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Biomedical subjects

M Don

Publications and source records attributed to M Don.

18 recordsLinked to original sources

Place-specific derived cochlear microphonics from human ears.

The high-pass noise masking technique was used to obtain derived frequency-specific cochlear microphonics (CM) from subtracted waveforms to rarefaction and condensation stimuli recorded with a tympanic membrane electrode. Two characteristics suggest that the response is place-specific CM: the derived response retains the same frequency as the stimulating toneburst and the response follows the stimulus polarity. For click stimulation, derived neural responses make the place-specific CM difficult to observe except in the 2-1 kHz derived band. In contrast, place-specific CM evoked by 0.5 and 1 kHz tonebursts can usually be detected in at least three derived bands. The amplitude of the response is largest in the derived band with center-frequency (CF) just above that of the toneburst. This discovery of a place-specific CM offers the possibility of assessing (outer) hair cell function in the apical part of the human cochlea.

Acoustic Stimulation

Absence of both auditory evoked potentials and auditory percepts dependent on timing cues.

An 11-yr-old girl had an absence of sensory components of auditory evoked potentials (brainstem, middle and long-latency) to click and tone burst stimuli that she could clearly hear. Psychoacoustic tests revealed a marked impairment of those auditory perceptions dependent on temporal cues, that is, lateralization of binaural clicks, change of binaural masked threshold with changes in signal phase, binaural beats, detection of paired monaural clicks, monaural detection of a silent gap in a sound, and monaural threshold elevation for short duration tones. In contrast, auditory functions reflecting intensity or frequency discriminations (difference limens) were only minimally impaired. Pure tone audiometry showed a moderate (50 dB) bilateral hearing loss with a disproportionate severe loss of word intelligibility. Those auditory evoked potentials that were preserved included (1) cochlear microphonics reflecting hair cell activity; (2) cortical sustained potentials reflecting processing of slowly changing signals; and (3) long-latency cognitive components (P300, processing negativity) reflecting endogenous auditory cognitive processes. Both the evoked potential and perceptual deficits are attributed to changes in temporal encoding of acoustic signals perhaps occurring at the synapse between hair cell and eighth nerve dendrites. The results from this patient are discussed in relation to previously published cases with absent auditory evoked potentials and preserved hearing.

Acoustic Stimulation

Pentamidine aerosol increases the number of alveolar macrophages in HIV-infected patients.

In order to determine the possible effect of aerosolized pentamidine on the cellular composition of the bronchoalveolar lavage fluid in HIV-infected patients, differential counts of 22 consecutive patients who had been rebronchoscopied after 3-19 months were reviewed. Eleven patients were started on pentamidine prophylaxis subsequent to their first presentation. Eleven patients had never taken pentamidine or had discontinued the prophylactic regimen. Compared to first bronchoscopy, the bronchoalveolar lavage (BAL) from patients on regular prophylaxis revealed a significant increase in absolute alveolar macrophage (AM) counts at second presentation (20.8 +/- 11.2 to 50.3 +/- 39.4 x 10(5) cells/100 ml BAL; P less than 0.01). The AM counts of those without pentamidine remained essentially unchanged. Lymphocytes, including CD4 and CD8 subtypes, and neutrophils did not change over time in either group. The results of this retrospective analysis suggest that, in addition to its antimicrobial action, pentamidine may modulate local lung defence mechanisms, particularly by increasing the absolute number of AM.

Administration, Inhalation

Effects of click rate and electrode orientation on threshold of the auditory brainstem response.

This study evaluated the effects of stimulus presentation rate and electrode orientation on ABR threshold. Six normal-hearing adults served as subjects. ABRs were recorded from three orthogonal electrode pairs in response to click stimuli at rates of 48 and 21/s. Psychophysical thresholds were determined for each of these stimuli, and ABRs were recorded with stimuli between 0 and 10 dB SL in 2-dB steps. A ratio of ABR signal strength to noise variance (Fsp) was the criterion used to define threshold. Specifically, an Fsp value of 2.25, equivalent to a 95% response confidence using 5 and 250 degrees of freedom, was the criterion used to determine response presence within a maximum of 10,000 sweeps per average. Results revealed that, for normal-hearing adult subjects, click rate up to 48/s does not influence the sensation level at which a detectable response can be found, and a nearly vertical electrode orientation is optimal for recording the response at low levels. The predicted difference between psychophysical and ABR thresholds with a vertical electrode orientation, using 10,000 sweeps per average, up to 48 clicks per second, and an Fsp criterion of 2.25 is 4.4 dB.

Auditory Threshold

Chemical modification of the actin binding site of rabbit muscle aldolase by diethylpyrocarbonate.

