Fluorescence in situ hybridization test for detection of endometrial carcinoma cells by non-invasive vaginal swab

Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future. Using array-based comparative genome hybridization (aCGH) on 65 endometrial carcinomas, most frequently imbalanced regions of the tumour genome were identified. Bacterial artificial chromosomes were used to generate FISH-probes homologue to these human regions. The FISH test was hybridized on swabs specimens collected from the vaginal cavity. Samples from six patients without EC were selected as a negative control and on 13 patients with known EC as a positive control. To distinguish between benign and EC cases, the cut-off value has been defined. A first validation of this EC-FISH Test was performed with swabs from 41 patients with suspected EC. The most common genomic imbalances in EC are around the CTNNB1, FBXW7 and APC genes. The cut-off is defined at 32% of analysed cells without diploid signal pattern. This differs significantly between the positive and negative controls (p < 0.001). In a first validation cohort of 41 patients with suspected EC, the EC-FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83%. The negative predictive value is 96%. This is the first report of a non-invasive EC-FISH Test to predict EC in women with suspected EC.     

Myelomeningocele: need for long-time complex follow-up—an observational study

The purpose of this study was to describe the relationship between pelvic inclination (PI) and lumbar lordosis (LL). Pelvic inclination and pelvic tilt are two different names for the same metric. The geometrical parameters of the spine and pelvis were measured using surface topography scanning, and the data was explored for any physical relationships using principal component analysis. Once widely assumed to be a direct correlation, research in the 1980s first cast doubt upon the PI to LL relationship. And yet, other studies have suggested a relationship does exist. Decades later, the rehabilitation professionals often still rely on this supposed correlation when making decisions about rehabilitation treatment interventions. This theoretical relationship requires further clarification, which is explored herein. Surface topography imaging is a technology that has proven to be a radiation-free way to produce accurate, reliable skeletal alignment measures. Patient data from one physical rehabilitation clinic was collected at the time of initial assessment. Patients presented with a wide range of musculoskeletal complaints. Surface topography scans were performed on 107 patients at the commencement and completion of their therapy. Principal component analysis was performed on the collected data to determine how these spine and pelvic alignment parameters changed between the two points in time and what trends and/or relationships exist between the parameters. Our analysis evaluated eight spinal and pelvic measurements as input and focused on LL and PI as the two principal components at time points of beginning and completion of treatment. Pelvic inclination and lumbar lordosis changed during treatment but were not correlated. Our data demonstrates that pelvic inclination and lumbar lordosis do not have a predictable relationship as previously assumed.     

1H, 13C and 15N resonance assignments of the Calmodulin-Munc13-1 peptide complex

Ca²⁺-Calmodulin binding to the variable N-terminal region of the diacylglycerol/phorbol ester-binding UNC13/Munc13 family of proteins modulates the short-term synaptic plasticity characteristics in neurons. Here, we report the sequential backbone and side chain resonance assignment of the Ca²⁺-Calmodulin/Munc13-1^458–492 peptide complex at pH 6.8 and 35°C (BMRB No. 15470).     

Analyzing protein-protein interactions in cell membranes

Interactions among membrane proteins regulate numerous cellular processes, including cell growth, cell differentiation and apoptosis. We need to understand which proteins interact, where they interact and to which extent they interact. This article describes a set of novel approaches to measure, on the surface of living cells, the number of clusters of proteins, the number of proteins per cluster, the number of clusters or membrane domains that contain pairs of interacting proteins and the fraction of one protein species that interacts with another protein within these domains. These data can then be interpreted in terms of the function of the protein-protein interactions.     

Long-term follow-up of spontaneous development in a boy with familial male precocious puberty

BACKGROUND/AIMS: Limited data are available about spontaneous growth, pubertal growth spurt and the long-term outcome of patients suffering from familial male precocious puberty (FMPP). We report on a boy with FMPP whose growth pattern and pubertal development was studied longitudinally without treatment. METHODS: Long-term prospective follow-up without treatment of a 6.2-year-old boy with FMPP having inherited a mutation of the LH receptor gene (A568V) from his father. RESULTS: The pubertal growth spurt was of unusual maximal amplitude (growth rate 12.4 cm/year at the age of 5-6 years) and of extraordinary duration lasting for 5.2 years from age 3.8 to 9.0 years. No deterioration of height potential was observed. Height (174 cm) was within target height range (171.5-188.5 cm) at age 13 years. No central precocious puberty occurred. CONCLUSION: FMPP is an experiment of nature demonstrating that the amplitude and duration of the pubertal growth spurt are much more variable than previously described. Furthermore, this case emphasizes that the indication for treatment is highly dependent on intrafamilial and individual factors.     

Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins

Mitochondria import nuclear-encoded precursor proteins to four different subcompartments. Specific import machineries have been identified that direct the precursor proteins to the mitochondrial outer membrane, inner membrane or matrix, respectively. However, a machinery dedicated to the import of mitochondrial intermembrane space (IMS) proteins has not been found so far. We have identified the essential IMS protein Mia40 (encoded by the Saccharomyces cerevisiae open reading frame YKL195w). Mitochondria with a mutant form of Mia40 are selectively inhibited in the import of several small IMS proteins, including the essential proteins Tim9 and Tim10. The import of proteins to the other mitochondrial subcompartments does not depend on functional Mia40. The binding of small Tim proteins to Mia40 is crucial for their transport across the outer membrane and represents an initial step in their assembly into IMS complexes. We conclude that Mia40 is a central component of the protein import and assembly machinery of the mitochondrial IMS.