32 results on '"Redl E"'
Search Results
2. 12. Immunoscintigraphy (IS) with granulocyte antibodies for the detection of perioperative septic foci
- Author
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Kroiss, A., Sporn, P., Auinger, Ch., Redl, E., Kriwanek, S., Armbruster, Ch., and Neumayr, A.
- Published
- 1992
3. Comparative transcriptomics enlarges the toolkit of known developmental genes in mollusks
- Author
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Oliveira, André Luiz, Wollesen, Tim, Kristof, Alen, Scherholz, M., Redl, E., Todt, Christiane, Bleidorn, Christoph, Wanninger, A., Oliveira, André Luiz, Wollesen, Tim, Kristof, Alen, Scherholz, M., Redl, E., Todt, Christiane, Bleidorn, Christoph, and Wanninger, A.
- Abstract
Mollusks display a striking morphological disparity, including, among others, worm-like animals (the aplacophorans), snails and slugs, bivalves, and cephalopods. This phenotypic diversity renders them ideal for studies into animal evolution. Despite being one of the most species-rich phyla, molecular and in silico studies concerning specific key developmental gene families are still scarce, thus hampering deeper insights into the molecular machinery that governs the development and evolution of the various molluscan class-level taxa. Results: Next-generation sequencing was used to retrieve transcriptomes of representatives of seven out of the eight recent class-level taxa of mollusks. Similarity searches, phylogenetic inferences, and a detailed manual curation were used to identify and confirm the orthology of numerous molluscan Hox and ParaHox genes, which resulted in a comprehensive catalog that highlights the evolution of these genes in Mollusca and other metazoans. The identification of a specific molluscan motif in the Hox paralog group 5 and a lophotrochozoan ParaHox motif in the Gsx gene is described. Functional analyses using KEGG and GO tools enabled a detailed description of key developmental genes expressed in important pathways such as Hedgehog, Wnt, and Notch during development of the respective species. The KEGG analysis revealed Wnt8, Wnt11, and Wnt16 as Wnt genes hitherto not reported for mollusks, thereby enlarging the known Wnt complement of the phylum. In addition, novel Hedgehog (Hh)-related genes were identified in the gastropod Lottia cf. kogamogai, demonstrating a more complex gene content in this species than in other mollusks. Conclusions: The use of de novo transcriptome assembly and well-designed in silico protocols proved to be a robust approach for surveying and mining large sequence data in a wide range of non-model mollusks. The data presented herein constitute only a small fraction of the information retrieved from the analysed mollus
- Published
- 2016
4. Comparative transcriptomics enlarges the toolkit of known developmental genes in mollusks
- Author
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De Oliveira, A. L., primary, Wollesen, T., additional, Kristof, A., additional, Scherholz, M., additional, Redl, E., additional, Todt, C., additional, Bleidorn, C., additional, and Wanninger, A., additional
- Published
- 2016
- Full Text
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5. Aplacophoran mollusks evolved from ancestors with polyplacophoran-like features
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Scherholz, M., Redl, E., Wollesen, T., Todt, C., and Andreas Wanninger
- Subjects
Mathematics and natural scienses: 400::Zoology and botany: 480::Systematic zoology: 487 [VDP] ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Matematikk og naturvitenskap: 400::Zoologiske og botaniske fag: 480::Systematisk zoologi: 487 [VDP] - Abstract
Mollusca is an animal phylum with vast morphological diversity and includes worm-shaped aplacophorans, snails, bivalves, and the complex cephalopods [1]. The interrelationships of these class-level taxa are still contentious [2 and 3], but recent phylogenomic analyses suggest a dichotomy at the base of Mollusca, resulting in a monophyletic Aculifera (comprising the shell-less, sclerite-bearing aplacophorans and the eight-shelled polyplacophorans) and Conchifera (all other, primarily univalved groups) [4 and 5]. The Aculifera concept has recently gained support via description of the fossil Kulindroplax, which shows both aplacophoran- and polyplacophoran-like features and suggests that the aplacophorans originated from a shelled ancestor [ 6], but the overall morphology of the last common aculiferan ancestor remains obscure. Here we show that larvae of the aplacophoran Wirenia argentea have several sets of muscles previously known only from polyplacophoran mollusks. Most of these are lost during metamorphosis, and we interpret them as ontogenetic remnants of an ancestor with a complex, polyplacophoran-like musculature. Moreover, we find that the first seven pairs of dorsoventral muscles develop synchronously in Wirenia, similar to juvenile polyplacophorans [ 7], which supports the conclusions based on the seven-shelled Kulindroplax. Accordingly, we argue that the simple body plan of recent aplacophorans is the result of simplification and does not represent a basal molluscan condition. publishedVersion
- Published
- 2013
6. Transesophageal echocardiography
- Author
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Stöllberger, C., Redl, E., Slany, J., and Sporn, P.
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- 1989
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7. Technical and biological sources of unreliability of Infinium probes on Illumina methylation microarrays.
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Nazarenko T, Vavourakis CD, Jones A, Evans I, Schreiberhuber L, Kastner C, Ishaq-Parveen I, Redl E, Watson AW, Brandt K, Carter C, Zaikin A, Herzog CMS, and Widschwendter M
- Subjects
- Humans, Reproducibility of Results, Female, Epigenesis, Genetic genetics, Epigenomics methods, CpG Islands genetics, DNA Methylation genetics, Oligonucleotide Array Sequence Analysis methods
- Abstract
The Illumina Methylation array platform has facilitated countless epigenetic studies on DNA methylation (DNAme) in health and disease, yet relatively few studies have so studied its reliability, i.e., the consistency of repeated measures. Here we investigate the reliability of both type I and type II Infinium probes. We propose a method for excluding unreliable probes based on dynamic thresholds for mean intensity (MI) and 'unreliability', estimated by probe-level simulation of the influence of technical noise on methylation β values using the background intensities of negative control probes. We validate our method in several datasets, including newly generated Illumina MethylationEPIC BeadChip v1.0 data from paired whole blood samples taken six weeks apart and technical replicates spanning multiple sample types. Our analysis revealed that specifically probes with low MI exhibit higher β value variability between repeated samples. MI was associated with the number of C-bases in the respective probe sequence and correlated negatively with unreliability scores. The unreliability scores were substantiated through validation in a new EPIC v1.0 (blood and cervix) and a publicly available 450k (blood) dataset, as they effectively captured the variability observed in β values between technical replicates. Finally, despite promising higher robustness, the newer version v2.0 of the MethylationEPIC BeadChip retained a substantial number of probes with poor unreliability scores. To enhance current pre-processing pipelines, we developed an R package to calculate MI and unreliability scores and provide guidance on establishing optimal dynamic score thresholds for a given dataset., (© 2024. The Author(s).)
- Published
- 2024
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8. High performance of the DNA methylation-based WID-qEC test for detecting uterine cancers independent of sampling modalities.
