J Dietl

Universität Würzburg, Würzburg, Bavaria, Germany

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Publications (153)291.32 Total impact

  • Article: Thrombopoietin modulates the proliferation, migration and cytokine profile of decidual cell subsets during early gestation.
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    ABSTRACT: During early gestation, a considerable increase of different leukocyte subsets can be observed in the decidualized endometrium concomitantly to the invasion of cytotrophoblast cells (CTB). To date, it is still in question which factors induce this accumulation of immune cells and whether it is evoked by an in-situ proliferation or by a migratory process. Studies on hepatoblastoma cells identified thrombopoietin (TPO) as a novel factor which elicits dose dependent chemotactic and chemokinetic effects. However, the impact and function of TPO on decidual cells has not been clarified yet.This study analyses the expression and function of TPO and its receptor c-Mpl in decidua during early gestation.Applying western blot analysis, we detected that TPO is expressed by decidual immune cells (uNK cells and CD14+ monocytes) as well as CTB and decidual stromal cells (DSC). Expression of the different isoforms of c-Mpl was found in uNK cells, CD14+ monocytes and DSC. Studying the signalling pathway proteins in uNK cells, an activation of STAT3/Tyr by TPO was detected. The investigation of the proliferative effects of TPO on the decidual cell subsets revealed that TPO enhances the proliferation of uNK cells and CTB. No change of the proliferative activity after TPO incubation was found in DSC and even a decrease in CD14+ monocytes. In addition, TPO was observed to induce significantly the migratory activity of uNK cells, CD14+ monocytes and CTB. Investigating the effects of TPO on the cytokine profile of the isolated decidual cells, we observed a decrease of the secretion of IL-8, IL-10 and IL-1β of isolated uNK cells, CD14+ monocytes and CTB, although these changes did not reach statistical significance.Thus, we here identified TPO as a novel factor modulating the proliferation, migration and possibly cytokine secretion of decidual cell subsets.
    Molecular Human Reproduction 01/2013; · 3.85 Impact Factor
  • Article: [Severe maternal hepatopathies in the peripartum period - a case series with review of the literature focusing on pathogenesis and differential diagnosis].
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    ABSTRACT: A severe hepatopathy constitutes a serious threat during pregnancy and poses considerable challenges to the treating physicians. A broad spectrum of pregnancy-dependent or independent diseases like HELLP-syndrome, liver infection or acute fatty liver of pregnancy (AFLP) is characterized by these affections of the liver. In this study, we present a series of 3 cases with life-threatening hepatopathies and discuss the current state of the literature. A special focus is placed on pathogenesis and differential diagnosis.Pathological, radiological and gynaecological/surgical procedures were performed according to the current German guidelines. Laboratory tests were conducted in the clinics' routine diagnostics section. The existing literature was reviewed via the US National Library of Medicine database "PubMed.gov".The first patient had been afflicted by a fulminant HELLP syndrome causing delivery after 32 weeks of pregnancy. Consecutively, she suffered a sub-total liver infarction followed by a severe coagulopathy and septic peritonitis. The second patient was diagnosed with HELLP syndrome at 36 weeks of pregnancy. The initially mild syndrome exacerbated after delivery leading to haemorrhagic shock and acute renal failure. In the third case, a woman with asymptomatic hepatitis B delivered in the 36th week of pregnancy. Post partum, her pre-existing condition worsened fulminantly resulting in sub-acute liver dystrophy and massive coagulopathy.Whenever a hepatopathy occurs during pregnancy, several divergent diagnoses with severe implications and different aetiopathologies have to be considered. Diagnostic and therapeutic strategies have to be weighed quickly to enable a fast, interdisciplinary cooperation in order to prevent fatal outcomes.
    Zeitschrift für Geburtshilfe und Neonatologie 12/2012; 216(6):277-84.
  • Article: Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro.
