  18. 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...

  19. Bone repair and stem cells.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2016-10-01

    Bones are an important component of vertebrates; they grow explosively in early life and maintain their strength throughout life. Bones also possess amazing capabilities to repair-the bone is like new without a scar after complete repair. In recent years, a substantial progress has been made in our understanding on mammalian bone stem cells. Mouse genetic models are powerful tools to understand the cell lineage, giving us better insights into stem cells that regulate bone growth, maintenance and repair. Recent findings about these stem cells raise new questions that require further investigations.

  20. 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.

  1. Laparoscopic repair of incisional hernia.

    Science.gov (United States)

    Lau, H; Lee, F; Patil, N G

    2001-09-01

    A 75-year-old man developed an incisional hernia over the upper abdomen following a wedge resection of a gastric stromal tumour in 1996. This is the first published report of a successful repair of an incisional hernia via a laparoscopic intraperitoneal on-lay technique using GORE-TEX DualMesh material in Hong Kong. Compared with conventional open repair of incisional hernia, long incisions and wound tension are avoided using the laparoscopic approach. This translates into a reduced risk of wound-related complications and facilitates recovery. In selected cases, minimally invasive surgery is a safe technique for the repair of incisional hernias.

  2. [Inguinal and femoral hernia repair].

    Science.gov (United States)

    Geissler, B; Anthuber, M

    2011-05-01

    With an incidence of 200,000 new cases per year in Germany, inguinal hernia has a significant socioeconomic impact. The 2009 guidelines from the European Hernia Society established treatment recommendations. Hernia repair is based on reinforcing the posterior wall of the inguinal canal by suture or mesh repair by an anterior or posterior approach. Lightweight mesh reduces recurrence rates and is the treatment of choice even in primary hernias. Laparoscopic hernia repair is associated with specific risks but is superior in postoperative pain and earlier return to work.

  3. Mononuclear Cells and Vascular Repair in HHT

    Directory of Open Access Journals (Sweden)

    Calinda eDingenouts

    2015-03-01

    Full Text Available Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber disease is a rare genetic vascular disorder known for its endothelial dysplasia causing arteriovenous malformations and severe bleedings. HHT-1 and HHT-2 are the most prevalent variants and are caused by heterozygous mutations in endoglin and ALK1, respectively. An undervalued aspect of the disease is that HHT patients experience persistent inflammation. Although endothelial and mural cells have been the main research focus trying to unravel the mechanism behind the disease, wound healing is a process with a delicate balance between inflammatory and vascular cells. Inflammatory cells are part of the mononuclear cells (MNCs fraction, and can, next to eliciting an immune response, also have angiogenic potential. This biphasic effect of MNC can hold a promising mechanism to further elucidate treatment strategies for HHT patients. Before MNC are able to contribute to repair, they need to home to and retain in ischemic and damaged tissue. Directed migration (homing of mononuclear cells following tissue damage is regulated by the stromal cell derived factor 1 (SDF1. MNCs that express the C-X-C chemokine receptor 4 (CXCR4 migrate towards the tightly regulated gradient of SDF1. This directed migration of monocytes and lymphocytes can be inhibited by dipeptidyl peptidase 4 (DPP4. Interestingly, MNC of HHT patients express elevated levels of DPP4 and show impaired homing towards damaged tissue. Impaired homing capacity of the MNCs might therefore contribute to the impaired angiogenesis and tissue repair observed in HHT patients. This review summarizes recent studies regarding the role of MNCs in the etiology of HHT and vascular repair, and evaluates the efficacy of DPP4 inhibition in tissue integrity and repair.

  4. Potentials of Endogenous Neural Stem cells in Cortical Repair

    Directory of Open Access Journals (Sweden)

    Bhaskar eSaha

    2012-04-01

    Full Text Available In the last few decades great thrust has been put in the area of regenerative neurobiology research to combat brain injuries and neurodegenerative diseases. The recent discovery of neurogenic niches in the adult brain has led researchers to study how to mobilize these cells to orchestrate an endogenous repair mechanism. The brain can minimize injury-induced damage by means of an immediate glial response and by initiating repair mechanisms that involve the generation and mobilization of new neurons to the site of injury where they can integrate into the existing circuit. This review highlights the current status of research in this field. Here, we discuss the changes that take place in the neurogenic milieu following injury. We will focus, in particular, on the cellular and molecular controls that lead to increased proliferation in the Sub ventricular Zone (SVZ as well as neurogenesis. We will also concentrate on how these cellular and molecular mechanisms influence the migration of new cells to the affected area and their differentiation into neuronal/glial lineage that initiate the repair mechanism. Next, we will discuss some of the different factors that limit/retard the repair process and highlight future lines of research that can help to overcome these limitations. A clear understanding of the underlying molecular mechanisms and physiological changes following brain damage and the subsequent endogenous repair should help us develop better strategies to repair damaged brains.