- Author
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Illah O, Scott M, Redl E, Barrett JE, Schreiberhuber L, Herzog C, Vavourakis CD, Jones A, Evans I, Reisel D, Chandrasekaran D, Doufekas K, Graham R, Kotsopoulos IC, MacDonald N, Arora R, Olaitan A, Rosenthal A, and Widschwendter M
- Subjects
- Humans, Female, Specimen Handling methods, Middle Aged, Sensitivity and Specificity, Uterine Neoplasms genetics, Uterine Neoplasms diagnosis, Aged, Early Detection of Cancer methods, Adult, Biomarkers, Tumor genetics, DNA Methylation, Endometrial Neoplasms genetics, Endometrial Neoplasms diagnosis
- Abstract
Endometrial cancer (EC) is the most prevalent gynaecological cancer in high-income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)-based women's cancer risk identification-quantitative polymerase chain reaction test for endometrial cancer (WID-qEC) test that could address this need. Here, we demonstrate that the stability of the WID-qEC test remains consistent regardless of: (i) the cervicovaginal collection device and sample media used (Cervex brush and PreservCyt or FLOQSwab and eNAT), (ii) the collector of the specimen (gynaecologist- or patient-based), and (iii) the precise sampling site (cervical, cervicovaginal and vaginal). Furthermore, we demonstrate sample stability in eNAT medium for 7 days at room temperature, greatly facilitating the implementation of the test into diagnostic laboratory workflows. When applying FLOQSwabs (Copan) in combination with the eNAT (Copan) sample collection media, the sensitivity and specificity of the WID-qEC test to detect uterine (i.e., endometrial and cervical) cancers in gynaecologist-taken samples was 92.9% (95% confidence interval [CI] = 75.0%-98.8%) and 98.6% (95% CI = 91.7%-99.9%), respectively, whilst the sensitivity and specificity in patient collected self-samples was 75.0% (95% CI = 47.4%-91.7%) and 100.0% (95% CI = 93.9%-100.0%), respectively. Taken together these data confirm the robustness and clinical potential of the WID-qEC test., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2024
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9. A validated HPLC-MS/MS method for the quantification of systemic mifepristone after subcutaneous application in mice.
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Tevini J, Aminzadeh-Gohari S, Weber DD, Catalano L, Stefan VE, Redl E, Herzog C, Lang R, Widschwendter M, Felder TK, and Kofler B
- Subjects
- Animals, Chromatography, High Pressure Liquid methods, Female, Mice, Reproducibility of Results, Tissue Distribution, Liquid Chromatography-Mass Spectrometry, Mifepristone pharmacokinetics, Tandem Mass Spectrometry methods, Mice, Inbred BALB C
- Abstract
Mifepristone (RU486, MIF) is a synthetic steroidal hormone with progesterone and glucocorticoid receptor antagonistic characteristics. MIF is commonly used for pharmalogical abortions, but also for the treatment of endometrial and endocrine disorders. The goal of the study was to establish and validate a targeted HPLC-MS/MS method for the quantification of MIF and one of its active metabolites metapristone (MET) in plasma after subcutaneous implantation of slow-release MIF pellets in female BALB/c mice. Additionally, we aimed to apply the analytical method to tissue of several organs to understand the tissue-specific distribution of both analytes after release into systemic circulation. Sample preparation comprised a simple liquid-liquid extraction with diethylether and required 100 μl of plasma or homogenates of approximately 50 mg of tissue. The presented HPLC-MS/MS method showed high sensitivity with baseline separation of MIF, MET, and the internal standard levonorgestrel within a run time of only 8.0 minutes and comparable limits of quantification for plasma and tissue homogenates ranging from 40 pg ml
-1 to 105 pg ml-1 for MIF and MET. The presented study is suitable for murine plasma and tissues and can be easily applied to human samples.- Published
- 2024
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10. Cervical cancer screening using DNA methylation triage in a real-world population.
- Author
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Schreiberhuber L, Barrett JE, Wang J, Redl E, Herzog C, Vavourakis CD, Sundström K, Dillner J, and Widschwendter M
- Subjects
- Humans, Female, Middle Aged, Adult, Human papillomavirus 18 genetics, Human papillomavirus 18 isolation & purification, Sweden epidemiology, Aged, Colposcopy, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms virology, DNA Methylation genetics, Early Detection of Cancer methods, Triage methods, Uterine Cervical Dysplasia diagnosis, Uterine Cervical Dysplasia genetics, Uterine Cervical Dysplasia virology, Human papillomavirus 16 genetics, Human papillomavirus 16 isolation & purification, Papillomavirus Infections diagnosis, Papillomavirus Infections virology, Papillomavirus Infections genetics
- Abstract
Cervical cancer (CC) screening in women comprises human papillomavirus (HPV) testing followed by cytology triage of positive cases. Drawbacks, including cytology's low reproducibility and requirement for short screening intervals, raise the need for alternative triage methods. Here we used an innovative triage technique, the WID-qCIN test, to assess the DNA methylation of human genes DPP6, RALYL and GSX1 in a real-life cohort of 28,017 women aged ≥30 years who attended CC screening in Stockholm between January and March 2017. In the analysis of all 2,377 HPV-positive samples, a combination of WID-qCIN (with a predefined threshold) and HPV16 and/or HPV18 (HPV16/18) detected 93.4% of cervical intraepithelial neoplasia grade 3 and 100% of invasive CCs. The WID-qCIN/HPV16/18 combination predicted 69.4% of incident cervical intraepithelial neoplasia grade 2 or worse compared with 18.2% predicted by cytology. Cytology or WID-qCIN/HPV16/18 triage would require 4.1 and 2.4 colposcopy referrals to detect one cervical intraepithelial neoplasia grade 2 or worse, respectively, during the 6 year period. These findings support the use of WID-qCIN/HPV16/18 as an improved triage strategy for HPV-positive women., (© 2024. The Author(s).)
- Published
- 2024
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11. Performance of the WID-qEC test versus sonography to detect uterine cancers in women with abnormal uterine bleeding (EPI-SURE): a prospective, consecutive observational cohort study in the UK.
