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  1. Article ; Online: Interference of mismatch and base excision repair during the processing of adjacent U/G mispairs may play a key role in somatic hypermutation.

    Schanz, Silvia / Castor, Dennis / Fischer, Franziska / Jiricny, Josef

    Proceedings of the National Academy of Sciences of the United States of America

    2009  Volume 106, Issue 14, Page(s) 5593–5598

    Abstract: ... recombination of Ig genes, where activation-induced cytidine deaminase (AID) generates multiple U/G mismatches ...

    Abstract In eukaryotic mismatch repair (MMR), degradation of the error-containing strand initiates at nicks or gaps that can be up to a kilobase away from the mispair. These discontinuities may be the ends of Okazaki fragments or the 3'-termini of the leading strands during replication, whereas the termini of invading strands may fulfill this role during recombination. Here we show that, in extracts of human cells, MMR can initiate also at sites of ongoing base excision repair. Although unlikely under normal circumstances, this situation may arise in vivo during somatic hypermutation (SHM) and class switch recombination of Ig genes, where activation-induced cytidine deaminase (AID) generates multiple U/G mismatches in the variable or switch regions. Uracil should normally be excised by base excision repair (BER), but we show here that MMR proteins activated by a nearby mismatch interfere with uracil processing to generate long single-stranded gaps. We postulate that, in a subset of the repair events, filling-in of the MMR-generated gaps might be catalyzed by the error-prone polymerase-eta, rather than by the high-fidelity polymerase-delta. Because polymerase-eta has a propensity to misinsertions opposite adenine residues, the above mechanism would help explain why SHM affects not only C/G, but also A/T base pairs.
    MeSH term(s) Cytidine Deaminase ; DNA Mismatch Repair ; DNA Repair ; DNA-Directed DNA Polymerase ; Genes, Immunoglobulin ; Guanosine ; Humans ; Immunoglobulin Class Switching/genetics ; Recombination, Genetic ; Somatic Hypermutation, Immunoglobulin/genetics ; Uracil
    Chemical Substances Guanosine (12133JR80S) ; Uracil (56HH86ZVCT) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Rad30 protein (EC 2.7.7.7) ; AICDA (activation-induced cytidine deaminase) (EC 3.5.4.-) ; Cytidine Deaminase (EC 3.5.4.5)
    Language English
    Publishing date 2009-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0901726106
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  2. Article: Interference of mismatch and base excision repair during the processing of adjacent U/G mispairs may play a key role in somatic hypermutation

    Schanz, Silvia / Castor, Dennis / Fischer, Franziska / Jiricny, Josef

    Proceedings of the National Academy of Sciences of the United States of America. 2009 Apr. 7, v. 106, no. 14

    2009  

    Abstract: ... recombination of Ig genes, where activation-induced cytidine deaminase (AID) generates multiple U/G mismatches ...

    Abstract In eukaryotic mismatch repair (MMR), degradation of the error-containing strand initiates at nicks or gaps that can be up to a kilobase away from the mispair. These discontinuities may be the ends of Okazaki fragments or the 3'-termini of the leading strands during replication, whereas the termini of invading strands may fulfill this role during recombination. Here we show that, in extracts of human cells, MMR can initiate also at sites of ongoing base excision repair. Although unlikely under normal circumstances, this situation may arise in vivo during somatic hypermutation (SHM) and class switch recombination of Ig genes, where activation-induced cytidine deaminase (AID) generates multiple U/G mismatches in the variable or switch regions. Uracil should normally be excised by base excision repair (BER), but we show here that MMR proteins activated by a nearby mismatch interfere with uracil processing to generate long single-stranded gaps. We postulate that, in a subset of the repair events, filling-in of the MMR-generated gaps might be catalyzed by the error-prone polymerase-η, rather than by the high-fidelity polymerase-δ. Because polymerase-η has a propensity to misinsertions opposite adenine residues, the above mechanism would help explain why SHM affects not only C/G, but also A/T base pairs.
    Keywords DNA repair ; adenine ; base pair mismatch ; cytidine deaminase ; genes ; humans ; proteins ; uracil
    Language English
    Dates of publication 2009-0407
    Size p. 5593-5598.
    Publishing place National Academy of Sciences
    Document type Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0901726106
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  3. Article ; Online: Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey.

