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PubMed1994

Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and age.

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning assay in a healthy pediatric population. Assays were performed on 49 subjects (29 males and 20 females) ranging in age from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant (TGr) mutant frequency (MF), unselected cloning efficiency (CE) and age was performed using data obtained in this study and those previously obtained in our laboratory on 66 newborn umbilical cord blood samples and 230 adult blood samples. For statistical comparisons pediatric subjects were divided into 4 groups. Group I included cord blood samples (age 0 years); Group II were subjects between 0 and 5 years; Group III were between 6 and 11 years and Group IV were between 12 and 17 years. The ln MF of Groups I and II were significantly lower than Groups III and IV (p < 0.05). The mean ln MF for each of Groups I-IV was significantly lower than the adult value. The cloning efficiency for Group I was significantly lower than that for Groups II-IV and adults. The relationships among the ln MF, unselected CE and age were expressed by the equations: ln (MF) = 0.945 -2.453 CE (p < 0.001) and ln (MF) = 0.114 + 0.063 age (p 0.004). The slope coefficients for unselected CE and age were significantly different from adults (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were performed using both age and unselected CE as well as terms to reflect differences in their relationships with ln MF in adults and children. The results showed that the intercept and the age coefficients differ significantly for children and adults after adjustment for CE and yielded the following equations: ln (MF) = 0.548 -1.676 CE + 0.075 age, (Groups I-IV) and ln (MF) = 2.263 -1.676 CE + 0.014 age (adults). An alternative statistical model using ln (age ), ln (MF) = 0.381 -1.767 CE + 0.673 ln (age + 1), (p < 0.001), describes the rapid increase in MF with age that levels off in late adolescence. These findings demonstrate the changing influence of age on mutant frequency in the pediatric population as compared to the adult populations. These studies also illustrate that the increase in background somatic mutant frequencies at the hprt locus in T-lymphocytes is not linear from birth to adolescence and is significantly different from that seen in the adult population.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed2004

HLA class II typing in newborns reveals a low frequency of the DRB104 allele and a high frequency of DRB111 allele in three regions of continental Italy.

As part of a longitudinal study aimed at defining the natural history of prediabetic autoimmunity and predicting the risk of future cases of type 1 diabetes, 3607 newborns from three regions of continental Italy (Lombardia, Liguria, and Lazio) were subjected to genetic testing to determine human leukocyte antigen-DRB1 (HLA-DRB1) and -DQB1 allele and phenotype frequencies. Polymerase chain reaction and immobilized sequence-specific oligonucleotide probe assays were used to identify ten DRB1 allele lineages and three DQB1 alleles. No major inter-regional differences emerged in the allelic distribution indicating homogeneous distribution of the HLA DRB1-DQB1 alleles among the three regions analyzed. Comparison of our data with those published for other Caucasian populations reveals that these three regions are characterized by a very low frequency of DRB1*04 (8%) and a high frequency of DRB1*11 (25%). The phenotype frequencies of HLA-DQB1*0302 and DQB1*0602 observed are also lower than those reported for other populations. Furthermore, the DRB1*04-DQB1*0302 haplotype was relatively infrequent in our population (5.3% of the newborns tested). These findings furnish a genetic "portrait" of the populations of the analyzed regions that will be useful not only for investigation of the genetic risk of type 1 diabetes mellitus in Italy but also for studies of other autoimmune diseases related to HLA genotypes.

Diabetes Mellitus, Type 1↗

PubMed1975

Moments for sum of an arbitrary function of gene frequency along a stochastic path of gene frequency change.

A diffusion model is developed to compute any moment of the sum of an arbitrary function of the gene frequency along sample paths between any two specified frequencies. This is used to calculate the mean age of a mutant of frequency chi, including or excluding the possibility of its having been at value chi equals 1 during the process, and the total frequency of heterozygotes involving an allele since its origin.

Alleles↗

PubMed1991

Isocapnic high frequency jet ventilation: dead space depends on frequency, inspiratory time and entrainment.