- Author
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Evans I, Reisel D, Jones A, Bajrami A, Nijjar S, Solangon SA, Arora R, Redl E, Schreiberhuber L, Ishaq-Parveen I, Rothärmel J, Herzog C, Jurkovic D, and Widschwendter M
- Subjects
- Female, Humans, Pregnancy, Prospective Studies, Sensitivity and Specificity, United Kingdom, Uterine Hemorrhage diagnostic imaging, Uterine Hemorrhage etiology, Uterine Hemorrhage pathology, Uterine Neoplasms diagnostic imaging
- Abstract
Background: To detect uterine cancer, simpler and more specific index tests are needed to triage women with abnormal uterine bleeding to a reference histology test. We aimed to compare the performance of conventional index imaging tests with the novel WID-qEC DNA methylation test in terms of detecting the presence or absence of uterine cancers in women with abnormal uterine bleeding., Methods: EPI-SURE was a prospective, observational study that invited all women aged 45 years and older with abnormal uterine bleeding attending a tertiary gynaecological diagnostic referral centre at University College London Hospital (London, UK) to participate. Women meeting these inclusion criteria who consented to participate were included. Pregnant women and those with previous hysterectomy were excluded. A cervicovaginal sample for the WID-qEC test was obtained before standard assessment using index imaging tests (ie, ultrasound) and, where applicable, reference histology (ie, biopsy, hysteroscopy, or both) was performed. Technicians performing the WID-qEC test were masked to the final clinical outcome. The result of the WID-qEC test is defined as the sum of the percentage of fully methylated reference (ΣPMR) of the ZSCAN12 and GYPC regions. Patients were followed until diagnostic resolution or until June 12, 2023. The primary outcome was to assess the real-world performance of the WID-qEC test in comparison with ultrasound with regard to the area under the receiver-operating-characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. EPI-SURE is registered with ISRCTN (16815568)., Findings: From June 1, 2022, to Nov 24, 2022, 474 women were deemed eligible to participate. 74 did not accept the invitation to participate, and one woman withdrew after providing consent. 399 women were included in the primary analysis cohort. Based on 603 index imaging tests, 186 (47%) women were recommended for a reference histology test (ie, biopsy, hysteroscopy, or both). 12 women were diagnosed with cancer, 375 were not diagnosed with cancer, and 12 had inconclusive clinical outcomes and were considered study dropouts. 198 reference histology test procedures detected nine cases of cancer and missed two; one further cancer was directly diagnosed at hysterectomy without a previous reference test. The AUC for detection of uterine cancer based on endometrial thickness in mm was 87·2% (95% CI 71·1-100·0) versus 94·3% (84·7-100·0) based on WID-qEC (p=0·48). Endometrial thickness assessment on ultrasound scan was possible in 379 (95%) of the 399 women and a prespecified cut-off of 4·5 mm or more showed a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 79·1% (74·5-82·9), a positive predictive value of 11·8% (6·5-20·3), and a negative predictive value of 99·6% (98·0-99·9). The WID-qEC test was possible in 390 (98%) of the 399 patients with a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 92·1% (88·9-94·4), a positive predictive value of 25·6% (14·6-41·1), and a negative predictive value of 99·7% (98·3-99·9), when the prespecified threshold of 0·03 ΣPMR or more was applied. When a higher threshold (≥0·3 ΣPMR) was applied the specificity increased to 97·3% (95% CI 95·1-98·5) without a change in sensitivity., Interpretation: The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and specifically reduce the false positive rate., Funding: The Eve Appeal, Land Tirol, and the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme., Competing Interests: Declaration of interests CH and MW are shareholders of Sola Diagnostics GmbH, which holds an exclusive licence to the intellectual property that protects the commercialisation of the WID-qEC test. DJ is an unpaid advisory board member of the International Society for Ultrasound in Obstetrics and Gynecology. MW received funding from the Land Tirol, The Eve Appeal, and the European Research Council. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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- View/download PDF
12. STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.
- Author
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Pencik J, Philippe C, Schlederer M, Atas E, Pecoraro M, Grund-Gröschke S, Li WJ, Tracz A, Heidegger I, Lagger S, Trachtová K, Oberhuber M, Heitzer E, Aksoy O, Neubauer HA, Wingelhofer B, Orlova A, Witzeneder N, Dillinger T, Redl E, Greiner G, D'Andrea D, Östman JR, Tangermann S, Hermanova I, Schäfer G, Sternberg F, Pohl EE, Sternberg C, Varady A, Horvath J, Stoiber D, Malcolm TI, Turner SD, Parkes EE, Hantusch B, Egger G, Rose-John S, Poli V, Jain S, Armstrong CWD, Hoermann G, Goffin V, Aberger F, Moriggl R, Carracedo A, McKinney C, Kennedy RD, Klocker H, Speicher MR, Tang DG, Moazzami AA, Heery DM, Hacker M, and Kenner L
- Subjects
- Animals, Humans, Male, Mice, AMP-Activated Protein Kinases metabolism, Mechanistic Target of Rapamycin Complex 1 metabolism, Neoplasm Recurrence, Local, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Diabetes Mellitus, Type 2, Metformin pharmacology, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology
- Abstract
Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa. Here we show a frequent genomic co-deletion of PTEN and STAT3 in liquid biopsies of patients with mPCa. Loss of Stat3 in a Pten-null mouse prostate model leads to a reduction of LKB1/pAMPK with simultaneous activation of mTOR/CREB, resulting in metastatic disease. However, constitutive activation of Stat3 led to high LKB1/pAMPK levels and suppressed mTORC1/CREB pathway, preventing mPCa development. Metformin, one of the most widely prescribed therapeutics against type 2 diabetes, inhibits mTORC1 in liver and requires LKB1 to mediate glucose homeostasis. We find that metformin treatment of STAT3/AR-expressing PCa xenografts resulted in significantly reduced tumor growth accompanied by diminished mTORC1/CREB, AR and PSA levels. PCa xenografts with deletion of STAT3/AR nearly completely abrogated mTORC1/CREB inhibition mediated by metformin. Moreover, metformin treatment of PCa patients with high Gleason grade and type 2 diabetes resulted in undetectable mTORC1 levels and upregulated STAT3 expression. Furthermore, PCa patients with high CREB expression have worse clinical outcomes and a significantly increased risk of PCa relapse and metastatic recurrence. In summary, we have shown that STAT3 controls mPCa via LKB1/pAMPK/mTORC1/CREB signaling, which we have identified as a promising novel downstream target for the treatment of lethal mPCa., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
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13. The WID-qEC test: Performance in a hospital-based cohort and feasibility to detect endometrial and cervical cancers.
- Author
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Schreiberhuber L, Herzog C, Vavourakis CD, Redl E, Kastner C, Jones A, Evans I, Zikan M, Cibula D, Widschwendter P, Pfau K, Math B, Seewald M, Amory S, Obrist P, and Widschwendter M
- Subjects
- Female, Humans, Feasibility Studies, Endometrium pathology, Cytodiagnosis, Sensitivity and Specificity, Uterine Hemorrhage diagnosis, Uterine Hemorrhage pathology, Vaginal Smears, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms pathology, Uterine Cervical Dysplasia diagnosis, Papillomavirus Infections diagnosis
- Abstract
The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2023
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14. DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test.
- Author
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Herzog C, Sundström K, Jones A, Evans I, Barrett JE, Wang J, Redl E, Schreiberhuber L, Costas L, Paytubi S, Dostalek L, Zikan M, Cibula D, Sroczynski G, Siebert U, Dillner J, and Widschwendter M
- Subjects
- Humans, Female, Adult, Early Detection of Cancer, DNA Methylation, Papillomaviridae genetics, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms genetics, Papillomavirus Infections diagnosis, Papillomavirus Infections genetics, Alphapapillomavirus, Uterine Cervical Dysplasia diagnosis, Uterine Cervical Dysplasia genetics
- Abstract
Background: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients., Results: The WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation., Conclusion: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial., (© 2022. The Author(s).)
- Published
- 2022
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15. A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets.
