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Tumor spectrum analysis in p53-mutant mice.

BACKGROUND: The p53 tumor suppressor gene is mutated in a large percentage of human malignancies, including tumors of the colon, breast, lung and brain. Individuals who inherit one mutant allele of p53 are susceptible to a wide range of tumor types. The gene encodes a transcriptional regulator that may function in the cellular response to DNA damage. The construction of mouse strains carrying germline mutations of p53 facilitates analysis of the function of p53 in normal cells and tumorigenesis. RESULTS: In order to study the effects of p53 mutation in vivo, we have constructed a mouse strain carrying a germline disruption of the gene. This mutation removes approximately 40% of the coding capacity of p53 and completely eliminates synthesis of p53 protein. As observed previously for a different germline mutation of p53, animals homozygous for this p53 deletion mutation are viable but highly predisposed to malignancy. Heterozygous animals also have an increased cancer risk, although the distribution of tumor types in these animals differs from that in homozygous mutants. In most cases, tumorigenesis in heterozygous animals is accompanied by loss of the wild-type p53 allele. CONCLUSION: We reaffirm that p53 function is not required for normal mouse development and conclude that p53 status can strongly influence tumor latency and tissue distribution.

Alleles↗

Modern spectrum analysis in multidimensional NMR spectroscopy: comparison of linear-prediction extrapolation and maximum-entropy reconstruction.

NMR spectroscopy is an inherently insensitive technique, and many challenging applications such as biomolecular studies operate at the very limits of sensitivity and resolution. Advances in superconducting magnet, cryogenic probe, and pulse sequence technologies have resulted in dramatic improvements in both sensitivity and resolution in the past decade. Conversely, the signal-processing method used most widely in NMR spectroscopy, extrapolation of the time domain signal by linear prediction (LP) followed by discrete Fourier transformation (DFT), was developed in the early 1980s and has not been subjected to detailed scrutiny for its impact on sensitivity and resolution. Here we report the first systematic investigation of the accuracy and precision of spectra obtained by LP extrapolation followed by DFT. We compare the results to spectra obtained by maximum-entropy (MaxEnt) reconstruction, which was developed contemporaneously to LP extrapolation but is not widely employed in NMR spectroscopy. Although it reduces truncation artifacts and increases the amplitudes of strong peaks, we find that LP extrapolation generates false-positive peaks and introduces frequency errors. These defects of LP extrapolation become less pronounced for longer data records and higher signal-to-noise ratio. MaxEnt generally yields more detectable peaks for a given number of data samples, more accurate peak frequencies, and fewer false-positive peaks than LP extrapolation. MaxEnt also permits the use of nonlinear sampling, which can give dramatic improvements in resolution. These results show that the use of MaxEnt together with nonlinear sampling, rather than LP extrapolation, could reduce the amount of instrument time required for adequate sensitivity and resolution by a factor of 2 or more.

Fourier Analysis↗

Studies on hemodynamic instability in paroxysmal supraventricular tachycardia: noninvasive evaluations by head-up tilt testing and power spectrum analysis on electrocardiographic RR variation.

Hemodynamic instability is a crucial determinant of the best therapeutic option in paroxysmal supraventricular tachycardia (PSVT). However, it is still unclear if hemodynamic instability is tachycardia dependent or independent. We performed frequency-domain analysis of electrocardiographic RR variations during induced PSVT and head-up tilt tests after successful ablation to investigate the role of autonomic vasomotor function in hemodynamic instability during PSVT. Thirty-six patients with (syncope group, n = 18) and without (nonsyncope group, n = 18) syncope and/or presyncope during PSVT were enrolled in this study. Serial blood pressure, heart rate, and variations in heart rate during induced PSVT and head-up tilt tests were examined. Initial blood pressure fall and heart rate changes during induced PSVT were greater in the syncope group than in the nonsyncope group. A significant positive linear relationship was found between these two. Delayed blood pressure fall was observed in the syncope group, independent of heart rate changes. Syncope in PSVT could be predicted from the results of head-up tilt tests with 82% accuracy. Heart rate responses after isoproterenol infusion were significantly greater in the syncope group than in the nonsyncope group. The changes in low frequency to high frequency (LF:HF) values during induced PSVT and head-up tilt tests were significantly greater in the syncope group than in the nonsyncope group, and an exponential correlation was found between LF:HF changes in both tests. We conclude that PSVT rate and vasomotor reaction are related with hemodynamic instability during PSVT and head-up tilt testing is a useful method for determining if patients will have syncope during PSVT.

Adolescent↗

[Duplex sonography of renal artery stenosis: potentials and limits of frequency spectrum analysis of arterial segments compared with angiography].

PURPOSE: The aim of this prospective study was to evaluate the potentials and limits of Doppler waveform analysis of intrarenal vessels in patients with suspected renal artery stenosis. MATERIAL AND METHODS: In a three-year study we compared our colour Doppler results of 111 patients with the angiography results. Evaluated parameters were acceleration time (AT), acceleration index (AI) and early systolic peak (ESP). RESULTS: The sensitivity of severe stenoses (> or = 70%) was 89%. In moderate stenoses (50-70%) it was possible to increase the sensitivity from 56% to 76% if a comparison with the contralateral side was included. The specificity was 91%. Causes for limited sensitivity and specificity were poor examination conditions, stenoses of accessory renal arteries and moderate stenoses as well as diffuse non-stenosing lesions. CONCLUSION: In comparison with angiography, the diagnostic value of Doppler waveform analysis in the detection of renal artery stenoses has specific limitations. In significant stenoses, however, additional valuable haemodynamic information, useful for PTA, can be obtained by this easy and accessible method.