Twelve healthy pigs were ventilated with high frequency jet ventilation via a Mallinckrodt HiLo jet tube. The expired gas was led to a conventional ventilator and CO2 analyzer which were used to measure CO2 elimination. There was no bias flow, so that the jet entrained only expired gas, i.e. rebreathing occurred. Frequency was varied between 2 and 11 Hz and the duration of inspiration, as a fraction of the ventilatory cycle (Ti/Ttot), from 5 to 20%. The minute ventilation, Vjet, delivered by the jet ventilator was adjusted to maintain a constant PaCO2. At 2 Hz and a Ti/Ttot of 5%, Vjet was of the same magnitude as ventilation during conventional intermittent positive pressure ventilation, and the total dead space fraction, VD/VT was 0.32. Both increasing frequency at a constant Ti/Ttot, and increasing Ti/Ttot at a constant frequency, increased VD/VT which was maximal (0.8) at 11 Hz and a Ti/Ttot of 20%. When entrainment was blocked, tidal jet volume had to be greatly increased. The continuous measurement of CO2 elimination was found to be useful for maintaining isocapnia when the jet ventilator setting was changed.

Animals↗

PubMed2005

Modulation of the catalytic activity of free and immobilized peroxidase by extremely low frequency electromagnetic fields: dependence on frequency.

A study of the influence of electromagnetic fields (EMF) of various frequencies, from 50 up to 400 Hz, on the catalytic activity of soluble and insoluble horseradish peroxidase (POD) was carried out. To simulate the conditions in which the enzyme operates in vivo, the POD was immobilized by entrapment on a gelatin membrane or by covalent attachment on a nylon graft membrane. The rate of inactivation of the soluble POD was found to exhibit positive and negative interactions with the 1 mT applied magnetic field, with an optimum positive effect at 130 Hz. The immobilized PODs, on the contrary, do not exhibit negative interactions, but show a maximum positive interaction at 150 Hz when entrapped and at 170 Hz when covalently attached. At 50 Hz and at frequencies higher than 250 Hz no effects were observed with insoluble POD. The optimum frequency of positive interaction between the EMF and the catalytic activity of the insoluble enzymes is shifted with respect to that of the soluble enzymes towards higher frequencies, the size of the shifts being dependent on the intensity of the physical forces involved in the immobilization process.

Catalysis↗

PubMed1991

Extremely-low-frequency and very-low-frequency magnetic fields emitted by video display units.

Extremely-low-frequency (ELF) and very-low-frequency (VLF) magnetic fields as emitted by monochrome and multichrome video display units (VDUs) were measured for their frequency domains. The rms magnetic-flux densities (MFDs) were measured as a function of distance from all six sides of VDUs of four types. The MFDs at a distance of 30 cm from the screen (defined as the operator's position) were between 0.06 and 0.6 microT in the ELF range and between 0.02 and 0.06 microT in the VLF range. The contribution of harmonics to the total MFD was the same for both frequency ranges, less than 6%. For the first three harmonics, the MFD of each higher harmonic was one-half that of the immediately lower harmonic.

Computer Terminals↗

PubMed1988

Myoelectric reactions to ultra-low frequency and low-frequency whole body vibration.

5 healthy males were exposed to vertical sinusoidal whole body vibration (WBV) at 5 frequencies (F1 = 0.315 Hz, F2 = 0.63 Hz, F3 = 1.25 Hz, F4 = 2.5 Hz, F5 = 5.0 Hz) and 2 intensities (I1 = 1.2 ms-2 rms, F1-F5; I2 = 2.0 ms-2 rms, F2-F5). Erector spinae EMGs were derived at the levels of the first thoracic (T1) and third lumbar (L3) spinous processes, rectified and synchronously averaged, as were the accelerations of the seat and the head. WBV induced vibration-synchronous EMG activity (T1 and L3) which exceeded the activity without WBV during enhanced gravitation and decreased during lowered gravitation from F1 to F3. At F4 and F5, these phase relations changed drastically, thus suggesting a different trigger mechanism. The extreme average EMG-amplitudes remained nearly constant at F1 to F3 and increased at higher frequencies. Maximum EMG activity was higher at I2 than at I1. WBV from F1 to F3 is supposed to cause tonic muscular activity triggered by the otoliths; at higher frequencies, stretch reflexes probably gain additional importance. The results hint at an increasing sensory conflict with decreasing frequency of WBV and are interpreted within the theoretical framework of different modes of motor control. Relations between transmissibility and muscle activity suggest the usefulness of including time-variant spring-characteristics into biomechanical models.

Adolescent↗

PubMed1995

High-frequency ultrasound: determination of the lowest frequency required for cellular imaging and detection of myocardial disease.