  5. 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

  6. Large myelomeningocele repair

    Directory of Open Access Journals (Sweden)

    Farideh Nejat

    2011-01-01

    Full Text Available Background: Wound closure is accomplished in most cases of myelomeningocele (MMC by undermining of the skin edges surrounding the defect. However, large defects cannot be closed reliably by this simple technique. Due to the technical challenge associated with large MMC, surgeons have devised different methods for repairing large defects. In this paper, we report our experience of managing large defects, which we believe bears a direct relationship to decrease the incidence of wound complications. Materials and Methods: Forty children with large MMCs underwent surgical repair and represent our experience. We recommend using all hairy skin around the defect as a way to decrease the tension on the edges of the wound and the possible subsequent necrosis. It is our experience that vertical incision on one or two flanks parallel to the midline can decrease the tension of the wound. Moreover, ventriculo-peritoneal shunting for children who developed hydrocephalus was performed simultaneously, which constitutes another recommendation for preventing fluid collection and build up of pressure on the wound. Results: Patients in this study were in the age range of 2 days to 8 years. The most common location of MMC was in the thoracolumbar area. All but four patients had severe weakness in lower extremities. We used as much hairy skin around the MMC sac as possible in all cases. Vertical incisions on one or both flanks and simultaneous shunt procedure were performed in 36 patients. We treated children with large MMC defects with acceptable tension-free closure. Nonetheless, three patients developed superficial skin infection and partial wound dehiscence, and they were managed conservatively. Conclusions: We recommend using all hairy skin around the MMC defect for closure of large defects. In cases that were expected to be at a higher risk to develop dehiscence release incisions on one or two flanks towards the fascia were found to be useful. Simultaneous

  7. 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.

  8. A Two-Unit Cold Standby Repairable System with One Replaceable Repair Facility and Delay Repair:Some Reliability Problems

    Institute of Scientific and Technical Information of China (English)

    WEI Ying-yuan; TANG Ying-hui

    2004-01-01

    This paper considers a two-unit same cold standby repairable system with a replaceable repair facility and delay repair .The failure time of unit is assumed to follow exponential distribution , and the repair time and delay time of failed unit are assumed to follow arbitrary distributions , whereas the failure and replacement time distributions of the repair facility are exponential and arbitrary . By using the Markov renewal process theory, some primary reliability quantities of the system are obtained.

  9. Chronic pain after open mesh and sutured repair of indirect inguinal hernia in young males

    DEFF Research Database (Denmark)

    Bay-Nielsen, M; Nilsson, E; Nordin, P;

    2004-01-01

    males operated on for an indirect inguinal hernia with a Lichtenstein mesh repair, Shouldice or Marcy (annulorrhaphy) repair. METHODS: This was a postal questionnaire study carried out within the Danish and Swedish Hernia Database Collaboration. Some 2612 patients responded (response rate 80.9 per cent...... it as worse after than before surgery, and 56.6 per cent stated that it interfered with social activities. CONCLUSION: Chronic pain is common after primary inguinal hernia repair in young males, but there is no difference in the pain associated with open mesh and non-mesh repair....

  10. 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...

  11. 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...

  12. 40 CFR 63.1005 - Leak repair.

    Science.gov (United States)

    2010-07-01

    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... 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...

  13. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    Directory of Open Access Journals (Sweden)

    Erhong Meng

    2015-07-01

    Full Text Available Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair. Aberrant activation of the Hedgehog (Hh signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  14. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Erhong; Hanna, Ann; Samant, Rajeev S.; Shevde, Lalita A., E-mail: lsamant@uab.edu [Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, WTI320D, 1824 6th Avenue South, Birmingham, AL 35233 (United States)

    2015-07-21

    Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  15. New tools to study DNA double-strand break repair pathway choice.

    Directory of Open Access Journals (Sweden)

    Daniel Gomez-Cabello

    Full Text Available A broken DNA molecule is difficult to repair, highly mutagenic, and extremely cytotoxic. Such breaks can be repaired by homology-independent or homology-directed mechanisms. Little is known about the network that controls the repair pathway choice except that a licensing step for homology-mediated repair exists, called DNA-end resection. The choice between these two repair pathways is a key event for genomic stability maintenance, and an imbalance of the ratio is directly linked with human diseases, including cancer. Here we present novel reporters to study the balance between both repair options in human cells. In these systems, a double-strand break can be alternatively repaired by homology-independent or -dependent mechanisms, leading to the accumulation of distinct fluorescent proteins. These reporters thus allow the balance between both repair pathways to be analyzed in different experimental setups. We validated the reporters by analyzing the effect of protein downregulation of the DNA end resection and non-homologous end-joining pathways. Finally, we analyzed the role of the DNA damage response on double-strand break (DSB repair mechanism selection. Our reporters could be used in the future to understand the roles of specific factors, whole pathways, or drugs in DSB repair pathway choice, or for genome-wide screening. Moreover, our findings can be applied to increase gene-targeting efficiency, making it a beneficial tool for a broad audience in the biological sciences.

