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Biomedical subjects

D R Moore

Publications and source records attributed to D R Moore.

At least 73 records · Page 4Linked to original sources
PubMed1993

Auditory brainstem responses in ferrets following unilateral cochlear removal.

To examine the effect of unilateral or asymmetric hearing loss on the developing brain, ferrets had the right cochlea removed at postnatal day (P)5, P25, P40 or P90. Auditory brainstem responses (ABR) to free-field click stimulation were obtained before and after cochlear removal in the P40 and P90 groups, and from P28 in the other groups. Acute cochlear removal did not lead to any change in the morphology of the ABR waveform or to any change in the ABR threshold in response to stimulation on the side of the intact ear. There was a small, progressive increase in the latency of the four main waves of the ABR. Long-term survival following cochlear removal did not lead to any change in ABR waveform or threshold, or to any further change in wave latency, regardless of age at the time of removal or survival time (up to 1-2 years). In contrast to initial expectations based on previous single-unit studies, these results suggest that cochlear removal in infancy does not produce any large compensatory change in the functional organization of the auditory brainstem.

Acoustic Stimulation↗
PubMed1993

Functional consequences of neonatal unilateral cochlear removal.

The physiological consequences of unilateral cochlear removal in infancy were assessed by recording the responses of neurones in the ferret inferior colliculus and superior colliculus to acoustic stimulation of the intact ear. Animals were lesioned between postnatal days P5 and P40 and survived for at least a year prior to recording. In the inferior colliculus ipsilateral to the intact ear, neurones had lower thresholds and wider dynamic ranges following earlier (P5) than following later (P40, adult) cochlear removal. In the superior colliculus contralateral to the intact ear, neurones had broader spatial tuning in response to high-level, free-field stimulation following cochlear removal at P25, than had neurones in normal, unlesioned adults. The neural map of auditory space was also disrupted in the lesioned animals. However, at low stimulus levels the auditory space map was unaffected by the cochlear removal. These results show a developmental sensitive period for the effects of unilateral cochlear removal on the responses of ferret inferior colliculus neurones, and a level-dependent effect of cochlear removal on the responses of superior colliculus neurones.

Acoustic Stimulation↗
PubMed1993

Plasticity of binaural hearing and some possible mechanisms following late-onset deprivation.

Evidence for binaural plasticity resulting from late-onset deprivation comes from behavioral adaptation in humans following experience of abnormal binaural cues, from physiologic changes in the organization of the cerebral cortex, and from anatomic rewiring of some of the pathways underlying binaural hearing in the brain stem. Some of this evidence is indirect, and the long-term functional consequences of these changes in the nervous system are unclear. Nevertheless, there are now sufficient data available on plasticity in mature nervous systems to warrant a substantially increased research effort in this field. Among the questions to be addressed are the site(s) of reorganization in the auditory system, the effects of different types of deprivation, and the neural mechanisms underlying the plasticity.

Acoustic Stimulation↗
PubMed1992

Rapid development of the auditory brainstem response threshold in individual ferrets.

The development of the ferret auditory system was examined using the auditory brainstem response (ABR). Longitudinal recordings were obtained under short-acting anaesthesia from individual animals at 4-h or 24-h intervals. Particular attention was focused on the period from postnatal day (P) 26 to P32 when the ferret auditory system becomes functional. ABR thresholds to click stimuli presented in a free-field were found to decline precipitously within a 4-h period during the first 24 h following initial responsiveness. Latencies of waves I and IV of the ABR also declined significantly during this period, but the 'central conduction time' remained stable. A temporal correlation was observed between the time of the precipitous threshold decline and the time of opening of the external ear canal. No changes in cochlear anatomy were observed during this time. We suggest that the opening of the ear canal and/or the clearance of fluid from the middle ear explain the major change in threshold of hearing following onset of function.

Aging↗
PubMed1992

Binaural masking level differences in infants with and without otitis media with effusion.

The binaural masking level difference (MLD) was measured in two groups of infants (aged 7-10 months) who either had or did not have a documented history of otitis media with effusion (OME). Subjects were trained to detect a 500 Hz signal (either in or out-of-phase between the ears) against an in-phase, narrow band noise masker centred at 500 Hz. Non-OME infants had elevated masked thresholds and reduced MLDs compared with normal-hearing older (7-12 years) children and adults (20-27 years). OME infants also had elevated masked thresholds and reduced MLDs but, in contrast to studies using older subjects, their results were similar to those of the non-OME infants. These results suggest that, during at least the first year of life, infants are disadvantaged compared with adults or children when listening in noisy environments. They also suggest that OME does not further compromise infants' ability to detect sounds in those environments.

