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Biomedical subjects

R A Butler

Publications and source records attributed to R A Butler.

At least 19 recordsLinked to original sources

An aryl hydrocarbon receptor (AHR) homologue from the soft-shell clam, Mya arenaria: evidence that invertebrate AHR homologues lack 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta-naphthoflavone binding.

The aryl hydrocarbon receptor (AHR) mediates numerous toxic effects following exposure of vertebrate animals to certain aromatic environmental contaminants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). To investigate possible effects of TCDD on invertebrates, a cDNA encoding an AHR homologue was cloned from the soft-shell clam, Mya arenaria. The predicted amino acid sequence contains regions characteristic of vertebrate AHRs: basic helix-loop-helix (bHLH) and PER-ARNT-SIM (PAS) domains and a glutamine-rich region. Phylogenetic analysis shows that the clam AHR sequence groups within the AHR subfamily of the bHLH-PAS family, in a clade containing AHR homologues from Drosophila melanogaster and Caenorhabditis elegans. AHR mRNA expression was detected in all tissue types tested: adductor muscle, digestive gland, foot, gill, gonad, mantle, and siphon. The in vitro-expressed clam AHR exhibited sequence-specific interactions with a mammalian xenobiotic response element (XRE). Velocity sedimentation analysis using either in vitro-expressed clam AHR or clam cytosolic proteins showed that this AHR homologue binds neither [(3)H]TCDD nor [(3)H]beta-naphthoflavone (BNF). Similarly, in vitro-expressed D. melanogaster and C. elegans AHR homologues lacked specific binding of these compounds. Thus, the absence of specific, high-affinity binding of the prototypical AHR ligands TCDD and BNF, is a property shared by known invertebrate AHR homologues, distinguishing them from vertebrate AHRs. Comparative studies of phylogenetically diverse organisms may help identify an endogenous ligand(s) and the physiological role(s) for this protein.

Amino Acid Sequence↗

Quantitative reverse transcription polymerase chain reaction of a molluscan metallothionein mRNA.

A quantitative assay based on competitive reverse transcription polymerase chain reaction (RT-PCR) was developed for metallothionein (MT) mRNA of the mollusc Crassostrea virginica and applied to analysis of MT mRNA of hemocytes. The assay was based on titration of a competitive external standard cRNA derived from the coding region of the oyster MT mRNA. Serial dilutions of the cRNA standard were coamplified with a constant amount of total RNA using biotinylated primers common to both target and standard sequences. Amplified products were bound to streptavidin-coated plates and hybridized to sequence-specific fluorescein-labeled probes. Detection was based on single photon counting of chemiluminescence generated by an alkaline phosphatase-conjugated antifluorescein antibody. For quantification, the target chemiluminescence was normalized to that of the standard, and the amount of target MT mRNA in the sample was derived from the titration. Cadmium-induced MT mRNA equivalent to that in 180 hemocytes was easily detected, and, for routine quantitative analysis, was sufficiently sensitive to quantify basal and induced MT mRNA. Basal hemocyte MT mRNA of 133+/-8 (1 S.E.) amol per microgram total RNA was induced 5-fold to 573+/-14 amol per microgram total RNA by in vitro exposure to 15 microM CdCl(2) for 20 h.

Animals↗

Disruption of metallothionein expression with antisense oligonucleotides abolishes protection against cadmium cytotoxicity in molluscan hemocytes.

The relationship between metallothionein (MT) induction and cytotoxicity was examined in isolated oyster hemocytes exposed in vitro to cadmium, copper, and zinc. In all cases MT induction increased to peak levels with increased metal dose, then declined with continued increases in dose. The effectiveness of these metals as inducers of MT was cadmium > copper > zinc, with cadmium the most effective inducer in magnitude of induction and sensitivity to dose. Cytotoxicity of the metals, based on decreases in lysosomal neutral red retention times, was copper > cadmium > zinc. Zinc was relatively nontoxic and a poor inducer of MT. Cadmium, which was intermediate in toxicity, required concentrations in excess of that causing peak induction of MT to have substantial effects on lysosomal membrane integrity. In contrast, copper was highly cytotoxic at concentrations below that which resulted in peak MT induction. This reversal in the rank order of cadmium and copper suggested that the toxicity of cadmium was tempered by the protective effects of MT. This was verified by disrupting MT expression with antisense phosphorothioate-substituted oligodeoxynucleotides. Administration of 2.5 microM CdCl(2), which induced MT but had no effect on lysosomal membrane stability when administered alone, reduced neutral red retention time to 41% of control levels when administered in the presence of antisense. The resulting toxicity was greater than that caused by a comparable concentration of copper. The findings represented evidence that expression of MT protects against cadmium toxicity in an estuarine mollusc.

