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Cardiac ankyrin repeat protein (CARP) and its two close homologs ankrd2 (Arpp) and DARP correspond to a conserved gene family of muscle ankyrin repeat proteins (MARPs). All three genes respond to a variety of stress/strain injury signals with their cytokine-like induction and can associate with the elastic region of titin/connectin. Recently, both CARP and ankrd2 were observed to be elevated in cardiac diseases as well as muscular dystrophies, implicating their joined signaling in muscle diseases. Here we show that CARP in the yeast two-hybrid system (YTH) interacts with itself and desmin. To further verify the YTH data and to investigate possible CARP subunit structure(s), we expressed CARP in E. coli. Expressed CARP has an apparent mobility of about 70 kDa on gel filtration, corresponding to a dimeric species. Yeast two-hybrid experiments using amino- and carboxyterminal deletion clones suggest that CARP, ankrd2, and DARP contain potential coiled-coil dimerization motifs within their unique aminoterminal domains that mediate the formation of homo-dimers. In contrast, we could not detect the formation of hetero-dimers between CARP, ankrd2, and DARP. Therefore, when CARP, ankrd2 and DARP are upregulated in disease/stress states, they are likely to be sorted into distinct structural protein complexes since CARP within the MARP family contains a unique aminoterminal dimerization motif.

Recently, it was shown that it is possible to isolate free circulating DNA from plasma/serum of patients with benign and malignant diseases. In addition, several groups were able to detect tumor-associated alterations in these nucleic acids. We wondered whether any nucleic acids are detectable in cell-free bronchial lavage supernatants, which until now have been discarded after cell harvest. Additionally, we wanted to find out if it is possible to detect tumor-associated alterations in these DNA molecules. DNA was isolated from cell-free lavage supernatants from 30 lung cancer patients, and the DNA was examined for microsatellite alterations. Intact DNA could be isolated from all cell-free bronchial lavage supernatants. Microsatellite alterations were found in lavage supernatants of 12 of 30 patients and in lavage cells of 6 of 30 patients. Altogether, alterations were found in 14 of 30 patients. Thus, we could demonstrate for the first time that it is possible to isolate intact DNA from cell-free bronchial lavage supernatants. Their quantity and quality are sufficient for further amplification via polymerase chain reaction. Altogether, tumor-associated changes were detected in the DNA of 47% of the patients that were analyzed.

Background: We compared the efficacy and safety of the low-molecular weight heparin enoxaparin with unfractionated heparin (UFH) for the prevention of venous thromboembolic disease in patients with heart failure or severe respiratory disease., Methods: This was a multicenter, controlled, randomized, open study in which patients received either enoxaparin (40 mg once daily) or UFH (5000 IU 3 times daily) for 10 +/- 2 days in 64 medical departments in Germany. Patients were stratified and enrolled according to their underlying disease: severe respiratory disease or heart failure. The primary efficacy parameter was a thromboembolic event up to 1 day after the treatment period., Results: Of the 665 patients enrolled, 451 patients were able to be evaluated in the primary efficacy analysis. The incidence of thromboembolic events was 8.4% with enoxaparin and 10.4% with UFH. Enoxaparin was at least as effective as UFH, with a 1-sided equivalence region of -4% (90% CI -2.5-6.5, P =.015). Enoxaparin was associated with fewer deaths, less bleeding, and significantly fewer adverse events (45.8% vs 53.8%, P =.044)., Conclusions: Enoxaparin is at least as effective as UFH in the prevention of thromboembolic events in patients with heart failure or severe respiratory disease. Its beneficial safety profile and once-daily administration is advantageous for inpatient and outpatient use.

The giant elastic protein titin contains an extensible segment that underlies the majority of physiological passive muscle stiffness. The extensible segment comprises mechanically distinct and serially-linked spring elements: the tandem Ig segments, the PEVK and the cardiac-specific N2B unique sequence. Under physiological conditions the tandem Ig segments are likely to largely consist of folded Ig domains whereas the N2B unique sequence and PEVK are largely unfolded and behave as wormlike chains with different persistence lengths. The mechanical characteristics of titin's extensible region may be tuned to match changing mechanical demands placed on muscle, using mechanisms that operate at different time scales and that include post-transcriptional and post-translational processes.

Background: Many ambulatory sleep apnea monitoring devices are equipped with software which allows an automated analysis of data as well as a visual analysis., Objective: The Merlin system which records heart rate, snoring sound, efforts, oronasal flow, body position and oxygen saturation was investigated to identify proper parameter settings for the automated analysis and to compare the automated with the visual analysis in patients with mild obstructive sleep apnea syndrome (OSAS). Sensitivity and specificity of the visual and automated analysis of ambulatory monitoring in comparison with visual polysomnographic (PSG) analysis were determined., Methods and Results: First, we tried to find the optimal parameters for the automated analysis, using 7 different settings in 17 OSAS patients. Furthermore, we applied the optimized setting to 66 OSAS patients who were admitted (age 50.9 +/- 9.9 years, BMI 32.9 +/- 5 kg/m(2)), and compared the results with the visual analysis of raw data. The patients slept for one night in the sleep laboratory with Merlin and PSG simultaneously to compare the visual and automated analysis of Merlin data with results from the visual analysis of PSG. Automated analysis leads to an underestimation of the respiratory disturbance index (RDI; p < 0.001) compared with both the visual analysis and results of PSG. Using a cutoff level of 5 apneas and hypopneas/h for the diagnosis of OSAS, the sensitivity of Merlin with the automated analysis is 40.6% and the specificity is 100%. With a cutoff level of 15/h, sensitivity and specificity rose to 91.3 and 100%, respectively, which is comparable to the visual analysis., Conclusion: Merlin is a reliable device for detection of sleep-related breathing disorders, but recordings should be analyzed visually, especially in patients with a low RDI., (Copyright 2002 S. Karger AG, Basel)