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Biomedical subjects

M C Brown

Publications and source records attributed to M C Brown.

At least 91 records · Page 5Linked to original sources
PubMed1994

Central trajectories of type II spiral ganglion cells from various cochlear regions in mice.

Type II spiral ganglion cells provide the afferent pathway from outer hair cells in the mammalian cochlea to neurons in the cochlear nucleus. The present study compares the projection patterns of type II fibers originating from spiral ganglion cells of apical, middle and basal cochlear regions in mice. Fibers were labeled by extracellular injections of horseradish peroxidase into the spiral ganglion. Type II fibers from all regions displayed many 'en passant' swellings (mean = 95) and had very few terminal swellings (mean = 6); fibers from the base had significantly more swellings than those from the apex. Type II fibers traveled into the cochlear nucleus together with type I fibers labeled by the same injection, and both types bifurcated in a cochleotopic manner. The bifurcations formed ascending and descending branches that traveled initially with type I branches in the magnocellular regions of the cochlear nucleus. Type II fibers differed from type I branches in that many fibers subsequently distributed collaterals and terminals to granule cell regions and to the boundaries of these regions that typically do not receive type I input. This projection into the granule cell regions depended on cochlear origin: ascending branches of type II fibers from the cochlea apex did not usually terminate in granule cell regions, whereas those from the base often ended in these regions. Descending branches of type II fibers from all regions, however, projected to the granule cell regions, particularly the granule cell lamina between ventral and dorsal cochlear nucleus. These observations suggest that afferent information from outer hair cells reaches a wide area of the magnocellular parts of the cochlear nucleus in a cochleotopic fashion, and reaches granule cell regions with a less distinct cochleotopic mapping.

Animals↗
PubMed1994

Central trajectories of type II (thin) fibers of the auditory nerve in cats.

This paper describes the central projections of thin fibers of the auditory nerve in cats. Both thin (type II) and thick (type I) fibers are labeled by extracellular injections of horseradish peroxidase (HRP) into the auditory nerve. Type I and almost all type II fibers bifurcate upon reaching the auditory nerve root of the cochlear nucleus. For a given bundle of auditory nerve fibers labeled by a discrete injection of HRP, bifurcations of type II and type I fibers are restricted to a narrow region of the nerve root. After the bifurcation, the pathways of type II branches within the anteroventral cochlear nucleus (AVCN) and posteroventral cochlear nucleus (PVCN) are similar to those of type I branches. This similarity in bifurcation and course of type I and type II fibers was observed in the ventral as well as dorsal parts of the ventral cochlear nucleus. The complete axonal course of most type II fibers could not be reconstructed, however, due to fading of the reaction product. Type II fibers produce very few collaterals in the cochlear nucleus (CN), but possess many 'en passant' swellings along their main processes and collaterals. Compared with type II fibers previously studied in mice (Berglund and Brown, 1989; 1994; Brown and Ledwith, 1990), cat type II fibers are similar in their general projections within the main body of the nucleus and in the frequency of 'en passant' swellings per length of fiber, but cat fibers have a higher percentage of 'complex' or pedunculated 'en passant' swellings.

Animals↗
PubMed1994

Pharmacology of epidural fentanyl, alfentanil, and sufentanil in volunteers.

