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The frequency of illegitimate TCRbeta/gamma gene recombination in human lymphocytes: influence of age, environmental exposure and cytostatic treatment, and correlation with frequencies of t(14;18) and hprt mutation.

Chromosome translocations in lymphoid malignancies often involve V(D)J recombinase mediated events giving rise to aberrant T-cell receptor (TCR) and immunoglobulin genes, which have been suggested to be useful as markers of genomic instability, genotoxic exposure and cancer risk. Illegitimate rearrangements involving the TCRbeta/gamma loci on chromosome 7 create TCRbeta/gamma hybrid genes which occur at low frequency in peripheral blood lymphocytes (PBLs) of normal healthy individuals. To evaluate the utility of this marker, we studied the possible effects of age and genotoxic exposures on the TCRbeta/gamma gene variant frequency (VF), and compared the frequencies of hypoxanthine guanine phosphoribosyl transferase (hprt) mutation, hprt exon 2/3 deletion, t(14;18) and TCRbeta/gamma gene rearrangements in cells from the same donors. The TCRbeta/gamma VF ranged five-fold among 16 middle aged blood donors with a mean of 0.74+/-0.29/10(5) PBLs, which is consistent with our previous estimate in healthy subjects. The TCRbeta/gamma VF was found to increase from birth until early adult life, and then to decrease with increasing age. Four testis cancer patients, who 6 years earlier had been treated with etoposide and other cytostatic drugs, showed TCRbeta/gamma VF similar to that in healthy controls. No increase of the TCRbeta/gamma VF was found among non-smoking PAH-exposed aluminum smelter workers compared to non-smoking controls. Smoking smelter workers showed decreased TCRbeta/gamma VF compared to non-smoking workers and controls, but in a follow-up study 2 years later the difference was no longer statistically significant, although the smoking smelter workers still showed a lower TCRbeta/gamma VF than the controls. No correlation was obtained between the TCRbeta/gamma VF and the t(14;18) or hprt mutant frequency (MF) in a group of healthy individuals. However, there was a statistically significant correlation between the TCRbeta/gamma VF and the hprt exon 2/3 deletion frequency in PBL DNA from the same donors. These results show that the TCRbeta/gamma VF in healthy individuals changes with age and correlates with the frequency of hprt exon 2/3 deletion, another marker of aberrant V(D)J recombination in T-cells. However, no effect of smoking or present or previous exposure to genotoxic agents on TCRbeta/gamma VF was observed in this study. Thus, further studies are needed to prove the utility of TCRbeta/gamma gene rearrangement as a marker of genotoxic exposure.

Adult↗

Transfer effects from listening to frequency-controlled and frequency-shifted accelerated speech.

Two experiments examined intelligibility of sentences reproduced with increased tonal frequency (the spectrum of the speech signal shifted upward), increased speech rate, or both frequency and speech rate increased. The first experiment showed that both the frequency and speech rate increases independently impaired sentence intelligibility. Sentences played back at increased rates and increased frequencies also were perceived as having been spoken more rapidly. In the second experiment subjects listened either to practice sentences played back at frequency-shifted (FS) or frequency-controlled (FC) accelerated rates. Subsequent to this practice, an intelligibility test was given on 10 FS and 10 FC accelerated sentences played back at double speed. The accelerated sentences were more intelligible for practice groups than for a no-practice control group, and FC accelerated rates produced more intelligible sentences than FS acceleration. The specific training experiences produced an interaction with the type of test-sentence acceleration early in transfer. The FS accelerated sentences were more intelligible following FS practice compared to FC practice, and the FC accelerated sentences were more intelligible following FC practice compared to FS practice.

Humans↗

Effect of frequency-altered feedback on stuttering frequency at normal and fast speech rates.

The purpose of this study was to determine the effect of the magnitude and direction of the frequency shift of frequency-altered auditory feedback (FAF) on stuttering frequency at both normal and fast speech rates. Twelve adult male and 2 adult female subjects who stutter read 10 different passages at either a normal or fast speech rate under nonaltered auditory feedback (NAF) and each of four FAF conditions in which the feedback signal was shifted: up one-half octave; up one octave; down one-half octave; and down one octave. Mean stuttering frequency for NAF was significantly higher than mean stuttering frequencies for all FAF conditions (p < 0.05). There were no statistically significant differences between the FAF conditions (p > 0.05). Subjects exhibited significantly more disfluencies under the fast speech rate condition relative to the normal speech rate condition. Future research should examine the relationship between frequency shifts of less than one-half octave and stuttering amelioration.

Adolescent↗

Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl.

