Expression of activation molecules in neutrophils, monocytes and lymphocytes from patients with unstable angina treated with stent implantation.

Coronary angioplasty is known to mediate an inflammatory response. Recently, we have characterized the transient systemic inflammatory response after coronary stent implantation in patients with unstable angina by measuring different soluble protein markers. In the present study we have characterized the expression of various cellular activation markers in neutrophils, monocytes and lymphocytes from the same group of patients. Peripheral blood samples were taken before and 24 h, 48 h and 7 days after successful coronary stenting in 58 patients. Cell surface markers (CD11b/CD18 and CD38) were analyzed by flow cytometry to determine the activation of neutrophils, monocytes and T lymphocytes. We found that coronary angioplasty with stent implantation produces an increase in the cell surface expression of CD11b/CD18 in neutrophils and CD38 in monocytes, following a similar time-course with a peak after 24 h, returning to basal levels after 48 h and a second peak after 7 days. However, T lymphocytes were not found to be activated. These results suggest that coronary stent implantation induces a different pattern inducing soluble and cellular inflammation markers, and therefore, they should be taken into account in patients undergoing stent implantation to study clinical correlations.     

Risk factors for decreased total body and regional bone mineral density in hemodialysis patients with severe secondary hyperparathyroidism.

Hyperparathyroidism contributes significantly to decreased bone mineral density (BMD) in end-stage renal disease patients, but this negative influence is not homogeneous throughout the skeleton. We studied the BMD by dual-energy X-ray absorptiometry on total body and on different regions of the skeleton in 42 patients with severe hyperparathyroidism on hemodialysis. We also evaluated the relationship between different risk factors and BMD found on the regions examined in these patients. The legs and other sites where cortical bone predominate were mostly affected, whereas trabecular bone was relatively preserved. This is probably the result of the different effects of hyperparathyroidism on cortical and trabecular bone, but we cannot rule out the interference of ectopic calcifications and sclerotic lesions of vertebral end-plates falsely increasing lumbar spine BMD. The main determinants of low total-body BMD were, in order of importance, immobility, high intact parathyroid hormone levels, low body mass index, and low albumin. Eleven patients presented with pathologic fractures, mainly in the legs, and BMD was lower in this group than in patients without fractures. In conclusion, our study makes clear that hyperparathyroidism is a great threat to bone density in hemodialysis patients, mainly in the legs, the site mostly affected by fragility fractures in our patients. Physicians must worry not only with high parathyroid hormone levels, but also with the nutritional state of these patients.     

<Emphasis Type="Italic">CYP2C19</Emphasis> and <Emphasis Type="Italic">ABCB1</Emphasis>gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background  

Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.     

Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1

The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low frequency in certain human cancers characterized by aneuploidy. Simian virus 40 large T antigen efficiently immortalizes rodent cells and occasionally transforms them to tumorigenicity. T antigen can also cause genomic instability, inducing chromosomal aberrations and aneuploidy. Here, we report an interaction between Bub1 and T antigen. T antigen coimmunoprecipitates with endogenous Bub1 and Bub3, another component of the spindle checkpoint complex. Genetic analysis demonstrates that the interaction of T antigen with Bub1 is not required for immortalization but is closely correlated with transformation. T antigen induces an override of the spindle checkpoint dependent on Bub1 binding. This interaction with proteins of the spindle checkpoint machinery suggests another role for T antigen and provides insight into its ability to cause chromosomal aberrations, aneuploidy, and transformation.