Marek Zygmunt

University of Greifswald, Griefswald, Mecklenburg-Vorpommern, Germany

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Publications (156)473.41 Total impact

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    ABSTRACT: Background: The shortage of skilled personnel is ubiquitous, basic and further training is a key aspect in the recruitment of new medical colleagues. The significance of the nursing practicum in its function as gateway to the gynaecology and obstetrics discipline is practically unexplored. Methods: In an online questionnaire, medical students in all German faculties were questioned about the practica in their courses. The questionnaire reached 9079 medical students. 149 participants in nursing practica were selectively asked to answer 140 questions. We analysed those students who could, on the basis of their experiences in nursing practica, imagine undertaking an internship (clinical elective) in gynaecology (internship yes “Iy”) separately from those who could not or were still undecided (internship no “In” or, respectively, internship perhaps “Ip”). Results: Altogether 149 medical students who participated in a nursing practicum in the gynaecology discipline were selected, of these 94.9 % were female. 92 (61.7 %) of the students replied that, after their gynaecological nursing practicum, they wanted to undertake an internship in gynaecology (Iy); 39 (26.2 %) answered negatively (In) and 18 (12.1 %) were still undecided (Ip). With regard to the parameters gender, age and duration of study, there were no significant differences among the 3 groups (χ2 0.83). Besides the didactic and professional quality of the training, Iy also mentioned having had a higher practical orientation. They attained their aims more frequently, were better integrated in the health-care team and acquired more practical competences. Satisfaction with the practicum was evaluated as highest among the Iy. Discussion: Those students who could imagine taking an internship in gynaecology were seen to be more satisfied with their practica than those participants who declined or were undecided. The high proportion of females is an early indicator for a feminisation of the specialty. If necessary this could be countered with the help of nursing management.
    No preview · Article · Dec 2015 · Geburtshilfe und Frauenheilkunde
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    Full-text · Dataset · Dec 2015
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    Full-text · Dataset · Dec 2015
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    ABSTRACT: Abiraterone provides significant survival advantages in prostate cancer (PC), however, the current understanding of the molecular mechanisms of abiraterone is still limited. Therefore, the abiraterone impact on androgen receptor (AR)-positive LNCaP and AR-negative PC-3 cells was assessed by cellular and molecular analyses. The present study demonstrated, that abiraterone treatment significantly decreased cell growth, AR expression, and AR activity of AR-positive LNCaP cells. Notably, AR-negative PC-3 cells exhibited comparable reductions in cellular proliferation, associated with DNA fragmentation and pro-apoptotic modulation of p21, caspase-3, survivin, and transforming growth factor β (TGFβ). Our observations suggest that the attenuation of AR signaling is not the only rationale to explain the abiraterone anticancer activity. Abiraterone efficacy may play a more global role in PC progression control than originally hypothesized. In this regard, abiraterone is not only a promising drug for treatment of AR-negative PC stages, even more, abiraterone may represent an alternative for treatment of other malignancies besides prostate cancer.
    Full-text · Article · Nov 2015 · International Journal of Oncology
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    ABSTRACT: Successful of eutherian mammal evolution was certainly supported by the ability of the already existing immune system to be adapted to the presence of the semi-allogeneic fetus without losing the capability to defend the mother against infections. This required the acquisition of highly regulated and coordinated immunological mechanisms. Failures in the development of these strategies lead not only to the interruption of pregnancy but also compromise maternal health. Alongside with changes on the cytokine profile, expansion of tolerogenic dendritic and regulatory T cells, a profound adaptation of the B cell compartment during pregnancy was recently described. Among others, suppression of B cell lymphopoiesis and B cell lymphopenia were proposed to be protective mechanisms tending to reduce the occurrence of auto-reactive B cells that might recognize fetal structures and put pregnancy on risk. On the other hand, expansion of the pre-activated marginal zone (MZ) B cell phenotype was described as a compensatory strategy launched to overcome B cell lymphopenia thus ensuring a proper defense. In this work, using an animal model of pregnancy disturbances we demonstrated that suppression of B cell lymphopoiesis as well as splenic B cell lymphopenia occur independently of pregnancy outcome. However, only animals undergoing normal pregnancies but not those suffering from pregnancy disturbances could induce an expansion and activation of the MZ B cells. Hence our results clearly show that MZ B cells, probably due to the production of natural protective antibodies, participate in the fine balance of immune activation required for pregnancy wellbeing.
