Dynamic Interplay between Varicelloviruses and their Primate Hosts

__Abstract__ Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus (αHHV). Most individuals become infected with VZV during childhood typically resulting in generalized vesicular skin rash, although a minority of individuals will not develop evident skin rash. During primary infection the virus gains access to ganglia along the entire neuraxis, where it establishes a life-long latent infection of mostly sensory neurons. Due to the long incubation period and restricted host range of the virus, the cell types involved in the dissemination of VZV from the site of primary infection to the virus’ t

Non-Invasive Diagnostic Imaging of Peripheral Arterial Disease

CTA could be improved by reducing the impact of vessel wall calcifications on image interpretation. With a 16-slice or recently introduced 64-slice MDCT scanner a higher resolution can be obtained compared to a 4-slice MDCT. This may result in less blooming of calcifications, which will improve image interpretation. However, the potential for radiation dose reduction with the 16- and 64-slice MDCT scanners, due to the differences in gantry geometry compared to a 4-slice MDCT, is lost when we obtain higher resolution images using thinner slices and lower pitch. Subtraction CTA is another approach to minimize the burden of vessel wall calcifications on image interpretation (55). However, this technique requires a high level of patient collaboration, is not feasible in 20% of the patients in spite of good collaboration, generates two times more images, and increases the radiation exposure. The possible solution for the calcification problem may be found in post-processing software or more likely in hardware improvements. A complete different solution lies not in the technique, but in selecting patients for whom CTA is contra-indicated due to extensive vessel wall calcifications. In this thesis we performed an initial evaluation of clinical predictors of vessel wall calcifications on CTA. A future study is needed to develop and validate a clinical prediction rule for this problem. The results from our study can help design such a future study and restrict the data collection to the most relevant variables. In summary, CTA is the optimal non-invasive imaging test for the initial evaluation of patients with PAD. In elderly patients, patients with diabetes mellitus, and those with cardiac disease a CTA is contra-indicated due to decreased clinical utility. In these patients a MRA should be considered as initial imaging test. With the current knowledge of the DIPAD trial it is not useful to perform another study on the costs and effects of non-invasive imaging test for PAD

Molecular Aspects of Varicella-Zoster Virus Latency

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, a lack of suitable in vitro models have seriously hampered molecular studies of VZV latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and provide novel insights into our understanding of VZV latency and factors that may initiate reactivation. Deducing the function(s) of VLT and the molecular mechanisms involved should now be considered a priority to improve our understanding of factors that govern VZV latency and reactivation. In this review, we summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies

Eicosanoids, endotoxins and liver disease

Endotoxins are cell wall lipopolysacharides of gram negative bacteria. The gut contains large numbers of bacteria and is generally accepted to be a large reservoir of endotoxins. In the normal state absorbed endotoxins are rapidly removed from the portal blood by especially the reticulo-endothelial cells of the liver. In patients with liver disease there is a diminished function of the reticulo-endothelial system, resulting in a raised frequency of systemic endotoxemia. Systemic endotoxemia in liver disease, as measured by the Limulus lysate test, correlates with a higher frequency of clotting disorders, renal failure and a high mortality rat

Burgerleden in raadscommissies: theorie, praktijk en juridisch kader

The Legitimacy and Effectiveness of Law & Governance in a World of Multilevel Jurisdiction

Severe hypokalaemic paralysis and rhabdomyolysis due to ingestion of liquorice

Chronic ingestion of liquorice induces a syndrome with findings similar to those in primary hyperaldosteronism. We describe a patient who, with a plasma K+ of 1.8 mmol/l, showed a paralysis and severe rhabdomyolysis after the habitual consumption of natural liquorice. Liquorice has become widely available as a flavouring agent in foods and drugs. It is important for physicians to keep liquorice consumption in mind as a cause for hypokalaemic paralysis and rhabdomyolysis

Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in β-cells

Islet cell autoantigen 512 (ICA512)/IA-2 is a receptor tyrosine phosphatase-like protein associated with the insulin secretory granules (SGs) of pancreatic β-cells. Here, we show that exocytosis of SGs and insertion of ICA512 in the plasma membrane promotes the Ca2+-dependent cleavage of ICA512 cytoplasmic domain by μ-calpain. This cleavage occurs at the plasma membrane and generates an ICA512 cytosolic fragment that is targeted to the nucleus, where it binds the E3-SUMO ligase protein inhibitor of activated signal transducer and activator of transcription-y (PIASy) and up-regulates insulin expression. Accordingly, this novel pathway directly links regulated exocytosis of SGs and control of gene expression in β-cells, whose impaired insulin production and secretion causes diabetes