Characteristics of arrhythmia and late ventricular potentials in patients with cardiological syndrome X

AIM: A comparative study of late ventricular potentials (LVP) in patients with cardiological syndrome X (SX) and stenotic atherosclerosis of coronary arteries (ACA) as well as their relations with arrhythmia, cardiac contractility, lipid metabolism and morphological characteristics of the myocardium. MATERIAL AND METHODS: The examination of 52 SX and 77 ACA patients as well as 17 healthy subjects included coronaroventriculography, bicycle exercise, 24-h ECG monitoring, echocardiography, signal-averaged high-resolution (SAHR) ECG, investigation of blood lipoproteins. Endomyocardial biopsy was made in 5 ACA and 5 SX patients. RESULTS: No differences were registered between SX and ACA patients by frequency and severity of arrhythmic episodes, percentage of patients with registered LVP, quantitative parameters of SAHR ECG. Frequency of high-gradation ventricular arrhythmia episodes was significantly higher in SX and ACA patients with LVP than such patients free of LVP. SX patients had correlation between parameters of SAHR ECG, myocardial contractility and lipid metabolism. Foci of diffuse cardiosclerosis are most probable anatomic substrate of LVP. CONCLUSION: The risk of prognostically unfavourable high-gradation ventricular arrhythmia episodes in SX and ACA patients is the same. LVP may predict severe ventricular arrhythmia episodes both in SX and ACA patients.     

Effects of vibration on contents of micronuclei in polychromatophilic erythrocytes of the rat bone marrow

The paper presents data on the impact of vibration (32 Hz) on spontaneous mutagenesis in mammals. Higher counts of micronuclei were found in the bone marrow polychromophilic red blood cells in rats on day 5 of exposure to vibration, there was a reduction in their counts by day 20 and their recovery by day 30, and their steady-state decrease within 30 days after vibration discontinuation. The involvement of emotional stress in the mechanism of antimutagenic action of vibration is considered.     

The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells

Sustained engagement of the B-cell receptor (BCR) increases apoptosis resistance in chronic lymphocytic leukemia (CLL) B cells, whereas transient stimulation usually has an opposite effect. The antiapoptotic BCR signal has been associated with prolonged activation of the PI3K/Akt and MEK/ERK pathways, which are key regulators of survival and proliferation in various cell types. To further define the relative contribution of the Akt and ERK kinases in regulating CLL B-cell survival, we introduced constitutively active mutants of Akt and MEK in primary CLL B cells and evaluated changes in the expression of relevant pro- and antiapoptotic proteins. Sustained activation of Akt resulted in increased leukemic cell viability and increased expression of the antiapoptotic proteins Mcl-1, Bcl-xL, and X-linked inhibitor of apoptosis protein (XIAP), thus largely recapitulating the effects of sustained BCR stimulation. Constitutively active MEK2 also up-regulated XIAP, but did not show a significant impact on leukemic cell survival. Down-regulation of Mcl-1 by siRNA treatment induced rapid and potent apoptosis in CLL B cells and blocked the antiapoptotic effect of sustained BCR stimulation, whereas down-regulation of Bcl-xL and XIAP did not affect leukemic cell viability. These data demonstrate that Akt and Mcl-1 are major components of a survival pathway that can be activated in CLL B cells by antigen stimulation.     

Computerized Stabilometry on a Four-Legged Platform for Comparative Analysis of Foot Positioning

Biomedical Engineering - Computerized stabilometry using a four-legged stabilometric platform allows “free” positioning of the feet to be used, which is of fundamental importance for...     

Overexpression of the autoimmunity-associated phosphatase PTPN22 promotes survival of antigen-stimulated CLL cells by selectively activating AKT

A polymorphic variant of the phosphatase PTPN22 has been associated with increased risk for multiple autoimmune diseases. The risk allele is thought to function by diminishing antigen-receptor signals responsible for negative selection of autoreactive lymphocytes. We now show that PTPN22 is markedly overexpressed in chronic lymphocytic leukemia (CLL), a common malignancy of autoreactive B lymphocytes. We also show that overexpression of PTPN22 significantly inhibits antigen-induced apoptosis of primary CLL cells by blocking B-cell receptor (BCR) signaling pathways that negatively regulate lymphocyte survival. More importantly, we show that PTPN22 positively regulates the antiapoptotic AKT kinase, which provides a powerful survival signal to antigen-stimulated CLL cells. This selective uncoupling of AKT from other downstream BCR signaling pathways is a result of inhibition of a negative regulatory circuit involving LYN, CD22, and SHIP. Finally, we show that PTPN22 can be effectively down-regulated by the PKC inhibitors ruboxistaurin and sotrastaurin, resulting in enhanced killing of CLL cells exposed to proapoptotic BCR stimuli. Collectively, these data suggest that PTPN22 overexpression represents a protective mechanism that allows autoantigen-activated CLL cells to escape from negative selection and indicate that this mechanism could be exploited for therapeutic purposes by targeting PTPN22 with PKC inhibitors.     

On Relationships between Gas-Phase Chemistry and Reactive Ion Etching Kinetics for Silicon-Based Thin Films (SiC,SiO2 and SixNy) in Multi-Component Fluorocarbon Gas Mixtures

This work summarizes the results of our previous studies related to investigations of reactive ion etching kinetics and mechanisms for widely used silicon-based materials (SiC, SiO₂, and Si_xN_y) as well as for the silicon itself in multi-component fluorocarbon gas mixtures. The main subjects were the three-component systems composed either by one fluorocarbon component (CF₄, C₄F₈, CHF₃) with Ar and O₂ or by two fluorocarbon components with one additive gas. The investigation scheme included plasma diagnostics by Langmuir probes and model-based analysis of plasma chemistry and heterogeneous reaction kinetics. The combination of these methods allowed one (a) to figure out key processes which determine the steady-state plasma parameters and densities of active species; (b) to understand relationships between processing conditions and basic heterogeneous process kinetics; (c) to analyze etching mechanisms in terms of process-condition-dependent effective reaction probability and etching yield; and (d) to suggest the set gas-phase-related parameters (fluxes and flux-to-flux ratios) to control the thickness of the fluorocarbon polymer film and the change in the etching/polymerization balance. It was shown that non-monotonic etching rates as functions of gas mixing ratios may result from monotonic but opposite changes in F atoms flux and effective reaction probability. The latter depends either on the fluorocarbon film thickness (in high-polymerizing and oxygen-less gas systems) or on heterogeneous processes with a participation of O atoms (in oxygen-containing plasmas). It was suggested that an increase in O₂ fraction in a feed gas may suppress the effective reaction probability through decreasing amounts of free adsorption sites and oxidation of surface atoms.     

Beta-thalassemia in Yugoslavia

This study concerned the evaluation of beta-thalassemia alleles in nearly 50 patients with beta-thalassemia major and in 130 -thalassemia heterozygotes using gene amplification and dot-blot hybridization with synthetic probes. Fourteen different mutations were observed; of these, three (IVS-I-110; IVS-I-6; IVS-I-1) account for some 75% of all beta-thalassemia alleles. Newly discovered variants, i.e. T----C in the initiation codon and AATAAA----AATGAA in the poly A site were observed in a few patients. The poly A mutation with classical beta-thalassemia alleles result in thalassemia intermedia. Hb Lepore is a rather common abnormality and combinations of this variant with beta-thalassemia often result in severe disease; a search for beta-thalassemia mutations among patients affected with this disease should include an analysis to detect this hemoglobin abnormality.