Hypnotic endpoints and/or EEG variables, e.g. bispectral index, 95% spectral edge frequency and median frequency, have been studied to monitor anaesthetic (hypnotic) depth during total intravenous anaesthesia. In this study, the relation between the hypnotic endpoints of unresponsiveness to verbal commands, loss of eyelash reflex and body movement response to mechanical nasal membrane stimulation vs. bispectral index, 95% spectral edge frequency and median frequency during propofol anaesthesia with or without fentanyl is presented. Forty-two patients were randomly assigned to receive either propofol infusion, 30 mg kg-1 h-1 (n = 22), or propofol infusion, 30 mg kg-1 h-1 + fentanyl bolus, 2 micrograms kg-1 i.v. (n = 20). Bispectral index, 95% spectral edge frequency and median frequency and propofol doses were monitored and recorded at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response. The bispectral index values were significantly higher in the propofol + fentanyl compared with the propofol group, i.e. 74.7 +/- 10.9, 73.1 +/- 10.5 and 47.1 +/- 9.2 vs. 65.8 +/- 9.8, 59.6 +/- 10 and 33.8 +/- 5.7 at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response respectively. Doses of propofol for achieving the hypnotic endpoints were significantly lower in the propofol + fentanyl compared with the propofol group. Plasma propofol concentrations at inhibition of nasal body movement response were lower in the propofol + fentanyl compared with the propofol group (9.2 +/- 2.0 micrograms mL-1 vs. 14.1 +/- 4.2 micrograms mL-1). Our results suggest that fentanyl pretreatment potentiates the effects of propofol and achieves the hypnotic endpoints at higher bispectral index values and lower propofol doses and concentrations (measured at inhibition of nasal body movement response).

Adjuvants, Anesthesia↗

Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for antidepressant-free, treatment-resistant depressed patients.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising relatively non-invasive alternative for the treatment of depression. The purpose of this study was to compare the apparent effectiveness of high frequency (20 Hertz) rTMS applied over the left dorsolateral prefrontal cortex (DLPFC) with that of low frequency (1 Hz) rTMS applied over the right DLPFC METHODS: Twenty-eight antidepressant-free adults with major depressive (n = 25) or bipolar (n = 3) disorder (not on mood stabilizers) in a current major depression (Hamilton Rating Scale for Depression [HAM-D-21] > or = 18; Mean = 24.5, SD = 5.51) were treated (14 right, 14 left) for 4 weeks. RESULTS: Overall paired t-tests revealed a significant reduction in mean HAM-D-21, Beck Depression Inventory (BDI-II), and Clinical Global Impression of Change (CGIC) scores at the end of treatment for both groups (high frequency left DLPFC and low frequency right DLPFC). The treatment response rate found (32%) was typical of other response rates reported in the literature (6,30). One-month follow-up data was obtained from 50% of participants. At 1-month follow-up no significant differences were noted as compared to patients' performance at last treatment visit, indicating moderate robustness of rTMS treatment over time. Furthermore, magnetic stimulation did not substantially alter patient memory over the course of treatment. CONCLUSION: rTMS given at low frequency over the right frontal cortex appears to be as effective treatment of refractory depression as high frequency treatment over the left frontal cortex.

Antidepressive Agents↗

A frequency shift maximum frequency follower Doppler demodulator with amplitude correction.

A commonly used maximum-frequency follower Doppler demodulator uses a variable-frequency voltage controlled filter that requires two good quality multipliers and can be difficult to set up and stabilise. An alternative presented here has the advantage of cheapness, easy setting-up and amplitude independence over about 25 dB giving the potential for quantitative as well as qualitative results. A switching modulator is first used to convert the Doppler spectrum into a pair of sidebands disposed about the modulating frequency. The modulation frequency is continually adjusted so that the lower sideband edge, representing the highest Doppler frequency, just passes the skirt of a low pass filter. The filter output, after rectification and smoothing, provides drive to the voltage controlled oscillator (VCO) generating the modulation frequency and also forms the flow signal output. The fixed low pass filter results in a stable feed-back loop in which high loop gain can be used so that linearity depends mostly on the VCO. The characteristic slope is independent of signal amplitude above a threshold, but increasing signal causes an increasing offset voltage. A simple signal rectifier enables this offset to be largely cancelled, giving amplitude independence.

Arterial Occlusive Diseases↗

Effects of different designs and extension of a food frequency questionnaire on response rate, completeness of data and food frequency responses.

