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Biomedical subjects

S J Norton

Publications and source records attributed to S J Norton.

At least 19 recordsLinked to original sources

The effects of limiting the number of Nucleus 22 cochlear implant electrodes programmed on speech perception.

The purpose of this double-blind study was to evaluate systematically the effects of varying programmed electrodes on speech perception. The performance of five subjects implanted with the Nucleus 22-electrode cochlear implant was compared on the Four-Choice Spondee test, the Central Institute for the Deaf Sentence test, and Speech Tracking across the following conditions: (1) five most apical electrodes eliminated from the subject's MAP (stimulus parameters); (2) five most basal electrodes eliminated from subject's MAP; (3) the middle five electrodes eliminated from subject's MAP; and (4) subject's current MAP. Statistically significant differences were found for the Four-Choice Spondee test and both the auditory-only and auditory-plus-lipreading Speech Tracking measures. Three subjects demonstrated poorer performance on all test measures when the five electrodes from the apical portion of the array were not programmed. Two subjects performed equally well, regardless of MAP condition. Group means for all test measures present a trend of consistently poorer performance when the -5 Apex MAPs were utilized. A subjective rating scale was consistent with the perceptual tests, with all subjects best liking their current MAP and least liking the -5 Apex MAP. Results suggest that for some subjects, a fixed place code may control their ability to use spectral information for speech discrimination. For these subjects, first formant information (F1) traditionally coded on the most apical electrodes could not be utilized as effectively when coded on the adjacent middle electrodes.

Acoustic Stimulation

Adaptive imaging in aberrating media: a broadband algorithm.

An adaptive algorithm is derived for imaging in an aberrating medium based on wideband (time-domain) linear array data. Image reconstructions using simulated scattering data are presented. An analogy is also drawn between broadband array imaging and limited-angle tomography. This analogy suggests some tomographic-like filtering schemes that can be applied to improve the quality of the image. The algorithm is designed for imaging in composite material, although the imaging of other heterogeneous media such as tissue may be feasible under certain conditions.

Algorithms

Development of otoacoustic emissions in gerbil: evidence for micromechanical changes underlying development of the place code.

The development of the acoustic distortion product (ADP) 2f1-f2 was studied in gerbils, beginning 12 days after birth (P12). ADPs were measured as a function of stimulus frequency region (1.0 to 13.0 kHz) and level (10 to 80 dB SPL). There was an orderly progression in the appearance and maturation of the emissions, with responses to high-frequency stimuli (f2 = 13.0 kHz) appearing first, at P13-14. Responses to mid and high frequencies (f2 = 3.9 to 13.0 kHz) matured earlier than responses to lower frequencies. Responses to low-frequency stimuli (f2 = 1.3 KHz) did not appear until P18-19 and were not mature until after one month of age. The first emissions to develop in a given frequency region had elevated thresholds, were reduced in amplitude, and displayed monotonic input-output functions. As the auditory system matured, emission growth functions became non-monotonic displaying saturation, but initially retained a reduced dynamic range. Data from the developing gerbil suggest that initially its cochlear mechanics are passive and that active elements associated with normal outer hair cell function mature first in the basal turn and last near the apex. Furthermore, the development of active nonlinear elements underlying ADP generation is consistent with the development of frequency selectivity and developmental shifts in the place code which have been demonstrated in the gerbil.

Acoustic Stimulation

Evoked otoacoustic emissions in normal-hearing infants and children: emerging data and issues.

Evoked otoacoustic emissions (EOAEs) are a promising tool for evaluating cochlear status in children. Preliminary data from normal-hearing subjects ranging from birth to 29.9 years old are discussed. EOAEs are present and robust in infant ears. However, there is a statistically significant decrease in EOAE amplitude for a fixed stimulus level with increasing age even in a carefully screened sample. At the present time it is unclear if these age-associated changes are due to normal developmental changes in the external and/or middle ear acoustics, normal developmental changes in cochlear mechanics and/or everyday cochlear wear and tear. Issues related to further application of evoked emissions to pediatric populations are discussed.

