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RMRP mutations in Japanese patients with cartilage-hair hypoplasia.

We examined 12 Japanese patients with metaphyseal chondrodysplasia (MCD) for mutations in the ribonuclease mitochondrial RNA processing gene (RMRP), and identified four novel mutations in two patients with typical and atypical cartilage-hair hypoplasia (CHH), a form of MCD characterized by extra-skeletal manifestations including hypoplastic hair and defective immunity. A patient with typical CHH had a 17-bp duplication at +3 and a de novo 182G > A. The other patient with atypical CHH had a 17-bp insertion at -20 and a 218A > G. Expression analysis revealed that the allele with this insertion mutation in the promoter region silenced the gene. Spectrum analysis of the mutations and polymorphisms in RMRP showed marked difference between the Japanese and other ethnic groups. Such ethnic and phenotypic difference should be taken into account in mutation analysis of the gene.

Adolescent↗

A computing system for the clinical and experimental investigation of cerebrovascular reactivity.

We present a computing system for the recording and on-line analysis of analogue signals derived from bedside cerebrovascular monitors in different pathophysiological conditions. These include arterial blood pressure and oxygen saturation, end-tidal carbon dioxide concentration, cerebral blood flow velocities using transcranial Doppler ultrasonography, and concentration changes in cerebral oxy- and deoxyhaemoglobin from near infrared spectroscopy. Configuration and analysis adopts arithmetic expressions of different signal processing functions, various statistical properties for each signal, frequency spectrum analysis using fast Fourier transformation, and correlation/cross-correlation. The software offers off-line analysis of non-invasive tests of cerebrovascular reactivity. Several examples of clinical assessment of cerebrovascular reactivity are presented, including cerebral haemodynamic stress tests which employ carbon dioxide, acetazolamide, the breath holding test, leg cuff inflation and deflation, and transient carotid artery compression. Application within the experimental setting with induced haemorrhagic hypotension can also be used.

Cardiovascular Diseases↗

iMARS--mutation analysis reporting software: an analysis of spontaneous cII mutation spectra.

The sensitivity of any mutational assay is determined by the level at which spontaneous mutations occur in the corresponding untreated controls. Establishing the type and frequency at which mutations occur naturally within a test system is essential if one is to draw scientifically sound conclusions regarding chemically induced mutations. Currently, mutation-spectra analysis is laborious and time-consuming. Thus, we have developed iMARS, a comprehensive mutation-spectrum analysis package that utilises routinely used methodologies and visualisation tools. To demonstrate the use and capabilities of iMARS, we have analysed the distribution, types and sequence context of spontaneous base substitutions derived from the cII gene mutation assay in transgenic animals. Analysis of spontaneous mutation spectra revealed variation both within and between the transgenic rodent test systems Big Blue Mouse, MutaMouse and Big Blue Rat. The most common spontaneous base substitutions were G:C-->A:T transitions and G:C-->T:A transversions. All Big Blue Mouse spectra were significantly different from each other by distribution and nearly all by mutation type, whereas the converse was true for the other test systems. Twenty-eight mutation hotspots were observed across all spectra generally occurring in CG, GA/TC, GG and GC dinucleotides. A mutation hotspot at nucleotide 212 occurred at a higher frequency in MutaMouse and Big Blue Rat. In addition, CG dinucleotides were the most mutable in all spectra except two Big Blue Mouse spectra. Thus, spontaneous base-substitution spectra showed more variation in distribution, type and sequence context in Big Blue Mouse relative to spectra derived from MutaMouse and Big Blue Rat. The results of our analysis provide a baseline reference for mutation studies utilising the cII gene in transgenic rodent models. The potential differences in spontaneous base-substitution spectra should be considered when making comparisons between these test systems. The ease at which iMARS has allowed us to carry out an exhaustive investigation to assess mutation distribution, mutation type, strand bias, target sequences and motifs, as well as predict mutation hotspots provides us with a valuable tool in helping to distinguish true chemically induced hotspots from background mutations and gives a true reflection of mutation frequency.

Animals↗

Power spectral analysis of heart rate in elderly hypertensive subjects with or without silent coronary disease.