BACKGROUND: Despite a large number of clinical investigations in postoperative patients, the pharmacology of epidural fentanyl, alfentanil, and sufentanil has not been well characterized in a human laboratory setting. In this double-blind, placebo-controlled crossover study, we evaluated analgesia and side effects produced by epidural fentanyl (30 and 100 micrograms), alfentanil (300 and 1,000 micrograms), and sufentanil (3 and 10 micrograms) in volunteers. METHODS: Each of 12 volunteers participated in four separate study sessions. The pain model was cutaneous electrical stimulation of intensity sufficient to produce a pain report of 5 on a 0-5 scale, delivered alternately to the finger and tow. Ventilatory drive, pupil size, and subjective ratings of alertness, nausea, and pruritus were measured using visual analog scales. On each study day, after baseline measurements, an epidural catheter was placed at the L2-L3 or L3-L4 interspace. Subjects received the small dose of study drug, and the tests were repeated at 2, 55, and 95 min after drug administration. Subjects then received the large dose of the same study drug, and the series of tests was repeated at 2, 55, and 95 min later. Plasma opioid concentrations were measured using gas chromatography-mass spectrometry. RESULTS: Dose-dependent analgesia was found for all study opioids. For both doses of all opioids, toe analgesia was significantly greater than finger analgesia. Epidural fentanyl and alfentanil provided greater analgesia than sufentanil at the doses investigated. Sedation, increased end-tidal carbon dioxide, and pupillary constriction occurred only after the large epidural doses of all opioids. Overall, the incidence of subjective side effects was low, but four subjects experienced pruritus after 100 micrograms fentanyl, and four were nauseated after 1,000 micrograms alfentanil. Plasma opioid concentrations were near minimum effective analgesic plasma concentrations only after larger epidural doses. CONCLUSIONS: Lumbar epidural fentanyl, alfentanil, and sufentanil produce selective lower-extremity analgesia. Low plasma opioid concentrations measured after small epidural opioid doses suggest a spinal mechanism for analgesia. Larger doses of epidural opioids result in systemic absorption and are likely to produce supraspinal analgesia and other side effects.

Adult↗
PubMed1994

The antidromic compound action potential of the auditory nerve.

1. The antidromic compound action potential (ACAP) of the auditory nerve was evoked by shocks to the auditory nerve root and recorded at the round window of the cochlea in anesthetized guinea pigs. The goal of this study was to determine the characteristics of the ACAP and compare these characteristics with those of the orthodromic, sound-evoked compound action potential (CAP). 2. The ACAP consists of an initial complex of a positive peak (p1) followed by a negative peak (n1). In contrast, the CAP consists of a negative peak (N1) followed by a positive peak (P1). These differences in waveform are likely due to the differences in conduction direction, antidromic for the ACAP vs. orthodromic for the CAP. 3. After the initial complex, the ACAP has a second complex of peaks (p2, n2) at a latency of approximately 1 ms; this complex is much smaller in amplitude than the initial complex (p1, n1). It is likely that the initial ACAP complex reflects firing of auditory-nerve fibers whereas the second complex reflects firing of neurons further centrally, perhaps in the cochlear nucleus, that are activated by orthodromic firing of auditory-nerve fibers. 4. Experiments with shock pairs are consistent with the idea that for auditory nerve fibers, the absolute refractory period is < 0.5 ms, and the relative refractory period is between 0.5 and at least 5 ms. 5. Experiments with click-shock pairs indicate that a shock interferes with the response to a click when the click and shock are given at about the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Antidromic responses of single units from the spiral ganglion.

1. Antidromic responses of single units in the guinea pig spiral ganglion were recorded in response to shocks to the auditory nerve root. The orthodromic responses of these units were also recorded in response to sound. The aim of this study was 1) to classify units according to their response patterns to shocks and to sound and 2) to propose anatomic types that might correlate with these responses. The four classes of units were as follows: type I, olivocochlear (OC), long-latency: locked, and long-latency: jittering. 2. Type I units responded antidromically to shocks with little jitter and short latency. Their responses to sound were also of short latency and had irregular interspike intervals. Some of these units had complex spike waveforms. These units likely correspond to type I primary afferent neurons, the majority population of spiral ganglion cells. 3. One-third of the OC units responded to shocks, with little jitter and intermediate latency (2 ms). OC unit responses to sound were of long latency and had regular interspike intervals. These units likely correspond to efferent neurons that originate in the superior olivary complex of the brain and end on outer hair cells in the cochlea. 4. Long-latency: locked units responded to shocks with little jitter and long latency (4-11 ms). Many of these units had complex spike waveforms and most did not respond to high-level noise bursts. Long-latency: locked units may correspond to type II spiral ganglion neurons. 5. Long-latency: jittering units responded to shocks with a jitter of several milliseconds and long latency. Some of these units responded to sound in a pattern reminiscent of OC units. These units may constitute a subgroup of OC units that respond to shocks via activation of the reflex pathway from the cochlea to the superior olive and back out to the cochlea. 6. Further data were collected on the type I response to shocks. Antidromic spikes lacked the inflections seen on the waveforms that are typically seen on orthodromic spikes. Type I shock responses depended on shock level and duration and were reduced when a click preceded the shock by approximately 2 ms. Several type I characteristics depended on the rate of spontaneous discharge: for units of low and medium spontaneous rates (when compared with units of high rates), the shock thresholds were lower, shock latencies were longer, and the probability of firing repetitive spikes to a single shock was higher.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Expression of GAP-43 mRNA in mouse spinal cord following unilateral peripheral nerve damage: is there a contralateral effect?