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Herzog C, Marín F, Jones A, Evans I, Reisel D, Redl E, Schreiberhuber L, Paytubi S, Pelegrina B, Carmona Á, Peremiquel-Trillas P, Frias-Gomez J, Pineda M, Brunet J, Ponce J, Matias-Guiu X, de Sanjosé S, Alemany L, Olaitan A, Wong M, Jurkovic D, Crosbie EJ, Rosenthal AN, Bjørge L, Zikan M, Dostalek L, Cibula D, Sundström K, Dillner J, Costas L, and Widschwendter M
- Subjects
- Humans, Female, Triage, Early Detection of Cancer methods, Vaginal Smears methods, Epigenesis, Genetic, Endometrial Neoplasms diagnosis, Endometrial Neoplasms genetics, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms genetics, Papillomavirus Infections diagnosis
- Abstract
Purpose: Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival., Methods: We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86)., Results: We describe the W omen's cancer risk ID entification - q uantitative polymerase chain reaction test for E ndometrial C ancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12 . In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology., Conclusion: The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits., Competing Interests: Chiara HerzogStock and Other Ownership Interests: Sola Diagnostics GmbHPatents, Royalties, Other Intellectual Property: Named inventor on a patent combining epigenetic signatures for detection and risk stratification for breast cancer (WID-qtBC, Women's cancer risk identification—quantitative trait Breast Cancer) Paula Peremiquel-TrillasHonoraria: WerfenTravel, Accommodations, Expenses: Werfen Joan BrunetConsulting or Advisory Role: MSD Oncology, AstraZeneca SpainTravel, Accommodations, Expenses: GlaxoSmithKline Jordi PonceConsulting or Advisory Role: Medtronic, Abex, KCI Xavier Matias-GuiuConsulting or Advisory Role: AstraZeneca, Lilly, Amgen, Janssen, GlaxoSmithKlineTravel, Accommodations, Expenses: GlaxoSmithKline, Roche Laia AlemanyOther Relationship: Integrated DNA Technologies (Inst), Roche (Inst)Uncompensated Relationships: Roche (Inst) Adam RosenthalConsulting or Advisory Role: AbcodiaResearch Funding: Abcodia (Inst) David CibulaConsulting or Advisory Role: AstraZeneca, Sotio, Roche, GlaxoSmithKline, Novocure, Akeso Biopharma, MSD, Mersana Karin SundströmConsulting or Advisory Role: Merck (Inst)Research Funding: Merck (Inst) Laura CostasHonoraria: Roche Sequencing SolutionsOther Relationship: Integrated DNA Technologies (Inst), Roche (Inst)Uncompensated Relationships: Roche (Inst) Martin WidschwendterPatents, Royalties, Other Intellectual Property: I am a shareholder of Sola Diagnostics GmbH, which holds an exclusive license to the intellectual property that protects the commercialization of the WID tests. I am an inventor on pending patents describing the various WID tests. I am a shareholder of BreOva, which aims to license IP for developing and applying cell-free DNA methylation tests. I am an inventor on two pending patents on cell-free DNA methylation analysis for breast and ovarian cancerNo other potential conflicts of interest were reported.
- Published
- 2022
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16. Identification of tumor tissue-derived DNA methylation biomarkers for the detection and therapy response evaluation of metastatic castration resistant prostate cancer in liquid biopsies.
- Author
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Dillinger T, Sheibani-Tezerji R, Pulverer W, Stelzer I, Hassler MR, Scheibelreiter J, Pérez Malla CU, Kuroll M, Domazet S, Redl E, Ely S, Brezina S, Tiefenbacher A, Rebhan K, Hübner N, Grubmüller B, Mitterhauser M, Hacker M, Weinhaeusel A, Simon J, Zeitlinger M, Gsur A, Kramer G, Shariat SF, Kenner L, and Egger G
- Subjects
- Computational Biology methods, Disease Management, Disease Susceptibility, Epigenesis, Genetic, Epigenomics methods, Gene Expression Profiling, Humans, Male, Prognosis, Prostatic Neoplasms, Castration-Resistant blood, Prostatic Neoplasms, Castration-Resistant therapy, Treatment Outcome, Biomarkers, Tumor, DNA Methylation, Liquid Biopsy methods, Prostatic Neoplasms, Castration-Resistant diagnosis, Prostatic Neoplasms, Castration-Resistant genetics
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- 2022
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17. Requirement of DNMT1 to orchestrate epigenomic reprogramming for NPM-ALK-driven lymphomagenesis.
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Redl E, Sheibani-Tezerji R, Cardona CJ, Hamminger P, Timelthaler G, Hassler MR, Zrimšek M, Lagger S, Dillinger T, Hofbauer L, Draganić K, Tiefenbacher A, Kothmayer M, Dietz CH, Ramsahoye BH, Kenner L, Bock C, Seiser C, Ellmeier W, Schweikert G, and Egger G
- Subjects
- Animals, Biomarkers, Tumor, Computational Biology methods, DNA (Cytosine-5-)-Methyltransferase 1 genetics, DNA Methylation, Disease Models, Animal, Disease Susceptibility, Epigenomics, Gene Deletion, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Immunohistochemistry, Immunophenotyping, Lymphoma drug therapy, Lymphoma pathology, Mice, Mice, Knockout, Mice, Transgenic, Protein-Tyrosine Kinases metabolism, STAT3 Transcription Factor metabolism, Signal Transduction, Xenograft Model Antitumor Assays, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, DNA (Cytosine-5-)-Methyltransferase 1 metabolism, Epigenesis, Genetic, Lymphoma etiology, Lymphoma metabolism, Protein-Tyrosine Kinases genetics
- Abstract
Malignant transformation depends on genetic and epigenetic events that result in a burst of deregulated gene expression and chromatin changes. To dissect the sequence of events in this process, we used a T-cell-specific lymphoma model based on the human oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) translocation. We find that transformation of T cells shifts thymic cell populations to an undifferentiated immunophenotype, which occurs only after a period of latency, accompanied by induction of the MYC-NOTCH1 axis and deregulation of key epigenetic enzymes. We discover aberrant DNA methylation patterns, overlapping with regulatory regions, plus a high degree of epigenetic heterogeneity between individual tumors. In addition, ALK-positive tumors show a loss of associated methylation patterns of neighboring CpG sites. Notably, deletion of the maintenance DNA methyltransferase DNMT1 completely abrogates lymphomagenesis in this model, despite oncogenic signaling through NPM-ALK, suggesting that faithful maintenance of tumor-specific methylation through DNMT1 is essential for sustained proliferation and tumorigenesis., (© 2020 Redl et al.)
- Published
- 2020
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18. Expression of six3 and otx in Solenogastres (Mollusca) supports an ancestral role in bilaterian anterior-posterior axis patterning.