    No preview · Article · Oct 2015 · Reproduction
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    ABSTRACT: Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
    No preview · Article · Sep 2015 · Nature Genetics
  • Julia Spratte · Anne Oemus · Marek Zygmunt · Herbert Fluhr
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    ABSTRACT: The pro-inflammatory T helper (Th)-1 cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are immunological factors relevant at the feto-maternal interface and involved in the pathophysiology of implantation disorders. The synergistic action of the two cytokines has been described with regard to apoptotic cell death and inflammatory responses in different cell types, but little is known regarding the human endometrium. Therefore, we examined the interaction of TNF-α and IFN-γ in human endometrial stromal cells (ESCs). ESCs were isolated from specimens obtained during hysterectomy and decidualized in vitro. Cells were incubated with TNF-α, IFN-γ or signaling-inhibitor. Insulin-like growth factor binding protein (IGFBP)-1, prolactin (PRL), leukemia inhibitory factor (LIF), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted protein (RANTES) and monocyte chemotactic protein (MCP)-1 were measured using ELISA and real-time RT-PCR. Nuclear factor of transcription (NF)-κB and its inhibitor (IκBα) were analyzed by in-cell western assay and transcription factor assay. TNF-α inhibited and IFN-γ did not affect the decidualization of ESCs. In contrast, IFN-gamma differentially modulated the stimulating effect of TNF-alpha on cytokines by enhancing IL-6, RANTES and MCP-1 and attenuating LIF mRNA expression. These effects were time- and dose-dependent. IFN-γ had no impact on the initial activation of NF-κB signaling. Histone-deacetylase activity was involved in the modulating effect of IFN-γ on RANTES secretion. These observations showed a distinct pattern of interaction of the Th-1 cytokines, TNF-α and IFN-γ in the human endometrium, which could play an important role in the pathophysiology of implantation disorders.
    No preview · Article · Sep 2015 · Reproductive biology
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    ABSTRACT: Options for pharmacological analgesia in patients who have undergone Caesarean section (CS) are often restricted. Acupuncture is a promising tool for treating postoperative pain. We aimed to study the feasibility and acceptability of acupuncture as an additional method of analgesia in CS patients in a prospective observational pilot investigation. Twenty-two patients scheduled for elective CS under spinal anaesthesia were enrolled according to set inclusion criteria. Each patient received auricular and body acupuncture with 20 indwelling fixed needles according to previously validated protocols of acupuncture for postoperative analgesia. Pain intensity on an 11-point verbal rating scale (VRS-11, where 0=no pain and 10=maximal pain), analgesia-related side effects, time to mobilisation and Foley catheter removal after CS, and patients' compliance and satisfaction with treatment of pain on a 5-point VRS (VRS-5, where 1=excellent; 5=bad) were recorded. Twenty patients were included in the final analysis. One patient was disturbed by paraesthesia at the site of needling. All other patients tolerated acupuncture well. Pain intensity on movement on the first postoperative day was 4.3±2.4 (mean±SD; VRS-11) and decreased to 2.2±1.2 on the day of discharge. Patient satisfaction was 1.9±0.8 (mean±SD; VRS-5) and compliance (rated by their nurses) was 1.5±0.5 (mean±SD; VRS-5). Acupuncture for additional analgesia after CS was well accepted. The primary outcome measurement was feasible and allowed the sample size to be calculated for a future randomised controlled trial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    No preview · Article · Aug 2015 · Acupuncture in Medicine
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    ABSTRACT: Both villous and extravillous trophoblast (EVT) cells produce a wide range of cytokines and also respond to them in autocrine and paracrine manner. Deregulation of cytokine secretion may lead to various pathologic conditions including preeclampsia. IL-8, a pro-inflammatory cytokine, regulates various cellular functions such as neutrophil trafficking, cell adhesion, tumor growth and has a role in placental development. IL-8 also promotes trophoblast cell migration and invasion, and stimulates the secretion of progesterone. The induction and mechanism of IL-8 secretion by EVT is still unknown. IL-8 mRNA expression and