We have previously demonstrated that a 600 MHz transducer enables the visualization of cellular detail in specimens of myocardium. However, lower-frequency transducers are more practical and provide better tissue penetration for possible in vivo application of this technique. This study was designed to ascertain the lowest frequency at which cellular detail can be imaged. We performed ultrasound imaging of 5 microns sections of 14 samples of myocardium. Each specimen was examined serially with 600 MHz, 400 MHz, 200 MHz, and 100 MHz transducers. Normal cardiac myocytes and pathologic phenomena such as fibrosis, cell fallout, and round cell infiltration were clearly identified with a 600 MHz transducer. Although there was a slight decrease in resolution, normal and pathologic phenomena were also identified with 400 and 200 MHz transducers. However, cellular detail could not be adequately identified with a 100 MHz transducer. In conclusion, transducer frequencies of 600 to 200 MHz enable visualization of cell detail and detection of pathologic changes in the myocardium. A transducer frequency of at least 200 MHz is probably required for possible in vivo application of this technique.

Cardiomyopathies↗

PubMed1991

Frequency dependence of cat vestibulo-ocular reflex direction adaptation: single frequency and multifrequency rotations.

Vertical and horizontal vestibulo-ocular reflex (VOR) eye movements were recorded in alert cats during horizontal rotation in total darkness before and after a 2 h vestibulo-ocular reflex direction adaptation procedure. Adaptation stimuli were whole body horizontal vestibular rotation coupled to synchronous vertical optokinetic motion. The waveform of the adaptation stimuli was either a sinusoid at 0.05, 0.1, 0.25, 0.5, or 1 Hz, or a sum of sinusoids containing 0.2, 0.3, 0.5, 0.7, 1.1, and 1.7 Hz. Exposure to single frequency stimuli produced adaptive vertical VOR with a gain that was greatest near the training frequency; adaptive VOR phases were advanced below, accurate at, and lagged above the training frequency. Exposure to the multifrequency waveform produced a uniform modest increase in gain across frequencies, with accurate adaptive VOR phase.

Acclimatization↗

PubMed1991

A model for perceived spatial frequency and spatial frequency discrimination.

The responses of labelled spatial frequency channels are combined to generate an index of perceived spatial frequency. Spatial frequency discrimination thresholds are shown to be inversely related to the slope of the function of the index vs spatial frequency, when it is plotted on log-log co-ordinates.

Discrimination, Psychological↗

PubMed1994

Speed, spatial-frequency, and temporal-frequency comparisons in luminance and colour gratings.

The perceived speed, temporal frequency, and spatial frequency of matched colour and luminance gratings were compared in separate experiments. The large factor by which colour gratings are perceived to be slower moving than matched luminance gratings cannot be explained by systematic differences in the perceived spatial frequency or in the perceived temporal frequency of the two types of grating.

Color Perception↗

PubMed2006

Frequency response characteristic of sympathetic mediated low-frequency blood pressure fluctuations in conscious rats.

A quantitative relationship between power densities of blood pressure (PBP) and sympathetic nerve activity (PSNA) in a low-frequency range (LF, 0.016-0.85 Hz), expressed as PSNA=PBPxax10bx(frequency) was proposed in pentobarbital-anesthetized rats. For evaluating the general applicability of this equation, the quantitative relationship of power density ratio Hf=PBP/PSNA across frequency was tested in a conscious state. Wistar rats were chronically instrumented with a femoral artery catheter and recording electrode around the renal sympathetic nerve. The blood pressure and renal sympathetic nerve activity were monitored both under pentobarbital anesthesia and in a conscious state. Linear regression analysis of the relationship between the frequency and logarithmic magnitude of the power density ratio in the LF range revealed excellent fit in both conditions (r=-0.96+/-0.01 and -0.93+/-0.01 for anesthetized and conscious rats, respectively). Comparing the regression lines, rats under pentobarbital anesthesia had significantly larger values for the y-intercept and slope compared to rats in a conscious state (y-intercepts: 0.80+/-0.09>0.53+/-0.08; slopes: -2.86+/-0.26>-1.62+/-0.21). Our results demonstrate that it is also feasible to use the weighted PBP in LF as a quantitative index of sympathetic variability in conscious rats, but the evaluation of possible complications controlling the regression parameters is called for.

Action Potentials↗

PubMed2005

Subthalamic oscillatory activities at beta or higher frequency do not change after high-frequency DBS in Parkinson's disease.