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    ABSTRACT: Platinum resistance is the most crucial problem for treatment of ovarian cancer. Increasing evidence points towards AKT overexpression as a mechanistic reason for this clinical condition. The present study evaluates the effect of overexpression and downregulation of AKT on the sensitivity to cisplatin in a platinum-resistant human ovarian cancer cell line and the corresponding platinum-sensitive parental cell line. A2780 and A2780cis ovarian cancer cell lines were stably transfected with an AKT-sense and AKT-antisense plasmid. Successful transfection was evaluated by western blot analysis. Cytotoxic effects of cisplatin were evaluated by metabolic (MTT) and clonogenicity assays as well as by FACS analysis. AKT overexpression (confirmed by western blotting) converted platinum-sensitive A2780 into platinum-resistant cells as shown by MTT assay. Importantly, platinum resistance of A2780cis cells could be reversed by downregulation of AKT, as demonstrated by MTT and clonogenicity assays and FACS analysis. Our data provide strong evidence that cisplatin resistance in ovarian cancer is mediated by AKT overexpression and can be overcome by AKT downregulation, thus, providing a rationale for clinical phase II/III studies combining AKT inhibitors with cisplatin.
    Oncology Reports 09/2012; 28(6):2023-8. · 1.84 Impact Factor
  • Article: [Acute foeto-foetal transfusion syndrome--case report and review of the literature].
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    ABSTRACT: The perinatal morbidity and mortality risk in monochorionic twin pregnancies are 3-5-fold increased compared to those of dichorionic twin pregnancies. Partially, this is due to the higher rate of preterm delivery but also to the twin-to-twin transfusion syndrome (TTTS). Caused by unidirectional blood flow via placental anastomoses, the TTTS leads to weight differences of more than 20% between monochorial twins. The blood donor often shows oligohydramnios, whereas the recipient shows polyhydramnios. Lewi et al. demonstrated, in a study with 202 monochorionic twin pregnancies, a 9% rate of severe TTTS. The mortality of this complication is about 90% when untreated. In contrast to the chronic TTTS, little is known about the acute intrapartal one, which is characterised by anaemia and hypovolaemia of the donor and polyglobulia of the recipient without significant weight differences between the two. In most cases, anaemia occurred after normal delivery of the first twin. Still, there are no means or signs for early detection. We describe the case of a 30-year-old primigravida with a monochorionic diamniotic twin pregnancy. During pregnancy, no evidence of TTTS could be detected. At 37 + 1 weeks gestation labour was induced with prostaglandin-containing gel. Both foetuses showed cephalic presentation. The CTG of the first twin showed a conspicuous heart rate. After labour the first twin presented with anaemia and hypovolaemic shock, the APGAR was 2/7/8. The infant's haemoglobin was 13.7 g/dL. After delivery, the second twin with APGAR 10/10/10 showed a haemoglobin of 19.6 g/dL, which is in the upper normal range. Their birth weights differed by merely 10.4%. Acute TTTS is frequently characterised by anaemia and hypovolaemia of the second twin. In our case of a monochorionic twin delivery with acute TTTS the donor was born first. Early diagnosis and neonatal intervention is essential for reducing postnatal morbidity and mortality.
    Zeitschrift für Geburtshilfe und Neonatologie 06/2012; 216(3):147-9.