To extend the available information on the significance of the interactions between glycolytic enzymes and the actin component of the cellular ultrastructure, investigations into the compositional characteristics of the actin binding site on one of the major glycolytic enzymes, aldolase, have been undertaken. As the electrostatic nature of the association has been previously reported indicative of a cationic region on the enzyme involved in the binding, these studies have investigated the possibility of the involvement of histidine residues in this binding region. By the use of the histidine specific reagent, diethylpyrocarbonate, we have been able to establish a difference in nature of an actin binding domain and the active site domain which does contain an essential histidine. The results have been discussed in relation to the significance of this finding with respect to the binding of aldolase to subcellular structure.

Actins

Glycolysis--new concepts in an old pathway.

A survey of the existing data on the interactions of glycolytic enzymes with the cellular structure in mammalian tissues has substantiated the occurrence of an extensive degree of such associations in all tissues and during all stages of development. Furthermore, a considerable specificity was evident between the individual multiple forms of the enzymes in relation to these associations. In reviewing these data, a model has been developed which proposes that the glycolytic sequence is best described as consisting of a number of segments in vivo, each segment formed by a cluster of isozymes, many of which can interact with the actin containing filaments of the cytomatrix. The novel features of this segmentation and compartmentation have been described, and evidence has been provided that these phenomena collectively play a key role in meeting the different types of energy requirement in the cytoplasm of divergent cell types, with the wide selection of isozymes in this system offering the potential for increased flexibility and control in this important area of metabolism.

Animals

Induced temporary threshold shift in guinea pigs.

The etiology of an incidentally discovered temporary threshold shift observed in an experimental animal (Harley guinea pig) is discussed with its potential implications for auditory research.

Animals

Threshold characteristics of the human auditory brain stem response.

Auditory brain stem responses (ABRs) were recorded from ten normal-hearing subjects in response to 100-microseconds clicks from a TDH 49 earphone at a rate of 48 pps and at levels randomly varied in 2-dB steps between 34 and 52 dB p.e. SPL. At each level, 10 000 epochs were averaged with use of a weighted concept and a running estimate was made of the signal-to-noise ratio (SNR). This quantity was used to detect the presence of the ABR and the median threshold was found at 38 dB p.e. SPL. The mean averaged background noise level was 11.3 nVrms, and the "true" ABRrms amplitude function crossed this value at 35.5 dB p.e. SPL, which indicates the level where the SNR = 1. By extrapolation, it was found that the ABR amplitude became zero at 32 dB p.e. SPL. The perceptual thresholds of the click were estimated by means of a modified block up-down procedure, and the median value was found at 33 dB p.e. SPL. The slope of the amplitude function and the magnitude of the averaged background noise are the two factors responsible for the ABR threshold sensitivity, which thus depends on both physiological and technical parameters. Therefore, these have to be considered together with the method of detection when the ABR is used to indicate the hearing sensitivity.

Auditory Threshold

Detection functions for the human auditory brainstem response.

Previously obtained data characterizing the auditory brainstem response near the threshold for detection in 10 normal-hearing subjects are used to evaluate the detection method applied. The basic detection formula is described in terms of rates of true positive and false positive ABR detection and in combination with the normative ABR values used to calculate the ABR detection functions as well as the corresponding receiver operating characteristics (ROC curves). The observed distribution of the ABR-threshold levels is similar to that derived from the detection function, and therefore verifies the present results which are based partly on theoretical considerations.

Auditory Pathways

The influence of deoxyribonuclease I and cytochalasin D on the release of glycolytic enzymes from digitonized cells.

In permeabilized cells, deoxyribonuclease I has been demonstrated to cause a decrease in the extent of binding to cellular structure of all of the glycolytic enzymes other than phosphofructokinase, with this decrease being most marked for aldolase and glyceraldehydephosphate dehydrogenase. Cytochalasin D, in contrast, did not produce this type of effect. These results have been discussed in relation to the evidence for the existence of a complex of glycolytic enzymes which binds to elements of the cytoplasmic matrix, and the possible organization of this complex.

Animals

Mechanisms of central conduction time prolongation in brain-stem auditory evoked potentials.