Two new oligonucleotide anti-sense probes and their corresponding sense probes specific for mouse GAP-43 mRNA were synthesized and end-labelled with digoxygenin. They were used to localize GAP-43 mRNA in the spinal cords of normal mice and in mice 3 and 7 days following unilateral sciatic nerve cut. GAP-43 mRNA was found to be expressed at low levels in motor and other neurons of the normal spinal cords. As expected from other studies, up-regulation occurred in the cell bodies of axotomized motor neurons but, in addition, up-regulation was also observed in the cell bodies of intact motor neurons contralateral to the lesion. Densitometer measurements showed that the up-regulation of GAP-43 mRNA was less in the intact, contralateral motor neuron cell bodies than in the axotomized motor neuron cell bodies and furthermore was transient, being higher at 3 days than at 7 days following axotomy. Both anti-sense probes gave the same result, although differences in cellular localization was observed, and the two sense probes were negative. Probe binding was abolished by pretreatment of the sections with ribonuclease and hybridization was carried out under different conditions of stringency in order to ascertain whether the contralateral expression of GAP-43 mRNA was a true reflection of its distribution in vivo. There is conflicting evidence on the presence or absence of contralateral effects following unilateral peripheral nerve injury in the literature, and it is suggested that these differences can be accounted for by the methodology and type of probe used.

Amino Acid Sequence↗
PubMed1993

Fiber pathways and branching patterns of biocytin-labeled olivocochlear neurons in the mouse brainstem.

Olivocochlear neurons have somata in the superior olivary complex in the brainstem and project fibers to the cochlea. The purpose of the present study was to demonstrate the fiber pathways and branching patterns of olivocochlear fibers within the brainstem. Olivocochlear fibers were labeled by extracellular injections of biocytin into the cochlea of mice. The injections labeled two populations of olivocochlear fibers. Thin olivocochlear fibers arose from small somata of the lateral olivocochlear group located ipsilaterally in the lateral superior olive. Thick olivocochlear fibers arose from larger somata of the medial olivocochlear group located bilaterally in the periolivary nuclei. The lateral olivocochlear and medial olivocochlear fibers had similar courses but differed in their branching patterns. Branches from lateral olivocochlear fibers terminated near their somata of origin in the lateral superior olive or in the lateral vestibular nucleus. Branches from medial olivocochlear fibers terminated in the inferior vestibular nucleus or in the cochlear nuclear complex. A few branches from medial olivocochlear fibers projected to the contralateral side. Although they project primarily to the cochlea, olivocochlear neurons also give off branches to a variety of nuclei in the brainstem, thus involving auditory and non-auditory nuclei in the olivocochlear reflex system.

Animals↗
PubMed1993

A gene affecting Wallerian nerve degeneration maps distally on mouse chromosome 4.