Much evidence indicates an involvement of the sympathetic nervous system in the genesis of silent myocardial ischemia. The authors assessed autonomic system activity by power spectrum analysis of heart rate variability in 21 elderly hypertensive men with and without angiographically confirmed coronary artery disease and compared the results with those from an age-matched control group. In the analysis an autoregressive algorithm was used to determine the power spectrum from an electrocardiographic recording of 512 consecutive RR intervals. The autonomic nervous system induces two distinct sinusoids: a low-frequency signal attributable to sympathetic activity and a high-frequency vagal response. In the hypertensive patients with coronary disease the authors also evaluated sympathetic activation after double-blind, placebo-controlled administration of metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20 mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day).

Aged↗

Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability.

OBJECTIVES: To assess the interaction between the sympathetic and parasympathetic systems in patients with fibromyalgia syndrome (FM), using power spectrum analysis (PSA) of heart rate variability (HRV). In addition, we explored the association between HRV, measures of tenderness, FM symptoms, physical function, psychological well being and quality of life. METHODS: We studied 22 women with FM and 22 age-matched healthy women. Twenty-minute electrocardiogram recordings were obtained in a supine position during complete rest. Spectral analysis of R-R intervals was done by the fast-Fourier transform algorithm. RESULTS: Heart rate was significantly higher in FM patients compared with controls (P < .006). FM patients had significantly lower HRV compared with controls (P= .001), and higher low-frequency (LF) and lower high-frequency (HF) components of PSA than controls (P < .001). Quality of life, physical function, anxiety, depression, and perceived stress were moderately to highly correlated with LF, HF (in normalized units), and LF/HF. No association was observed between HRV parameters and measures of tenderness and FM symptoms. CONCLUSIONS: The basal autonomic state of patients with FM is characterized by increased sympathetic and decreased parasympathetic tones. Autonomic dysregulation may have implications regarding the symptomatology, physical and psychological aspects of health status.

Algorithms↗

Visual and computer-based analysis of 24 h sleep-waking patterns in the dog.

Sleep and waking EEG patterns recorded over 24 h periods in 7 adult beagle dogs were studied both visually and by computer. Online analysis was carried out using a mini-computer. The following quantitative data were computed and listed (and/or stored on disc) at 30 sec intervals: power spectrum analysis of one cortical derivation by means of Fast Fourier Transformation, the spectrum being divided in 4 bands (0.5-3.5, 3.5-7.5, 7.5-13.5, 13.5-25 c/sec); the power contained in the 3.5-7.5 c/sec band of the hippocampal derivation; a spindle detection algorithm empirically defined and based on the power contained in the 10.5-14.5 c/sec band of subepochs of 0.8 sec and the background power; average EMG and EOG amplitudes. Plots were made of the quantitative data (on the y axis) showing evolution with time (on the x axis). Comparisons with the y ordinates enabled a visual estimate of stage to be made. Automatic classification was done by means of minimal distance, using visually selected epochs and calculated parameters as references. Visual and computer-based analyses allowed the following patterns to be defined: wakefulness, transitional stage, light slow wave sleep, deep slow wave sleep and REM sleep. Sleep-waking cycles of 20-30 min alternated during the 24 h period with rapid transitions from one stage to another.

Animals↗

[Power spectral analysis of electromyograms in fast and slow fibers of cats extraocular muscles].

Electromyogram (EMG) was recorded from the muscle fibers in the orbital layers through the global layers of superior rectus muscle of the cat. Power spectrum analysis was applied to investigate the quantitative differences between EMG patterns in both layers. The median of the power spectrum in frequency from the global layers was 400-700 Hz, which was considered to be an EMG pattern of the fast fibers. On the other hand, EMG from the orbital layers showed a small amplitude of 35-70 microV and two different types of power spectrum; one had the median frequency of more than 1,000 Hz and the other, about 500 Hz. It was suggested that the high frequency component was due to multi-innervated slow fibers and the low frequency component was due to singly innervated and intermediate fibers. The study of the power spectrum of interference electromyograms provides an advantage to differentiate the electrical activities of the slow fibers from the fast ones.

Animals↗

Expression of human brain carboxypeptidase B, a possible cleaving enzyme for beta-amyloid precursor protein, in peripheral fluids.

