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Biomedical subjects

C H Markham

Publications and source records attributed to C H Markham.

119 records · Page 7Linked to original sources

Transplantation of human neuroblastoma cells, catecholaminergic and non-catecholaminergic: effects on rotational behavior in Parkinson's rat model.

Cultured human catecholaminergic and non-catecholaminergic donor cells were used in neural transplantation experiments in a rat model of Parkinson's disease. Using two different human catecholaminergic neuroblastoma cell lines, one control non-catecholaminergic neuroblastoma cell line, and one sham control (tissue culture medium), transplants were made into the striatum using a modified Ungerstedt hemiparkinsonian rat model. Significant decreases in apomorphine-induced rotational behavior were produced by two of three catecholaminergic cell lines. Grafted cells staining positively for tyrosine hydroxylase (TH) and catecholamine fluorescence indicated viable catecholamine activity in the two cell lines which produced reductions in rotational behavior. Catecholamine fluorescence was not detected in either of the two controls. These data suggest a link between catecholamine secretion by transplanted cells and motor improvement using a rat rotational behavior model.

Animals↗

Response of first order vestibular neurons to lidocaine hydrochloride.

Changes in behavior and electrical activity of primary vestibular neurons were observed following injection of lidocaine hydrochloride into the middle ear of cats. After injection the cats exhibited head and ocular nystagmus, head and neck deviation and pupillary changes. Mean preinjection resting discharge rate for first order vestibular neurons was 46.0 spikes/sec. Two hours after lidocaine application the resting rate decreased to a mean of 22.2 spikes/sec and then recovered to 43.0 spikes/sec four hours, and 47.4 spikes/sec six hours after the experimental treatment. The increment sensitivity (increased rate of firing) of horizontal canal neurons to constant angular acceleration for the control period was 2.0 extra spikes/sec/deg/sec2; two hours after the application, 70% of the recorded neurons were unresponsive to angular acceleration or tilt. The sensitivity after four hours was 1.0 spikes/sec/deg/sec2 and 2.1 spikes/sec/deg/sec2 at six hours. The distinct depression of sensitivity by lidocaine at four hours compared to normal mean resting rate at this time suggests these functions may be governed by two modes of action in the receptor or first order afferents.

Animals↗

Semicircular canal structure during postnatal development in cat and guinea pig.

The gain of the vestibulo-ocular reflex in the cat continues to increase for some time after birth. The reason for this increase is not presently known and one possibility if that it occurs because the cat semicircular canals increase in size. The present study examined this possibility by measuring the radii of curvature (R) of individual semicircular canals and the angular relationships of the semicircular canal planes within a labyrinth in cats and guinea pigs during postnatal growth. It was found that the labyrinths do move apart substantially during postnatal development in both species, but neither the planar relations nor the radii of curvature change significantly during postnatal development. The stability of semicircular canal structure during postnatal skull growth indicates that postnatal developmental changes in canal-related function, such as increased gain in the vestibulo-ocular reflex, in these species are probably due to receptor cell or neural maturational factors.

Animals↗

Binocular counterrolling during sustained body tilt in normal humans and in a patient with unilateral vestibular nerve section.

Two normal persons and a patient with unilateral vestibular nerve section were held motionless for ten minutes in the upright position, at 60 degrees tilt right ear down, and at 60 degrees tilt left ear down. In addition, one normal subject was held for ten minutes at each of 30, 60, and 90 degrees tilt left ear down. Photographs were taken of both eyes every ten seconds. Measurements of ocular counterrolling during these trials revealed torsional eye movements in all positions, including the upright, even though the head and body were stationary. Variations in torsion in the upright position ranged up to 2.75 degrees. At the tilt positions, variations ranged up to 4 degrees. Disconjugate movements were seen in all subjects in all positions. There were no significant differences in measurements of ocular counterrolling during static tilt between the normal subjects and the patient with the vestibular nerve section, in contrast to measures obtained during slow velocity dynamic testing.

Adult↗

Neural transplantation of cells expressing the anti-apoptotic gene bcl-2.

Long-term survival of grafted neural cells is a major goal of neural transplantation, but typical survival rates of grafted fetal neurons are in the range of 5-10%. Whether the death of transplanted neural cells is apoptotic or necrotic is unknown. The expression of the proto-oncogene bcl-2 inhibits both apoptotic and necrotic neural cell death. In a 6-OHDA induced rat model of Parkinson's disease, Hoechst 33258 prelabelled conditionally immortalized nigral cells engineered to express bcl-2 were stereotactically transplanted into the striatum ipsilaterally to the lesioned nigrostriatal pathway. Sixteen rats received bcl-2 transfected cells, 15 received cells transfected with vector alone, and 12 received either a nondopaminergic cell line or were sham transplanted as controls. Four wk following transplantation, the rats with grafts containing bcl-2 expressing cells showed an approximately 43% decrease in apomorphine-induced rotational behavior. In contrast, 12% improvement occurred in the rats with transplanted cells transfected with vector alone (p < 0.05), and no improvement occurred in sham-operated animals (p < 0.05). Histological examination showed no tumor formation. Despite the difference in behavioral effect, no clear difference in Hoechst fluorescent staining or staining for TH, GFAP was noted; therefore, it is unknown at present whether the observed effect was due to a difference in survival or to increased efficacy per surviving transplanted neural cell, or both.