  • Article: Fetale gastrointestinale Anomalie
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    ABSTRACT: Eine 17-jährige I-Gravida stellte sich mit 20SSW wegen einer fetalen Anomalie vor. Sonographisch zeigte sich ein extraabdominal gelegenes Darmkonvolut, sodass die Diagnose Gastroschisis gestellt wurde. Bei gleichzeitig vorhandener Dilatation der intraabdominal gelegenen Darmschlingen wurde die Verdachtsdiagnose Darmatresie gestellt. Aufgrund der Zunahme sowohl der extra- als auch der intraabdominal gelegenen Darmschlingen wurde mit 31SSW eine elektive Sectio durchgeführt. Bei der am gleichen Tag durchgeführten Operation zeigte sich neben der Gastroschisis eine Duodenalatresie, die primär versorgt werden konnte. A 17-year-old primigravida in the 20th week of gestation was investigated due to a suspected fetal anomaly. Gastroschisis was diagnosed based on extraabdominal bowels in the prenatal ultrasound examination. Because of intraabdominal bowel dilation, atresia was suspected. An increase in extra- and intraabdominal bowel dilation led to an elective ceserean section at 31 weeks of gestation. On the same day, surgery was performed with primary closure of the abdominal wall and resection of the duodenum because of duodenal atresia. SchlüsselwörterGastroschisis–Bauchwanddefekt–Darmdilatation–Darmatresie–Duodenalobstruktion KeywordsGastroschisis–Abdominal wall defect–Bowel dilation–Atresia–Duodenal obstruction
    Der Gynäkologe 05/2012; 44(2):150-154.
  • Article: Intrathorakale zystisch-solide Raumforderung, Mediastinalverlagerung und Polyhydramnion
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    ABSTRACT: Im Zweittrimesterscreening (19. SSW) sonographisch auffällige zystisch-solide Raumforderung in der linken Lunge, Polyhydramnion, Mediastinalverschiebung mit konsekutiver Rechtsverlagerung des Herzens und hypoplastische rechte Lunge. Keine weiteren Fehlbildungen. Sectio caesarea mit 26SSW wegen vorzeitigem Blasensprung und fetaler Bradykardie. Frühgeborenes mit schwerem Atemnotsyndrom, Bestätigung der vermuteten kongenitalen zystisch-adenomatoiden Lungenmalformation. Teilresektion des linken Unterlappens im Alter von vier Monaten. Gute Kindsentwicklung ohne schwerwiegende pulmonale Beeinträchtigung nach einem Jahr. Computertomographisch Nachweis von Restbefunden beschränkt auf linken Unterlappen. Second trimester screening (19 gestational weeks) with sonography showed a cystic solid mass of the left lung, polyhydramnios and mediastinal shift causing cardiac dextroposition and a hypoplastic right lung. No other anomalies were present. At 26 gestational weeks a cesarean section was carried out due to preterm rupture of membranes and fetal bradycardia. The preterm infant presented with severe respiratory distress syndrome and the suspected congenital pulmonary airway malformation was confirmed. A partial resection of the left lower pulmonary lobe was carried out at the age of 4 months. The infant showed good development without severe impairment of pulmonary function after 1 year. Computed tomography revealed residuals of the malformation restricted to the left lower pulmonary lobe. SchlüsselwörterHamartom–Malformation–Hypoplasie–Amnionflüssigkeit–Pränatale Diagnose KeywordsHamartoma–Malformation–Hypoplasia–Amniotic fluid–Prenatal diagnosis
    Der Gynäkologe 05/2012; 44(7):563-565.
  • Article: PI3K inhibitor D-116883 is effective in in vitro models of ovarian cancer.
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    ABSTRACT: D-116883 (Aeterna Zentaris GmbH, Frankfurt, Germany) is an orally effective drug that acts via inhibition of phosphatidylinositol 3-kinase (PI3K). The PI3K/AKT signal transduction pathway is involved in ovarian cancer tumorigenesis. Phosphatase and Tensin homolog (PTEN) loss and other activating mutations frequently contribute to the activation of this pathway. We tested whether D-116883 exerts cytostatic effects in in vitro models of ovarian cancer and analyzed the induced programmed cell death. We evaluated the potency of D-116883 in four ovarian carcinoma cell lines with different cellular assays. The effects of D-116883 on cell proliferation was analysed by crystal-violet staining and tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay. The capacity for anchorage-independent growth was analyzed in two ovarian carcinoma cell lines without and with D-116883 addition by using the soft agar assay. Fluorescence activated cell sorting (FACS) cell cycle analyses were performed. Cells were incubated with multicaspase inhibitor benzyloxycarbonyl-val-ala-asp(OMe)-fluoromethylketone (zVAD) and inhibitor of necroptosis necrostatin. Growth inhibition occurred in all ovarian carcinoma cell lines studied (A2780, A2780cis, OAW42 and SKOV3) in a micromolar range (IC(50)<1 μM). By using soft agar assay, a reduced capacity for anchorage-independent growth, a hallmark of tumor cells, caused by D-116883 was demonstrated. Cell cycle analyses showed that D-116883 dose-dependently increased apoptotic cells. Multicaspase inhibitor zVAD and inhibitor of necroptosis necrostatin did not abrogate the growth-inhibiting effect of the compound. PI3K inhibitor D-116883 showed substantial cytotoxic effects in various in vitro models of ovarian cancer. Our results make D-116883 a good candidate for further ovarian cancer research including in vivo experiments.