Human brain carboxypeptidase B (HBCPB) is a novel brain protease that processes native brain beta-amyloid precursor protein (APP) in vitro. Immunoblot analysis of human serum and cerebrospinal fluid (CSF) using anti C14-module antibody, which recognizes the C-terminal peptide unique to HBCPB, detected the 30 and 40 kDa immunoreactive bands. Analysis of HBCPB prepared from both serum and CSF demonstrated proteolytic activities for brain APP. Protease inhibitor spectrum analysis also supports that these bands correspond to the mature form and and prepro form of HBCPB, respectively. As is the case in brain parenchyma, the prepro-form is dominant in CSF. In serum, however, the majority of HBCPB exists in the mature form, possibly due to an abundant trypsin-like proteolytic activity in serum. HBCPB expressed in serum and CSF, therefore, may have a significance as a peripheral marker of the brain protease, which participates in APP processing in human brain.

Alzheimer Disease↗

Linear and non-linear properties of heart rate in postnatal maturation.

OBJECTIVE: An investigation was made of how postnatal maturation of cardiac control can be described by linear and non-linear methods of time series analysis. METHODS: Sixteen healthy and term newborns were studied during their first 6 months of life. Power spectrum analysis including total power (TP), low frequency power (LF), high frequency power (HF) and LF/HF ratio were performed on the instantaneous heart rate (IHR) time series and mean heart rate (HR) was derived. The largest Lyapunov exponent (LLE) was calculated using a modified Wolf algorithm and checked by means of the surrogate-data test. RESULTS: There is an age dependency for the parameters LLE, HR, TP, HF, LF, LF/HF for active and LLE, HR, TP, HF, LF/HF for quiet sleep. HR is characterised by a steep increase between the 5th and 7th day. HF demonstrates a distinct development with high values around the first week and 90-180th day and low values around the 10-60th day. TP, LF and LF/HF show significantly higher values in active sleep in comparison to quiet sleep. For all ages and sleep stages, positive LLE were found, indicating sensitivity to initial conditions, a hall-mark of chaos. For the period between the 7 and 90th days of life, the LLE for active sleep took on larger values compared with the LLE of quiet sleep. CONCLUSIONS: This study shows that by linear as well as non-linear analysis one can reveal the complexity of the IHR development in humans and may gain insight into the system controlling the heart during the period considered. The positive LLE indicate that there is a non-linear component in the heart rate control. There is no "straight line" development for the parameters analysed within the first 6 months. This may result from manifold influences on the autonomic system, due to structural and functional maturation in this period of life.

Heart↗

Computer-based recognition of EEG patterns.

A critical "mini-overview" is presented of several computer-based techniques proposed for the automated recognition of specific EEG patterns, important in visual EEG analysis. Both phasic and tonic EEG patterns are addressed. The techniques discussed include methods based on power spectrum analysis and on period-amplitude analysis, "mimetic" methods and related implementations in an expert system approach, and methods based on artificial neural networks.

Electroencephalography↗

Comparison of different methodologies of heart rate variability analysis.

Two methodological aspects of heart rate variability (HRV) are tested. Heart rate variability and RR interval variability (RRV) are compared in 109 healthy subjects using 24-h Holter recordings. Autoregressive power spectrum analysis was performed, and the power in three frequency bands was evaluated by two different methods: the peak power and the mean power within the band. The power in the low frequency (LF) and high frequency (HF) ranges showed greater changes between day and night values when RRV was analysed compared with HRV. The mid frequency (MF) range power showed no significant change at night with RRV analysis compared with a significant decrease with HRV analysis. The different pattern of changes between day and night values when using RRV or HRV analysis is explained by the non-linear nature of the relationship between RR interval and heart rate and the lower heart rate at night. Therefore, depending on the heart rate, there may be amplification or attenuation of fluctuations when transforming from one heart rate variability method to another. When comparing peak power and mean power measurements within the frequency bands, the changes in LF and MF powers were similar. However, HF mean power with RRV analysis showed less change at night than the peak power and no change with HRV analysis. The explanation lies in the fact that respiratory fluctuations at night are much more regular, resulting in a sharp high peak in the power spectrum. The peak power is therefore higher at night, whereas the total power changes much less or remains unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Bias↗

[An acoustical analysis of TMJ sounds and its clinical importance].