Acoustic Stimulation↗
PubMed1992

Trophic influences of excitatory and inhibitory synapses on neurones in the auditory brain stem.

The effects of a reduction during development of excitatory and inhibitory synaptic input on CNS neurones were studied in the lateral superior olivary nucleus (LSO) of the ferret following neonatal, unilateral cochlear removal. LSO neurones normally receive excitatory input from the ipsilateral ear and inhibitory input from the contralateral ear. After cochlear removal, the ipsilateral LSO was smaller and contained fewer neurones than either the contralateral or the normal LSO. No difference was found between the volume or number of neurones in the latter nuclei. Remaining neurones in the LSO ipsilateral to the removal were smaller than those in the contralateral LSO of the same ferrets. These data show that activity in excitatory pre-synaptic terminals can be sufficient for post-synaptic target maintenance, but that activity in inhibitory terminals alone is not.

Animals↗
PubMed1992

Effect of aging on enzymatic antioxidant defenses in rat liver mitochondria.

Antioxidant defenses within liver mitochondria are pivotal in preventing liver damage from oxidative toxicants. In this study we determined the activities of glutathione peroxidase (GPO), superoxide dismutase (SOD) and glutathione reductase (GRD) in mitochondria from livers of variously aged Fischer 344 rats. A mixed pattern of age-associated alterations in mitochondrial antioxidant activities was observed. In male rats, GRD activity decreased in old age, whereas GPO and SOD activities increased. In female rats, GPO activity decreased with age, but SOD activity increased and GRD activity was unchanged. Age-associated decreases in antioxidant protection from mitochondrial enzymes appeared to be counterbalanced by increases in protection from other enzymes.

Aging↗
PubMed1991

Sex-dependent differences in the effects of aging on antioxidant defense mechanisms of rat liver.

Information about age-related factors that influence sensitivity to hepatotoxic injury is important to geriatric medicine and environmental health. The purpose of the present study was to determine whether age-associated changes occur in hepatic antioxidant defense mechanisms of male and female Fischer 344 rats. Liver homogenates and post-mitochondrial supernatant fractions from rats aged 4, 14, 24 and 29 months were analyzed for antioxidant enzyme activities and for vitamin E and malondialdehyde content. Age-associated changes in catalase and glutathione reductase activities were observed that could be described as sex-determined differences that disappeared in old age. Cytosolic superoxide dismutase and glutathione peroxidase activities displayed sex-dependent variations in activity but were unaffected by aging. Hepatic vitamin E concentrations were lower in male rats than in female malondialdehyde concentrations also were lower in males than in females; malondialdehyde content increased in old males and decreased in old females. The results indicate that age-associated changes in enzymatic and nonenzymatic antioxidant defense mechanisms of rat liver are sex-dependent. In addition, comparison with findings from other studies in rats suggests that the effects of aging may also depend on the strain of rat.

Aging↗
PubMed1991

Behavioral changes in fetal sheep caused by vibroacoustic stimulation: the effects of cochlear ablation.

We measured the effects of 2 minutes of vibroacoustic stimulation on the activity of unanesthetized fetal sheep in utero. We were unable to detect any changes in activity after stimulation with a model 5C electrolarynx. With more powerful stimulation using a mechanical oscillator, fetal electrocortical activity desynchronized. Fetal breathing and eye movements changed with electrocortical activity and there was an increase in nuchal muscle activity. Stimulation caused a small decrease in fetal heart rate. Responses to stimulation were not seen in four of the five fetuses with bilateral cochlear ablation. These results indicate that in fetal sheep the auditory apparatus is necessary for the detection of vibroacoustic stimuli. The difference in responsiveness of the sheep and human fetus appears to be because of a difference in central processing after detection of the stimulus.

Acoustic Stimulation↗
PubMed1991

Plasticity of auditory maps in the brain.

The central auditory pathway contains maps of sound frequency that reflect the functional organization of the cochlea, as well as topographic representations of other stimulus features, such as sound location, that are synthesized within the brain. Both types of map undergo changes during development and are shaped by experience. This is particularly true of the representation of auditory space in the superior colliculus, which can be modified by alteration of auditory and visual inputs early in life. Although experience-induced plasticity in this map is restricted primarily to the developmental period, the frequency representation in the cortex of adult animals can re-organize following partial deafness.

Acoustic Stimulation↗
PubMed1991

Binaural masking level differences in children with a history of otitis media.