    Anticancer research 05/2012; 32(5):2035-41. · 1.73 Impact Factor
  • Article: Peptidomimetic GnRH antagonist AEZS-115 inhibits the growth of ovarian and endometrial cancer cells.
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    ABSTRACT: AEZS-115 (Aeterna Zentaris GmbH, Frankfurt/M, Germany) is an orally active peptidomimetic antagonist of gonadotropin-releasing hormone (GnRH). In various tumors, an autocrine growth-promoting loop has been described for GnRH. The current study evaluates the antitumor activity and mechanism of action of AEZS-115 in models of ovarian and endometrial cancer. Human A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells were analyzed for GnRH receptor expression by reverse transcription polymerase chain reaction (RT-PCR). These cell lines were incubated with AEZS-115 at 1, 10 and 100 μM for 24 h, 48 h, and 72 h and the number of viable cells was determined. Fluorescence activated cell sorting (FACS) cell cycle analyses were performed with increasing concentrations of AEZS-115. Co-treatment experiments of cancer cells with GnRH antagonist cetrorelix and peptidomimetic GnRH antagonist AESZ-115 were carried out. A2780, Acis2780, OAW-42, Ovcar-3, SKOV-3, Hec1A and Ishikawa cells expressed GnRH receptors as demonstrated by RT-PCR. GnRH antagonist AEZS-115 inhibited growth of all cell lines in a dose- and time-dependent manner. Half maximal inhibitory concentration (IC(50)) values at 48 h of incubation were between 7 and 17.5 μM and for 72 h between 4.5 and 12.5 μM. IC(50) values for ovarian and endometrial cancer cells were rather similar. These results were obtained by tetrazolium salt [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTT] assay and confirmed by additional crystal violet staining. Cell cycle FACS analysis revealed that AEZS-115 dose-dependently increased the fraction of apoptotic cells. Co-treatment experiments carried out with AEZS-115 and peptidic GnRH-antagonist cetrorelix suggest that the antitumor effect of AEZS-115 is not mediated by blockade of the GnRH receptor. GnRH antagonist AEZS-115 exhibited substantial antitumor activity in ovarian as well as endometrial cancer cell lines. However, this antitumor effect was not mediated by the tumoral GnRH receptors. To identify the mechanism of action of this compound, further research is warranted. Its in vitro antitumor activity makes AEZS-115 a promising candidate for in vivo studies of ovarian and endometrial cancer.