Adolescent

Tinnitus and otoacoustic emissions: is there a link?

Attempts to identify the mechanisms underlying tinnitus and to develop effective treatments have been frustrating, in part because there are no objective measures of tinnitus. Following Kemp's initial reports of evoked and spontaneous otoacoustic emissions (OAEs), many people hoped that OAEs were an objective correlate of tinnitus. The results of several studies suggest that in about 6 to 12% of normal-hearing persons with tinnitus and spontaneous otoacoustic emissions (SOAEs), the SOAEs are at least partly responsible for the tinnitus. In addition, recent work indicates that some subjects with tinnitus display oscillating or ringing evoked otoacoustic emissions (EOAEs). In these cases, it is hypothesized that the oscillating EOAEs and tinnitus are related to a common underlying pathology rather than the emissions being the source of the tinnitus.

Adult

Glyoxalase I and glyoxalase II from Aloe vera: purification, characterization and comparison with animal glyoxalases.

Glyoxalase I and glyoxalase II from the outer green rind of Aloe vera leaves were purified by (matrix) affinity ligand-enzyme binding methods. The purified enzymes exhibited single protein bands on SDS-PAGE electrophoresis, with MW values of approximately 44,000 and 27,000 for glyoxalase I and glyoxalase II, respectively. The glyoxalase I is a basic protein (pI 7.8), while the glyoxalase II (3 protein bands) is acidic (pI 4.7, 4.8 [prevalent form], and 5.0). The kinetic constants, Km and Vmax, and Ki values for certain inhibitors are reported for both glyoxalase I and glyoxalase II. The glyoxalase enzymes from Aloe vera were compared with reported animal and plant glyoxalases.

Aloe

Presence of glyoxalase II in mitochondria from spinach leaves: comparison with the enzyme from cytosol.

Glyoxalase II has been purified from cytosol and mitochondria of spinach leaves. Electrophoresis and isoelectric focussing have resolved cytosolic and mitochondrial glyoxalase II in multiple forms: pl 5.3, 5.8 and 6.2 (cytosol) and pl 4.8 (mitochondria). The enzyme of both localizations is a monomer showing a relative molecular mass of about 26 kDa. The values of kinetic constants using several glutathione thiolesters as substrates, are similar for the enzymes from cytosol and mitochondria. These results extend also to plant the presence in mitochondria of peculiar forms of glyoxalase II, likewise recently demonstrated in mammalians.

Cytosol

Presence of a plant-like glyoxalase II in Candida albicans.

Glyoxalase II from Candida albicans was purified by affinity chromatography on S-carbobenzoxyglutathione-Affi Gel 10. The enzyme was characterized and compared with the glyoxalases II from animal and plant sources. The relative molecular mass is 29 kDa, and the isoelectric point (pI) is 6.0. The acidic pI value appears to be typical for plant glyoxalase II, in contrast to the uniformly basic glyoxalase II pI values from animals. S-D-Lactoylglutathione and S-acetoacetylglutathione are the best substrates, and S-carbobenzoxyglutathione is the best inhibitor of the yeast enzyme. Glutathione derivatives with a thioether bond are not inhibitory. Glyoxalase II from Candida albicans is compared either with animal and plant enzymes.

Animals

Isolation of glyoxalase II from bovine liver mitochondria.

Bovine liver mitochondria contain about 10% of the total glyoxalase II activity in the homogenate. Electrophoresis and isoelectric focussing of either crude mitochondrial extract or the purified mitochondrial glyoxalase II resolved the enzyme activity into five forms (pl 6.3, 6.7, 7.1, 7.7, and 7.9). Since bovine liver cytosol contains a single form of glyoxalase II (pl 7.5), at least four forms are exclusively mitochondrial with no counterpart in the cytosol. The relative molecular mass of mitochondrial glyoxalase II is about 23-24 kDa, similar to the cytosolic form. The kinetic constants obtained using S-D-lactoyl, S-acetyl-, S-acetoacetyl-, and S-succinyl-glutathione as substrates are similar to those reported for glyoxalase II from rat liver mitochondria. S-D-Lactoyl- and S-acetoacetyl-glutathione are the best substrates. S-Acetylglutathione is the poorest substrate with respect to both Vmax and Km values.