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Redl E, Scherholz M, Wollesen T, Todt C, and Wanninger A
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- Animals, Biological Evolution, Body Patterning, Brain anatomy & histology, Brain embryology, Brain metabolism, Gene Expression Regulation, Developmental, Head anatomy & histology, Head embryology, Mollusca embryology, Mollusca physiology, Homeobox Protein SIX3, Eye Proteins genetics, Homeodomain Proteins genetics, Mollusca anatomy & histology, Mollusca genetics, Nerve Tissue Proteins genetics, Otx Transcription Factors genetics
- Abstract
The homeodomain transcription factors six3 and otx are involved in patterning the anterior body and parts of the central nervous system (CNS) in bilaterians. Their similar expression patterns have been used as an argument for homology of heads, brains, segmentation, and ciliated larvae. We investigated the developmental expression of six3 and otx in the aplacophoran mollusk Wirenia argentea. Six3 is expressed in subepithelial cells delimiting the apical organ of the solenogaster pericalymma larva. Otx is expressed in cells of the prototroch and adjacent regions as well as in posterior extensions of the prototrochal expression domain. Advanced larvae also show pretrochal otx expression in the developing CNS. Comparative analysis of six3 and otx expression in bilaterians argues for an ancestral function in anterior-posterior body axis patterning but, due to its presence in animals lacking a head and/or a brain, not necessarily for the presence of these morphological structures in the last common ancestor (LCA) of bilaterians. Likewise, the hypothesis that the posterior border of otx expression corresponds to the border between the unsegmented head and the segmented trunk of the LCA of protostomes is not supported, since otx is extensively expressed in the trunk in W. argentea and numerous other protostomes., (© 2017 The Authors. Evolution and Development Published by Wiley Periodicals, Inc.)
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- 2018
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19. Brain regionalization genes are co-opted into shell field patterning in Mollusca.
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Wollesen T, Scherholz M, Rodríguez Monje SV, Redl E, Todt C, and Wanninger A
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- Animals, Gene Expression Regulation, Developmental, Larva genetics, Phylogeny, Animal Shells growth & development, Animal Shells metabolism, Body Patterning genetics, Brain growth & development, Brain metabolism, Mollusca genetics, Mollusca growth & development
- Abstract
The 'brain regionalization genes' Six3/6, Otx, Pax2/5/8, Gbx, and Hox1 are expressed in a similar fashion in the deuterostome, ecdysozoan, and the cephalopod brain, questioning whether this holds also true for the remaining Mollusca. We investigated developmental Gbx-expression in representatives of both molluscan sister groups, the Aculifera and Conchifera. Gbx is expressed in the posterior central nervous system of an aculiferan polyplacophoran and solenogaster but not in a conchiferan bivalve suggesting that Gbx, together with Six3/6, Otx, Pax2/5/8, and Hox1, is involved in central nervous system regionalization as reported for other bilaterians. Gbx is, however, also expressed in the anterior central nervous system, i.e. the anlagen of the cerebral ganglia, in the solenogaster, a condition not reported for any other bilaterian so far. Strikingly, all Gbx-orthologs and the other 'posterior brain regionalization genes' such as Pax2/5/8 and Hox1 are expressed in the mantle that secretes shell(s) and spicules of mollusks (except cephalopods). In bivalves, the ancestral condition has even been lost, with Gbx and Pax2/5/8 not being expressed in the developing central nervous system anymore. This suggests an additional role in the formation of the molluscan shell field(s) and spicule-bearing cells, key features of mollusks.
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- 2017
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20. Ancestral and novel roles of Pax family genes in mollusks.
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Scherholz M, Redl E, Wollesen T, de Oliveira AL, Todt C, and Wanninger A
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- Amino Acid Sequence, Animals, Eye metabolism, Larva growth & development, Mollusca classification, Mollusca growth & development, Mollusca metabolism, Paired Box Transcription Factors chemistry, Phylogeny, Sequence Alignment, Mollusca genetics, Paired Box Transcription Factors genetics, Paired Box Transcription Factors metabolism
- Abstract
Background: Pax genes are transcription factors with significant roles in cell fate specification and tissue differentiation during animal ontogeny. Most information on their tempo-spatial mode of expression is available from well-studied model organisms where the Pax-subfamilies Pax2/5/8, Pax6, and Paxα/β are mainly involved in the development of the central nervous system (CNS), the eyes, and other sensory organs. In certain taxa, Pax2/5/8 seems to be additionally involved in the development of excretion organs. Data on expression patterns in lophotrochozoans, and in particular in mollusks, are very scarce for all the above-mentioned Pax-subfamilies, which hampers reconstruction of their putative ancestral roles in bilaterian animals. Thus, we studied the developmental expression of Pax2/5/8, Pax6, and the lophotrochozoan-specific Paxβ in the worm-shaped mollusk Wirenia argentea, a member of Aplacophora that together with Polyplacophora forms the Aculifera, the proposed sister taxon to all primarily single-shelled mollusks (Conchifera)., Results: All investigated Pax genes are expressed in the developing cerebral ganglia and in the ventral nerve cords, but not in the lateral nerve cords of the tetraneural nervous system. Additionally, Pax2/5/8 is expressed in epidermal spicule-secreting or associated cells of the larval trunk and in the region of the developing protonephridia. We found no indication for an involvement of the investigated Pax genes in the development of larval or adult sensory organs of Wirenia argentea., Conclusions: Pax2/5/8 seems to have a conserved role in the development of the CNS, whereas expression in the spicule-secreting tissues of aplacophorans and polyplacophorans suggests co-option in aculiferan skeletogenesis. The Pax6 expression pattern in Aculifera largely resembles the common bilaterian expression during CNS development. All data available on Paxβ expression argue for a common role in lophotrochozoan neurogenesis.
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- 2017
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21. Cell Proliferation Pattern and Twist Expression in an Aplacophoran Mollusk Argue Against Segmented Ancestry of Mollusca.
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Redl E, Scherholz M, Wollesen T, Todt C, and Wanninger A
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- Animals, Biological Evolution, Cell Proliferation, Larva cytology, Larva growth & development, Larva metabolism, Mollusca growth & development, Muscle Development, Phylogeny, Mollusca cytology, Mollusca metabolism, Twist-Related Protein 1 metabolism
- Abstract
The study of aplacophoran mollusks (i.e., Solenogastres or Neomeniomorpha and Caudofoveata or Chaetodermomorpha) has traditionally been regarded as crucial for reconstructing the morphology of the last common ancestor of the Mollusca. Since their proposed close relatives, the Polyplacophora, show a distinct seriality in certain organ systems, the aplacophorans are also in the focus of attention with regard to the question of a potential segmented ancestry of mollusks. To contribute to this question, we investigated cell proliferation patterns and the expression of the twist ortholog during larval development in solenogasters. In advanced to late larvae, during the outgrowth of the trunk, a pair of longitudinal bands of proliferating cells is found subepithelially in a lateral to ventrolateral position. These bands elongate during subsequent development as the trunk grows longer. Likewise, expression of twist occurs in two laterally positioned, subepithelial longitudinal stripes in advanced larvae. Both, the pattern of proliferating cells and the expression domain of twist demonstrate the existence of extensive and long-lived mesodermal bands in a worm-shaped aculiferan, a situation which is similar to annelids but in stark contrast to conchiferans, where the mesodermal bands are usually rudimentary and ephemeral. Yet, in contrast to annelids, neither the bands of proliferating cells nor the twist expression domain show a separation into distinct serial subunits, which clearly argues against a segmented ancestry of mollusks. Furthermore, the lack of twist expression during the development of the ventromedian muscle argues against homology of a ventromedian longitudinal muscle in protostomes with the notochord of chordates., (© 2016 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals, Inc.)