    Anticancer research 05/2012; 32(5):2063-8. · 1.73 Impact Factor
  • Article: Endokrine Therapie der Zukunft
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    ABSTRACT: Der vorliegende Beitrag behandelt die medikamentöse Tumortherapie, basierend auf dem Einsatz von Antagonisten des Gonadotropin-Releasing-Hormon (GnRH) und des Growth-Hormon-Releasing-Hormon (GHRH) sowie Analoga des GnRH als Trägersubstanz für Chemotherapeutika. Mammakarzinome exprimieren Rezeptoren für GnRH in 50% und für GHRH in 35% der Fälle. Die Expression und der wachstumsstimulierende Effekt der jeweiligen Liganden GnRH und GHRH sind in dieser Tumorentität ebenfalls nachgewiesen, sodass sich hier eine „targeted therapy“ mit antagonistischen Analoga dieser Peptidhormone anbietet. Andererseits können GnRH-Rezeptoren auf Mammakarzinomzellen auch als Zielstrukturen für eine rezeptorvermittelte Chemotherapie mit zytotoxischen Hybriden, bestehend aus einem GnRH-Analogon und einem zytotoxischen Radikal, dienen. Durch diese Therapieform soll eine höhere Wirkstoffkonzentration des Chemotherapeutikums im Tumor erreicht werden. So soll die antitumorale Wirkung gesteigert und gleichzeitig sollen die Nebenwirkungen minimiert werden. Im Folgenden werden die zu diesem Thema durchgeführten präklinischen und klinischen Studien zusammengefasst. This article reviews the recent literature on directed systemic tumor therapy based on antagonists of gonadotropin-releasing hormone (GnRH) and growth hormone-releasing hormone (GHRH) as well as analogs of GnRH as carriers for chemotherapeutic agents. Human breast cancer is known to express receptors for GnRH and GHRH in 50% and 35% of the cases, respectively. The expression and the growth-stimulating effect of GnRH and GHRH ligands have been previously described for breast cancer. Thus, targeted therapy with antagonistic analogs of these peptide hormones is a promising option in this tumor entity. Alternatively, GnRH receptors on breast cancer cells can be used as target structures for cytotoxic hybrid molecules comprising an agonistic analog of GnRH and a cytotoxic radical. This therapeutic approach aims at achieving a higher concentration of the cytotoxic radical in the vicinity of the tumor, thus maximizing antitumor effects and minimizing unwanted side effects. The recent preclinical and clinical data on this subject are reviewed. SchlüsselwörterGnRH-GHRH-Zytotoxische Peptidanaloga-Agonisten-Antagonisten KeywordsGnRH-GHRH-Cytotoxic peptide analogs-Agonists-Antagonists
    Gynäkologische Endokrinologie 04/2012; 8(1):47-54.
  • Article: Bildgebende Diagnostik und präoperatives Staging des Endometriumkarzinoms
    N. Dietz, M. Rehn, J. Dietl
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    ABSTRACT: Bei der Therapie des Endometriumkarzinoms steht heute der operative Weg im Vordergrund und ermöglicht den stadiengerechten Einsatz zusätzlicher adjuvanter Maßnahmen. Die Aufgabe der Diagnostik besteht darin, das operative Vorgehen möglichst individuell festzulegen. Der transvaginale Ultraschall ist eine kostengünstige, zumeist schmerz- und komplikationslose Methode in der Diagnostik des Endometriumkarzinoms. Sonographisch beurteilt werden Endometriumdicke, Echostruktur und Endometriumbegrenzung sowie – falls vorhanden – eine intrakavitäre Flüssigkeitsansammlung. Neben der konventionellen transvaginalen Sonographie (TVS) besteht die Möglichkeit einer Dignitätsbeurteilung mittels Farb- und Pulsdopplersonographie, z.B unter Verwendung von Pulsatility-Index und Resistance-Index. Bei der präoperativen Stadieneinteilung stellt die MRT bezüglich der Myometriuminfiltration und des zervikalen Befalls im Vergleich zu TVS und CT die präziseste Methode dar. The surgical approach is nowadays the method of choice for therapy of endometrial carcinoma and permits a stage appropriate application of additional adjuvant measures. The aim of diagnostics is to make the operative procedure as individual as possible. Transvaginal ultrasound is an economic, mostly pain and complication-free method for the diagnostics of endometrial carcinoma. Endometrial thickness, echo structure and endometrial limits as well as the amount of intracavernous fluid when present can all be determined by sonography. In addition to conventional TVS, there is also the possibility to assess the dignity using color and pulse Doppler sonography, e.g. using pulsatility and resistance indices. For preoperative staging MRI is the most precise method for assessing myometrium infiltration and cervical involvement in comparison to TVS and CT.