secretion was determined using real-time PCR and ELISA respectively. To identify the mechanism of IL-8 expression and secretion, selective antagonists and agonist of S1P receptor subtypes, Rac1 and Rho-kinase inhibitors were used. We found that S1P induces IL-8 gene expression and protein secretion in EVT derived HTR-8/SVneo cells but not in BeWo cells. SEW2781, the selective agonist of S1PR1, induced IL-8 gene expression but not protein secretion. The specific S1PR2 inhibitor JTE-013 could drastically inhibit IL-8 secretion. Furthermore, pre-treatment of cells with the selective S1PR1/S1PR3 antagonist VPC23019 inhibited IL-8 secretion by ∼45%. Selective Rho-kinase inhibitor Y27632 and Rac1 inhibitor NSC23766 could block IL-8 secretion in these cells. In this study, we could show for the first time that S1P induces IL-8 mRNA expression and protein secretion in EVT cell line. S1P-induced IL-8 gene expression is mainly regulated via S1PR1 and its secretion is regulated through S1PR2 receptor subtype. Rho GTPases signaling is essential for S1P-induced IL-8 secretion. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Aug 2015 · Placenta
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    ABSTRACT: Ovarian cancer (OC) is a major problem in gynecological oncology. Options for diagnosis and treatment of advanced stages and thus for patient prognosis have not been improved substantially over the past decades. Heat shock proteins (HSP) are characterized as stress-induced molecular chaperones performing cell survival factor functions. In cancer cells, various crucial and clinically important cell responses are vitally influenced and modulated by HSPs, e.g., cell growth and treatment resistance. Despite the limited knowledge on HSPs in OC progression, their roles as biomarkers, prognostic factors and their drug target properties appears promising for future clinical applications and therapeutic approaches. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Aug 2015 · Critical reviews in oncology/hematology
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    ABSTRACT: More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
    No preview · Article · Aug 2015 · Nature Communications
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    ABSTRACT: To study the impact of heparins on chemokines in decidualized human endometrial stromal cells (ESCs) in vitro. In vitro experiment. Research laboratory. Premenopausal women undergoing hysterectomy for benign reasons. ESCs were isolated from hysterectomy specimens, decidualized in vitro and incubated with unfractionated heparin and low-molecular-weight heparins (LMWHs) as well as tumor necrosis factor (TNF) α or thrombin with or without heparins. Chemokines CXCL1, CXCL5, CXCL8, CCL2, and CCL5 were measured with the use of ELISA, and CXCL5, CXCL8, CCL2, and CCL5 were detected with the use of real-time reverse-transcription polymerase chain reaction. Cell viability was determined with the use of a fluorometric assay. TNF-α and thrombin stimulated distinct patterns of chemokines in ESCs. Unfractionated heparin and LMWHs attenuated the TNF-α-mediated induction of CXCL8 and enhanced CXCL5, CCL2, and CCL5. The stimulating effect of thrombin on CXCL8 could be inhibited by heparin, whereas heparin had no impact on thrombin-induced CXCL1 and CCL2. Nuclear factor of transcription κB signaling mediated the effects of TNF-α. The effects of thrombin were mediated via extracellular signal-regulated protein kinases 1/2. Heparins have modulating effects on TNF-α- and thrombin-induced endometrial chemokines, which might have implications in the regulation of endometrial receptivity and early implantation. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Fertility and sterility
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    ABSTRACT: AdditionDamián O. Muzzio, Rocío Soldati, Jens Ehrhardt, Kirsten Utpatel, Matthias Evert, Ana C. Zenclussen, Marek Zygmunt, and Federico Jensen. B Cell Development Undergoes Profound Modifications and Adaptations During Pregnancy in Mice. Biol Reprod 2014; 91(5):115, 1-11. DOI:10.1095/biolreprod.114.122366The corresponding author for the manuscript referenced above, Dr. Federico Jensen, has recently moved. The new contact information for Dr. Jensen is listed below.Correspondence: Federico Jensen, Laboratory for Immunology of Pregnancy, Center for Pharmacological and Botanical Studies (CEFYBO-CONICET-UBA), Paraguay 2155 floor 16th, Buenos Aires C1121ABG, Argentina. E-mail: federico.jensen@outlook.com. Copyright 2015 by The Society for the Study of Reproduction.