The wave I-wave V delay in the auditory brain-stem response is commonly used as a diagnostic tool in otoneurology. Normative values have been established for different populations and different types of stimuli. This I-V delay has been known for some time as "central conduction time" or "central transmission time." This implies that the measure reflects in normal and in pathologic cases delays due to nerve conduction, synaptic transmission, and neural integration and is not caused by cochlear processes. By virtue of the traveling wave delay in the cochlea, amounting to some 4 ms from the base to the "500-Hz place," it is conceivable that this delay contributes to the I-V delay. From a series of 69 pontine angle tumors in which the auditory brain-stem response was recorded, we selected cases with an apparent peripheral origin of a prolonged I-V delay by comparing the whole-click response to responses derived from high-pass noise masking. It seems that cases with an increased I-V delay in the whole-click response but (almost) normal I-V delays in the narrow-band response are indicative of small intracanalicular acoustic neuroma.

Brain Stem

Analysis of the click-evoked brainstem potentials in man unsing high-pass noise masking.

Brainstem electrical responses (BSER) to 60-dB-SL click in noise high passed at various cutoff frequencies separated b 1/2-octave steps were recorded in normal-hearing adult subjects. By applying a derived response technique, narrow-band contributions to the BSER from specific portions of the basilar membrane were revealed. Latencies and amplitudes of the various waves in the derived BSER were recorded. Results indicate that nearly the whole cochlear partition can contribute to the brainstem response. The shifts in latency of waves I, III, and V and amplitude changes of waves I and III as a function of CF appear to be fully comparable to those of the AP. In contrast, the amplitude behavior of wave V as a function of CF is different from waves I and III depending upon frequency range. The discrepency in the behavior of wave V with respect to the earlier waves suggests some sort of neural reorganization at the level where was V is generated. The fact that there are contributions to the brainstem response from apical portions of the cochlea opens the possibility for extending the brainstem technique in assessing the higher cochlear turn function.

Acoustic Stimulation

On the application of affinity chromatography to turnover studies on the lactate dehydrogenase isoenzymes.

1. The suitability of a combined application of the techniques of affinity chromatography, double labelling and gel electrophoresis in the determination of the turnover characteristics of the lactate dehydrogenase isoenzymes (L-lactate:NAD+ oxidoreductase EC 1.1.1.27) in rat tissues has been studied. 2. Affinity chromatography was established as affording the advantages of rapidity, high yield and purity to such studies, and the double-labelling procedure was modified to encompass the differential decay kinetics in the separate rat tissues. In addition, a convenient method for the resolution and separate collection of radioactively labelled isoenzymes has been described. 3. Using this methodology, comparative turnover values for the isoenzymes of lactate dehydrogenase and for total soluble protein have been determined. 4. The comparability of these results with other methodologies, and the advantages of this approach in facilitating broad comparative studies on turnover are discussed.

Animals

Effect of click rate on the latency of auditory brain stem responses in humans.

Auditory brain stem responses are the far-field reflections of electrical activity originating in the auditory pathway in its course from the cochlea to cortex that can be recorded from scalp electrodes using computer averaging techniques. There are seven components in the initial 10 msec following a click signal which have been shown to have an orderly change in latency as a function of signal intensity. The results of this study show that click repetition rate can also significantly affect the response latency measure. Responses were measured in six normal hearing subjects at click rates of 10, 30, 50 and 100/sec and af four intensity levels (30, 40, 50, and 60 dB sensation level). The mean latency shift of component V was approximately 0.5 msec when the responses at 10 and 100/sec were compared. This is equivalent to a 15-20 dB decrease in signal intensity at the 10/sec click rate. An analysis of the time of occurrence of this shift using brief click trains at 100/sec showed the shift in latency to be complete by the fifth click. The latency shift was similar at the four signal levels tested. The latency shift was similar at the four signal levels tested. The latency shift of component V appeared to be a monaural and therefore a potentially peripheral process. The results are interpreted as an objective measure of adaptation in the human auditory system with implications for the measurement in disorders of hearing.

Acoustic Stimulation

Reconstruction of the audiogram using brain stem responses and high-pass noise masking.

Contributions to the brain stem electrical responses (BSER) presumably initiated from specific frequency regions of the cochlea with center frequencies similar to the major audiometric frequencies (0.5, 1, 2, 4, and 8 kHz) are derived by the application of a high-pass noise masking technique utilizing click stimuli. In normal hearing subjects, these derived narrow-band responses from the midfrequency regions (4, 2, and 1 kHz) can be recognized at click levels as low as 10 dB HL. For the frequency regions around 8 kHz and 0.5 kHz, these derived responses can be discerned at click levels of 30 dB HL and higher. When one uses the lowest click level at which these derived responses can be obtained from a given frequency region, the differences between a patient with a hearing loss and a normal hearing subject correlate well with the amount of hearing loss (air conduction) recorded by conventional pure tone audiometry. Use of the high-pass noise masking technique to reconstruct the audiogram may be of great potential value in assessing young children and other individuals who cannot or will not respond to conventional audiometry.

Adolescent