Animals

Induction of mouse liver glyoxalase I by hypobaric hypoxia.

Hypobaric hypoxia at 0.45 atm induced a reversible increase of mouse liver glyoxalase I. The levels of this enzyme increased after an exposure of 20 h and 20 + 20 h, whereas the activity decreased to the control values after 20 h at room pressure. Before the treatment, some animals received tritiated leucine (i.p.). Glyoxalase I was purified to homogeneity. The pure enzyme from the treated animals showed 20-times more radioactivity than the controls. Thus, the increase in specific activity is due to new protein synthesized in response to the treatment at 0.45 atm. The activities of glyoxalase II and glutathione S-transferase were not affected by the treatment.

Animals

Changes in spontaneous otoacoustic emissions produced by acoustic stimulation of the contralateral ear.

Spontaneous otoacoustic emissions (SOAEs) were measured in human ear canals before, during and after presentation of tonal stimuli to the contralateral ear. Stimuli were presented in 1/8 octave steps from 2 octaves below to 1 octave above the SOAE frequency at sound levels below the observed contralateral acoustic reflex threshold. For certain conditions there was an abrupt upward frequency shift at stimulus onset. For a fixed level the effect was frequency selective; the maximum frequency shift was obtained with tones approximately 1/2 octave below the SOAE. SOAE amplitude usually decreased but in some cases increased or remained unchanged. When amplitude changes were observed, the maximum shifts were observed for tones at or near the SOAE frequency. Changes in SOAEs were not observed for stimulus levels below 60 dB SPL. The effect is believed to be mediated by medial efferent neurons of the uncrossed olivocochlear bundle which arise in the medial region of the superior olivary complex and terminate on outer hair cells (OHCs). These results support those models which attribute SOAE generation to OHCs, and are indicative of an efferent influence on cochlear mechanics. A simple model is presented that proposes that efferent activity alters the tuning of the emission generator by causing changes in OHC membrane conductance.

Acoustic Stimulation

Behavior of spontaneous otoacoustic emissions following intense ipsilateral acoustic stimulation.

Following presentation of brief, intense pure tones spontaneous otoacoustic emissions (SOAEs) were reduced in frequency and/or amplitude. The effects were highly tuned with exposures between 1/8 and 5/8 of an octave below the SOAE producing the maximum changes. Exposure frequencies above the SOAE had no effect. The degree of tuning observed depended upon the post-exposure time sampled, with sharpness maximal between 3 and 120 s post-exposure. The effects increased nonlinearly as exposure level and duration were increased. The recovery functions were biphasic, the first phase being rapid and non-monotonic over about 2 min, while the second phase was monotonic and slow, sometimes taking several hours. These data are consistent with changes in outer hair cell (OHC) function and support the hypothesis that OHC changes underlie behavioral temporary threshold shift (TTS).

Acoustic Stimulation

Glyoxalase II from Zea mays: properties and inhibition study of the enzyme purified by use of a new affinity ligand.