The binaural hearing of children with and without a history of otitis media (OM) was assessed by determining their binaural masking level differences (BMLDs). The test was also administered to a group of adults. BMLDs for the non-OM children were not significantly different from those of adults. However the mean BMLD of the OM children was significantly lower than that of non-OM children. Some children in the OM group had small (15-25 dB HL) sensitivity deficits in one or both ears. However, no correlation was found between BMLD and hearing level in cases of either symmetric or asymmetric loss. Exclusion of OM children with residual middle ear abnormalities did not abolish the significant difference between the OM and non-OM groups. We suggest that the small BMLDs in the OM group may be associated with these children having difficulties detecting and attending to signals in noisy environments.

Acoustic Impedance Tests↗
PubMed1991

Anatomy and physiology of binaural hearing.

Binaural hearing improves performance in most auditory tasks and is essential for some. This paper introduces the brain stem pathways and nuclei involved in binaural interaction and outlines some recent approaches to understanding binaural mechanisms. It also provides examples of basic science approaches to the effects of infant hearing loss on those pathways and mechanisms. Binaural interaction occurs primarily and almost simultaneously at three levels of the brain: the superior olivary complex (SOC), the nuclei of the lateral lemniscus (NLL) and the inferior colliculus (IC). The SOC derives its input from the anterior ventral cochlear nucleus (CN) through branching axons that innervate several SOC subdivisions on both sides of the brain. At least some of these anteroventral CN axons project on up to the contralateral NLL and IC. The IC and NLL also receive direct, major projections from the contralateral CN, via the dorsal and intermediate acoustic striae, and from the SOC bilaterally. The IC receives additional input from the NLL bilaterally, and is thus innervated by every nuclear group within the auditory brain stem. There is little evidence for strict, functional segregation in these binaural pathways, although subdivisions of the SOC appear to be predominantly involved in analysing either interaural time or level differences (ITD, ILD). ITD- and ILD-sensitive neurones are also found in abundance in the central IC. There is emerging evidence that binaural information is coupled with spectral cues derived from the outer ear in several auditory mid-brain regions [the NLL, the external IC and the superior colliculus (SC)] to produce topographic representations of auditory space. Throughout the higher auditory system the response of neurones to stimulation of each ear is either excitatory or inhibitory, and there is a spatial segregation of neurones receiving predominantly excitatory or inhibitory input from the ipsilateral ear in both the medial geniculate body of the thalamus and the auditory cortex. Neonatal, unilateral hearing loss leads to a rearrangement of binaural connections in the auditory brain stem, to changes in the physiology of IC neurones in response to stimulation of the normal ear and to compensatory alterations in the auditory space map in the SC. The same hearing losses in adulthood do not produce these changes. The evidence from this and other work suggests that binaural mechanisms are more sensitive to hearing loss, over a longer developmental period, than mechanisms subserving monaural processing.

Auditory Pathways↗
PubMed1990

Auditory brainstem of the ferret: early cessation of developmental sensitivity of neurons in the cochlear nucleus to removal of the cochlea.

The role of primary afferent innervation in the maintenance of neurons in the mammalian auditory system was assessed by performing unilateral removals of the cochlea in neonatal and mature ferrets of known birth dates. Removals were performed under steroid anesthesia and resulted in the complete destruction of the organ of Corti and the loss of at least 80% of type I spiral ganglion neurons. Four main age groups [postnatal days (P)5, P24, P90, and P180] were used. Additional animals received no surgery, partial removals, or complete removals at older ages. Three months after the cochlear removal the animals were reanesthetized and perfused. The brainstem and the temporal bones were wax-embedded, frontally sectioned, and Nissl-stained. Sections of the right and left cochlear nuclei were compared quantitatively. Removal of the cochlea at P5 resulted in the loss of more than 50% of large (nongranular) neurons throughout the ipsilateral cochlear nucleus. Lesions at older ages did not produce any neuron loss. The size of the remaining neurons was reduced by 10-15% in all age groups. Partial lesions at P5 produced a graded response in the cochlear nucleus that was related to the extent of the lesion. The developmental sensitive period for the effects of cochlear removal on the ferret cochlear nucleus is therefore over before the age (P28-P30) at which the animal begins to hear. The present result differs markedly from the chicken, in which the sensitive period for removal of the cochlea persists for at least 2 months after the onset of hearing.

Afferent Pathways↗
PubMed1990

Addition of uridines to edited RNAs in trypanosome mitochondria occurs independently of transcription.