Adult↗

Spectrum analysis, aliasing, and the perception of musical tones.

A signal-processing model is proposed in which the phenomenon of 'aliasing' is invoked to explain certain phenomena in the perception of musical tones, for which a really satisfactory explanation has not hitherto been available. It is shown that this model offers a reason why the harmonic series appears to play such a central role in tone and pitch perception, and can throw light on 'virtual pitch', 'harmonic beats', etc. Some preliminary results from a computer simulation of the model are described which are consistent with empirical data on tone perception.

Humans↗

Autonomic changes during hypnosis: a heart rate variability power spectrum analysis as a marker of sympatho-vagal balance.

Spectral analysis of beat-to-beat variability in electrocardiography is a simple, noninvasive method to analyze sympatho-vagal interaction. The electrocardiogram is analyzed by means of an automatic, autoregressive modeling algorithm that provides a quantitative estimate of R-R interval variability by the computation of power spectral density. Two major peaks are recognizable in this specter: a low-frequency peak (LF, -0.1 Hz), related to the overall autonomic activity (ortho+parasympathetic) and a high-frequency peak (HF, -0.25 Hz), representative of the vagal activity. The LF/HF ratio is an index of the sympatho-vagal interaction. This technique was applied, using a computer-assisted electrocardiograph, to 10 healthy volunteers (6 high and 4 low hypnotizable subjects as determined by the Stanford Hypnotic Susceptibility Scale, Form C) in randomized awake and neutral hypnosis conditions. Preliminary results indicated that hypnosis affects heart rate variability, shifting the balance of the sympatho-vagal interaction toward an enhanced parasympathetic activity, concomitant with a reduction of the sympathetic tone. A positive correlation between hypnotic susceptibility and autonomic responsiveness during hypnosis was also found, with high hypnotizable subjects showing a trend toward a greater increase of vagal efferent activity than did low hypnotizables.

Adult↗

The accuracy of power-spectrum analysis of heart-rate variability from annotated RR lists generated by Holter systems.

The accuracy of spectral analysis of heart-rate variability performed on annotated RR interval lists obtained from several commercial Holter systems was appraised. Five tape-recorder-based systems (Del Mar 750, Marquette 8000, Oxford Medilog Excel, Remco Cardioline AD 35 and Reynolds Pathfinder PA3) and four solid-state systems (Hewlett Packard 43420B, Marquette Seer, Oxford 6000FD2, Reynolds E-Ram) were considered. Two ECG signals with fixed real morphology but characterized by a different degree of modulation of the RR interval (reduced and normal variability) were fed into the recorders evaluated. The total power and the power in the very low-, low- and high-frequency bands were then estimated on all Holter-generated RR sequences. Spectral analysis was performed by both the autoregressive and fast-Fourier-transform methods. The estimation error of each parameter was statistically characterized and, for tape-recorder-based systems, inferential analysis was used to test for differences between recorders, tapes and times of recording. The centre and dispersion of the estimation error changed markedly from system to system. Some tape-recording systems showed large inter-recorder differences. The degree of spectral distortion was never uniform among selected bands. Solid-state systems performed better than tape-recording ones but both were limited in the accuracy by the quantization of RR interval measurement. The fast Fourier method yielded spectral estimates more stable than the autoregressive method. Our data clearly show that spectral analysis of very low-variability signals may be seriously affected by Holter recording and preprocessing of ECG signals.

Electrocardiography↗

Electromyographic power spectrum analysis of the paraspinal muscles. Long-term reliability.

As a prerequisite to the use of electromyographic power spectral analysis of the paraspinal muscles as a low-back pain treatment outcome measure, the long-term reliability of the technique was assessed. The myoelectric signals of the multifidus and iliocostalis lumborum muscles of healthy sedentary women were analyzed with regard to spectral parameters during a constant-force contraction, before and after a 3-month period. Results indicated that for both muscles, estimates of initial median frequency and amplitude had high test/retest reliability, but that the recovery and left-right difference parameters were not stable. Using a confidence interval method, test/retest variation for the fatigue parameter was found to be within the range of variability of potentially underlying metabolic processes.

Adult↗

Factors in the reproducibility of electromyographic power spectrum analysis of lumbar paraspinal muscle fatigue.

STUDY DESIGN: An investigation of the reliability of various factors used to analyze electromyograms of paraspinal muscles of the lumbar spine. OBJECTIVES: To determine the reproducibility of several electromyographic variables over time and to assess the influence of confounding factors. SUMMARY OF BACKGROUND DATA: Previous reliability studies have included small numbers of subjects and often have not explored the factors that can influence the reliability of this technique. METHODS: In the first study, 39 volunteers underwent electromyographic tests on three occasions at two loads. The time interval was 1 week between tests. Electromyographic variables measured included half-width (spectral width at half maximum amplitude), initial median frequency, median frequency slope, initial root mean square, root mean square, and root mean square slope. In the second study to determine the influence of posture, nine volunteers were tested on two occasions with a change in posture between tests. RESULTS: Reliability was better for tests at the higher loads. Initial median frequency, half-width, and root mean square all had acceptable reproducibility over time, with a coefficient of variation less than 10. Initial median frequency and half-width proved to be the most suitable variables; they yielded the largest between-subject variation and, of all variables, were affected the least by changes in load. The remaining variables were very load-dependent. A change in posture greatly influenced the reproducibility. CONCLUSION: These results demonstrate that only initial median frequency and half-width have acceptable reproducibility over time and at different loads, with the potential to be useful in discriminating between individuals. Changes in posture can greatly change an electromyographic result.

Adult↗