- Published
- 2016
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22. Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.
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Hassler MR, Pulverer W, Lakshminarasimhan R, Redl E, Hacker J, Garland GD, Merkel O, Schiefer AI, Simonitsch-Klupp I, Kenner L, Weisenberger DJ, Weinhaeusel A, Turner SD, and Egger G
- Subjects
- Adolescent, Adult, Aged, Cell Differentiation genetics, Cell Line, Tumor, Child, Female, Humans, Lymphocyte Activation genetics, Lymphoma, Large-Cell, Anaplastic pathology, Male, Middle Aged, Signal Transduction, Young Adult, DNA Methylation genetics, Genome, Human genetics, Lymphoma, Large-Cell, Anaplastic genetics, Protein-Tyrosine Kinases genetics
- Abstract
Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+) and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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23. From complex to simple: myogenesis in an aplacophoran mollusk reveals key traits in aculiferan evolution.
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Scherholz M, Redl E, Wollesen T, Todt C, and Wanninger A
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- Animals, Biological Evolution, Larva growth & development, Metamorphosis, Biological, Mollusca classification, Phylogeny, Mollusca genetics, Mollusca growth & development, Muscle Development
- Abstract
Background: Recent studies suggest a bifurcation at the base of Mollusca, resulting in the primarily single-shelled Conchifera (Bivalvia, Gastropoda, Scaphopoda, Monoplacophora, Cephalopoda) and the spicule-bearing Aculifera (Polyplacophora, Neomeniomorpha, Chaetodermomorpha). A recent study revealed a complex larval musculature exclusively shared by Neomeniomorpha and Polyplacophora, supporting a close relationship of both taxa. However, the ontogenetic transition from the complex larval to the simple adult neomeniomorph musculature, which mainly consists of a three-layered body-wall musculature and serially iterated dorsoventral muscles, remains unknown. To close this gap in knowledge, we studied remodeling of the larval musculature during metamorphosis in the neomeniomorph Wirenia argentea. A comparative analysis with a novel data set of a polyplacophoran, Leptochiton asellus, allows us to infer the morphology of the last common ancestor of Aculifera and the evolution of its subclades therefrom., Results: The complex larval musculature of Wirenia argentea persists through metamorphosis and becomes modified to form two of the three muscle layers of the adult body wall. The innermost longitudinal layer of the three-layered body wall musculature is generated by transformation and expansion of distinct larval longitudinal muscle bundles. The larval ventrolateral muscle strands are remodeled and eventually become the most ventral part of the adult longitudinal layer of the body wall musculature. The paired larval enrolling muscle forms the lateral parts and the former rectus muscle is destined to become the most dorsal part of the longitudinal layer of the body wall musculature. The transient ventromedian muscle is lost during postmetamorphic development., Conclusions: Postmetamorphic remodeling in W. argentea supports the hypothesis of a complex myoanatomy rather than a three-layered body wall musculature at the base of Aculifera, and thus argues against homology of the body wall musculature of adult Neomeniomorpha and other potential molluscan sister groups. Our data show that the neomeniomorph body wall musculature is a derived condition and not an aculiferan or molluscan plesiomorphy.
- Published
- 2015
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24. Insights into the organization of plumatellid larvae (lophotrochozoa, Bryozoa) by means of 3D-imaging and confocal microscopy.
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Schwaha TF, Handschuh S, Redl E, and Wanninger A
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- Animals, Biological Evolution, Imaging, Three-Dimensional, Larva anatomy & histology, Microscopy, Confocal, Phylogeny, Bryozoa anatomy & histology
- Abstract
Within the Lophotrochozoa, the Bryozoa or Ectoprocta remain one of the phyla whose phylogenetic relation to other lophotrochozoans is still controversely discussed. To complement existing data and to gain more insight into bryozoan character evolution, we analyzed the morphology of the larva of the phylactolaemate Plumatella sp. The larva of Plumatella spp. consists of an outer ciliated mantle that covers two differentiated polypides. The muscular and serotonergic nervous system of the polypides correspond to previous studies. The two polypides and their corresponding buds differ in size, which, together with a comparison among bryozoans, indicates that a single polypide is the basal condition. The whole larval mantle and mantle fold are supplied with circular and longitudinal muscles, the former being more pronounced in the mantle fold. The apical plate on the anterior side contains a diffuse mesh of crossing fibers and thus differs from previous descriptions, which recognized a regular muscular grid. The serotonergic nervous system in the mantle and mantle fold consists of a diffuse basiepidermal nerve net with its highest concentration at the apical plate. Serotonin immunoreactivity so far has not been detected in the mantle fold. However, the presence of other neurotransmitters in the mantle fold shown by previous studies indicates that this nerve net is a common feature of phylactolaemate larvae. The main difference between currently analyzed phylactolaemate larvae seems to be the complexity of the larval mantle musculature, which most likely plays an important role during metamorphosis. This study confirms previous interpretations that the apical plate pole does not correspond to the apical pole of gymnolaemate larvae but to their oral side. Accelerated asexual development on the aboral pole leads to the suggestion that an apical organ is never formed and the apical plate compensates for its absence in the free-swimming period., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2015
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25. Development of the nervous system in Solenogastres (Mollusca) reveals putative ancestral spiralian features.
- Author
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Redl E, Scherholz M, Todt C, Wollesen T, and Wanninger A
- Abstract
Background: The Solenogastres (or Neomeniomorpha) are a taxon of aplacophoran molluscs with contentious phylogenetic placement. Since available developmental data on non-conchiferan (that is, aculiferan) molluscs mainly stem from polyplacophorans, data on aplacophorans are needed to clarify evolutionary questions concerning the morphological features of the last common ancestor (LCA) of the Aculifera and the entire Mollusca. We therefore investigated the development of the nervous system in two solenogasters, Wirenia argentea and Gymnomenia pellucida, using immunocytochemistry and electron microscopy., Results: Nervous system formation starts simultaneously from the apical and abapical pole of the larva with the development of a few cells of the apical organ and a posterior neurogenic domain. A pair of neurite bundles grows out from both the neuropil of the apical organ and the posterior neurogenic domain. After their fusion in the region of the prototroch, which is innervated by an underlying serotonin-like immunoreactive (-LIR) plexus, the larva exhibits two longitudinal neurite bundles - the future lateral nerve cords. The apical organ in its fully developed state exhibits approximately 8 to 10 flask-shaped cells but no peripheral cells. The entire ventral nervous system, which includes a pair of longitudinal neurite bundles (the future ventral nerve cords) and a serotonin-LIR ventromedian nerve plexus, appears simultaneously and is established after the lateral nervous system. During metamorphosis the apical organ and the prototrochal nerve plexus are lost., Conclusions: The development of the nervous system in early solenogaster larvae shows striking similarities to other spiralians, especially polychaetes, in exhibiting an apical organ with flask-shaped cells, a single pair of longitudinal neurite bundles, a serotonin-LIR innervation of the prototroch, and formation of these structures from an anterior and a posterior neurogenic domain. This provides evidence for an ancestral spiralian pattern of early nervous system development and a LCA of the Spiralia with a single pair of nerve cords. In later nervous system development, however, the annelids deviate from all other spiralians including solenogasters in forming a posterior growth zone, which initiates teloblastic growth. Since this mode of organogenesis is confined to annelids, we conclude that the LCA of both molluscs and spiralians was unsegmented.