    Der Onkologe 04/2012; 15(9):856-864. · 0.17 Impact Factor
  • Article: Umbilical cord entanglement in monoamniotic twins.
    Ultrasound in Obstetrics and Gynecology 02/2012; 40(1):121-2. · 3.01 Impact Factor
  • Article: [Sonographic abnormalities of the fetal CNS in the second trimester screening--clarifications according to the new maternity directives].
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    ABSTRACT: Malformations of the central nervous system are among the most frequent congenital anomalies. At best, a qualified and standardised screening of the foetal brain is possible between the 18th and the 22nd week. The newly decided modification of the maternity directives envisages an extended screening upon request. This extended screening refers to the central nervous system and the representation of the ventricles, the evaluation of the head shape and the cerebellum and the back. The examination of the foetal brain should be carried out in a structured way. Three axial planes, the transventricular, the transthalamic and the transcerebellar planes, suffice to represent and measure all structures which are of importance for the screening. In case of ventricular anomalies, anomalies of the head shape, anomalies of the cerebellum and irregularities of the dorsal skin outlined in the second screening a further diagnostic procedure should be initiated. This diagnostic work-up should include a detailed neurosonography, a diagnostic evaluation of the organs and eventually further examination in the form of a caryotyping, determination of the infectology or a foetal MRI. The present article offers an overview of possible CNS abnormalities which could be recognised during the second screening according to the extended maternity directives and describes which differential diagnostics should be considered. In detail, anomalies of the head size (microcephaly, macrocephaly), of the head size (brachycephaly, dolichocephaly, cavities of the cranium, banana sign, etc.,), ventricular abnormalities, anomalies of the cerebellum (cerebellum hypoplasia, abnormal cerebellum shape) and abnormalities of the intermediate line and the intracerebral space requirements are discussed.
    Zeitschrift für Geburtshilfe und Neonatologie 02/2012; 216(1):1-10.
  • Article: [Late interruption of pregnancy due to foetal disease: is an inductive method for the generation of ethical principles applicable?].
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    ABSTRACT: The current study investigates if an inductive method for the generation of ethical principles can be applied to the crucial moral question if late interruption of pregnancy due to fetal disease is ethically adequate. This method originates from the US American philosopher John Rawls and puts a group of so-called competent moral investigators in the beginning of the decision process. These competent moral investigators should be objective, tolerant and sensitive. Thus, real cases which lead to an intuitive, unanimous and clear decision of the competent moral investigators are analysed for the underlying ethical principles. The ethical principles thus detected are then applied to more complicated cases which could not be assessed clearly. In the current study, the case of foetal trisomy 18 and foetal palate cleft could be clearly judged with a yes and a no, respectively, with regard to an approval of late interruption of pregnancy. The underlying ethical principle leading to these decisions is the utilitaristic principle of minimising harm for mother and fetus. We then tried to apply this principle to a case of foetal trisomy 21, however, no clear decision for an approval or a disapproval of the interruption of pregnancy could be found as it was not possible to assess foetal interests.
    Zeitschrift für Geburtshilfe und Neonatologie 12/2011; 215(6):230-3.
  • Article: The fimbria/ovarian surface junction.
    Human Reproduction 12/2011; 26(12):3494-5; author reply 3495. · 4.47 Impact Factor
  • Article: MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts.
