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Biomedical subjects

C H Markham

Publications and source records attributed to C H Markham.

At least 55 records · Page 3Linked to original sources
PubMed1987

Immunohistochemical localization of monoamine oxidase-B in the cat brain: clues to understanding N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity.

The immunohistochemical localization of monoamine oxidase-B in normal cat brain was examined. The enzyme was localized in both neural and nonneural elements of the cat brain. Neurons in the hypothalamus (lateral, dorsal, ventromedial, dorsomedial, and supraoptic nuclei), raphe system, dorsal tegmental nucleus, locus ceruleus, Kölliker-Fuse nucleus, dorsal parabrachial region, and central tegmental field were positive. No substantia nigra pars compacta, retrorubral, or ventral tegmental neurons stained positively. Glial cells (astrocytes) stained positively for monoamine oxidase-B in many regions of the central nervous system, however, there was a significantly greater number of monoamine oxidase-B-positive glial cells in the substantia nigra pars compacta than in other adjacent dopaminergic regions. Because nigra compacta neurons are specifically damaged by the neurotoxin MPTP and because the toxicity of the drug is expressed only in the presence of monoamine oxidase-B, it is possible that the preferential loss of substantia nigra pars compacta neurons in the cat brain may be related to the regional and cellular localization of monoamine oxidase-B.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Modification of vestibular-induced pause neuron firing during anesthesia and light sleep.

Anatomic and electrophysiologic evidence suggests there is a vestibular input to eye movement-related pause neurons in the midline of the pontine reticular formation of the cat. The present investigation sought to explore the functional significance of this vestibular drive by examining pause neuron response to horizontal rotational stimulation as cats were anesthetized with halothane or went into natural light sleep. Anesthesia unmasks the vestibular input to pause neurons in that during anesthesia, pause neurons continue to fire but their firing rate is modulated by vestibular stimulation. The particular response patterns of pause neurons to anesthesia are not uniform. We suggest that the results observed could be explained if pause neurons received input from both vestibular nuclei, either directly or possibly via the prepositus hypoglossi.

Abducens Nerve↗
PubMed1987

Vestibular control of muscular tone and posture.

The vestibulospinal system helps to maintain upright posture and head stability. The semicircular canals and their short latency connections to the neck motoneurons, largely via the medial vestibulospinal tract, respond to angular accelerations so as to stabilize the head in space. The paired otolith organs, the utricles placed approximately horizontally, and the saccules vertically, respond to linear acceleration including gravity. Their influence leads, via the lateral vestibulospinal tract, to excitation of ipsilateral extensor motoneurons of the limbs and trunk, and to inhibition of reciprocal flexor motoneurons. Linear displacement of the otoliths leads to bracing of the limbs and body so as to maintain upright posture, and to extend the limbs so as to help in landing after sudden falls.

Humans↗
PubMed1987

Parkinson's disease: sensory and motor problems in arms and hands.

Fifteen undemented patients with Parkinson's disease (PD) and 15 age-matched controls were given a battery of tests to assess sensorimotor integration in the arms. PD patients made more errors (p less than 0.01) than controls, particularly in tests of proprioception. Age was not related to errors. Compared with controls, two-point discrimination thresholds were significantly higher (p less than 0.02) on the index finger of PD patients, but not on the forearm. Results confirm the sensorimotor deficits found earlier in an orofacial study, and imply that PD involves a generalized dysfunction of sensorimotor integration and proprioception, probably a result of impaired basal ganglia function in processing and integrating sensory input to organize and guide movement.

Aged↗
PubMed1986

Neurotoxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the cat. Tyrosine hydroxylase immunohistochemistry.