Animals↗

Patients' perception of pain after total hip arthroplasty.

A study was undertaken to determine the frequency with which patients had pain that they attributed to their hip after total hip arthroplasty. Pain drawings were used to allow patients to localize the area of their symptoms, and the degree of pain was quantified with visual analog scales. Complete clinical and radiographic data were collected on all patients so that the occurrence of pain could be correlated with a number of parameters previously reported to affect the incidence of pain, including age, sex, activity level, length of follow-up, stem size, bone type (Dorr index), and type of stem fixation (proximally coated, fully coated, or cemented). Results indicated that type of stem fixation was the only parameter statistically correlated with a higher incidence of thigh pain. Patients with proximally coated stems were more than twice as likely to complain of pain than patients with fully coated or cemented hips (P < .01). Although the incidence of thigh pain was significantly higher with proximally coated stems, the severity was not, averaging 3.0 to 3.5 out of 10 on visual analog scale in all 3 groups. The results indicate that patients perceived pain as originating in the hip in a high percentage of cases, particularly when proximally coated stems were used.

Adult↗

Computer simulation of trabecular remodeling using a simplified structural model.

A simplified three-dimensional simulation of trabecular bone remodeling has been developed. The model utilizes 441 planar structural units to represent approximately 50 mm3 of initial bone volume with 199 basic multicellular units (BMUs). The simulation takes into account trabecular perforation in the structural model. The cases of male bone remodeling with no menopause and female bone remodeling with menopause are examined from the period of simulated age 25-80 years. Menopause is arbitrarily started at age 45 and extends for 7.5 years. Zero-, first-, and second-order BMU activation responses are employed to examine how the bone would be affected by the method of increase of BMU activation during menopause. At age 80, the female bone remodeling simulation produced a bone volume loss of approximately 49% for all three activation responses. This compared to a 38% bone volume loss for the case of no menopause. For the menopause simulations, an average of about 40% of the total bone loss was due to perforation.

Adult↗

A swine model for the evaluation of efficacy of anti-microbial catheter coatings.

A swine model was developed to investigate the efficacy of percutaneous venous catheters with anti-microbial coatings. The catheters used in the study consisted of silver-coated and uncoated catheters, both designed for percutaneous venous access. Five commercial pigs were each implanted with three venous catheters and followed for a period of 90 days. Two of the three catheters were coated and one was uncoated. To evaluate the percutaneous aspects of the catheters in the model, two venous access catheters were implanted percutaneously, parallel to the dorsal midline. These catheters were just caudal to the region that is dorsal to the scapula in each animal. In each case, the catheter to the left of the dorsal midline was silver-coated while the catheter to the right of the dorsal midline was uncoated. A silver-coated catheter was also implanted in the left external jugular vein of each animal and buried subcutaneously in order to evaluate the elution of the coating through the body under venous contact. Over the 90 day period, the concentration of silver in the blood rose to a mean peak level of 23.2 ppb following implantation of the catheters and then decreased after the second post-surgery week. The histological evaluation and macroscopic inspection at necropsy revealed minimal tissue response to both coated and uncoated materials. Data on bacterial growth indicated that bacteria were present at the terminal subcutaneous end of two of the uncoated percutaneous catheters. Based upon serum silver levels, exudate formation, histological examination, and bacterial growth information, the swine model was deemed to be suitable for testing the efficacy of catheters containing anti-microbial coatings.

Animals↗

The effects of attenuation of frequency segments on binaural localization of sound.

Perceived location of tonal stimuli d and narrow noise bands presented in two-dimensional space varies in an orderly manner with changes in stimulus frequency. Hence, frequency has a referent in space that is most apparent during monaural listening. The assumption underlying the present study is that maximum sound pressure level measured at the ear canal entrance for the various frequencies serves as a prominent spectral cue for their spatial referents. Even in binaural localization, location judgments in the vertical plane are strongly influenced by spatial referents. We measured sound pressure levels at the left ear canal entrance for 1.0-kHz-wide noise bands, centered from 4.0 kHz through 10.0 kHz, presented at locations from 60 degrees through -45 degrees in the vertical plane; the horizontal plane coordinate was fixed at -90 degrees. On the basis of these measurements, we fabricated three different bandstop stimuli in which differently centered 2.0-kHz-wide frequency segments were filtered from a broadband noise. Unfiltered broadband noise served as the remaining stimulus. Localization accuracy differed significantly among stimulus conditions (p < .01). Where in the vertical plane most errors were made depended on which frequency segment was filtered from the broadband noise.