The aim of this report was to establish a method for objective examination of TMJ sounds which is required for preventive care of the TMJ dysfunction, and to confirm its clinical importance by means of analysis of mandibular border movement and EMG. The subjects for the acoustical analysis of TMJ sounds consisted of 13 temporomandibular joints as the clicking group, 4 as the crepitus group, and 11 as the control group. The subjects for the analysis of the mandibular movement and EMG consisted of 8 adults with clicking as the clicking group and 11 without TMJ sounds as the control. The results obtained were as follows: 1. Clear and stable TMJ sounds waves could be recorded from the external auditory meatuses. 2. Clicking sounds waves showed a sharper rising and shorter duration than crepitus sounds waves. Comparing the three groups on the basis of the data of power spectrum analysis of frequencies using FFT, the spectrum of frequencies of the crepitus group was the highest and broadest, and that of control group was the lowest. 3. The deviation of the trace of mandibular border movement in the clicking group tended to be larger than in the control group. 4. In the clicking group, the frequency of occurrence of the silent period of EMG bursts during tooth tapping was lower and the duration of the silent period was shorter than in the control group. Duration, interval and cycle of EMG bursts during gum chewing in the clicking group was longer than in the control group. 5. From the above, it was suggested that the ones with TMJ sounds had the TMJ dysfunction latently, therefore it was considered valuable to use an analysis of TMJ sounds in the examination for the preventive care of the TMJ dysfunction.

Humans↗

Mechanisms of spontaneous mutagenesis: an analysis of the spectrum of spontaneous mutation in the Escherichia coli lacI gene.

We have obtained via DNA sequence analysis a spectrum of 174 spontaneous mutations occurring in the lac I gene of Escherichia coli. The spectrum comprised base substitution, frameshift, deletion, duplication and insertion mutations, of which the relative contributions to spontaneous mutation could be estimated. Two thirds of all lacI mutations occurred in the frameshift hotspot site. An analysis of the local DNA sequence suggested that the intensity of this hotspot may depend on structural features of the DNA that extend beyond those permitted by the repeated tetramer at this site. Deletions comprised the largest non-hotspot class (37%). They could be divided into two subclasses, depending on whether they included the lac operator sequence; the latter was found to be a preferred site for deletion endpoints. Most of the deletions internal to the lacI gene were associated with the presence of directly or invertedly repeated sequences capable of accounting for their endpoints. Base substitutions comprised 34% of the non-hotspot events. Unlike the base substitution spectrum obtained via nonsense mutations, G . C----A . T transitions do not predominate. A new base substitution hotspot was discovered at position +6 in the lac operator; its intensity may reflect specific features of the operator DNA. IS1 insertion mutations contributed 12% of the non-hotspot mutations and occurred dispersed throughout the gene in both orientations. Since the lacI gene is not A + T-rich, the contribution of IS1 insertion to spontaneous mutation in general might be underestimated. Single-base frameshift mutations were found only infrequently. In general, they did not occur in runs of a common base. Instead, their occurrence seemed based on the "perfection" of direct or inverted repeats in the local DNA sequence. Three (tandem) duplication events were recovered. No repeated sequences were found that might have determined their endpoints.

Base Sequence↗

Spatio-temporal representation of multichannel EMG firing patterns and its clinical applications.

Analyzing motor unit (MU) activity is essential for studying the neurological dysfunction of upper motor neuron disorders (UMND). This study employs multichannel surface electromyographic (EMG) signals, as recorded from the upper arm during elbow flexion and extension, to analyze the temporal changes and spatial distribution of the dominant firing rate. To estimate the dominant firing rate, the autoregressive (AR) spectrum analysis method is utilized to detect the peaks and poles of the AR model, of the surface EMG spectrum below 40 Hz. The temporal changes in firing rates are also observed by using the spectrogram representation of low-frequency EMG spectra. The EMG spectrogram facilitates examination of the time-varying characteristics of firing rates and recruitment of MUs from surface EMG signal. The low-frequency spectra of multichannel EMG are then represented in a polar form to visualize the spatial distribution of firing patterns across muscles. Via spatio-temporal representation techniques, this study provides a viable approach of observing both the spatial and temporal patterns of MU activities in normal subjects and patients with UMND, including cerebrovascular disease and Parkinson's disease.

Cerebrovascular Disorders↗

[The identification of microscopic, physical and chemistrical analysis on Curculigo orchiode and its counterfeit].