RNA editing is a novel RNA processing event of unknown mechanism that results in the introduction of nucleotides not encoded in the DNA into specific RNA molecules. We have examined the post-transcriptional addition of nucleotides into the mitochondrial RNA of Trypanosoma brucei. Utilizing an isolated organelle system we have determined that addition of uridines to edited RNAs does not require ongoing transcription. Trypanosome mitochondria incorporate CTP, ATP, and UTP into RNA in the absence of transcription. GTP is incorporated into RNA only as a result of the transcription process. Post-transcriptional CTP and ATP incorporation can be ascribed to known enzymatic activities. CTP is incorporated into tRNAs as a result of synthesis or turnover of their 3' CCA sequences. ATP is incorporated into the 3' CCA of tRNAs and into mitochondrial messenger RNAs due to polyadenylation. In the absence of transcription, UTP is incorporated into transcripts known to undergo editing, and the degree of UTP incorporation is consistent with the degree of editing occurring in these transcripts. Cytochrome b mRNAs, which contain a single editing site near their 5' ends, are initially transcribed unedited at that site. Post-transcriptional labeling of cytochrome b mRNAs in the organelle with [alpha-32P]UTP results in the addition of uridines near the 5' end of the RNA but not in a 3' region which lacks an editing site. These results indicate that RNA editing is a post-transcriptional process in the mitochondria of trypanosomes.

Adenosine Triphosphate↗
PubMed1990

Auditory brainstem of the ferret: bilateral cochlear lesions in infancy do not affect the number of neurons projecting from the cochlear nucleus to the inferior colliculus.

Unilateral cochlear removal in infancy produces a number of changes in the structure and physiology of the central auditory system. To test the role that interaural competition plays in this plasticity, ferrets were reared with bilateral cochlear removals from the fourth postnatal week; before the time of the normal onset of auditory function. The totality of the removals was confirmed using brainstem response audiometry and cochlear histology. Following 3-month survival, the animals were injected with wheatgerm horseradish peroxidase in the left inferior colliculus. Retrogradely labeled neurons in the cochlear nucleus on each side were counted. Neither the absolute number nor the bilateral symmetry of the labeled neurons differed significantly from normal adult ferrets. Thus, bilateral cochlear removal does not produce the same change in brainstem connections as unilateral removal or unilateral conductive hearing loss. The results are consistent with the competitive hypothesis.

Animals↗
PubMed1990

Influence of aging on ethanol and acetaldehyde oxidation in female rat liver.

Rates of ethanol metabolism by alcohol dehydrogenase, the microsomal ethanol oxidizing system (MEOS), and catalase were similar in liver preparations from young (4-5 months) and old (24-27 months) female Fischer 344 rats. On the other hand, rates of acetaldehyde metabolism by mitochondrial aldehyde dehydrogenase (ALDH) were 15-20% lower in livers of old rats than in those of younger ones. Results with the ALDH inhibitor cyanamide indicated that a decline in ALDH activity of this magnitude would not increase acute ethanol hepatotoxicity.

Acetaldehyde↗
PubMed1989

Lysis of Trypanosoma brucei by a toxic subspecies of human high density lipoprotein.

Trypanosoma brucei brucei is an important pathogen of domestic cattle in sub-Saharan Africa and is closely related to the human sleeping sickness parasites, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. However, T. b. brucei is non-infectious to humans. The restriction of the host range of T. b. brucei results from the sensitivity of the parasite to lysis by toxic human high density lipoproteins (HDL) (Rifkin, M. R. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3450-3454). We show in this report that trypanosome lytic activity is not a universal feature of all human HDL particles but rather that it is associated with a minor subclass of HDL. We have purified the lytic activity about 8,000-fold and have identified and characterized the subspecies of HDL responsible for trypanosome lysis. This class of HDL has a relative molecular weight of 490,000, a buoyant density of 1.21-1.24 g/ml, and a particle diameter of 150-210 A. It contains apolipoproteins AI, AII, CI, CII, and CIII, and monoclonal antibodies against apo-AI and apo-AII inhibit trypanocidal activity. In addition to these common apolipoproteins, the particles also contain at least three unique proteins, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. Treatment of the particles with dithiothreitol resulted in the disappearance of two of the proteins and abolished trypanocidal activity. Two-dimensional gel electrophoresis showed that these proteins were a disulfide-linked trimer of 45,000, 36,000, and 13,500-Da polypeptides and dimers of the 36,000- and 13,500-Da polypeptides or of 65,000- and 8,500-Da polypeptides. Studies on the lysis of T. b. brucei by the purified particle suggest that the lytic pathway may involve the uptake of the trypanocidal subspecies of HDL by endocytosis.

Animals↗