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    ABSTRACT: Macrophage inhibitory cytokine-1 (MIC-1) is a multifunctional cytokine produced in high amounts by placental tissue. Inhibiting trophoblast invasion and suppressing inflammation through inhibition of macrophage activation, MIC-1 is thought to provide pleiotropic functions in the establishment and maintenance of pregnancy. So far, little is known about the decidual cell subsets producing MIC-1 and the effect of this cytokine on dendritic cells (DCs), which are known to play a distinct role in the development of pro-fetal tolerance in pregnancy. To identify the decidual cell types expressing and secreting MIC-1, immunohistochemical staining, PCR experiments, western blot analysis and ELISAs were performed. Immature DCs (iDCs) were generated from peripheral blood-derived monocytes and differentiated in the presence of MIC-1 or dexamethasone (Dex) for control. Migratory and proliferative activity of DCs after MIC-1 exposure was investigated by migration and proliferation assay. Cytokine secretion after MIC-1 exposure was tested in isolated uNK cells, isolated CD14+ monocytes, monocyte-derived iDCs and mature DCs. Subsequently, the phenotype of DCs was studied using FACS analysis. To test the T-cell stimulatory capacity of pre-incubated DCs, mixed lymphocyte reaction was applied. Finally, the expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) after the exposure of MIC-1 to maturing DCs was analysed by western blot. Immunohistochemical staining, PCR and western blot experiments demonstrated that MIC-1 is mainly expressed by trophoblast cells and decidual stromal cells. Analysis of the MIC-1 secretion of decidual cell types by ELISA again characterized trophoblast and stromal cells as main producers. The migratory activity of iDCs was significantly induced by MIC-1. No changes in proliferative activity of DCs were observed after MIC-1 pre-incubation. The secretion of pro- or anti-inflammatory cytokines was not affected significantly by MIC-1. Studying the phenotype of DCs after MIC-1 exposure by FACS analysis, we observed that MIC-1 suppresses the expression of typical maturation molecules such as CD25 and CD83 as well as of CD86 during cytokine-induced DC maturation similar to Dex. In addition, T-cell stimulatory capacity of DCs was significantly reduced after MIC-1 exposure. MIC-1 was also able to increase slightly the expression of IDO (a key immunomodulatory enzyme promoting periphereal tolerance) in maturing DCs. We have identified MIC-1 as a novel factor (secreted by decidual cells in early pregnancy) that could promote the increase of a tolerogenic subtype of DC in decidua.
    Human Reproduction 11/2011; 27(1):200-9. · 4.47 Impact Factor
  • Article: [Myocardial infarction in the 34th week of gestation: case report].
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    ABSTRACT: Acute myocardial infarction during pregnancy is a rare event that is often associated with a very high maternal mortality, estimated to be from 19 to 37%. During the last decades the incidence of myocardial infarction during pregnancy has increased . The main contributing factor could be a higher prevalence of the metabolic syndrome. The strongest predictors correlated with a myocardial infarction are hypertension, diabetes mellitus and advanced maternal age. In addition, improved diagnostic tools could explain the elevated incidence of myocardial infarction during pregnancy. In general gestation is not considered a risk factor for myocardial infarction but gravidity is accompanied by an increase in oestrogen and progesterone levels. It is generally accepted that oral contraceptives increase the risk of coronary heart disease. We present a case where a 37-year-old gravida was admitted to hospital with diffuse thoracic pain. In the patient's history, we found several putative reasons for the thoracic pain that pointed to a musculoskeletal cause. Based on an elevation of ischaemic heart markers and continuous non-specific thoracic pain we performed a primary Cesarean section. In the coronary angiography procedure that followed, a thrombotic occlusion of the ramus diagonalis was diagnosed. We here describe the differential diagnosis as well as the problems associated with diagnosing myocardial infarction in the third trimester of pregnancy.
    Zeitschrift für Geburtshilfe und Neonatologie 10/2011; 215(5):209-11.
  • Article: The post-reproductive Fallopian tube: better removed?
