Cell biological and biochemical characterization of drebrin complexes in mesangial cells and podocytes of renal glomeruli

Drebrins are actin-binding proteins (ABP) initially identified in and thought to be specific for neuronal cells, where they appear to contribute to the formation of cell processes. Recent studies have also detected the isoform drebrin E2 in a wide range of non-neuronal cell types, notably in and near actin-rich lamellipodia and filopodia. The present study demonstrates drebrin enrichment in renal glomeruli. Immunohistochemistry and double-label confocal laser scanning microscopy have shown intense drebrin reactions in the mesangial cells of diverse mammalian species. In adult human and bovine kidneys, drebrin is, in addition, markedly enriched in the foot processes of podocytes, as also demonstrable by immunoelectron microscopy. By contrast, the podocytes of rodent glomeruli appear to contain significant drebrin concentrations only during early developmental stages. In differentiated murine podocytes cultured in vitro, however, drebrin is concentrated in the cell processes, where it partially codistributes with actin and other ABP. In biochemical analyses using protein extracts from renal cortices, large (approximately 20S) complexes ("drebrosomes") were found containing drebrin and actin. These findings confirm and extend our hypothesis that drebrin is involved in the regulation of actin dynamics also outside the nervous system. Clearly, drebrin has to be added to the ensemble of ABP regulating the actomyosin system and the dynamics of mesangial cells and foot processes in podocytes.     

Polyarteritis nodosa and cutaneous polyarteritis nodosa

Cutaneous vasculitis can present with a variety of lesions and associated symptoms. It is important for the clinician to be able to recognize vasculitis lesions and know when to pursue further laboratory studies that will determine the extent of the disease process in a patient. This review compares and contrasts polyarteritis nodosa with its cutaneous counterpart. The diagnostic workup and management of these two entities as well as the overall approach to a patient with a possible vasculitic condition are emphasized.     

Information flow in the mental lexicon during speech planning: evidence from event-related brain potentials

A major issue in speech production research is the question of how speakers retrieve words from the so-called mental lexicon. Current models of lexical retrieval converge on the assumption that category associates of a target word are semantically activated during speech planning. However, the question of whether these competitors are also phonologically activated is less agreed on. Past research has addressed this issue by testing whether lexical retrieval of a picture name (e.g. sheep) affects, or is affected by, the processing of a word that is phonologically related to a semantic category associate to the picture name (e.g. goal, phonologically related to goat). Behavioral studies have failed to obtain such so-called mediated priming effects, but have been questioned on the grounds of possibly insufficient task sensitivity. As such priming effects have reliably been obtained with event-related brain potentials in word recognition, we used this approach for testing these effects in lexical retrieval during speech planning. Our results consistently demonstrate the absence of mediated priming effects, putting strong constraints on the activation flow in the mental lexicon during speech planning.     

Thrombin-activatable fibrinolysis inhibitor (TAFI): a novel predictor of angiographic coronary restenosis

The fibrinolytic system is closely related to several processes that are involved in restenosis. We previously showed that low PAI-1 plasma levels predicted restenosis. Recently, a different fibrinolytic inhibitor, TAFI, has been described. The aims of this study were to evaluate the relationship between pre-procedural plasma levels of TAFI and late angiographic restenosis and the interaction between TAFI and PAI-1.We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty or stenting of de novo native coronary artery lesions. TAFI and PAI-1 antigen levels were measured in plasma samples drawn before the procedure. Follow-up coronary angiography was performed in 92% of patients. There was a significant correlation between pre-procedural TAFI levels and 6-month % diameter stenosis (DS) (r = 0.21; p = 0.013). The overall angiographic restenosis rate (DS>50%) was 31%. Pre-procedural TAFI levels were significantly higher in patients with restenosis (108 +/- 33% versus 94+/-30%, p = 0.011). Restenosis rates for patients in the upper tertile of TAFI levels were 2-fold higher than for those in the lowest tertile (45% versus 22%; p = 0.016). A combination of high TAFI and low PAI-1 levels identified patients at the highest risk of restenosis (53%) compared to 14% in patients with low TAFI and high PAI-1 levels; p = 0.027. In conclusion, pre-procedural plasma TAFI antigen levels identify patients at increased risk for restenosis after PCI.     

Monitoring of 4-hydroxybutyric acid levels in body fluids during vigabatrin treatment in succinic semialdehyde dehydrogenase deficiency

We report the successful treatment using low-dose vigabatrin (21.5-34 mg/kg/day) of a 10-year-old girl with succinic semialdehyde dehydrogenase (SSADH) deficiency We verified that 4-hydroxybutyric acid (GHB) concentrations in serum, cerebrospinal fluid, and urine continuously decreased in parallel with significant clinical improvement. Our results suggest that GHB quantification in physiological fluids may be a useful laboratory parameter for monitoring efficacy of vigabatrin treatment in SSADH deficiency.     

Workflow and cost analysis on MODULAR ANALYTICS

Four stand-alone analyzers in a centralized laboratory were replaced by two modular analytical systems processing 45 methods of the general chemistry and specific protein segment. This consolidation led to a reduction of the daily workflow and operational costs. The cost saving with 1.3 million reported results per year was 53,000 Euro, which can be assessed as an important contribution to cost reduction in the health care system.