The role of sterol carrier protein 2 in the regulation of Leydig cell steroidogenesis

The aim of the studies described in this thesis was to clarify the rele of SCP2 in the regulation of steroid production in rat Leydig cells. The ra te of steroid production in the adrenal, the ovary, the placenta and the testis is determined by the rate of conversion of cholesterol to pregnenolone. The complex of reactions and the localization of the enzymes involved in this so called cholesterol side chain cleavage are well known. The P- 450scc enzyme complex catalyzing the production of pregnenolone from cholesterol is located in the inner mitochondria! membrane of steroidogenic cells (Fig.l.l). Several substances that regulate steroidogenesis, regulate the rate of pregnenolone formation via an intracellular transducing mechanism after binding to the plasma membrane of the cell. Different "second messengers" are involved in the transduetion of the signal from the plasma membrane to other processesjmessengers in the cell which are involved in regulation of steroid production. It is also known that protein synthesis and the transfer of cholesterol to the inner mitochondria! membrane are important in regulation of steroidogenesis. It is not known, however, if, and in which way the induction of secend messenger systems in steroidogenic cells is linked with protein synthesis, cholesterol transfer and activatien of the cholesterol side chain cleavage reaction inside the mitochondria. In this respect, sterol carrier protein 2 (SCP2) is one of the possible proteins that could be involved in transduetion of the signal from the secend messengers to the cscc enzyme complex

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

The 10 micron amorphous silicate feature of fractal aggregates and compact particles with complex shapes

We model the 10 micron absorption spectra of nonspherical particles composed of amorphous silicate. We consider two classes of particles, compact ones and fractal aggregates composed of homogeneous spheres. For the compact particles we consider Gaussian random spheres with various degrees of non-sphericity. For the fractal aggregates we compute the absorption spectra for various fractal dimensions. The 10 micron spectra are computed for ensembles of these particles in random orientation using the well-known Discrete Dipole Approximation. We compare our results to spectra obtained when using volume equivalent homogeneous spheres and to those computed using a porous sphere approximation. We conclude that, in general, nonspherical particles show a spectral signature that is similar to that of homogeneous spheres with a smaller material volume. This effect is overestimated when approximating the particles by porous spheres with the same volume filling fraction. For aggregates with fractal dimensions typically predicted for cosmic dust, we show that the spectral signature characteristic of very small homogeneous spheres (with a volume equivalent radius r_V<0.5 micron) can be detected even in very large particles. We conclude that particle sizes are underestimated when using homogeneous spheres to model the emission spectra of astronomical sources. In contrast, the particle sizes are severely overestimated when using equivalent porous spheres to fit observations of 10 micron silicate emission.Comment: Accepted for publication in A&

Highly improved method for in-depth post-translational modification profiling: example of Timothy grass (Phleum pratense) pollen proteomes from polluted and preserved environments

Field-realistic exposure studies provide the most relevant assessment of the effects of the intensity and diversity of urban and industrial contamination on pollen structure and allergenicity. The significance of in-depth post-translational modification (PTM) studies of pollen proteomes, when compared with studies on other aspects of pollution and altered pollen allergenicity, has not yet been determined; hence, little progress has been made within this field

Risk factors for pelvic girdle pain postpartum and pregnancy related low back pain postpartum:a systematic review and meta-analysis

Contains fulltext : 221001.pdf (Publisher’s version ) (Closed access)BACKGROUND: Although pelvic girdle pain postpartum and pregnancy related low back pain postpartum (combined and named PGPP in this study) have a natural favourable course, there is a subgroup of women who have persistent complaints. The objective of this study was to identify personal-, (pre)pregnancy-, obstetric-, and child related risk factors on PGPP by means of a systematic literature review and meta-analysis. METHODS: Literature searches of PubMed, EMBASE, CINAHL and Cochrane up to October 2018 were conducted. Prospective cohort studies in English or Dutch describing three or more risk factors for PGPP were included. We assessed articles for inclusion and risk of bias. Studies with high risk of bias were excluded from data extraction. Data was extracted and checked for accuracy confirming to the CHARMS-checklist. Homogeneous variables were pooled. RESULTS: Twelve full text studies were assessed. Seven studies were excluded due to high risk of bias. Data was extracted from five studies. Multivariate analysis was not possible due to heterogeneity in included risk factors as well as outcome measures on risk factor per study. Pooled univariate significant risk factors on PGPP were: a history of low back pain, pre-pregnancy body mass index >25, pelvic girdle pain in pregnancy, depression in pregnancy, and a heavy workload in pregnancy. No significant obstetric and child related risk factors were reported. CONCLUSIONS: Risk factors on PGPP have been identified. Since multivariate analysis was not possible the outcome should be treated with care, because interaction between risk factors could not be analysed

Impact of established prognostic factors and molecular subtype in very young breast cancer patients: pooled analysis of four EORTC randomized controlled trials

Young age at the time of diagnosis of breast cancer is an independent factor of poor prognosis. In many treatment guidelines, the recommendation is to treat young patients with adjuvant chemotherapy regardless of tumor characteristics. However, limited data on prognostic factors are available for young breast cancer patients. The purpose of this study was to determine the prognostic value of established clinical and pathological prognostic factors in young breast cancer patients. Data from four European Organisation for Research and Treatment of Cancer (EORTC) clinical trials were pooled, resulting in a dataset consisting of 9,938 early breast cancer patients with a median follow-up of 11 years. For 549 patients aged less than 40 years at the time of diagnosis, including 341 node negative patients who did not receive chemotherapy, paraffin tumor blocks were processed for immunohistochemistry using a tissue microarray. Cox proportional hazard analysis was applied to assess the association of clinical and pathological factors with overall and distant metastasis free survival. For young patients, tumor size (P = 0.01), nodal status (P = 0.006) and molecular subtype (P = 0.02) were independent prognostic factors for overall survival. In the node negative subgroup, only molecular subtype was a prognostic factor for overall survival (P = 0.02). Young node negative patients bearing luminal A tumors had an overall survival rate of 94% at 10 years' follow-up compared to 72% for patients with basal-type tumors. Molecular subtype is a strong independent prognostic factor in breast cancer patients younger than 40 years of age. These data support the use of established prognostic factors as a diagnostic tool to assess disease outcome and to plan systemic treatment strategies in young breast cancer patient