  16. Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

    Science.gov (United States)

    Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

    2014-12-01

    Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability.

  17. Dual daughter strand incision is processive and increases the efficiency of DNA mismatch repair

    NARCIS (Netherlands)

    N. Hermans (Nicolaas); C. Laffeber; M. Cristovao (Michele); Artola-Borán, M. (Mariela); Mardenborough, Y. (Yannicka); P. Ikpa (Pauline); Jaddoe, A. (Aruna); H.H.K. Winterwerp (Herrie); C. Wyman (Claire); J. Jiricny (Josef); R. Kanaar (Roland); P. Friedhoff (Peter); J.H.G. Lebbink (Joyce)

    2016-01-01

    textabstractDNA mismatch repair (MMR) is an evolutionarily-conserved process responsible for the repair of replication errors. In Escherichia coli, MMR is initiated by MutS and MutL, which activate MutH to incise transiently-hemimethylated GATC sites. MMR efficiency depends on the distribution of th

  18. Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair.

    Science.gov (United States)

    Rupp, W Dean

    2013-12-13

    The discovery of nucleotide excision repair in 1964 showed that DNA could be repaired by a mechanism that removed the damaged section of a strand and replaced it accurately by using the remaining intact strand as the template. This result showed that DNA could be actively metabolized in a process that had no precedent. In 1968, experiments describing postreplication repair, a process dependent on homologous recombination, were reported. The authors of these papers were either at Yale University or had prior Yale connections. Here we recount some of the events leading to these discoveries and consider the impact on further research at Yale and elsewhere.

  19. Construction, repair and maintenance

    Energy Technology Data Exchange (ETDEWEB)

    Hinger, R. [Terasen Pipelines, Calgary, AB (Canada); Wong, P. [KC Integrity Corp., Calgary, AB (Canada); Yeomans, M.; Glover, A. [TransCanada PipeLines Ltd., Calgary, AB (Canada)

    2003-07-01

    The presentations by Working Group 4 focused on construction, repair and maintenance of pipelines with particular reference to high-strength steels and their applications for natural gas transmission pipelines. Discussions focused on how technology can be used to provide cost-effective design and construction solutions for long distance pipelines in a manner that does not compromise safety and reliability. The role that carbon plays in increasing the toughness of steel was also discussed. A few fundamental changes in steel production technology and a reduction in carbon content can result in a simultaneous increase in strength and toughness of steels. The cost impact of this technology was summarized. It was concluded that high strength steels offer effective solutions to deliver cost-effective pipelines to transport natural gas from northern basins. This session also presented pipeline routes that transport diluted bitumens from the Athabasca Oil Sands Project and the Muskeg River Mine to upgrader facilities in Alberta. Construction issues included design conservatism, water course crossings, winter construction, winter ditching, and public consultation. Examples of high strength steel pipe applications were also included with reference to experience gained by TransCanada and Corridor Pipeline. tabs., figs.

  20. Experimental acrylonitrile butadiene styrene and polyamide evisceration implant: a rabbit clinical and histopathology study

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    D.C. Gomes Júnior

    Full Text Available ABSTRACT The purpose of this study was to evaluate acrylonitrile butadiene styrene (ABS and polyamide implants in rabbits submitted to evisceration at the macroscopic and microstructure level and to assess clinical response and histopathological changes as well. For the experimental study implants of 12mm diameter were prepared by rapid prototyping, weighed and the outer and inner surfaces evaluated macroscopically and by electron microscopy. In addition, a compression test was performed and ultrastructural damage was then determined. After evisceration of the left eyeball, nine New Zealand rabbits received ABS implants and nine others received polyamide implants. The animals were assessed daily for 15 days after surgery and every seven days until the end of the study (90 days. Histopathological evaluation was performed at 15, 45 and 90 days after surgery. The ABS implants weighed approximately 0.44g, while the polyamide ones weighed 0.61g. Scanning electron microscopy demonstrated that the ABS implants had regular-sized, equidistant micropores, while the polyamide ones showed micropores of various sizes. The force required to fracture the ABS implant was 14.39 ±0.60 Mpa, while for the polyamide one, it was 16.80 ±1.05 Mpa. Fifteen days after surgery, we observed centripetal tissue infiltration and scarce inflammatory infiltrate. Implants may be used in the filling of anophthalmic cavities, because they are inert, biocompatible and allow tissue integration.