Dichotic Listening Tests↗

Asymmetric performances in binaural localization of sound in space.

Twenty right-handers and 20 left-handers were tested on a sound localization task. Broadband noise was presented from either the left or right hemifield. Localization accuracy was significantly greater (P = 0.002) when sounds emanated from the left hemifield thereby suggesting a paramount role played by the right hemisphere. Correcting for front-rear reversals, attributable to impoverished spectral cues and/or faulty processing of such cues, rendered differences in error scores linked to hemifield nonsignificant. The data were interpreted to mean that the special contribution of the right hemisphere to this task was its greater fidelity in processing spectral cues. No differences in localization proficiency between right- and left-handers were observed.

Adult↗

Asymmetric performances in monaural localization of sound in space.

Ten subjects localized a 3.5-kHz high-pass noise originating in the median sagittal plane (MSP)--a plane along which location judgments are highly dependent on spectral cues. Three different experimental conditions were established: (1) binaural listening, (2) monaural listening with the left ear, and (3) monaural listening with the right ear. All subjects performed best when listening binaurally. In comparison with the right ear, location judgments of source elevation was significantly more accurate when listening with the left ear (P = 0.048). Also, perceived displacement from midline, a common occurrence when listening monaurally, was less when localizing with the left ear (P = 0.059). These data, in conjunction with the animal literature demonstrating that auditory cortex contralateral to the ear stimulated is essential for accurate localization, suggest that the right hemisphere is better in processing complex spectral information.

Acoustic Stimulation↗

Binaural localization: influence of stimulus frequency and the linkage to covert peak areas.

The influence of selectively filtering a broadband stimulus on binaural localization was investigated. First, head-related-transfer-functions were obtained by placing a miniature microphone at the entrance of the ear canal and presenting broadband noise bursts from each of 104 loudspeakers arrayed in the listener's left hemifield. The microphone's output was transformed into frequency spectra using a Fast Fourier Transform. The microphone and loudspeaker characteristics were accounted for by repeating the procedure with the microphone suspended in space. The in-ear data were divided by the in-space data thereby providing an account of the pinna's interaction with the incident sound wave. Extracted from these data were the covert peak areas (CPAs) associated with different frequency segments. A CPA was defined as the spatial location of those loudspeakers, which when generating the stimulus, produced a sound pressure level at the ear canal entrance within 1 dB of the maximum level recorded for a particular frequency segment. A series of localization tests was conducted using a bandstop stimulus--one in which differently-centered 2.0-kHz wide frequency segments were filtered from a broadband noise. We predicted that when a given frequency segment was filtered, binaural listeners would less often report a sound as originating from the CPA associated with that segment compared to their performances when the sound was unfiltered. This prediction was substantiated by the data (P < 0.0001). While localization accuracy was decreased for the filtered stimuli, the decrement was significantly greater (p < 0.01) for sounds originating in the CPA. We interpreted the results to mean that monaural spectral cues contribute significantly to the accuracy of binaural localization and that the basis of the contribution is the spatial referents of stimulus frequencies.

Acoustic Stimulation↗

The linkage between stimulus frequency and covert peak areas as it relates to monaural localization.

Head-related transfer functions for differently centered narrow noise bands were obtained on 6 subjects. Derived from these measurements were covert peak areas (CPAs), defined as the spatial constellation of loudspeakers that generates maximal sound pressure at the entrance of the ear canal for specific bands of frequency. On the basis of previous data, we proposed that different frequency bands served as important spectral cues for monaural localization of sounds from different loci and that location judgments were directed toward the CPAs associated with the different bands. In the first study, the stimuli were bandpass filtered so that they contained only those frequencies whose associated CPAs occupied either the monaural listener's "upper" or "lower" spatial regions. Loudspeakers, separated by 15 degrees, were stationed in the left hemifield, ranging from 0 degree to 180 degrees azimuth and -45 degrees to 60 degrees elevation. Subjects reported the loudspeaker from which the sound appeared to originate. Judgments of the sound's elevation were in general accord with the CPAs associated with the different frequency segments. In the second study, monaural localization tests were administered in which different 2.0-kHz-wide frequency bands linked with specific CPAs were notch filtered from a 3.5-kHz highpass noise band. For the control condition, the highpass noise was unfiltered. The data demonstrated that filtering a frequency segment linked with specific CPAs resulted in significantly fewer location responses directed toward that particular spatial region. These results demonstrate in greater detail the relation between the directional filtering properties of the pinna and monaural localization of sound.