    Hofer, Kevin D / Bühler, Marco M / Roncador, Marco / Rechsteiner, Markus / Maggio, Ewerton M / Tchinda, Joëlle / Schanz, Urs / Haralambieva, Eugenia / Widmer, Corinne C

    Leukemia & lymphoma

    2024  , Page(s) 1–8

    Abstract: There is increasing evidence that therapy-related acute lymphoblastic leukemia (trALL) resulting from chemo- and/or radiotherapy represents a distinct entity. However, apart ... ...

    Abstract There is increasing evidence that therapy-related acute lymphoblastic leukemia (trALL) resulting from chemo- and/or radiotherapy represents a distinct entity. However, apart from
    Language English
    Publishing date 2024-02-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1042374-6
    ISSN 1029-2403 ; 1042-8194
    ISSN (online) 1029-2403
    ISSN 1042-8194
    DOI 10.1080/10428194.2024.2315171
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  4. Article ; Online: EXPOSURE OF A SERVICE TECHNICIAN REPAIRING A BIPLANE X-RAY SYSTEM.

    Elmiger, R / Schanz, U / Ott, B / Frei, D

    Radiation protection dosimetry

    2018  Volume 182, Issue 1, Page(s) 18–19

    Abstract: While repairing a biplane cardiovascular X-ray system in a hospital, a service technician accidentally activated the system's floor pedal. He continued his work under unnoticed exposure for about 5 min until the system alarm was automatically activated. ... ...

    Abstract While repairing a biplane cardiovascular X-ray system in a hospital, a service technician accidentally activated the system's floor pedal. He continued his work under unnoticed exposure for about 5 min until the system alarm was automatically activated. About 2 h after the exposure, the technician developed an erythema on parts of his left face and neck. The next day, he reported his incident to the competent authorities and was hospitalised in a unit specialised in treating heavily irradiated patients. Frequent blood analysis did not show any signs for a significant exposure to radiation. The Federal Office of Public Health then conducted extensive dose estimations. It could be shown that the dismounted collimator was always in front of the lateral X-ray tube, shielding the technician from the direct beam. The dose estimations came to the following conservative results: an effective dose of 5 mSv, a skin dose of 200 mSv, an eye lens dose of 100 mSv and an extremity dose (arm) of 700 mSv. The cause of the erythema remains unclear since the estimated doses are thought to be too low to induce any visible effect on the skin.
    MeSH term(s) Erythema/etiology ; Humans ; Lens, Crystalline/radiation effects ; Occupational Exposure/adverse effects ; Occupational Exposure/analysis ; Personnel, Hospital ; Phantoms, Imaging ; Radiation Dosage ; Radiation Protection/standards ; Radioactive Hazard Release ; Skin/radiation effects ; X-Rays/adverse effects
    Language English
    Publishing date 2018-09-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 225912-6
    ISSN 1742-3406 ; 0144-8420
    ISSN (online) 1742-3406
    ISSN 0144-8420
    DOI 10.1093/rpd/ncy131
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  5. Article ; Online: Thrombocytopaenia in cyanotic CHD.

    Danioth, Simona / Schanz, Urs / Greutmann, Matthias

    Cardiology in the young

    2020  Volume 31, Issue 3, Page(s) 429–434

    Abstract: Introduction: Thrombocytopaenia is common in adults with cyanotic heart disease. Our aim was to explore potential mechanisms for thrombocytopaenia in these vulnerable patients.: Methods: Adults with cyanotic heart defects were identified from our ... ...