The synthesis of N-(p-nitrocarbobenzoxy)glutathione (N-pNCBG) is reported. N-pNCBG and glutathione (GSH) were coupled to Affi-gel 10 by a thioester linkage and resulted in very effective bound ligands for a fast purification of glyoxalase II from corn. The S-(N-pNCBG)-affinity column showed a glyoxalase II binding capacity of up to 2-fold higher than that of the glutathione-affinity column. A single form of glyoxalase II was evidenced by PAGE in both crude extracts and in the affinity purified enzyme. A 45% recovery of glyoxalase II activity (purification, approx. 433-fold) was obtained for both matrices by a single chromatography. The purified glyoxalase is an acidic protein (pI 4.5) of about 26,000 relative molecular mass. Substrate studies for the corn glyoxalase II show, among possible substrates tested, that S-D-lactyl-glutathione is the preferred substrate. An inhibition study was performed with methyl-, propyl-, hexyl-, p-nitrobenzyl-, p-chlorophenacyl-, carbobenzoxy-, and p-nitrocarbobenzoxy-S-glutathione. Methyl-S-glutathione did not inhibit corn glyoxalase II; the others were found to be linear competitive inhibitors. The derivatives containing a thioether bond are weaker inhibitors than those containing a thioester bond or a carbonyl group. p-Nitrobenzyl-S-glutathione is the weakest inhibitor; the carbobenzoxy-S-derivatives are stronger inhibitors than the p-chlorophenacyl S-derivative.

Chromatography, Affinity

Effects of some S-blocked glutathione derivatives on the prevalent glyoxalase II (a form) of rat liver.

The prevalent glyoxalase II (S-2-hydroxyacylglutathione hydrolase, EC 3.1.2.6, a form) of rat liver cytosol has been studied with a series of seven S-blocked glutathione derivatives. At pH 7.4 and 20 degrees C, only p-nitrobenzyl-S-glutathione was found completely inactive. All the other derivatives are linear competitive inhibitors of the enzyme. Ki values using S-D-lactoylglutathione as substrate are reported. Alkyl-S-glutathiones are weak inhibitors and their inhibition increases with the decrease of the length of the alkyl chain. The best inhibitors are those glutathione derivatives which contain a thioester bond (carbobenzoxy- and p-nitrocarbobenzoxy-S-glutathione) or a carbonyl group (p-chlorophenacyl-S-glutathione). Inhibition by carbobenzoxy-S-glutathione seems to be more complex since the double reciprocal plot shows deviation from linearity at low substrate concentration.

Animals

Latency of auditory brain-stem responses and otoacoustic emissions using tone-burst stimuli.

A comparison of the latency of auditory brain-stem responses (ABR) and evoked otoacoustic emissions (EOAE) has led to an interpretation for the travel of transients in the peripheral auditory system that is consistent with both sets of data. The "cochlear echo" theory for the origin of the EOAE indicates that the latency of a particular frequency component back to the ear canal should be twice the forward latency of its characteristic place in the cochlea. The latency of wave V of the ABR to tone-burst stimuli can be described as the sum of two components: (1) a component that varies with intensity and frequency in an orderly and predictable manner and (2) a component that is independent of both intensity and frequency. Because the EOAE data can be predicted by taking twice the value of component (1) of the ABR latency, this component is interpreted to be due to mechanical travel through the cochlea. A consequence of this interpretation is that the remaining neural component of the ABR latency must be relatively independent of frequency and intensity.

Acoustic Stimulation

Tone-burst-evoked otoacoustic emissions from normal-hearing subjects.

Tone-burst-evoked otoacoustic emissions were measured as a function of tone-burst sound pressure level and frequency in normally hearing ears. Although the spectral and temporal properties varied across individual ears, there was a close correspondence between stimulus and response spectra. Both the spectral and latency characteristics of tone-burst-evoked emissions are consistent with the hypothesis that they are generated at sites along the cochlear partition corresponding to their frequency.

Acoustic Stimulation

Effects of auditory fatigue on psychophysical estimates of cochlear nonlinearities.

Two-tone-suppression (2TS) effects and cubic-difference-tone (CDT) levels were measured using a forward-masking procedure, before and after exposure to an intense tonal stimulus. Changes in 2TS effects were consistent with a change in the nonlinearity, such that the system became more linear, in addition to changes due to attenuation of the primary stimuli F1 and F2. Changes in CDT levels could be accounted for on the basis of a temporary threshold shift at F1 and F2. These results indicate at least a partial dissociation of the mechanisms underlying 2TS and CDT generation.

Acoustic Stimulation