Promoter switching in response to changing environment and elevated expression of protein-coding genes overlapping at their 5' ends.

Despite the number of studies focused on sense-antisense transcription, the key question of whether such organization evolved as a regulator of gene expression or if this is only a byproduct of other regulatory processes has not been elucidated to date. In this study, protein-coding sense-antisense gene pairs were analyzed with a particular focus on pairs overlapping at their 5' ends. Analyses were performed in 73 human transcription start site libraries. The results of our studies showed that the overlap between genes is not a stable feature and depends on which TSSs are utilized in a given cell type. An analysis of gene expression did not confirm that overlap between genes causes downregulation of their expression. This observation contradicts earlier findings. In addition, we showed that the switch from one promoter to another, leading to genes overlap, may occur in response to changing environment of a cell or tissue. We also demonstrated that in transfected and cancerous cells genes overlap is observed more often in comparison with normal tissues. Moreover, utilization of overlapping promoters depends on particular state of a cell and, at least in some groups of genes, is not merely coincidental.

Thermionic Electron Beam Current and Accelerating Voltage Controller for Gas Ion Sources.

Thermionic emission sources are key components of electron impact gas ion sources used in measuring instruments, such as mass spectrometers, ionization gauges, and apparatus for ionization cross-section measurements. The repeatability of the measurements taken with such instruments depends on the stability of the ion current, which is a function, among other things, of the electron beam current and electron accelerating voltage. In this paper, a laboratory thermionic electron beam current and accelerating voltage controller is presented, based on digital algorithm implementation. The average value of the percentage standard deviation of the emission current is 0.021%, and the maximum electron accelerating voltage change versus the emission current is smaller than 0.011% in the full operating range of the emission current. Its application as a trap current or emission current-regulated ion source power supply could be useful in many measuring instruments, such as in microelectromechanical system (MEMS) mass spectrometers as universal gas sensors, where a stable emission current and electron energy are needed.

A novel circuit for independent control of electron energy and emission current of a hot cathode electron source.

The implementation of a non-linear combination of two reference voltages to control the anode voltage in the previously described biasing system of an electron source with a hot cathode allows elimination of the correlation between the emission current and the accelerating voltage. The presented system is highly suitable for applications in electron-impact mass spectrometers, ionization gauges and other instruments (for example, electron microscopes).

[Effect of localization of pulmonary arterial changes on echocardiographic indices of right heart function and their correlation with exercise capacity: comparison of arterial and thromboembolic pulmonary hypertension]. / Wplyw umiejscowienia zmian w lozysku plucnym na echokardiograficzne wskazniki czynnosci prawego serca i ich zwiazek z tolerancja wysilku: porównanie tetniczego i zakrzepowo-zatorowego nadcisnienia plucnego.

AIM: To assess correlation between exercise tolerance and Doppler-derived indices of right ventricular (RV)--pulmonary arterial coupling in patients with different location of vascular lesions causing pulmonary hypertension (PH). MATERIAL: 45 patients: 21 with thromboembolic (TE-PH) and 24 with arterial PH defined as systolic pulmonary arterial pressure (SPAP) > 40 mm Hg. The two groups were similar as far as SPAP (74,8 +/- 15,2 vs 76.5 +/- 14,1 mm Hg, p = ns) and distance covered during 6 minute walk test (339 +/- 116 vs 320 +/- 127, p = ns) are concerned. RESULTS: Flow velocity curve in the RV outflow tract were different in the two groups. Time from onset to peak velocity of ejection (acceleration time, AcT) as well as to midsystolic deceleration were shorter in TE-PH then in arterial PH (59.0 +/- 6.3 vs 68.1 +/- 15.4 msec, p = 0.015 and 123.8 +/- 17.9 vs 137.9 +/- 29.7 msec, p = 0.071, respectively). In the whole studied group as well as in arterial PH significant correlation between exercise tolerance and Doppler-derived indices of RV--pulmonary arterial coupling were found (r = 0.51, p < 0.001 and r = 0.72, p = < 0.001, respectively). Interestingly, no such relationship was found in TE-PH, (r = 0.16, p = ns). CONCLUSION: In contrast to arterial PH, pressure wave prematurely reflected from the intraluminal thrombi seem to disturb the RV ejection pattern and its correlation with exercise tolerance in TE-PH. Whether progression or effects of treatment on arterial PH can be assessed by monitoring changes in Doppler-derived indices of RV--pulmonary arterial coupling requires further studies.