N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces substantia nigra pars compacta (SNc) cell death in several species including the mouse, dog and monkey. MPTP is presently shown to cause apparent nigral cell death in the SNc of the cat as noted by a long-lasting decrease in tyrosine-hydroxylase (TH)-like cell staining. A transient loss of TH-like staining is also observed in the ventral tegmental area, locus coeruleus and retrorubral area. These latter areas appear normal 1.5-5.0 months after MPTP administration. The caudate nucleus (CD) showed a greater TH depletion than the nucleus accumbens (ACC) and only recovered slightly over time. After 7 days of MPTP, an apparent axonopathy, characterized by lightly staining fibers with large TH-positive varicosities, is seen in the CD and to a lesser extent, in the ACC. These findings demonstrate that MPTP is toxic to the cat's nigrostriatal dopaminergic system and suggests that the cat is a good intermediate species in which to study the responses of dopaminergic neurons to MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Deficits in orofacial sensorimotor function in Parkinson's disease.

Orofacial sensorimotor function was assessed in patients with Parkinson's disease and in age-matched controls. Tests were designed to assess sensory function, motor abilities, and the integration of sensory information for the performance of specific movements. Patients with Parkinson's disease and normal subjects both made more errors with increasing age; however, overall, patients with Parkinson's disease made significantly more errors in our tests than did normal subjects. Interestingly, patients with Parkinson's disease showed greater deficits in tests of sensory function and sensorimotor integration than in tests of motor function. These results suggest that one aspect of Parkinson's disease consists of complex deficits in the utilization of specific sensory inputs to organize and guide movements. The results are further discussed in relation to a proposed sensory gating or filtering schema of basal ganglia motor functioning.

Aged↗
PubMed1986

Long-term follow-up of early dopa treatment in Parkinson's disease.

A group of 19 patients with Parkinson's disease, who began dopa therapy 1 to 3 years after onset of symptoms, were followed for 12 years. They were evaluated every 3 to 4 months on the UCLA disability scale and the Hoehn and Yahr functional classification scale. This present group was compared to two other historical groups reported on earlier [8], one that began treatment with dopa 4 to 6 years after onset of symptoms and the other that began dopa treatment 7 to 9 years after onset of symptoms. Results on both scales showed that the mean disability scores of the three groups did not differ significantly when duration of disease was matched, even though duration of dopa therapy among the groups varied from 1 to 12 years. The highly significant differences between the groups prior to dopa treatment continued throughout the study. These longitudinal data support the conclusion that the worsening over time is the result of progression of Parkinson's disease and not a result of the duration of dopa treatment. Early treatment improves the beginning years of the disease and has no adverse effect on later years. Twelve years after beginning dopa therapy, 32% of the present group had died at a mean age of 76.0, in contrast to 50% (mean age, 74.7) and 57% (mean age, 71.5) in the groups who began dopa increasingly later in the course of their disease. Incidence of dementia increased with disease duration regardless of treatment duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Dementia↗
PubMed1986

Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): behavior, histology, and biochemistry.

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a potent dopaminergic neurotoxin, was administered to cats systemically for 5 to 7 days. This treatment produced a behavioral syndrome characterized by akinesia, ataxia, bradykinesia, and feeding difficulties, lasting for several weeks. During this period of severe behavioral impairment, caudate and nucleus accumbens dopamine and norepinephrine concentrations were quite depleted. Behavioral recovery ensued over the next several weeks as did some recovery of striatal catecholamines. MPTP destroyed the majority of substantia nigra pars compacta neurons while affecting a much lesser number of locus ceruleus and ventral tegmental neurons. These results demonstrated for the first time that MPTP can cause long-lasting deficits in nigrostriatal functioning in the cat and may provide a means for studying the apparently selective neurotoxic effects of MPTP as well as for understanding the pathophysiology of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Direct projection of type II vestibular neurons to eye movement-related pause neurons in the cat pontine reticular formation.

Brain stem pause neurons play an important role in the regulation of rapid eye movements. However, the input sources that drive pause neurons are uncertain. In the present study, horizontal canal type II neurons in the medial vestibular nucleus were antidromically activated by electrical stimulation of the pause neuron region. Systematic microstimulation tracks within that region showed an antidromic activation pattern of low-threshold sites separated by high-threshold sites consistent with axonal branching of type II neurons in the pause neuron region. Spike-triggered averaging of single spontaneously firing type II vestibular neuronal discharges in the pause neuron region resulted in short-latency, positive field responses. These results supported the conclusion that horizontal canal type II neurons of the medial vestibular nucleus project to and inhibit pause neurons monosynaptically.

