The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPβ during epithelial tumour progression

The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPα, -β, -δ and -ζ in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPα and C/EBPβ were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPβ was located in the nuclei of the cells, in contrast to C/EBPα, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPβ indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPα. C/EBPδ and -ζ demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPδ and -ζ. Western blotting demonstrated that C/EBPα, -β, -δ and -ζ were present in a majority of the samples. The amount of C/EBPβ increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPβ as a potential marker for these tumours. As C/EBPβ is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression. © 1999 Cancer Research Campaig

Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials

Transperineal and endovaginal ultrasound for evaluating suburethral masses: comparison with magnetic resonance imaging

Objective To evaluate the utility of pelvic floor ultrasound (US) in the detection and evaluation of suburethral masses, using magnetic resonance imaging (MRI) as the reference standard. Methods This was a retrospective analysis of US and MRI scans of all women with a suburethral mass on clinical examination at a single urogynecology clinic over a 13-year period (February 2007 to March 2020). All women were examined using two-dimensional transperineal US (2D-TPUS) with or without three-dimensional endovaginal US (3D-EVUS). All patients underwent unenhanced T1-weighted and T2-weighted MRI, which was considered the reference standard in this study. Presence of a suburethral mass and its size, location, connection with the urethral lumen and characteristics were evaluated on both pelvic floor US and MRI. Agreement between pelvic floor US and MRI was assessed using intraclass correlation coefficients (ICC; 3,1). Results Forty women suspected of having a suburethral mass on clinical examination underwent both MRI and US (2D-TPUS with or without 3D-EVUS). MRI detected a suburethral mass in 34 women, which was also detected by US. However, US also identified a suburethral mass in the remaining six women. Thus, the agreement between US and MRI for detecting a suburethral mass was 85% (95% CI, 70.2–94.3%). The ICC analysis showed good agreement between MRI and 2D-TPUS for the measured distance between the suburethral mass and the bladder neck (ICC, 0.89; standard error of measurement (SEM), 3.64 mm) and excellent agreement for measurement of the largest diameter of the mass (ICC, 0.93; SEM, 4.31 mm). Good agreement was observed between MRI and 3D-EVUS for the measured distance from the suburethral mass to the bladder neck (ICC, 0.88; SEM, 3.48 mm) and excellent agreement for the largest diameter of the suburethral mass (ICC, 0.94; SEM, 4.68 mm). Conclusions 2D-TPUS and 3D-EVUS are useful in the imaging of suburethral masses. US shows good-to-excellent agreement with MRI in identifying and measuring suburethral masses; therefore, the two modalities can be used interchangeably depending on availability of equipment and expertise

C/EBPα knock-in hepatocytes exhibit increased albumin secretion and urea production

10.1007/s00441-007-0505-4Cell and Tissue Research3303427-43

C/EBPalpha mutations in acute myeloid leukaemias.

Specific mutations in the gene that encodes the multifunctional transcription factor C/EBPα are frequently associated with acute myeloid leukaemias. Are only a specific subset of the functions of C/EBPα therefore involved in leukaemogenesis

Molecular mechanisms underlying deregulation of C/EBP alpha in acute myeloid leukemia

The CEBPA gene encodes a transcription factor protein that is crucial for granulocytic differentiation, regulation of myeloid gene expression and growth arrest. Mutations in one or both alleles of CEBPA are observed in about 10% of patients with acute myeloid leukemia (AML). Moreover, other genetic events associated with AML have been identified to deregulate C/EBP alpha expression and function at various levels. Recently developed mouse models that accurately mimic the genetic C/EBP alpha alterations in human AML demonstrate C/EBP alpha's gatekeeper function in the control of self-renewal and lineage commitment of hematopoietic stem cells (HSCs). Moreover, these studies indicate that CEBPA mutations affect HSCs in early leukemia development by inducing proliferation and limiting their lineage potential. However, the exact relationship between 'pre-leukemic' HCSs and those cells that finally initiate leukemia (leukemia-initiating cells) with disturbed differentiation and aberrant proliferation remains elusive. More research is needed to identify and characterize these functionally distinct populations and the exact role of the different genetic alterations in the process of leukemia initiation and maintenance

Children at Risk of Poor Educational Outcomes: In Search of a Transdisciplinary Theoretical Framework

In most western countries, the number of \u27children at risk\u27 for poor educational outcomes seems to have been increased in recent years. Nearly 20 % of the students in those countries meanwhile fail to acquire the levels of literacy, mathematics and science achievement that are required to effectively participate in today\u27s knowledge-based society. Thus, there is a strong need to extend research focusing on the identification of risk factors associated with these undesired educational outcomes in children. Although attempts have been made to conceptualize the issue of \u27children at risk\u27 for poor educational outcomes from the perspective of different scientific disciplines, the interplay of multiple risk factors located on the different levels focused by different disciplines has been rarely addressed. Thus, we advocate for more transdisciplinary activities integrating multiple scientific perspectives on the concept of \u27children at risk\u27 for poor educational outcomes. These activities should include at least three dimensions affecting developmental trajectories being important for children\u27s individual academic outcomes: (1) individual characteristics including both biological as well as psychological features, (2) contextual factors, as well as dynamics defined by (3) time changes and interactions between individual and contextual categories of risk factors. (DIPF/Orig.