1,721,053 research outputs found
Maternal recognition of the (semi) allogeneic fetus during implantation and pregnancy
Get PDFThe recognition of __self__ and __none-self__ is one of the most important mechanisms for the human immune system whether or not to mediate a response. Cells identified as __self__ are tolerated whereas __non-self__ cells induce a cytotoxic reaction. However, during pregnancy the maternal immune system has to tolerate the presence of __non-self__ cells in maternal tissue, as the fetus is semi-allogeneic expressing both maternal and paternal antigens. This immunological acceptance of the __non-self__ fetus for the duration of pregnancy is called the immunological paradox. In this thesis we focused on the maternal immune recognition during implantation, pregnancy and pregnancy complications. Though pregnancy is sometimes considered as an immune deficient condition, both the innate as the adaptive immunity are activated and several aspects of these immune systems are studied in this thesis.Afdeling Verloskunde LUMC, BMA BV (Mosos), Chipsoft BV, Greiner Bio-One, Memidis Pharma BV, Nationaal Referentie Centrum voor Histocompatibiliteit , Stichting HELLP Syndroom , ZonMWUBL - phd migration 201
Immunological challenges during pregnancy : preeclampsia and egg donation
Get PDFHuman pregnancy is an interesting immunological paradox. The fetus is a semi-allograft, carrying paternal and maternal genes but is not rejected by the maternal immune system. The placenta is a key player in maintaining the pregnancy, since this fetus-derived organ is in direct contact with the mother. This thesis describes the results of investigations on the immune regulation at the fetal-maternal interface with emphasis on two immunological challenges during pregnancy. First, preeclampsia, which might be immunologically related to host versus graft disease as seen in solid organ transplantation and second, egg donation (ED) pregnancies, which show that even complete allogeneic fetal allografts can be tolerated by the mother. The immunological mechanisms involved in acceptance of the totally allogeneic fetus in ED pregnancies are not well understood yet. It is possible that it leads to differential immunological regulation. This hypothesis is tested in this thesis. We found differential immunological interactions in successful ED and in preeclamptic pregnancies compared with naturally conceived pregnancies. These results indicate that preeclampsia and ED pregnancies are indeed immunological challenges during pregnancy. It is a scientific challenge to further reveal the immunological mechanisms, contributing to precious information for the fields of immunology, transplantation and obstetrics.Beckman Coulter BV, BMA BV (Mosos), Clean Air Techniek BV, Corning BV, Freya; vereniging voor mensen met vruchtbaarheidsproblemen, Greiner Bio-One, J.E. Juriaanse Stichting, Medical Dynamics, Memidis Pharma BV, Nationaal Referentie Centrum voor Histocompatibiliteit, Rabobank Medicidesk, Stichting HELLP-syndroom, Stichting Oranjekliniek and VPS Diagnostics.UBL - phd migration 201
Rapid aneuploidy detection in prenatal diagnosis : the clinical use of multiplex ligation-dependent probe amplication
Get PDFThe aim of prenatal diagnosis is to provide information on chromosomal abnormalities, in order to allow parents an informed choice on the course of pregnancy. Karyotyping is the diagnostic test used to detect chromosomal abnormalities. It is highly accurate, but labour-intense, costly and slow. Karyotyping detects chromosomal abnormalities with no, mild, or unclear clinical consequences. Rapid aneuploidy detection (RAD) techniques can detect the most common chromosomal abnormalities (trisomies 13, 18, 21, X and Y). Multiplex Ligation-dependent Probe Amplification (MLPA) is a RAD test. Its diagnostic accuracy, tested on 4585 amniotic fluid samples in routine clinical practice, is comparable to that of karyotyping (P<0.001) and it reduces waiting time with 14.5 days at lower costs (-__240 per sample). Patient quality of life does not differ significantly. While caregivers prefer RAD, experts prefer a test detecting all severe chromosomal abnormalities. Patients' preferences are equally divided; they value the detection of severe chromosomal abnormalities most. Since RAD and karyotyping both detect the most common chromosomal abnormalities with severe consequences, both tests are appropriate for prenatal diagnosis. Based on decision analytic considerations and our study results, women should be offered a choice, since they will bear the responsibility of raising the child.Afdeling verloskunde, LUMC J.E. Jurriaanse Stichting Ferring BV MRC Holland Medical DynamicsUBL - phd migration 201
Induction of labour : Foley catheter revisited
Get PDFIn the 1980s prostaglandin analogues were introduced for induction of labour without good evidence of superiority over older methods, such as Foley catheter. The aim of this thesis was to investigate the use of Foley catheter as an induction agent in women with an unfavourable cervix at term, compared to prostaglandins. The studies in this thesis demonstrate that Foley catheter yields similar caesarean sectio rates compared to vaginally administered prostaglandins, making both methods equally effective. Findings from RCTs and meta-analysis in this dissertation show reduced side effects with Foley catheter. Costs are comparable, and could further be reduced in favour of Foley catheter when used in an outpatient setting. This makes Foley catheter a superior method, with potential for outpatient cervical ripening, cervical ripening in low-resource settings, and cervical ripening in women with prior caesarean birth.UBL - phd migration 201
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Placental characteristics in twin-to-twin transfusion syndrome and twin anemia-polycythemia sequence
Get PDF
This thesis presents a number of articles studying the placental angioarchitecture of both TTTS and TAPS to investigate the pathogenesis of these diseases.