Attention↗

Localization of sound in the vertical plane with and without high-frequency spectral cues.

Binaural localization of 3.0-kHz high- and lowpass noise presented in the median vertical plane (MVP) and lateral vertical plane (LVP) was investigated. We anticipated superior performance when localizing the highpass noise by virtue of the availability of pinna cues. The viability of this supposition was strengthened by monaural localization tests in which performance proficiency for the highpass noise exceeded that for the lowpass noise (p less than .01). The main result showed that binaural localization of proficiency for highpass noise surpassed that for lowpass noise for all listening conditions (p less than .01). However, the importance of binaural temporal and level differences in vertical-plane localization was demonstrated by the highly respectable performances when the lowpass noise was presented in the LVP. Data from binaural localization in the MVP and monaural localization in the LVP suggested that the influence of pinna cues diminishes for source elevations above 45 degrees.

Adult↗

Binaural and monaural localization of sound in two-dimensional space.

Two experiments were conducted. In experiment 1, part 1, binaural and monaural localization of sounds originating in the left hemifield was investigated. 104 loudspeakers were arranged in a 13 x 8 matrix with 15 degrees separating adjacent loudspeakers in each column and in each row. In the horizontal plane (HP), the loudspeakers extended from 0 degrees to 180 degrees; in the vertical plane (VP), they extended from -45 degrees to 60 degrees with respect to the interaural axis. Findings of special interest were: (i) binaural listeners identified the VP coordinate of the sound source more accurately than did monaural listeners, and (ii) monaural listeners identified the VP coordinate of the sound source more accurately than its HP coordinate. In part 2, it was found that foreknowledge of the HP coordinate of the sound source aided monaural listeners in identifying its VP coordinate, but the converse did not hold. In experiment 2, part 1, localization performances were evaluated when the sound originated from consecutive 45 degrees segments of the HP, with the VP segments extending from -22.5 degrees to 22.5 degrees. Part 2 consisted of measuring, on the same subjects, head-related transfer functions by means of a miniature microphone placed at the entrance of their external ear canal. From these data, the 'covert' peaks (defined and illustrated in text) of the sound spectrum were extracted. This spectral cue was advanced to explain why monaural listeners in this study as well as in other studies performed better when locating VP-positioned sounds than when locating HP-positioned sounds. It is not claimed that there is inherent advantage for localizing sound in the VP; rather, monaural localization proficiency, whether in the VP or HP, depends on the availability of covert peaks which, in turn, rests on the spatial arrangement of the sound sources.

Attention↗

The contribution of the near and far ear toward localization of sound in the sagittal plane.

Eight listeners were required to locate a train of 4.5-kHz high-pass noise bursts emanating from loudspeakers positioned +/- 30, +/- 20, +/- 10, and 0 deg re: interaural axis. The vertical array of loudspeakers was placed at 45, 90, and 135 deg left of midline. The various experimental conditions incorporated binaural and monaural listening with the latter utilizing the ear nearest or ear farthest from the sound source. While performance excelled when listening with only the near ear, the contribution of the far ear was statistically significant when compared to localization performance when both ears were occluded. Based on head related transfer functions for stimuli whose bandwidth was 1.0 kHz, four spectral cues were selected as candidates for influencing location judgments. Two of them associated relative changes in energy across center frequencies (CFs) with vertical source positions. The other two associated an absolute minimum (maximum) energy for specific CFs with a vertical source position. All but one cue when measured for the near ear could account for localization proficiency. On the other hand, when listening with the far ear, maximum energy at a specific CF outperformed the remaining cues in accounting for localization proficiency.

Acoustic Stimulation↗

The bandwidth effect on monaural and binaural localization.

Listeners located, monaurally and binaurally, an 8.0 kHz centered noise burst whose bandwidth was set at 2.0, 4.0, 6.0 and 8.0 kHz. Loudspeakers, placed 7.5 degrees apart, covered an arc extending from 15 degrees to 165 degrees to the left of midline. Listeners reported the number of that loudspeaker from which the noise bursts appeared. A significant reduction in localization errors was associated with increments in bandwidth and for binaural localization, this was attained largely through fewer instances of confusing sounds from the front with those from the rear. While overall, binaural accuracy exceeded monaural accuracy when sounds came from the front or rear, no appreciable differences between the two listening conditions were noted when the sounds came from the middle section of the arc. Only when broadband noise was employed, as it was in a supplementary set of observations, did binaural localization uniformly surpass monaural localization in accuracy - a finding attributed to the introduction of low frequencies which resulted in the addition of interaural ongoing phase differences to the constellation of localization cues.

Acoustics↗