When a nerve axon is cut or crushed, the nerve fibers in the distal part of the axon, separated from the cell body, undergo a form of spontaneous degeneration, known as Wallerian degeneration. A substrain of the mouse inbred strain C57BL, known as C57BL/Ola, carries a mutant form of a gene involved in Wallerian degeneration in the peripheral and central nervous systems, and in retrograde degeneration of retinal ganglion cells. Wallerian degeneration in this substrain is abnormally slow. Previously the defect had been shown to be due to an autosomal dominant gene. The locus has been given the name and symbol Wallerian degeneration Wld, with the mutant allele Wlds (Wallerian degeneration-slow). The Wld locus has now been mapped, by using conventional and molecular markers, to the distal end of chromosome 4, near the locus of pronatriodilatin (Pnd). The order of loci (with recombination distances in centimorgans, cM) is cen-D4Mit11-8.9 +/- 1.7 cM-Fuca-2.5 +/- 0.93 cM-Akp-2-3.2 +/- 1.1 cM-D4Mit48-3.5 +/- 1.1 cM-(Wld, Pnd, D4Mit49)-0.71 +/- 0.50 cM-(Eno-1, D4Mit33)-1.4 +/- 0.70 cM-D4Mit42-2.5 +/- 0.93 cM-D4Smh6b. The information on the position of the Wld locus should be valuable in further characterization of this gene involved in nerve degeneration and regeneration.

Animals↗
PubMed1993

Lipopolysaccharide stimulates both nuclear localization of the nuclear factor kappa B 50-kDa subunit and loss of the 105-kDa precursor in RAW264 macrophage-like cells.

Nuclear factor kappa B (NF-kappa B) is an important regulator of gene expression in cells of the immune system. One such gene, tumor necrosis factor, is induced by bacterial lipopolysaccharide (LPS) in macrophages, and this induction has been shown to be mediated in part by NF-kappa B activation in murine macrophages. In this study, immunochemical analysis was used to follow LPS activation of the NF-kappa B 50-kDa subunit in the RAW264 macrophage-like cell line. The recombinant NF-kappa B 50-kDa subunit was used as an immunogen to produce a rabbit antiserum, which was then affinity-purified using a portion of the NF-kappa B 50-kDa subunit that does not have homology to other members of the c-rel gene family. Untreated macrophages had little NF-kappa B in the nucleus as detected by Western immunoblotting. The protein was predominantly localized in the cytoplasmic fraction. Interestingly, NF-kappa B was found as the 50-kDa mature protein and 105-kDa precursor. After LPS treatment, there was a rapid nuclear translocation of NF-kappa B as detected by immunoblot analysis. There was also a rapid decrease in the amount of the cytoplasmic 105-kDa protein. This may indicate that the 105-kDa protein is a reservoir for the 50-kDa protein and that one of the actions of LPS is to increase the rate of 105-kDa precursor processing.

Animals↗
PubMed1993

Vesicular transport of myelin proteolipid and cerebroside sulfates to the myelin membrane.

The possibility that cerebroside sulfates and myelin proteolipid (PLP) could be simultaneously located in transport vesicles destined to be assembled in myelin was investigated in the brain of 20 day old rats. The brain was homogenized and fractionated according to Burkart et al. (J Biol Chem 257:3151-3156, 1982) to obtain a microsomal fraction that was further subfractionated in a linear sucrose density gradient following the procedure of Siegrist et al. (J Neurochem 33:497-504, 1979) to obtain a vesicular fraction which has been shown to transport cerebroside sulfates (Burkart et al., as above). This fraction was associated with acid hydrolase activity and had a lipid composition different from that of myelin and microsomal fractions. Studied by slab gel electrophoresis, dot blot, and Western blot analysis, using a highly specific anti-PLP antibody, it was found to contain myelin PLP. In view of previous findings of several laboratories including our own, the presence of myelin proteolipid in a vesicular fraction which is related to the transport of cerebroside sulfates gives further support to the hypothesis that the delivery of both constituents to the myelin membrane could be associated.

Animals↗
PubMed1993

Do physicians locate as spatial competition models predict? Evidence from Alberta.