    Abstract Introduction: Thrombocytopaenia is common in adults with cyanotic heart disease. Our aim was to explore potential mechanisms for thrombocytopaenia in these vulnerable patients.
    Methods: Adults with cyanotic heart defects were identified from our clinical database. Haemoglobin levels, platelet counts, and resting oxygen saturations were determined at baseline and during follow-up. Associations between patient characteristics and cardiac physiology with these parameters at baseline and during follow-up were analysed using regression models. Survival estimates were determined by the Kaplan-Meier method.
    Results: We included 79 patients (mean age 32.2 ± 12.4, 48 (61%) Eisenmenger syndrome, 20 (25%) Down syndrome). Mean oxygen saturation was 84.1 ± 5.9%; 38 (48%) had thrombocytopaenia. There was a strong inverse correlation between platelet count and haemoglobin level (R = -0.655, R2 = 0.429, p < 0.0001) and a weaker but significant positive correlation between platelet count and oxygen saturation (R = 0.345, R2 = 0.119, p = 0.002). There was a significant inverse correlation between decrease in platelet count and increase in haemoglobin level during follow-up (R = -0.401, R2 = 0.161, p = 0.001) but not to changes in oxygen saturation (R = 0.043, R2 = 0.002, p = 0.726). Survival estimates were lower for patients with thrombocytopaenia at baseline (log-rank test p < 0.0001).
    Conclusions: Our findings suggest a direct inverse correlation between platelet counts and haemoglobin levels in adults with cyanotic heart disease. Further studies are required to explore the mechanisms of thrombocytopaenia in cyanotic heart disease and its potential role as an independent marker of risk.
    MeSH term(s) Adult ; Cyanosis/etiology ; Eisenmenger Complex ; Heart Defects, Congenital/complications ; Humans ; Platelet Count ; Thrombocytopenia/complications ; Thrombocytopenia/epidemiology ; Young Adult
    Language English
    Publishing date 2020-12-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 1078466-4
    ISSN 1467-1107 ; 1047-9511
    ISSN (online) 1467-1107
    ISSN 1047-9511
    DOI 10.1017/S1047951120004230
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  6. Article ; Conference proceedings: Algorithm-Based Detection of Acute Kidney Injury According to Full KDIGO Criteria Including Urine Output following Cardiac Surgery: A Descriptive Analysis

    Schmid, N. / Ghinescu, M. / Schanz, M. / Christ, M. / Schricker, S. / Ketteler, M. / Alscher, M. D. / Franke, U. / Göbel, N.

    The Thoracic and Cardiovascular Surgeon

    2023  Volume 71, Issue S 01

    Event/congress 52nd Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery (DGTHG), Congress Center Hamburg, 2023-02-11
    Language English
    Publishing date 2023-01-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 800050-5
    ISSN 1439-1902 ; 0171-6425 ; 0946-4778 ; 0172-6137
    ISSN (online) 1439-1902
    ISSN 0171-6425 ; 0946-4778 ; 0172-6137
    DOI 10.1055/s-0043-1761716
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  7. Article: Verlängertes sommerliches Trockenfallen von Bächen gefährdet die Vorkommen der reliktischen Moose Tetrodontium repandum, Geocalyx graveolens und Harpanthus scutatus in Nordbayern

    Schanz, Mario / Meve, Ulrich / Feulner, Martin

    Herzogia. 2021 June 29, v. 34, no. 1

    2021  

    Abstract: Schanz, M., Meve, U. & Feulner, M. 2021. Prolonged summer drying of streams threatens the relict ...

    Abstract Schanz, M., Meve, U. & Feulner, M. 2021. Prolonged summer drying of streams threatens the relict mosses Tetrodontium repandum, Geocalyx graveolens and Harpanthus scutatus in northern Bavaria. – Herzogia 34: 173 –188. The deeply incised gorges and rock formations of the Rhätium in the west of Bayreuth are an outstanding habitat for bryophyte species with montane distributions such as Tetrodontium repandum, Geocalyx graveolens and Harpanthus scutatus. The special site requirements such as constantly wet microclimate (cold air congestion, high humidity, mostly sites along streams) and the high water capacity of the sandstone rocks are prerequisites for the occurrence of these relict mosses. Due to rapid climate change and its consequences such as increasing dry periods in the summer, prolonged drying of streams and rising temperatures, the question arises to which extent the survival of the investigated species is endangered. To investigate drought damage of the mosses, the population sizes and percentage of dead moss layers as well as exposition, slope, distance to the river and the accompanying species were examined. In addition, the microclimate was measured at three sites using data loggers that recorded temperature and humidity hourly over a period of five months. On average, moss mats of Tetrodontium repandum were reduced by drought damage to 31 % of their former size. Geocalyx graveolens was reduced by 9 %. Desiccation damage to Harpanthus scutatus could not be detected, probably due to rapid die-off after heat periods. The relative humidity at the investigated sites of Tetrodontium repandum was close to 100 % and the temperature was with about 3°C significantly below the comparative values of a reference site outside the gorge. Both parameters showed significantly lower fluctuations inside the gorge than outside. Geocalyx graveolens exhibited a significant increase in drought damage with increasing distance to the stream. Tetrodontium repandum also showed a significant negative correlation between population size and distance to the stream. In conclusion, this study identifies the prolongation of drought periods of streams as the main threat for the persistence of relict moss species. Furthermore, it outlines the importance of reducing the drainage of the environment for achieving both higher water storage in the landscape and shorter drought periods in the streams.
    Keywords Alces alces ; Bryophyta ; air ; climate change ; cold ; die-off ; drainage ; drought ; habitats ; heat ; landscapes ; microclimate ; mosses and liverworts ; population size ; relative humidity ; rivers ; sandstone ; streams ; summer ; temperature ; water storage ; Germany
    Language English
    Dates of publication 2021-0629
    Size p. 173-188.
    Publishing place Bryological and Lichenological Association for Central Europe (BLAM)
    Document type Article
    ZDB-ID 2754551-9
    ISSN 2700-2829 ; 0018-0971
    ISSN (online) 2700-2829
    ISSN 0018-0971
    DOI 10.13158/heia.34.1.2021.173
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  8. Article ; Online: Real-world outcomes in elderly ALL patients with and without allogeneic hematopoietic stem cell transplantation: a single-center evaluation over 10 years.