Animals↗

Planar relationships of the semicircular canals in man.

Principal-component analyses were determined on a series of points measured from the dissected bony labyrinth of ten human skulls, resulting in planar equations for each of the six semicircular canals. Following this, angles were calculated between the ipsilateral canal planes, between opposite synergistically acting canal planes and between each canal and the Reid stereotaxic planes. Results indicated that pairs of ipsilateral canals were nearly perpendicular, with the excpetion of the angle formed between the anterior and horizontal canal (mean = 111 degrees). Pairs of contralateral synergistic canal planes formed angles of 19 degrees between right and left horizontal canal planes and 23-24 degrees between vertical canal pairs. The horizontal canals formed an angle of 25 degrees with the Reid horizontal plane. Mathematical equations of the semicircular canals were used to predict the optimal head position for rotational and caloric stimulation.

Humans↗

The orientation of the semicircular canals in the guinea pig.

In 10 adult guinea pigs the stereotaxic coordinates of a series of points along each osseous semicircular canal were analysed to yield an equation of that canal plane in stereotaxic space. Angular relationships among the canal planes and between the canal planes and the major stereotaxic planes are presented together with the optimal positions of the head for physiological stimulation of each canal or pair of synergistic canals. The planes of the semicircular canals in each labyrinth are not perpendicular to one another and the planes of contralateral synergistic canals depart from parallelism by about 30 degrees.

Acceleration↗

Binocular counterrolling in humans during dynamic rotation.

Seven subjects 18 to 66 years old underwent 360 degrees rotation at a constant velocity of 3 degrees/sec, in 27 trials beginning randomly right ear down or left ear down. A camera on the rotating chair photographed both eyes every 10 degrees. Dual projectors measured counterrolling, the image from one projector being aligned and rotated until it was superimposed on the image from the other. Right and left eyes were measured independently. The group reached maximum counterrolling at about 70 degrees and 270 degrees in rotations to the right, with values of about -6 degrees and 4 degrees respectively. Rotations to the left reached maximum at 50 degrees and 270 degrees with about 4.5 degrees and -5.25 degrees respectively. Individual subjects showed ranges of counterrolling varying from 4.03 degrees to 17.44 degrees, mean 11.30 degrees. More counterrolling was observed when subjects were tilted to right than to left. The downward eye counterrolled more than the upward. Amount of counterrolling was inversely correlated with age.

Adolescent↗

Modification of single neural elements in vestibular nystagmus by anesthesia.

This study sought to identify, at a single neuron level, the mechanism by which the quick phase of vestibular nystagmus depends on the level of consciousness. The activity of one group of neurons in the reticular formation known to project to abducens motoneurons was recorded together with the activity of the contralateral abducens and medial rectus nerves before, during and after 80% nitrous oxide anesthesia. The anesthetic resulted in a progressive reduction of the bursting activity of these premotor neurons with accompanying changes in the abducens and medial rectus discharges. It is concluded that the quick phase of nystagmus is easily affected by anesthesia because at least one group of reticular formation neurons which have been shown to be important in the production of rapid eye movements is particularly susceptible to the effects of even week anesthetics.

Anesthesia↗

The effect of space missions on gravity-responsive torsional eye movements.

Three astronauts underwent preflight, inflight, and postflight testing of spontaneous ocular torsion and of ocular counterrolling (OCR), reflexes governed by the gravity-responsive otolith organs in the inner ear. One astronaut, A, had a 30-day space mission on Euromir '94 and was examined monocularly with SensoMotoric Instruments video-oculography (VOG). The other two astronauts, B and C, were studied with a binocular VOG and flew an 180-day mission on Euromir '95. In space, spontaneous eye torsion in the upright position was found to be substantially offset from baseline Earth-based recordings in all three subjects for the duration of the flights. In addition, the binocular studies showed a marked torsional disconjugacy. On return to Earth, offset and torsional disconjugacy persisted for many days. OCR in response to 30 degrees right and left tilt was examined preflight and postflight. Compared to preflight, Astronaut A showed reduced OCR immediately postflight, which increased over the next few days. Both Astronauts B and C had increased OCR postflight, which gradually approached but did not achieve the preflight values over 13 days postflight. The adaptation of ocular torsion in space in one astronaut and not in the other two, and slow adaptation postflight, may reflect the lack of visual feed-back and the open loop nature of the otolith-ocular torsion reflex.

Adaptation, Ocular↗