This article analyses how physicians choose locations of practice in response to spatial competition forces and considers the implications of such choices for public policy to alleviate shortages of practitioners in rural areas. The predicted geographic distribution of physicians, as determined through spatial competition modelling, was compared with the actual distribution of physicians in 1990 among Alberta's 19 census divisions. Physicians were found to respond to spatial competition forces in choosing where to practise, with the qualification that 1 urban patient had a demand weight equal to 2.32 rural patients. A policy to attract more physicians to rural areas by means of income subsidies is technically feasible but expensive. The high cost means that alternative policies such as a bigger and more effective ambulance network to transport patients to medical centres should become the focus of public policies to improve health care in rural areas.

Alberta↗
PubMed1993

Comprehensive evaluation of left hemisphere type I schizencephaly.

We report the neuropsychological, magnetic resonance imaging, electroencephalographic telemetry, and sodium amytal test findings of a 32-year-old, left-handed man with unilateral left hemisphere type I schizencephaly. The patient was referred for treatment of medically refractory left temporal complex partial seizures that developed at age 26 years. Sodium amytal testing revealed complete incorporation of speech and language function by the right hemisphere. Detailed neuropsychological evaluation indicated average to above-average performance on all measures of language skills, judgment and reasoning, visuospatial abilities, and memory function. This case demonstrates that extensive but lateralized neuronal migration disorders can be associated with complete reorganization and full recovery of function by the contralateral hemisphere. Furthermore, this case supports the view that the degree of recovery is greatest when compensatory mechanisms are activated antenatally.

Adult↗
PubMed1993

Laser-Doppler measurements and electrocochleography during ischemia of the guinea pig cochlea: implications for hearing preservation in acoustic neuroma surgery.

Interruption of cochlear blood flow has been implicated as one of the causes of the sensorineural hearing loss that may occur during acoustic neuroma surgery. With the guinea pig as an animal model for cerebellopontine angle surgery, laser-Doppler measurements were used to estimate the cochlear blood flow changes caused by compression of the eighth nerve complex. With compression, the laser-Doppler measurements decreased abruptly; somewhat later, the electrocochleographic potentials declined. When compression was released, laser-Doppler measurements usually returned immediately, followed later by return of the electrical potentials. Some of these potentials, including the compound action potential of the auditory nerve, often became transiently larger than their precompression values. Interposing bone between the laser-Doppler probe and the otic capsule, so that the total bone thickness approximated the thickness of the human otic capsule, decreased the laser-Doppler measurement, but changes caused by compression were still apparent. Thus, although the human otic capsule is much thicker than the guinea pig capsule, it may still be possible to make laser-Doppler estimates of human cochlear blood flow. Laser-Doppler monitoring during acoustic neuroma surgery may be beneficial, because it could give earlier warning of ischemia than is currently available from electrocochleographic monitoring, thereby enabling earlier corrective action. Electrocochleography complements laser-Doppler measurements by indicating the physiologic state of the cochlea.

Animals↗
PubMed1992

[125I]His-neurokinin A binds selectively to NK2 receptors of the B-type in rat small intestine smooth muscle membranes.

The high-affinity, reversible binding of [125I]His-neurokinin A (NKA) to rat small intestine smooth muscle membranes was investigated. Endogenous neurokinin agonists, selective neurokinin analogues, both agonist and antagonist, were used to define the selectivity of the binding. Both the endogenous and selective neurokinin analogue agonists displayed orders of potency indicating that [125I]His-NKA was binding to NK2 receptors. The use of recently developed NK2-selective antagonists indicated that the NK2 receptors present in this preparation were similar to those described in hamster trachea preparations (NK2B), and not endothelium-denuded rabbit pulmonary artery (NK2A). The absence of NK2A receptors and the predominance of NK2B was confirmed by blocking experiments using MEN10376 and L659877. Low-affinity binding of NKA was also observed with this preparation, which was not sensitive to the NK2-selective agonist, [beta-Ala8]NKA4-10. This was shown not to be due to the presence of NK1 or NK3 receptors by using selective agonists for NK1 and NK3 to block any such receptors. (No evidence for the presence of these receptors was obtained during these blocking experiments.) Guanylylimidodiphosphate appears to discriminate between the high- and low-affinity binding sites for NKA. It was thus concluded that high-affinity binding of [125I]His-NKA to rat small intestine smooth muscle membranes was selective for NK2B receptors. No evidence was found for the binding of [125I]His-NKA to NK1, NK3 or NK2A receptors.