    Hofer, Kevin D / Schanz, Urs / Schwotzer, Rahel / Nair, Gayathri / Manz, Markus G / Widmer, Corinne C

    Annals of hematology

    2022  Volume 101, Issue 5, Page(s) 1097–1106

    Abstract: Elderly patients (EP) of 60 years and above with acute lymphoblastic leukemia (ALL) have a dismal prognosis, but pediatric-inspired chemotherapy and allogeneic stem cell transplantation (allo HCT) are used reluctantly due to limited data and historical ... ...

    Abstract Elderly patients (EP) of 60 years and above with acute lymphoblastic leukemia (ALL) have a dismal prognosis, but pediatric-inspired chemotherapy and allogeneic stem cell transplantation (allo HCT) are used reluctantly due to limited data and historical reports of high treatment-related mortality in EP. We analyzed 130 adult ALL patients treated at our center between 2009 and 2019, of which 26 were EP (range 60-76 years). Induction with pediatric-inspired protocols was feasible in 65.2% of EP and resulted in complete remission in 86.7% compared to 88.0% in younger patients (YP) of less than 60 years. Early death occurred in 6.7% of EP. Three-year overall survival (OS) for Ph - B-ALL was significantly worse for EP (n = 16) than YP (n = 64) with 30.0% vs 78.1% (p ≤ 0.001). Forty-nine patients received allo HCT including 8 EP, for which improved 3-year OS of 87.5% was observed, whereas EP without allo HCT died after a median of 9.5 months. In Ph + B-ALL, 3-year OS did not differ between EP (60.0%, n = 7) and YP (70.8%, n = 19). Non-relapse mortality and infection rate were low in EP (14.3% and 12.5%, respectively). Our data indicate that selected EP can be treated effectively and safely with pediatric regimens and might benefit from intensified therapy including allo HCT.
    MeSH term(s) Adult ; Aged ; Child ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Remission Induction ; Retrospective Studies
    Language English
    Publishing date 2022-02-19
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-022-04793-z
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  9. Book: ENDOKARDMYXOME

    Schanz, Urs

    NEUE ASPEKTE ZUR HISTOPATHOGENESE

    1984  

    Size S. 850-857
    Document type Book
    Note AUS: SCHWEIZ. MED. WOCHENSCHR. ; 114, 24, 1984. - ZUERICH, UNIV, DISS., 1984
    HBZ-ID HT002721495
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
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  10. Article ; Online: Autologous hematopoietic stem cell transplantation in multiple sclerosis: a global approval and availability review.

    Stathopoulos, P / Léger, K / Foege, M / Lutterotti, A / Müller, A / Schanz, U / Jelcic, I / Martin, R

    Bone marrow transplantation

    2021  Volume 56, Issue 7, Page(s) 1754–1756

    MeSH term(s) Hematopoietic Stem Cell Transplantation ; Humans ; Multiple Sclerosis/therapy ; Transplantation, Autologous
    Language English
    Publishing date 2021-04-06
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/s41409-021-01276-z
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