This study aimed to assess whether changes in the patterns of local field potential (LFP) oscillations of the subthalamic nucleus (STN) underlie to the clinical improvement within 60 s after turning off subthalamic DBS. We studied by spectral analysis the STN LFPs recorded in 13 nuclei from 7 patients with Parkinson's disease before and immediately after unilateral high-frequency (130 Hz) stimulation of the same nucleus, when the clinical benefit of DBS was unchanged. The results were compared with LFP data previously reported [A. Priori, G. Foffani, A. Pesenti, F. Tamma, A.M. Bianchi, M. Pellegrini et al., Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease. Exp. Neurol. 189 (2004) 369-379]--namely 13 STN from 9 parkinsonian patients recorded before and after levodopa administration--which were used as a control. Before DBS, in the 'off' clinical state after overnight withdrawal of dopaminergic therapy, the STN spectrum did not significantly differ from the control nuclei, showing prominent activity at beta frequencies (13-20 and 20-35 Hz). After DBS (10-15 min) of the STN, the recorded nuclei significantly differed from the control, failing to show significant changes either in the beta bands or at higher frequencies (60-90 and 250-350 Hz). The patterns of subthalamic LFP oscillations after DBS therefore differ from those after dopaminergic medication. These results suggest (1) that subthalamic LFP modulations are not the epiphenomenon of peripheral motor improvement and (2) that the transitory clinical efficacy maintained after discontinuation of subthalamic DBS is not associated with local modulation of LFP activity at beta or higher frequencies within the STN.

Action Potentials↗

PubMed2004

Appearance of high-frequency alpha band with disappearance of low-frequency alpha band in EEG is produced during voluntary abdominal breathing in an eyes-closed condition.

This study examined the effects of voluntary abdominal breathing (VAB) on the electroencephalogram (EEG) in 22 healthy subjects. VAB was characterized by prolonged rhythmic contraction of abdominal muscles for 20 min in an eyes-closed condition. The breathing rate was instructed to be very slow, i.e., 3-4 breaths/min (inspiratory time for 6-8s and expiratory time for 9-12s). A low-frequency alpha band appeared immediately after eye closing, but it later disappeared and was replaced by a new development of a high-frequency alpha band 4-5 min after the onset of VAB. The subjects had a feeling of vigor-activity with a tendency of reduced anxiety during and/or after VAB, as assessed by POMS and STAI questionnaire scores. On the other hand, during resting in the eye-closed condition, the disappearance of the low-frequency alpha band was replaced by the occurrence of a theta/delta band. The subjects became drowsy in this condition. We therefore conclude that the increase in high-frequency alpha activity is linked to the state of vigor-activity with a tendency of reduced anxiety. Since the urinary serotonergic level significantly increased after the VAB, we suggest that the serotonergic neurons within the brain may produce the changes in the EEG patterns.

Abdominal Muscles↗

PubMed1990

Temperature dependence of the low frequency dynamics of myoglobin. Measurement of the vibrational frequency distribution by inelastic neutron scattering.

Inelastic neutron scattering spectra of myoglobin hydrated to 0.33 g water (D2O)/g protein have been measured in the low frequency range (1-150 cm-1) at various temperatures between 100 and 350 K. The spectra at low temperatures show a well-resolved maximum in the incoherent dynamic structure factor Sinc(q, omega) at approximately 25 cm-1 and no elastic broadening. This maximum becomes gradually less distinct above 180 K due to the increasing amplitude of quasielastic scattering which extends out to 30 cm-1. The vibrational frequency distribution derived independently at 100 and 180 K are very similar, suggesting harmonic behavior at these temperatures. This result has been used to separate the vibrational motion from the quasielastic motion at temperatures above 180 K. The form of the density of states of myoglobin is discussed in relation to that of other amorphous systems, to theoretical calculations of low frequency modes in proteins, and to previous observations by electron-spin relaxation of fractal-like spectral properties of proteins. The onset of quasielastic scattering above 180 K is indicative of a dynamic transition of the system and correlates with an anomalous increase in the atomic mean-squared displacements observed by Mössbauer spectroscopy (Parak, F., E. W. Knapp, and D. Kucheida. 1982. J. Mol. Biol. 161: 177-194.) and inelastic neutron scattering (Doster, W., S. Cusack, and W. Petry, 1989. Nature [Lond.]. 337: 754-756.) Similar behavior is observed for a hydrated powder of lysozyme suggesting that the low frequency dynamics of globular proteins have common features.

Deuterium↗

PubMed1994

Stationary and nonstationary correlation-frequency analysis of heterodyne mode laser light scattering: magnitude and periodicity of canine tracheal ciliary beat frequency in vivo.