LUMC / Geneeskund
Fetus specific immune recognition and regulation by T cells at the fetal-maternal inferface in human pregnancy
Get PDFDuring pregnancy the maternal immune system tolerates the persistence of fetal cells in maternal tissue. The fetus expresses maternal as well as paternal encoded molecules but is not rejected by the maternal immune system. The aim of this thesis was to determine whether maternal T cells contribute to fetus specific immune recognition and if mechanisms of fetus specific immune regulation exist in human pregnancy. A special emphasis is given to fetus specific immune recognition and immune regulation by maternal T cells at the fetal-maternal interface. In this thesis, we demonstrate that CD4+CD25bright regulatory T cells which are concentrated in decidual tissue have the capacity to down regulate fetus specific and 3rd party (non-specific) responses. In contrast, CD4+CD25bright T cells in maternal peripheral blood can regulate 3rd party (non-specific) responses, comparable to non-pregnant controls, while the capacity to regulate the fetus specific response is absent. These data suggest a preferential recruitment of fetus specific regulatory T cells from the peripheral blood to the fetal maternal interface. Analysis of the CD8+ T cell pool during pregnancy shows that decidual CD8+ T cells mainly consist of differentiated Effector-Memory T cells, while unprimed Na_ve cells are almost absent. Decidual Effector-Memory CD8+ T cells contain significantly reduced levels of the cytolytic molecule perforin. These data are suggestive for an alternative CD8+ T cell differentiation and regulation process that may play a crucial role in maintenance of maternal immune tolerance to the fetus. Database analysis of clinical pregnancy data, fetal-maternal HLA mismatches and decidual lymphocyte responses led to the conclusion that a fetal-maternal HLA-C mismatch is crucial for decidual CD4+ T cell activation and required for induction of functional CD4+CD25bright regulatory T cells in decidua. Hereby we provide the first evidence that decidual T cells specifically recognize a fetal HLA-C mismatch at the fetal-maternal interface, possibly using the indirect allorecognition pathway. However HLA-C recognition does not induce a destructive immune response in uncomplicated pregnancies. Besides TCR mediated allorecognition, low frequencies of decidual T cells express NK receptors that can specifically recognize HLA-C allotypes. Engagement of NK receptors on T cells can result in down regulation of TCR mediated T cell activation. Although, no experimental evidence is present so far, NK receptor expression on decidual T cells may provide an alternative way for decidual T cells to recognize allogeneic fetal cells and modulate the decidual immune response. In conclusion, this thesis shows that decidual T cells comprise a very heterogenic subset of T cells that include activated CD4+ and Effector-Memory type CD8+ T cells. However, these highly activated T cells are found together with T cell subsets that are capable to suppress the decidual lymphocyte response. Furthermore, we show that decidual T cells can specifically recognize a fetal-maternal HLA-C mismatch. Hereby we demonstrate that mechanisms of fetus specific allorecognition and T cell regulation are present at the fetal-maternal interface in uncomplicated human pregnancy. In summary our data show that the maternal T cells in the uterus recognize foreign fetal cells, however, due to the presence of immune suppressive regulatory T cells no detrimental immune reaction is induced. In future research it is important to translate our results to aberrant pregnancies where fetal growth retardation, maternal hypertension, pre-term birth or miscarriages may occur. Hereby, it is important to determine whether these immune suppressive regulatory T cells are present in the uterus, if they function properly and what factors (proteins or cells) attract or induce regulatory T cells at the fetal-maternal interface. Further unravelling of the mechanisms immune regulation during pregnancy may be crucial to understand why some pregnancies are successful whereas others are not.UBL - phd migration 201
Identify, appraise and individualize: clinical practice and prediction models in recurrent pregnancy loss
Get PDFThis thesis has shed light on RPL practice and the management of RPL couples in need of counselling towards future pregnancies. Both clinical practice research and prediction research indicate that there is room for improvements in RPL practice and RPL counselling. We studied quality of care by diving into clinical practice variation and quality of counselling by diving into prediction research.In the absence of effective treatment options that increase live birth rates in RPL couples, counselling towards future pregnancies plays a key role and enables couples to make an informed decision regarding further pregnancy attempts. This will still be present when future treatment options are investigated or discovered, as these models could then evaluate the effects of these treatments on performance of the model. It is therefore of utmost importance that prediction models are well developed and validated for use in clinical practice.In an era of technological advancement bringing societies, researchers and clinicians from all over the world more closely together, it is time to step up and work together, to unify RPL care and to create collaborations that hugely impact RPL research which can lead to high impact publications that can unravel the mysteries of RPL.Stichting Oranjekliniek; Department of Obstetrics and Gynaecology of the Leiden University Medical Centre; Moeders voor Moeders; Canon Medical Systems; Ferring B.V.; Goodlife Pharma; Bridea Medical and ChipSoftLUMC / Geneeskund
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