[Effect of long-term therapy with oral Beraprost on survival of patients with arterial and inoperable thromboembolic pulmonary hypertension]. / Wplyw przewleklego leczenia Beraprostem sodu na rokowanie pacjentów z tevtniczym i zakrzepowo-zatorowym nadcisnieniem plucnym.

Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves haemodynamic parameters and quality of life in group of patients with pulmonary arterial hypertension. Effect of long-term therapy with BPS is not well defined. This study assesses influence of long-term therapy with BPS on the survival of patients with precapillary pulmonary hypertension. Studied group consisted of 25 patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen patients were diagnosed with primary PH, 3 pts had PH associated with connective tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were in functional class III. All studied subjects had complete hemodynamic assessment of right heart and obtained values were used for estimation of hypothetic survival using prognostic equation proposed by D'Alonzo et al. On follow-up period patients received BPS in the highest tolerated dose (80-480 mg daily). During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival rate BPS group was significantly higher in BPS group comparing to hypothetical survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02) and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At 18 and 24 months differences between BPS virtual and hypothetical survival were not statistically significant. There was no correlation between survival and maximal achieved dose of BPS. These results suggest, that BPS improves prognosis of patients with precapillary PH during 12 months after initiation of therapy. Later effect of BPS seems to decrease, requiring changing or intensification of therapy.

Atrial septostomy for severe primary pulmonary hypertension - report on two cases.

Atrial septostomy (AS) emerges as a potential therapeutic option in severe primary pulmonary hypertension (PH). AS isa transluminal intervention consisting of perforation of interatrial septum and balloon dilatation. During the procedure an atrial septal defect is created to a diameter permitting right-to-left shunt with the aim of correcting abnormal preload of both ventricles, leading to hemodynamic and functional consequences. We present two patients characterised by severe right ventricular failure. The second patient with rapid clinical deterioration required ,,rescue" rather than elective AS. Despite similar, small sizes of balloons (8 and 6 mm, respectively) used during both procedures, elective AS resulted in a significant and persistent hemodynamic (CI increased from 2.0 to 2.3 1/min/m(2)) and functional improvement while ,,rescue" AS despite short term improvement resulted in an uncontrolled systemic hypoxemia and did not prevent death 28 days after the procedure. Although AS is an invasive and palliative method, it offers persistent functional improvement in patients with primary PH. In view of poor prognosis and limited therapeutic options in Poland, elective AS should be considered as a potentially valuable intervention in patients with primary PH in our country.

Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension.

BACKGROUND: Right ventricular failure is a leading cause of death in patients with chronic pulmonary hypertension (PH). We checked whether detection of cardiac troponin T (cTnT), a specific marker of myocyte injury, could be useful in prognostic stratification of those patients. METHODS AND RESULTS: Initial evaluation of 56 clinically stable patients (age 41+/-15 years) with pulmonary arterial (51 patients) or inoperable chronic thromboembolic (5 patients) PH (mean pulmonary arterial pressure 60+/-18 mm Hg) included cTnT test, allowing detection of its serum levels > or =0.01 ng/mL [cTnT(+)]. cTnT was detectable in 8 of 56 (14%) patients (mean+/-SD, 0.034+/-0.022; range, 0.010 to 0.077 ng/mL). Despite similar pulmonary hemodynamics, they had higher heart rate (92+/-15 versus 76+/-14 bpm, P=0.004), lower mixed venous oxygen saturation (50+/-10% versus 57+/-9%, P=0.04), and higher serum N-terminal pro-B-type natriuretic peptide (4528+/-3170 versus 2054+/-2168 pg/mL, P=0.03) and walked less during the 6-minute walk test (298+/-132 versus 396+/-101 m, P=0.02). Cumulative survival estimated by Kaplan-Meier curves was significantly worse at 24 months in cTnT(+) compared with cTnT(-) (29% versus 81%, respectively, log-rank test P=0.001). Multivariate analysis revealed cTnT status (hazard ratio, 4.89; 95% CI, 1.18 to 20.29; P=0.03), 6-minute walk test (hazard ratio, 0.93 for each 10 m; P=0.01), and pulmonary vascular resistance (hazard ratio, 1.13; P=0.01) as independent markers of mortality. All 3 cTnT(+) patients who survived the follow-up period converted to cTnT(-) during treatment. CONCLUSIONS: Detectable cTnT is a so-far ignored independent marker of increased mortality risk in patients with chronic precapillary PH, supporting the role of progressive myocyte injury in the vicious circle leading to hemodynamic destabilization.