The authors studied how the introduction of several modifications to a basic food frequency questionnaire can influence the results of dietary surveys. Modifications covered eight combinations based on three levels: increasing versus decreasing order of frequency categories; questionnaires without versus with questions about portion sizes, and questionnaires without versus with extra non-dietary questions. The sample included 6783 women between the ages of 40 and 70 years who took part in mammography screening. The women were randomly assigned to one of the eight study groups. All of the women in each group received one of the eight differently modified questionnaires. The forms extended in length by extra non-dietary questions and portion size categories resulted in a 20% higher total non-response compared to the shorter basic form. Partial non-response was significantly lower for all four questionnaire types that included portion sizes. When portion sizes were included in the questionnaire, the reported mean frequency of consumption was significantly reduced for fat (-10 times per month), milk (-6), bread (-5), vegetables (-2) and fish (-0.4). The decreasing order of responses to the frequency categories was associated with a statistically significant increase in the frequency responses for bread (2.6 times per month), vegetables (2) and fish (0.6). These data provide evidence that the design and extension of food frequency questionnaires influence the results of dietary studies.

Adult↗

Donor-specific hyporeactivity after liver transplantation: prominent decreases in donor-specific cytotoxic T lymphocyte precursor frequencies independent of changes in helper T lymphocyte precursor frequencies or suppressor cell activity.

BACKGROUND: The development of immunological donor-specific hyporeactivity may account for the low incidence of chronic rejection after clinical liver transplantation. We investigated whether hyporeactivity commonly develops after liver transplantation by analyzing precursor frequencies of donor-reactive cytotoxic (CTLp) and helper (HTLp) T lymphocytes and mixed lymphocyte culture (MLC) reactivity in liver allograft recipients. We further studied whether CTLp hyporeactivity correlated with changes in donor-specific HTLp frequencies or suppressor cell activity. METHODS: CTLp and HTLp frequencies and MLC reactivity against donor and third-party spleen cells were determined in pre- and posttransplantation peripheral blood samples from 18 recipients with good graft function 2 years after transplantation. By mixing posttransplantation samples (with "putative" suppressor cell activity) with pretransplantation samples (in which normal CTL activity with no suppressor cell activity is expected), the presence of suppressor cell activity in peripheral blood was analyzed. RESULTS: Two years after transplantation, all but one (94%) of the recipients had developed CTLp hyporeactivity as evidenced by reduced donor-specific CTLp frequencies. The development of hyporeactivity was not specific for any particular underlying disease. The occurrence of HTL hyporeactivity, however, was less frequent: 38% and 20% of recipients were HTLp and MLC hyporeactive, respectively. Decreases in CTLp frequencies did not correlate with decreased donor-specific HTL function or suppressor cell activity in peripheral blood samples. CONCLUSIONS: Donor-specific CTLp hyporeactivity can develop in the majority of liver allograft recipients, irrespective of underlying disease. Donor-specific HTL hyporeactivity, however, occurs infrequently. A reduction in donor-specific CTLp frequencies was found to be independent of changes in donor-specific HTLp or suppressor cell activity, suggesting that other mechanisms (e.g., clonal deletion) are operative in the reduction of donor-specific CTLp after liver transplantation.

Humans↗

Time-frequency plane Wiener filtering of the high-resolution ECG: background and time-frequency representations.

This paper introduces the concept of a posteriori Wiener filtering (APWF), performed in the time-frequency plane. The objective is to improve the signal-to-noise ratio (SNR) of the ensemble-averaged high-resolution electrocardiogram (HRECG). APWF was developed to address the problem of a limited ensemble size for estimating ensemble-averaged evoked potentials. For the HRECG, we identify the major challenge as adapting the time-frequency structure of the filter to that of low-level cardiac signals. Technical limitations and the characteristics of HRECG signals make time-frequency analysis of the ensemble average problematic. Normal and abnormal signal components are difficult to distinguish due to low time-frequency energy concentration and limited spectrotemporal resolution. However, considering the entire ensemble of repetitive ECG records, signal and noise components are separable in the time-frequency plane. This forms the basis of the new time-frequency plane Wiener (TFPW) filter, applicable to any ensemble averaging problem involving repetitive deterministic signals mixed with uncorrelated noise.

Electrocardiography↗

Improved maximum frequency estimation with application to instantaneous mean frequency estimation of surface electromyography.

The purpose of this study was to improve the maximum-frequency estimation. Three methods to estimate the maximum frequency of a bandlimited signal with additive white noise were compared. Two existing methods, the threshold-crossing method (TCM) and the hybrid method, were modified for time-frequency representations. A novel approach, the running-block threshold method (RBTM), was introduced. Based on calculation of detection probability (sensitivity) the RBTM improved the maximum-frequency estimate as compared with the TCM. The maximum-frequency estimation methods were also used to determine the integration interval for instantaneous mean-frequency (IMNF) estimation from synthesized surface electromyography containing white noise. Results showed that the IMNF estimate was improved by using any of the three methods and that the RBTM gave the best IMNF estimate.