OBJECTIVE: To identify sham Curculigo orchiode from the genuine. METHODS: Using the distinguishing method of morphology and histology, TLC and UV spectrum analysis. RESULTS: The tissue structrue, the physical and chemical featrures of Curculigo orchiode and its counterfeit have obvious differences. CONCLUSION: The counterfeit of Curculigo orchiode come from Paeonia lactifora's axillary root.

Chromatography, Thin Layer↗

Discharge pattern of renal sympathetic nerve activity in the conscious rat: spectral analysis of integrated activity.

We investigated the periodic characteristics of bursting discharge in renal sympathetic nerve activity (RSNA) in conscious rats. Employing a discrete fast Fourier transform algorithm, a power spectrum analysis was used to quantify periodicities present in rectified and integrated RSNA whose signal-to-noise ratio in the recordings was greater than six. In conscious rats with intact baroreceptors, RSNA was characterized by four frequency components occurring at about 0.5, 1.5, 6, and 12 Hz, which corresponded to the low-frequency fluctuation of heart rate, respiration, and frequency of heart beat, and its harmonics, respectively. After intravenous infusion of sodium nitroprusside (SNP) to elicit reflex increases in RSNA and heart rate, the power for the component at 6 Hz followed the changes in heart beat frequency and was significantly increased, while those for the three other components were attenuated or experienced no change. In sino-aortic denervated (SAD) conscious rats, all four components were abolished, and the power spectrum was well fitted by a flat or Lorentzian curve, suggesting an almost random pattern. Only a respiratory-related component, which suggested common central modulation, appeared sporadically for short periods but was absent for the most part. Therefore most of this component together with the low-frequency component was also likely due to the baroreceptor-dependent peripheral modulation. The activity was sorted in 15 subgroups on the basis of spike amplitudes in the RSNA. Each subgroup showed frequency characteristics similar to the whole nerve activity. These results suggest that all periodicity in the RSNA of conscious rats with intact baroreceptors is caused by the baroreceptor input.

Action Potentials↗

Effects of single and repeated cognitive tasks on autonomic balance as observed by an analysis of R-R intervals.

The effects on sympathic-parasympathetic nervous system balance of single exposure and repeated exposures to a cognitively demanding task were examined by power spectrum analysis of cardiac R-R intervals. In the single task experiment, 32 healthy subjects engaged in a 90-min English language transcription task and in 90-min reading as a nontask control. In the repeated task experiment, 14 subjects experienced either intermittent exposure to the transcription task until late at night, or daytime exposure to the transcription task followed by relax wakefulness until sleep onset. The single task exposure significantly increased the normalized low frequency component (%LF; 0.05-0.15 Hz) of the R-R interval spectrum compared with the nontask control, but there was no significant task difference in the normalized high frequency component (0.15-0.50 Hz). The increased %LF values immediately returned to control levels after cessation of the task. Repeated exposure to the cognitive task until late at night produced a significantly greater %LF during the first nonrapid eye movement sleep period when compared to relaxed wakefulness. These results would suggest that a single exposure to a cognitive task may produce a shift to sympathetic nervous system dominance only during the period of the task, whereas repeated exposures to a cognitive task until late at night may produce a shift to sympathetic nervous system dominance which lasts into the subsequent sleep period.

Adult↗

Monte Carlo simulations to advance characterisation of landmines by pulsed fast/thermal neutron analysis.

The performance of a detection system based on the pulsed fast/thermal neutron analysis technique was assessed using Monte Carlo simulations. The aim was to develop and implement simulation methods, to support and advance the data analysis techniques of the characteristic gamma-ray spectra, potentially leading to elemental characterisation of innocuous objects using the full spectrum analysis (FSA) approach. The simulations were carried out with a simplified tool, based on a 14MeV DT pulse-neutron source and a bismuth-germanate detector. A MCNP-based method for de-coupling the radiation transport in mixed (n,gamma) fields, to generate separate sets of standard detector gamma-ray responses for individual elements, is outlined. When normalised and experimentally benchmarked in terms of the pulse-neutron source production rate, the standard spectra can be incorporated into algorithms for the FSA of in situ measurements and elemental fingerprinting of the inspected object.

Blast Injuries↗