Stationary and nonstationary correlation-frequency analysis of heterodyne laser light scattering were utilized to make automated, on-line, objective measurements of tracheal ciliary beat frequency (CBF) in intact, anesthetized canines. The stationary correlation-frequency analysis laser light-scattering technique was used to assess the magnitude of the CBF stimulatory responses induced by aerosolized 10(-5) M fenoterol (sympathomimetic), and 10(-8) M and 10(-6) M methacholine (parasympathomimetic) delivered to the whole lungs of eight barbiturate-anesthetized beagles. The nonstationary correlation-frequency analysis laser light-scattering technique was used to measure the effect on tracheal CBF of increasing the cytosolic calcium ion concentration with a calcium ionophore, A23187. Aerosolized A23187 was delivered to the isolated tracheal lumens of eight beagle dogs in cumulative doses ranging from 10(-9)M to 10(-6) M. Administration of the ionophore synchronized the CBF with a period of 5.3 min. Dose dependencies were observed in both the time to the peak CBF stimulation and the magnitude of the stimulatory response. The magnitude of CBF stimulation was inhibited by prior administration of aerosolized nifedipine (2 mg/ml), a voltage-operated calcium channel blocker. The A23187-induced modulation period of tracheal CBF, was unchanged by nifedipine. These are the first data to demonstrate that the magnitude and periodicity of CBF are two independent coupled processes. The cooperativity of these two processes could be determined in the effectiveness of mucociliary transport.

Algorithms↗

PubMed1998

Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies.

A survey of glycophorin A (gpa) in vivo somatic cell mutation in a population of 394 healthy people from 8 to 77 years of age (mean age +/- SD 41 +/- 15 years) revealed a subset of 37 individuals with stably elevated allele-loss and/or allele-loss with duplication variant erythrocyte frequencies (Vf) exceeding 30 x 10(-6). These 37 individuals with gpa outlier Vf are significantly older (P < 0.001) than the remainder of the larger study population from which they were drawn reflecting a highly significant increase in the prevalence of these individuals in the population beyond age 40 years. A study of hpt mutant frequencies (Mf) in the peripheral blood T-lymphocytes of 27 of these individuals, together with 15 matched control individuals with unremarkable gpa Vf, was undertaken to determine if these subjects also displayed elevated mutation frequencies at this independent locus indicative of globally elevated somatic mutation. The hprt Mf in these 27 subjects (geometric mean 11.5 x 10(-6)(dispersion interval 5.8 x 10(-6) to 22.8 x 10(-6)) was not significantly different from that observed in the 15 controls (geometric mean 12.1 x 10(-6)(dispersion interval 5.7 x 10(-6) to 25.5 x 10(-6)). These Mf are higher than typically reported values reflecting the older age distribution of these individuals (arithmetic mean age +/- SD 53 +/- 12 and 50 +/- 16 years for the subjects and controls, respectively). Taken together, these data suggest that several genetic mechanisms may be responsible for producing the gpa outlier Vf observed in these subjects. The observation that hprt Mf were not increased indicates that the majority did not arise by a genome-wide increased rate of somatic mutation detectable at both loci. The fixation and subsequent expansion of 'jackpot' mutations at the gpa locus occurring early in embryonic/fetal development also does not appear to be a predominant mechanism. Some cases may result from a stable over-representation of gpa variant cells, perhaps associated with a marked age-dependent decrease in the number of contributing erythroid stem cells in the bone marrow. The subset that displays elevated allele-loss with duplication Vf involving both gpa alleles may represent individuals with increased rates of somatic recombination. Elevations arising by this mechanism are not detected in the hprt assay, but could be confirmed using a autosomal locus in vivo somatic cell mutation endpoint such as the hla-a assay. Of primary biological significance, these results demonstrate that genetics/stochastic processes leading to the loss of heterozygosity of somatic cells occur ubiquitously in humans and in some individuals this level of somatic mosaicism can approach a frequency of 10(-3) at the gpa locus in erythroid lineage cells.

Adolescent↗

PubMed2002

The frequency width of symmetric modes of an aluminum plate: manifestation of a complex slowness on a frequency spectrum.

The evolution of the experimental frequency width of symmetric modes of an aluminum plate is studied as a function of the angle of incidence below the first critical angle. It is found that the frequency width predicted by resonant scattering theory, corrected for the directivity of emitter and receiver, generally explains the experimental frequency width well. However, large discrepancies remain for the frequency width of the S1 mode at angles of incidence larger than 9 degrees. It is demonstrated that these are caused by not taking into account the complex nature of the slowness of the plate mode. This suggests that there is a need for a theory that models the interaction of a beam of ultrasound, bounded in space and time, with an elastic plate.

Journal Article↗