Action Potentials↗

The perceived spatial frequency shift: evidence for frequency-selective neurones in the human brain.

1. Prolonged observation of a high-contrast grating pattern causes an apparent shift in the spatial frequency of gratings subsequently viewed with the same retinal region. Gratings of higher and lower frequency than the adapting pattern seem, respectively, higher and lower than in fact they are.2. There is no significant after-effect at the adapting frequency itself nor at frequencies more than two octaves away.3. For very low adapting frequencies, the after-effect remains centred at about 3.0 c/deg and declines in strength as the adapting frequency is successively lowered.4. The magnitude of the after-effect increases with the contrast of the adapting grating and the length of time spent in adaptation. It takes several hours to recover completely from 30 min adaptation.5. The phenomenon is orientation-specific: a horizontal adapting grating has no effect on vertical test gratings. There is partial interocular transfer of the after-effect.6. These findings provide further evidence that the visual system of man, like those of the cat and the monkey, contains neurones selectively sensitive to the orientation and dimensions of retinal images, and that these adaptable cells are actually involved in the encoding and perception of the size of simple patterns.

Adaptation, Ocular↗

The apparent immunity of high-frequency "transposed" stimuli to low-frequency binaural interference.

Discrimination of interaural temporal disparities (ITDs) was measured with either conventional or transposed "targets" centered at 4 kHz. The targets were presented either in the presence or absence of a simultaneously gated diotic noise centered at 500 Hz, the interferer. As expected, the presence of the low-frequency interferer resulted in substantially elevated threshold-ITDs for the conventional high-frequency stimuli. In contrast, these interference effects were absent for ITDs conveyed by the high-frequency transposed targets. The binaural interference effects observed with the conventional high-frequency stimuli were well accounted for, quantitatively, by the model described by Heller and Trahiotis [L. M. Heller and C. Trahiotis, J. Acoust. Soc. Am. 99, 3632-3637 (1996)]. The lack of binaural interference effects observed with the high-frequency transposed stimuli was not predicted by that model. It is suggested that transposed stimuli may be one of a class of stimuli that do not foster an obligatory combination of binaural information between low- and high-frequency regions. Under those conditions that do foster such an obligatory combination, one could still consider models of binaural interference, such as the one described in Heller and Trahiotis, to be valid descriptors of binaural processing.

Acoustic Stimulation↗

Encoding voice fundamental frequency into vibrotactile frequency.

Measured in this study was the ability of eight hearing and five deaf subjects to identify the stress pattern in a short sentence from the variation in voice fundamental frequency (F0), when presented aurally (for hearing subjects) and when transformed into vibrotactile pulse frequency. Various transformations from F0 to pulse frequency were tested in an attempt to determine an optimum transformation, the amount of F0 information that could be transmitted, and what the limitations in the tactile channel might be. The results indicated that a one- or two-octave reduction of F0 vibrotactile frequency (transmitting every second or third glottal pulse) might result in a significant ability to discriminate the intonation patterns associated with moderate-to-strong patterns of sentence stress in English. However, accurate reception of the details of the intonation pattern may require a slower than normal pronounciation because of an apparent temporal indeterminacy of about 200 ms in the perception of variations in vibrotactile frequency. A performance deficit noted for the two prelingually, profoundly deaf subjects with marginally discriminable encodings offers some support for our previous hypothesis that there is a natural association between auditory pitch and perceived vibrotactile frequency.

Adult↗

Theory of frequency modulation detection for low modulation frequencies.

There is general agreement that the frequency difference limen measured in a two-sine-tone frequency discrimination experiment is smaller than that measured in a frequency modulation (FM) experiment. We present a model of frequency modulation detection for low modulation frequencies, within the framework of signal detection theory, which accounts well for the observed difference between frequency discrimination experiments and FM detection experiments. The FM detection model also predicts psychometric functions for detection of FM with different modulation waveforms. FM detection experiments with square, sine, trapezoid, and triangle FM are in reasonable agreement with the model predictions.

Acoustic Stimulation↗

Temporal integration, frequency resolution, and off-frequency listening in normal-hearing and cochlear-impaired listeners.