Animals↗
PubMed1986

Synaptic connections of horizontal canal mediated ascending Deiters tract axons on medial rectus motoneurons in cat.

This study demonstrates the termination of ascending tract of Deiters' (ATD) axons on ipsilateral medial rectus (MR) motoneurons. Horseradish peroxidase (HRP) was iontophoretically injected into ATD axons which were recorded in the MR motoneuron pool of the oculomotor nucleus. MR motoneuron cell bodies were identified by retrograde transport of HRP injected into MR muscles in the orbit. ATD axons were identified by Type I responses to horizontal rotation, monosynaptic responses on stimulation of the ipsilateral labyrinth, and no response on contralateral labyrinth or contralateral abducens nucleus or on ipsilateral MR nerve stimulation. Light microscopic examination showed the main stem axons to be lateral to the medial longitudinal fasciculus, and terminal boutons were in contact with ipsilateral identified MR motoneurons (Furuya and Markham: Exp. Brain Res. 43: 289-303, 1981). Light microscopy and semi-thin sections showed boutons of ATD in contact with identified MR motoneuron cell bodies and proximal dendrites. The electron micrographs (EM) showed the HRP-injected ATD axons have synapses on MR motoneurons. ATD boutons made axosomatic and axodendritic synapses on MR motoneurons. The boutons contained numerous spheroidal synaptic vesicles. Several examples showed clear asymmetrical post-synaptic membrane specialization. This confirms the synaptic connection between horizontal canal activated elements in the ATD and MR motoneurons.

Abducens Nerve↗
PubMed1985

Planar relationships of the semicircular canals in rhesus and squirrel monkeys.

The technique of principal-component analysis was used to define anatomically the semicircular canal planes of the rhesus and squirrel monkeys with respect to the stereotaxic coordinate system. The analyses were performed on a series of points obtained from the dissected osseous labyrinths. A planar equation was defined for each canal plane in the stereotaxic coordinate system and angles were calculated between the 3 ipsilateral canal planes, between synergistic canal pairs and between each canal plane and the stereotaxic planes. The data from both species are similar: the ipsilateral canal planes are nearly orthogonal; synergistic pairs of canal planes are approximately parallel with angles of 2 degrees-12 degrees between pairs in the rhesus monkey and 13 degrees-16 degrees between pairs in the squirrel monkey. The horizontal canal planes form angles of 22 degrees and 18 degrees with the horizontal stereotaxic plane in the rhesus and squirrel monkeys, respectively. A head position of 15 degrees (pitch nose-down) was calculated to produce an optimal head position in both species for maximally stimulating the horizontal canals and minimally stimulating the vertical canals during horizontal angular acceleration. The radii of curvature (R) of the horizontal, anterior and posterior canals were also measured for both species using a calibrated reticle. These measurements indicate that the anterior canal of both species has the largest radius of curvature. This anatomical information is discussed in relation to the available physiological data.

Animals↗
PubMed1985

Double-blind trial of pergolide for Parkinson's disease.

Pergolide mesylate, a dopamine agonist, was studied as adjunctive therapy in a 6-month double-blind trial in 20 patients with Parkinson's disease who were achieving less than optimal response from Sinemet. As pergolide or placebo was administered in increasing dosage, Sinemet was reduced if side effects developed. Both the pergolide and placebo groups improved significantly (p less than 0.05). The pergolide group improved 30% at the end of 24 weeks, and the placebo group 23%. There was no significant difference between drug and placebo groups, possibly due to a fortuitous support group and the side effects that may have burdened the pergolide group. Nevertheless, pergolide had a definite antiparkinsonian effect.