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    ABSTRACT: Recently, the distal Fallopian tube has attracted considerable attention not only as site of origin for serous cancer in women with BRCA mutations, but also as the anatomical location where the majority of serous ovarian cancers apparently develop. Consequently, the Fallopian tube may be the unique location where early 'ovarian' cancers can be found--which would contradict the long-standing impression that the ovaries and the Fallopian tubes are always simultaneously involved. Based on the dismal prognosis associated with ovarian cancer and our inability to screen for early-stage disease, we discuss the rationale for introducing salpinges-hysterectomy as new clinical standard for women in need of hysterectomy and further weigh the arguments for and against bilateral salpingectomy as a sterilization method. There is no known physiological benefit of retaining the post-reproductive Fallopian tube during hysterectomy or sterilization, especially as this does not affect ovarian hormone production. On the other hand, the consequences associated with a surgical menopause provide a rationale for preserving the ovaries in premenopausal women. Prophylactic removal of the Fallopian tubes during hysterectomy or sterilization would rule out any subsequent tubal pathology, such as hydrosalpinx, which is observed in up to 30% of women after hysterectomy. Moreover, this intervention is likely to offer considerable protection against later tumour development, even if the ovaries are retained. Thus, we recommend that any hysterectomy should be combined with salpingectomy. In addition, women over 35 years of age could also be offered bilateral salpingectomy as means of sterilization.
    Human Reproduction 08/2011; 26(11):2918-24. · 4.47 Impact Factor
  • Article: [Early diagnosis of gestational diabetes by amniotic fluid insulin levels?].
    U Zollner, M Ahmadi, J Dietl
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    ABSTRACT: Gestational diabetes mellitus (GDM) occurs in 3-5% of all pregnant women. As there is no general screening in Germany, many cases remain undetected. Maternal as well as foetal morbidity are increased in GDM. The aim of this study was to investigate whether amniotic fluid insulin or C-peptide levels, collected by genetic amniocentesis in early pregnancy, are predictive for gestational diabetes. Patients at risk for developing GDM might be identified and treated very early. 260 patients having a genetic amniocentesis were included in this prospective trial. Insulin and C-peptide levels were identified in frozen amniotic fluid samples. All patients should undergo an oral glucose tolerance (oGTT) test at 24-28 weeks of gestation. Only cases with normal genetic screening, normal foetal sonomorphology and birth at term were included in this trial. 90 of 260 patients having an amniocentesis underwent the oGTT and fulfilled all inclusion criteria. GDM was diagnosed in 8 patients, in another 6 patients only one glucose level was out of the normal range. Neither amniotic fluid insulin nor C-peptide levels showed significant differences between normal and GDM pregnancies. The insulin and C-peptide levels did not correlate with blood glucose levels or with foetal weight. In contrast to literature reports, according to these data no relationship between amniotic fluid insulin or C-peptide levels and gestational diabetes can be assumed. Amniotic fluid insulin or C-peptide levels are not predictive for GDM.
    Zeitschrift für Geburtshilfe und Neonatologie 06/2011; 215(3):98-104.
  • Article: [Obstetric management of fetal growth retardation].
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    ABSTRACT: Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment.
    Zeitschrift für Geburtshilfe und Neonatologie 04/2011; 215(2):49-59.
  • Article: Pleomorphic adenoma of the breast initially misdiagnosed as metaplastic carcinoma in preoperative stereotactic biopsy: a case report and review of the literature.
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    ABSTRACT: Pleomorphic adenoma (PA) is a benign mixed tumor found commonly in the salivary glands but rarely in the breast. PA might be misinterpreted clinically and pathologically as a malignant tumor. The differential diagnoses include fibroadenoma, phyllodes tumor and metaplastic carcinoma. Metaplastic carcinoma is the most important entitiy with respect to differential diagnoses, as surgical overtreatment, i.e., mastectomy may be the result. We describe one of the first cases of PA initially misdiagnosed as metaplastic carcinoma (osteoid-chondroid type) in a preoperative stereotactic biopsy and review the literature regarding this entity.
    European journal of gynaecological oncology 01/2011; 32(4):427-30. · 0.47 Impact Factor

Institutions

  • 1970–2013
    • Universität Würzburg
      • Frauenklinik und Poliklinik
      Würzburg, Bavaria, Germany
  • 1989–1999
    • Eberhard-Karls-Universität Tübingen
      • • Institute of Pathology and Neuropathology
      • • Department of Gynecology and Obstetrics
      Tübingen, Baden-Wuerttemberg, Germany
  • 1993
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Wuerttemberg, Germany