22 research outputs found
Layered Fibrotic Plaques Are the Predominant Component in Cardiac Allograft Vasculopathy Systematic Findings and Risk Stratification by OCT
Cardiovascular Aspects of Radiolog
2012 ESC STEMI guidelines and reperfusion therapy: Evidence base ignored, threatening optimal patient management
Dedicated plug based closure for large bore access –The MARVEL prospective registry
Objectives: To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers. Background: The MANTA is a novel plug-based devic
Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes
KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models.Kptn−/− mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants.Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1.By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.Genetics of disease, diagnosis and treatmen
Early Changes in the Coronary Microstructure After Heart Transplantation: A Prospective Optical Coherence Tomography Study
Incremental Value to Coronary Angiography by Optical Coherence Tomography for Detection and Interpretation of Cardiac Allograft Vasculopathy
Cardiovascular Aspects of Radiolog
Early Changes in the Coronary Microstructure After Heart Transplantation: A Prospective Optical Coherence Tomography Study
Cardiovascular Aspects of Radiolog
Co-registration of Optical Coherence Tomography and X-ray Angiography in Percutaneous Coronary Intervention. The Does Optical Coherence Tomography Optimize Revascularization (DOCTOR) Fusion Study
Cardiovascular Aspects of Radiolog
Detection of early changes in the coronary artery microstructure after heart transplantation: A prospective optical coherence tomography study
Cardiovascular Aspects of Radiolog
Co-registration of optical coherence tomography and X-ray angiography in percutaneous coronary intervention. The Does Optical Coherence Tomography Optimize Revascularization (DOCTOR) fusion study
Cardiovascular Aspects of Radiolog