Aged↗
PubMed1985

Local cerebral glucose utilization in symptomatic and presymptomatic Huntington's disease.

Patterns of local cerebral glucose utilization were measured with positron emission CT using the 18F-fluorodeoxyglucose method in 13 patients with HD, 15 subjects at risk for HD, and control subjects. These data were compared with CT measures of cerebral atrophy, age, and duration and severity of symptoms. The results indicate that in HD there is a characteristic decrease in glucose utilization in the caudate and putamen and that this local hypometabolism appears early and precedes bulk tissue loss. In contrast to demented patients with Alzheimer's disease or Parkinson's disease, in these HD patients glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite apparent shrinkage of brain tissue. Our results indicate that the caudate is hypometabolic in some asymptomatic persons who are carriers of the autosomal-dominant gene for HD.

Adolescent↗
PubMed1984

Patterns of cerebral glucose utilization in Parkinson's disease and Huntington's disease.

Patterns of local cerebral glucose utilization were measured with positron emission tomography using the fluorine-18-labeled fluorodeoxyglucose (18FDG) method in 8 patients with Parkinson's disease, in 13 patients with Huntington's disease, in 15 subjects at risk for Huntington's disease, and in aged-matched normal control subjects. On the average, global cerebral metabolism in patients with Parkinson's disease was moderately reduced (20%), but the relative distribution of glucose utilization throughout the brain in these patients was normal. These results support the conclusion that alterations of the nigrostriatal pathway in Parkinson's disease have no major selective effect on the metabolism of particular cerebral regions. In Huntington's disease, however, there was a characteristic decrease in glucose utilization in the caudate nuclei and putamen, and this local hypometabolism appeared early and preceded bulk tissue loss. In patients with Huntington's disease, glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite the apparent shrinkage of brain tissue. The results also suggest the possibility that the caudate nuclei may be hypometabolic in some asymptomatic subjects who are potential carriers of the autosomal dominant gene for Huntington's disease.

Adolescent↗
PubMed1984

Neural correlates of compensation after hemilabyrinthectomy.

Vestibular brain stem neurons responsive to angular acceleration in the plane of the horizontal canal were examined in cats 30 to 52 days after contralateral labyrinthectomy and compared with similar units in cats with intact labyrinths and in other cats immediately after transection of the contralateral eighth nerve. In the compensated state, the mean spontaneous firing rate of type I neurons was 24 spikes/s, in contrast to the mean of 45/s observed immediately after contralateral labyrinthectomy. In intact cats, mean firing rate was 19 spikes/s. Sensitivity, as measured in spikes/s/deg/s2, was significantly lower immediately after labyrinthectomy than in intact controls and remained so in compensated cats. On the other hand, time constants and the ratio of adapting:nonadapting units was unchanged. Ablation of the midline cerebellum including vermis and fastigial nuclei did not materially affect these results. We concluded that (i) the main defects in static posture and nystagmus in the uncompensated state were due to the striking difference in resting firing rates between the ipsi- and contralateral vestibular nuclei; (ii) compensation in the static posture was the result of a tendency to equalize the resting firing rates in the two vestibular nuclei; and (iii) recovery in the dynamic, head-turning situation was due to partial recovery of sensitivity on the ipsilateral side, bringing it to the relatively constant, unchanging depressed sensitivity on the contralateral side.

Acceleration↗
PubMed1984

Projections to eye movement-related pause neuron region in cat using HRP.

The origins of the afferent connections to the eye movement-related pause neurons in cats were examined using retrograde transport of horseradish peroxidase with wheat germ agglutinin. The major input sources to the pause neuron region were nucleus prepositus hypoglossi, medial vestibular nucleus, gigantocellular reticular nucleus, parvocellular reticular nucleus, nucleus reticularis tegmentis pontis, nucleus reticularis pontis caudalis, nucleus reticularis pontis oralis, and superior colliculus. Less heavily labeled sources included the lateral and descending vestibular nuclei, the locus ceruleus, and the dorsal raphe.

Animals↗