- Published
- 2014
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26. Aplacophoran mollusks evolved from ancestors with polyplacophoran-like features.
- Author
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Scherholz M, Redl E, Wollesen T, Todt C, and Wanninger A
- Subjects
- Animals, Larva anatomy & histology, Larva classification, Larva growth & development, Microscopy, Confocal, Microscopy, Fluorescence, Mollusca growth & development, Muscles anatomy & histology, Norway, Phylogeny, Biological Evolution, Mollusca anatomy & histology, Mollusca classification
- Abstract
Mollusca is an animal phylum with vast morphological diversity and includes worm-shaped aplacophorans, snails, bivalves, and the complex cephalopods. The interrelationships of these class-level taxa are still contentious, but recent phylogenomic analyses suggest a dichotomy at the base of Mollusca, resulting in a monophyletic Aculifera (comprising the shell-less, sclerite-bearing aplacophorans and the eight-shelled polyplacophorans) and Conchifera (all other, primarily univalved groups). The Aculifera concept has recently gained support via description of the fossil Kulindroplax, which shows both aplacophoran- and polyplacophoran-like features and suggests that the aplacophorans originated from a shelled ancestor, but the overall morphology of the last common aculiferan ancestor remains obscure. Here we show that larvae of the aplacophoran Wirenia argentea have several sets of muscles previously known only from polyplacophoran mollusks. Most of these are lost during metamorphosis, and we interpret them as ontogenetic remnants of an ancestor with a complex, polyplacophoran-like musculature. Moreover, we find that the first seven pairs of dorsoventral muscles develop synchronously in Wirenia, similar to juvenile polyplacophorans, which supports the conclusions based on the seven-shelled Kulindroplax. Accordingly, we argue that the simple body plan of recent aplacophorans is the result of simplification and does not represent a basal molluscan condition., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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27. Organogenesis in the budding process of the freshwater bryozoan Cristatella mucedo Cuvier, 1798 (Bryozoa, Phylactolaemata).
- Author
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Schwaha T, Handschuh S, Redl E, and Walzl MG
- Subjects
- Animals, Bryozoa anatomy & histology, Bryozoa classification, Bryozoa genetics, Digestive System anatomy & histology, Digestive System growth & development, Bryozoa growth & development, Organogenesis, Phylogeny
- Abstract
The phylogenetic position of bryozoans has been disputed for decades, and molecular phylogenetic analyzes have not unequivocally clarified their position within the Bilateria. As probably the most basal bryozoans, Phylactolaemata is the most promising taxon for large-scale phylogenetic comparisons. These comparisons require extending the morphological and developmental data by investigating different phylactolaemate species to identify basal characters and resolve in-group phylogeny. Accordingly, we analyzed the bud development and the organogenesis of the freshwater bryozoan Cristatella mucedo, with special focus on the formation of the digestive tract and differentiation of the coelomic compartments. Most parts of the digestive tract are formed as an outpocketing at the future anal side growing towards the mouth area. The ganglion is formed by an invagination between the anlagen of the mouth and anus. The lophophoral arms develop as paired lateral protrusions into the lumen of the bud and are temporarily connected by a median, thin bridge. All coelomic compartments are confluent during their development and also in the adult. The epistome coelom develops by fusion of two peritoneal infolds between the gut loop and overgrows the ganglion medially. The coelomic ring canal on the oral side develops by two lateral ingrowths and supplies the oral tentacles. On the forked canal, supplying the innermost row of tentacles above the epistome, a bladder-shaped swelling, probably with excretory function, is present in some adults. It remains difficult to draw comparisons to other phyla because only few studies have dealt with budding of potentially related taxa in more detail. Nonetheless, our results show that comparative organogenesis can contribute to phylactolaemate systematics and, when more data are available, possibly to that of other bryozoan classes and bilaterian phyla., (Copyright © 2010 Wiley-Liss, Inc.)
- Published
- 2011
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28. Long-term outcome after open treatment of severe intra-abdominal infection and pancreatic necrosis.
- Author
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Kriwanek S, Armbruster C, Dittrich K, Beckerhinn P, Schwarzmaier A, and Redl E
- Subjects
- Adult, Aged, Critical Care economics, Female, Follow-Up Studies, Humans, Infections etiology, Length of Stay economics, Male, Middle Aged, Necrosis, Pancreatic Diseases mortality, Pancreatic Diseases pathology, Quality of Life, Reoperation economics, Treatment Outcome, Abdomen surgery, Digestive System Surgical Procedures economics, Hospital Costs, Infections economics, Infections surgery, Pancreatic Diseases economics, Pancreatic Diseases surgery
- Abstract
Background: Outcome assessment after surgical treatment of intra-abdominal infections and pancreatic necrosis has concentrated on postoperative complications and survival, while long-term results have received little attention., Objectives: To evaluate hospital costs and long-term outcome for patients undergoing open treatment of intra-abdominal infection or pancreatic necrosis and to determine whether results justify costs., Design: Cohort study and cost-effectiveness analysis., Setting: Referral center., Patients: From January 1, 1988, through June 30, 1996, we used open treatment for 147 patients with pancreatic necrosis (n=75; group 1), severe intra-abdominal infections due to benign diseases (n=50; group 2), and infections due to malignant neoplasm (n=22; group 3). All surviving patients (n=92) were followed up. Fifty-seven patients in group 1, 25 patients in group 2, and 10 patients in group 3 survived., Interventions: The effective costs of treatment per surviving patient (including restorative surgery) were calculated. The patients were interviewed, and the residence location, medical treatment, degree of recovery, functional state, and employment status were assessed. We assessed the quality of life by using the short general health survey (SF-36)., Main Outcome Measures: Costs, survival, and long-term outcome., Results: The effective costs per survivor studied were $175000 (group 1) and $232400 (groups 2 and 3). Most patients experienced good long-term results, ie, employment status was unchanged for 69 (75%) of the patients, and the functional state was unchanged for 81 (88%) of the patients. Readmission to a hospital was necessary for 14 (15%) of the patients, and 5 (6%) required care in nursing homes. Of the patients studied, 75% described their quality of life as good. Patients in group 3 had significantly worse results for survival, functional status, and quality of life (P<.01, log-rank test)., Conclusions: Our study demonstrated that open treatment of severe intra-abdominal infection and pancreatic necrosis is a cost-effective treatment with good long-term results for most patients. However, patients with malignant neoplasms did not benefit from this therapy and, therefore, should not be treated by laparostomy.
- Published
- 1998
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29. Improved results after aggressive treatment of colonic involvement in necrotizing pancreatitis.