    Full-text · Article · Jan 2015 · Biology of Reproduction
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    Full-text · Article · Dec 2014
  • Prof. Dr. M. Zygmunt · C. Kampe
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    ABSTRACT: Hintergrund Im Beitrag wird die wachsende Bedeutung von Drittmitteln für die Finanzierung von Innovation und Forschung im Hochschulbereich mit besonderem Blick auf das Fach Gynäkologie und Geburtshilfe beleuchtet. Die Finanzierung der Hochschulen ist – nicht zuletzt durch stagnierende Grundmittel – zunehmend abhängig von Drittmitteln. In diesem Zusammenhang werden vor allem die Möglichkeiten dargestellt, die sich durch die Drittmittelfinanzierung für die Forschenden ergeben – mit dem Fokus auf die Entwicklung von Forschungskarrieren. Diskussion Noch zu wenige junge Nachwuchswissenschaftler können bisher in unserem Fach für den Weg der Forschung motiviert werden – der erste Schritt, ein Forschungsstipendium, wird von ihnen nur sehr selten in Erwägung gezogen. Umfangreiche Unterstützung bieten sowohl Projektträger, wie die DFG des BMBF, als auch die Drittmittelabteilungen an den Hochschulen. Hier werden Förderquellen für konkrete Forschungsideen identifiziert und entsprechende Hilfestellungen in der Phase der Antragstellung und darüber hinaus gegeben. Es liegt an uns, innovative Ideen zu entwickeln und diese Chancen der Förderung von innovativen Forschungsvorhaben in unserem Fachbereich besser zu nutzen. Denn die Möglichkeiten sind zahlreich, gleich ob wir an den wissenschaftlichen Nachwuchs oder große Kooperationsprojekte denken. Fazit Für den Fachbereich ist es von großer Bedeutung, die Sichtbarkeit in der hochschulmedizinischen Forschung neben den anderen Bereichen zu erhöhen.
    No preview · Article · Dec 2014 · Der Gynäkologe
  • S. Wetzka · S. Fleßa · A. Lange · M. Zygmunt

    No preview · Article · Nov 2014 · Value in Health
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    ABSTRACT: According to the literature, ductoscopy is gaining increasing importance in the diagnosis of intraductal anomalies in cases of pathologic nipple discharge. In a multicenter study, the impact of this method was assessed in comparison with that of standard diagnostics. Between 09/2006 and 05/2009, a total of 214 patients from 7 German breast centers were included. All patients underwent elective ductoscopy and subsequent ductal excision because of pathologic nipple discharge. Ductoscopy was compared with the following standard diagnostics: breast sonography, mammography, magnetic resonance imaging (MRI), galactography, cytologic nipple swab, and ductal lavage cytology. The histological and imaging results were compared and contrasted to the results obtained from the nipple swab and cytologic assessment. Sonography had the highest (82.9%) sensitivity, followed by MRI (82.5%), galactography (81.3%), ductoscopy (71.2%), lavage cytology (57.8%), mammography (57.1%), and nipple swab (22.8%). Nipple swabs had the highest (85.5%) specificity, followed by lavage cytology (85.2%), ductoscopy (49.4%), galactography (44.4%), mammography (33.3%), sonography (17.9%), and MRI (11.8%). Currently, ductoscopy provides a direct intraoperative visualization of intraductal lesions. Sensitivity and specificity are similar to those of standard diagnostics. The technique supports selective duct excision, in contrast to the unselective technique according to Urban. Therefore, ductoscopy extends the interventional/diagnostic armamentarium. © 2014 S. Karger GmbH, Freiburg.