Animals↗
PubMed1992

Transneuronal labeling of cochlear nucleus neurons by HRP-labeled auditory nerve fibers and olivocochlear branches in mice.

Auditory nerve fibers were labeled by extracellular injections of horseradish peroxidase into the spiral ganglion in mice. The labeled fibers were traced in an anterograde direction through the auditory nerve into the cochlear nucleus. In almost half of the injections, the labeled endings of auditory nerve fibers contacted cochlear nucleus neurons that were also labeled with horseradish peroxidase and were presumably transneuronally labeled. Only darkly labeled endings were associated with transneuronally labeled neurons, but not all darkly labeled endings had targets that were transneuronally labeled. Transneuronal labeling occurred almost exclusively in the ventral cochlear nucleus, often between endbulbs and bushy cells. Both "modified" endbulbs and the larger endbulbs of Held transneuronally labeled the bushy cells that they contacted. At the ultrastructural level, transneuronal labeling was evident as a darkening of ribosomes and the membrane surfaces of mitochondria, endoplasmic reticulum, and the nucleus. Transneuronal labeling occurred rarely in octopus, small, and stellate cells, and in neurons of the dorsal cochlear nucleus. Spiral ganglion injections also label olivocochlear fibers, efferent fibers that pass through the ganglion en route to the hair cells. These fibers give off branches to the cochlear nucleus that were rarely associated with transneuronal labeling. In eight instances, the targets of olivocochlear branches were stellate cells or small cells. We suggest that in our mouse preparation, horseradish peroxidase is effective as a transneuronal marker because the short distance from injection site to the cochlear nucleus results in a high concentration of horseradish peroxidase in the endings of the auditory nerve fibers.

Afferent Pathways↗
PubMed1992

Role of macrophages in peripheral nerve degeneration and repair.

A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that the degenerating distal segment is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there.

Animals↗
PubMed1992

Consequences of slow Wallerian degeneration for regenerating motor and sensory axons.

The time course of Wallerian degeneration in the tibial and saphenous nerves was compared in Balb/c mice and mice of the C57BL/Ola strain (Lunn et al., 1989). Axons, particularly myelinated ones, in nerves of C57BL/Ola mice are very slow to degenerate, many still being present 3 weeks after axotomy. Nuclear numbers in the distal stump peak much later and do not reach the levels found in Balb/c mice; debris removal is very slow, and Schwann cell numbers only rise slightly above normal levels in the long term. Regeneration was investigated electrophysiologically and by electron microscopy (EM). Myelinated sensory axons regenerated slowly and incompletely compared with motor ones which were only slightly slowed after nerve crush (although they were significantly hindered after nerve section). Total myelinated axon numbers were still some 20% less than normal even after 200 days in sensory nerves. Even after all axons had degenerated in C57BL/Ola mice, regeneration rates of neither myelinated nor unmyelinated sensory axons reached those achieved in Balb/c mice. It is concluded that while regeneration can eventually proceed slowly when Wallerian degeneration is much delayed, the usual rapid time course of Wallerian degeneration is necessary if axons, particularly sensory ones, are to regenerate at optimal rates and to maximum extent. While local obstruction to axon growth probably impedes the early phase of regeneration in C57BL/Ola mice, it seems possible that a lack of adequate early signals affects regeneration permanently by minimizing the cell body reaction to injury.

Animals↗