- Author
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Kriwanek S, Armbruster C, Beckerhinn P, Dittrich K, and Redl E
- Subjects
- Adult, Aged, Aged, 80 and over, Colon pathology, Colonic Diseases pathology, Colonic Diseases surgery, Female, Humans, Male, Middle Aged, Necrosis, Treatment Outcome, Colectomy, Colonic Diseases etiology, Ileostomy, Pancreatitis, Acute Necrotizing complications
- Abstract
Background/aims: Colonic involvement is a rare but serious event in necrotizing pancreatitis. Early detection of this complication is difficult; a delay of diagnosis may lead to perforation and peritonitis. Two strategies of therapy have been developed in the past few years: an aggressive regimen of early resection and a conservative approach by ileostomy and observation., Materials and Methods: Fourteen of 118 patients treated for necrotizing pancreatitis from 1988 to 1995 presented with colonic necrosis. The diagnosis of necrosis was made if the color of the bowel wall demonstrated ischemia or hemorrhagic infarction or pulsations of the mesocolic vessels could not be palpated. The first two patients were treated by a conservative approach, the following 12 patients by immediate large bowel resection. Follow-up results of all surviving patients were obtained., Results: Patients with colonic lesions demonstrated an advanced septic state compared to patients who did not present this complication. Differences in the average Apache 2 scores on admission and the incidence of multiple organ failure were significant (Apache 2 score; 16.6 versus 11.9, p = 0.028, Wilcoxon; multiple organ failure; 71% versus 35%, p = 0.028, Fisher's exact test). Results after establishment of early discontinuity-resection of colonic necrosis compared favorably to those of a conservative strategy (mortality 4/12; 33% versus 2/2; 100%). The overall mortality was 43% (6 of 14 patients). Restorative surgery was performed in 6 patients without substantial morbidity and no mortality. Follow-up results were satisfactory in the majority of the patients., Conclusions: Early resection of colonic lesions improves results in this dangerous complication of necrotizing pancreatitis.
- Published
- 1997
30. Improved results after aggressive treatment of colonic involvement in necrotizing pancreatitis.
- Author
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Kriwanek S, Armbruster C, Beckerhinn P, Dittrich K, and Redl E
- Subjects
- Adult, Aged, Aged, 80 and over, Colon pathology, Colonic Diseases mortality, Colonic Diseases pathology, Female, Humans, Male, Middle Aged, Pancreatitis, Acute Necrotizing mortality, Retrospective Studies, Survival Rate, Treatment Outcome, Colectomy, Colonic Diseases etiology, Colonic Diseases surgery, Pancreatitis, Acute Necrotizing complications
- Abstract
Background/aims: Colonic involvement is a rare but serious event in necrotizing pancreatitis. Early detection of this complication is difficult; a delay of diagnosis may lead to perforation and peritonitis. Two strategies of therapy have been developed in the last few years: an aggressive regimen of early resection and a conservative approach with ileostomy and observation., Materials and Methods: Fourteen of 118 patients treated for necrotizing pancreatitis from 1988 to 1995 presented with colonic necrosis. The diagnosis of necrosis was made if the color of the bowel wall demonstrated ischemia or hemorrhagic infarction or pulsations of the mesocolic vessels could not be palpated. The first two patients were treated by a conservative approach the following 12 by immediate large bowel resection. Follow-up results of all surviving patients were obtained., Results: Patients with colonic lesions demonstrated an advanced septic state compared to patients who did not present this complication. Differences in the average Apache 2 scores on admission and the incidence of multiple organ failure were significant (Apache 2 score; 16.6 versus 11.9, p = 0.028, Wilcoxon; multiple organ failure; 71% versus 35%, p = 0.028, Fisher's exact test). Results after establishment of early discontinuity-resection of colonic necrosis compared favorably to those of a conservative strategy (mortality 4/12; 33% versus 2/2; 100%). The overall mortality was 43% (6 of 14 patients). Restorative surgery was performed in 6 patients without substantial morbidity and no mortality. Follow-up results were satisfactory in the majority of the patients., Conclusions: Early resection of colonic lesions improves results in this dangerous complication of necrotizing pancreatitis.
- Published
- 1996
31. [Long-term outcome of surgical therapy of acute necrotizing pancreatitis].
- Author
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Kriwanek S, Armbruster C, Dittrich K, Beckerhinn P, Redl E, and Balogh B
- Subjects
- Abdominal Muscles surgery, Acute Disease, Adult, Diabetes Mellitus etiology, Female, Follow-Up Studies, Humans, Male, Necrosis, Quality of Life, Pancreatectomy, Pancreatitis surgery, Postoperative Complications etiology
- Abstract
This paper discusses the long-term results after surgical treatment of necrotizing pancreatitis. Thirty-one patients were examined 3 years after the operation. The development of diabetes was the main problem in 29% of the patients and depended on the amount of pancreatic tissue resected (never after necrosectomy, in 47% after pancreatic resection; P = 0.005, Fischer's exact test). Of the patients, 77% were in good general condition and 68% were able to work. In 50% of the patients abdominal wall function was impaired but most of them could cope with this insufficiency. Of the patients with alcohol-induced pancreatitis, 75% were abstinent. Considering the severity of the disease, long-term results after surgical treatment of necrotizing pancreatitis are satisfactory.
- Published
- 1996
32. [Immunoscintigraphy for detection of inflammatory perioperative foci].
- Author
-
Kroiss A, Sporn P, Auinger C, Redl E, Böck F, Dinstl K, and Neumayr A
- Subjects
- Abscess diagnostic imaging, Adult, Female, Humans, Male, Middle Aged, Technetium, Radioimmunodetection, Surgical Wound Infection diagnostic imaging, Tomography, Emission-Computed, Single-Photon
- Abstract
The aim of our study was to evaluate the clinical usefulness of a monoclonal antibody (MAB; BW 250/183; Behringwerke, Germany) in patients with suspected perioperative septic foci. The MAB is directed against the nonspecific crossreacting antigen (NCA 95) which has been found on the surface of human neutrophil granulocytes and which represents a murine immunoglobulin isotype of IgG1. Immunoscintigraphy was performed by labelling the MAB with 740 MBq (20mCi) Tc-99m. Data acquisition followed 4 and 18 to 24 hours after administration by a digital Anger camera (APEX 409A, Elscint). 53 patients were investigated (31 female, 22 male; average age 39 years), 4 patients were twice, 1 patient was 3 times evaluated, which results in a total of 59 studies. 45 patients experienced operation within 12 hours after our investigation, which resulted in 36 true positive, 5 true negative, 3 false negative, and 1 false positive findings. This means a sensitivity of 92%, and specificity of 83%. Immunoscintigraphy with granulocyte antibodies can be performed at any time, the preparation of the radiopharmaceutical is simple, the image quality is high; the obtained information concerning localization and size of perioperative septic infections permits the determination of the optimal point of time for surgical intervention. The accumulation of activity was visible as early as 4 hours post application. SPECT would enhance the diagnostic accuracy, but this technique cannot be applied in all such patients.
- Published
- 1993
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