Temporal integration for a 1000-Hz signal was determined for normal-hearing and cochlear hearing-impaired listeners in quiet and in masking noise of variable bandwidth. Critical ratio and 3-dB critical band measures of frequency resolution were derived from the masking data. Temporal integration for the normal-hearing listeners was markedly reduced in narrow-band noise, when contrasted with temporal integration in quiet or in wideband noise. The effect of noise bandwidth on temporal integration was smaller for the hearing-impaired group. Hearing-impaired subjects showed both reduced temporal integration and reduced frequency resolution for the 200-ms signal. However, a direct relation between temporal integration and frequency resolution was not indicated. Frequency resolution for the normal-hearing listeners did not differ from that of the hearing-impaired listeners for the 20-ms signal. It was suggested that some of the frequency resolution and temporal integration differences between normal-hearing and hearing-impaired listeners could be accounted for by off-frequency listening.

Adult↗

Speech identification under simulated hearing-aid frequency response characteristics in relation to sensitivity, frequency resolution, and temporal resolution.

Word identification in noise was measured adaptively under flat and rising frequency response conditions to represent basic alternatives for a hearing-aid characteristic. The speech test results were compared with measures of sensitivity, loudness tolerance, frequency resolution, and temporal resolution in 23 hearing-aid users with mild or moderate sensorineural hearing losses. Subjects also rated the two frequency responses for preference and subjective quality. A paradoxical relationship was found whereby superior speech performance under the flat condition was associated with preference for the rising condition, and vice versa. No combinations of psychoacoustic variables satisfactorily explained either relative performance or preference, although high-frequency sensitivity and upward spread of masking were implicated. Absolute speech performance was related to sensitivity at 2 kHz, age, and sex, but not to frequency resolution once other factors were partialed. Temporal resolution was also a factor, but this was due largely to the influence of extreme values in two subjects. It is concluded that, for moderate degrees of hearing loss, speech identification in noise can be predicted from age, sex, and sensitivity with little advantage from recourse to measurement of frequency or temporal resolution.

Adult↗

Spectrotemporal analysis and cochlear hearing impairment: effects of frequency selectivity, temporal resolution, signal frequency, and rate of modulation.

The detection of 500- or 2000-Hz pure-tone signals in unmodulated and modulated noise was investigated in normal-hearing and sensorineural hearing-impaired listeners, as a function of noise bandwidth. Square-wave modulation rates of 15 and 40 Hz were used in the modulated noise conditions. A notched noise measure of frequency selectivity and a gap detection measure of temporal resolution were also obtained on each subject. The modulated noise results indicated a masking release that increased as a function of increasing noise bandwidth, and as a function of decreasing modulation rate for both groups of listeners. However, the improvement of threshold with increasing modulated noise bandwidth was often greatly reduced among the sensorineural hearing-impaired listeners. It was hypothesized that the masking release in modulated noise may be due to several types of processes including across-critical band analysis (CMR), within-critical band analysis, and suppression. Within-band effects appeared to be especially large at the higher frequency region and lower modulation rate. In agreement with previous research, there was a significant correlation between frequency selectivity and masking release in modulated noise. At the 500-Hz region, masking release was correlated more highly with the filter skirt and tail measures than with the filter passband measure. At the 2000-Hz region, masking release was correlated more with the filter passband and skirt measures than with the filter tail measure. The correlation between gap detection and masking release was significant at the 40-Hz modulation rate, but not at the 15-Hz modulation rate. The results of this study suggest that masking release in modulated noise is limited by frequency selectivity at low modulation rates, and by both frequency selectivity and temporal resolution at high modulation rates. However, even when the present measures of frequency selectivity and temporal resolution are both taken into account, significant variance in masking release still remains unaccounted for.

Acoustic Stimulation↗

The effect of frequency-selective attenuation on the speech-reception threshold of sentences in conditions of low-frequency noise.

Within a study on the merits of a multichannel automatic gain control in hearing aids, the effect of frequency-selective amplification on the masked speech-reception threshold (SRT) for sentences is measured in conditions of seriously disturbing low-frequency noise, with the effect of wideband amplification as a reference. Speech and noise are both spectrally shaped according to the bisector line of the listener's dynamic-range of hearing, but with the noise in a single octave band (0.25-0.5 or 0.5-1 kHz) increased by 20 dB relative to this line. The increase of noise level is steady state in the first experiment, and time varying in the second experiment. Results for 12 normal-hearing and 12 hearing-impaired listeners indicate that, in both experiments, frequency-selective compression of the signal in the octave band with the 20-dB increase of noise is more beneficial than wideband compression. For the hearing-impaired group, wideband compression does not give any systematic change in intelligibility. Frequency-selective compression in steady-state conditions may, for both groups of listeners, give a decrease of masked SRT (relative to a condition without compression) of up to 4 dB for a compression factor of 100%. Roughly comparable effects are seen for frequency-selective compression in time-varying conditions. The superiority of frequency-selective over wideband compression is attributed to a more effective reduction of upward spread of masking.

Adult↗