    No preview · Article · Oct 2014 · Oncology Research and Treatment
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    ABSTRACT: Background and purpose 40% of all initial infections with Toxoplasma gondii during pregnancy develop into connatal toxoplasmosis, which is associated with the risk of severe damage to the CNS, frequent premature deliveries, and stillbirths. In Germany, toxoplasmosis immunity screenings are not covered by the state health insurance as a general preventive care service, in contrast to screening for rubella immunity. Therefore, we analysed the impact of socioeconomic factors on the efficiency of private toxoplasmosis screening during pregnancy in a population-based study. Material and methods Toxoplasmosis and rubella screening data were collected from 5403 mothers during the period from May 2002 to June 2008 within the population-based Survey of Neonates in Pomerania (SNiP). Results At the first screening, 34.2% of expecting mothers were immune to toxoplasmosis, 75.2% had immunity against rubella after active immunisation. Negative immunity for toxoplasmosis was found in 39.7% and in 7.7% for rubella (missing information: toxoplasmosis: 25.8%; rubella 17.2%). Less than 10% of the women without immunity participated in a second toxoplasmosis screening. An active toxoplasmosis infection was found in 0.3% (n = 17) women during pregnancy. There were no infections with the rubella virus. Pregnant women with a higher socioeconomic status participated in screenings considerably more frequently. Conclusion Our population-based sample demonstrated a substantial risk of toxoplasmosis infection during pregnancy in contrast to the rubella risk. Furthermore, lower socioeconomic status adversely affects the rate of toxoplasmosis screening. This data support the need for toxoplasmosis screening for pregnant women as a general health care benefit covered by insurance.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Pregnancy hides an immunological riddle combining two antagonistic characteristics of immunology: the existence of a tolerance that allows the gestation of a semi-allogeneic fetus, and the proper protection against pathogens threatening health of the immunocompromised mother. Despite the fundamental role that B cells play in orchestrating an immune response, their behavior in the context of pregnancy has been barely investigated. Here we demonstrated that numbers of pre/pro and immature B cells were progressively diminished in the bone marrow (BM) of pregnant mice, leading to a reduced influx of B cells in blood and spleen. Correspondingly, lower levels of B cell-activating factor of the TNF family (BAFF) were observed in serum of pregnant mice. In contrast to immature B cells, mature B cells were accumulated in the BM during pregnancy. Accordingly, higher numbers of mature B cells were observed in the lymph nodes draining the uterus as well as in the peritoneal cavity of pregnant mice, both tissues in close contact with the fetuses. Despite an increase in spleen size, pregnant mice showed lower numbers of splenic B cells, which was mirrored by lower numbers of immature and FO B cells. However, marginal zone (MZ) B cells in the spleen increased during pregnancy. Additionally, serum IgM, IgA and IgG3 titers were elevated in pregnant mice. Collectively, our data show how the B cells compartment adapts to the presence of the semi-allogeneic fetus during gravidity. Summary sentence: A diversity of B cell subsets is altered during pregnancy; a possible attempt of physiological adaptation to the new challenges affecting this period.
    Full-text · Article · Sep 2014 · Biology of Reproduction
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    ABSTRACT: Ovarian cancer still represents a challenge in gynecological oncology. Most patients are diagnosed in an advanced tumor stage. No specific screening or prevention strategies for ovarian cancer exist as of yet. Interleukin 8 (IL-8) is a pro-inflammatory chemokine known for its angiogenetic activity, and is supposedly responsible for tumor-associated angiogenesis in several malignant tumors. The aim of the study was to investigate the susceptibility of patients with an IL-8 gene polymorphism to developing ovarian cancer. Four single nucleotide polymorphisms (SNPs) (IL-8 −251, IL-8 +781, IL-8 +1633 and IL-8 +2767) of the IL-8 gene were screened, using the PCR method in 268 patients with ovarian cancer and 426 healthy women as a control group. Significant associations were noted in patients with the IL-8 +781 (T/T) genotype (p = 0.0048) with increased frequencies of ovarian cancer, while women with the IL-8 +781 (C/C) allele suffer from ovarian cancer significantly less frequently (p = 0.0003). Furthermore, the IL-8 +2767 (T/T) genotype is also associated with a higher risk of ovarian cancer (p = 0.0177). Our results indicate, for the first time, that IL-8 polymorphism is associated with ovarian cancer.
    Full-text · Article · Aug 2014 · Cytokine

Publication Stats

2k Citations
473.41 Total Impact Points

Institutions

  • 2007-2015
    • University of Greifswald
      • Department of Obstetrics and Gynecology
      Griefswald, Mecklenburg-Vorpommern, Germany
  • 1997-2008
    • Justus-Liebig-Universität Gießen
      • Department of Obstetrics and Gynaecology
      Giessen, Hesse, Germany
  • 2006
    • Universitätsklinikum Gießen und Marburg
      • Abteilung Frauenheilkunde und Geburtshilfe
      Marburg, Hesse, Germany
  • 1999-2005
    • Lawson Health Research Institute
      London, Ontario, Canada