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Biomedical subjects

D A Robinson

Publications and source records attributed to D A Robinson.

At least 73 records · Page 4Linked to original sources

Magnetic resonance imaging of the solitary hepatic mass: direct correlation with pathology and computed tomography.

Magnetic resonance images (MRI) of the liver were obtained using a combination of short time inversion recovery (STIR) and spin echo (SE) sequences. These were correlated with comparable tissue slices generated from resected specimens obtained at partial hepatectomy. All 10 cases appeared to have solitary masses on contrast enhanced computed tomography (CT). Histological examination revealed five primary tumours (two hepatocellular carcinomas, two haemangiomas and one cholangiocarcinoma) and five metastatic tumours. The STIR images demonstrated a high signal intensity in all areas of viable tumour involvement and reduced signal intensity in regions of confluent necrosis with superimposed haemorrhage or calcification. This sequence also demonstrated additional areas of high signal intensity adjacent to several lesions which were not visible on CT. Microscopy of these regions in the specimens demonstrated no tumour involvement or steatosis and their precise cause remains obscure. All the lesions demonstrated on the CT images were visible on MRI and no additional lesions were discovered on detailed microscopical examination of the specimens. Delineation of the extent of the cholangiocarcinoma was a problem with both techniques. MRI showed no major advantage over CT except for a higher contrast of the lesion compared with normal liver and also a better delineation of the tumour mass.

Adenoma, Bile Duct↗

Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family.

Two cDNA clones, lambda RHM-MF and lambda RHB-DAR, encoding the muscarinic cholinergic receptor and the beta-adrenergic receptor, respectively, have been isolated from a rat heart cDNA library. The cDNA clones were characterized by restriction mapping and automated DNA sequence analysis utilizing fluorescent dye primers. The rat heart muscarinic receptor consists of 466 amino acids and has a calculated molecular weight of 51,543. The rat heart beta-adrenergic receptor consists of 418 amino acids and has a calculated molecular weight of 46,890. The two cardiac receptors have substantial amino acid homology (27.2% identity, 50.6% with favored substitutions). The rat cardiac beta receptor has 88.0% homology (92.5% with favored substitutions) with the human brain beta receptor and the rat cardiac muscarinic receptor has 94.6% homology (97.6% with favored substitutions) with the porcine cardiac muscarinic receptor. The muscarinic cholinergic and beta-adrenergic receptors appear to be as conserved as hemoglobin and cytochrome c but less conserved than histones and are clearly members of a multigene family. These data support our hypothesis, based upon biochemical and immunological evidence, that suggests considerable structural homology and evolutionary conservation between adrenergic and muscarinic cholinergic receptors. To our knowledge, this is the first report utilizing automated DNA sequence analysis to determine the structure of a gene.

Amino Acid Sequence↗

Loss of the neural integrator of the oculomotor system from brain stem lesions in monkey.

Eye movement were recorded from four juvenile rhesus monkeys (Macaca mulatta) before and after the injection of neurotoxins (kainate or ibotenate) in the region of the medial vestibular and prepositus hypoglossi nuclei, an area hypothesized to be the locus of the neural integrator for horizontal eye movement commands. Eye movements were measured in the head-restrained animal by the magnetic field/eye-coil method. The monkeys were trained to follow visual targets. A chamber implanted over a trephine hole in the skull permitted recordings to be made in the brain stem with metal microelectrodes. The abducens nuclei were located and used as a reference point for subsequent neurotoxin injections through cannulas. The effects of these lesions on fixation, vestibuloocular and optokinetic responses, and smooth pursuit were compared with predicted oculomotor anomalies caused by a loss of the neural integrator. Kainate and ibotenate did not create permanent lesions in this region of the brain stem. All the eye movements returned toward normal over the course of a few days to 2 wk. Histological examination revealed that the cannula tips were mainly located between the vestibular and prepositus hypoglossi nuclei, in their rostral 2 mm, bordered rostrally by the abducens nuclei. Dense gliosis clearly demarcated the cannula tracks, but for most injections there were no surrounding regions of neuronal loss. Thus the eye movement disorders were due to a reversible, not a permanent, lesion. The time constant for the neural integrator was determined from the velocity of the centripetal drift of the eyes just after an eccentric saccade in total darkness. For intact animals this time constant was greater than 20 s. Shortly after bilateral injections of neurotoxin, the time constant began to decrease and reached a minimum of 200 ms; every horizontal saccade was followed by a rapid centripetal drift with a time constant of approximately 200 ms. For vertical eye movements, in this acute phase, the time constant was approximately 2.5 s. The vestibuloocular reflex (VOR) was drastically changed by the lesions. A step of constant head velocity in total darkness evoked a step change in eye position rather than in velocity. In the absence of the neural integrator, the step velocity command from the canal afferents was not integrated to produce a ramp of eye position (normal slow phases); rather this signal was relayed directly to the motoneurons and caused a step in eye position. The per- and postrotatory decay of the head velocity signal was decreased to 5-6 s indicating that vestibular velocity storage was also impaired.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Motion of the eye immediately after a saccade.

Dynamic overshoot is a small saccade that follows a main saccade, in the opposite direction, with no delay. To re-examine prior reports of dynamic overshoot, the properties of dynamic over-shoot were studied in six normal subjects. The post-saccadic drift of eye movements was studied as well. Horizontal eye movements were recorded with the magnetic-field/search-coil method. System noise level was 0.05 deg. Dynamic overshoot occurred with a frequency of about 13% and was more frequent for saccades 10 deg or less. Its mean size was 0.15 deg and its peak velocity showed it to be saccadic in nature. Binocular recordings for three subjects showed that when dynamic overshoot occurred it was almost always in the abducting eye which also had the least post-saccadic drift. The abducting eye seldom had dynamic overshoot and consistently had a more pronounced post-saccadic drift, almost always in the onward direction. We suggest that, at the end of a saccade, the eye normally is brought to rest by a braking pulse and dynamic overshoot occurs when the braking pulse is accidentally too large. It would appear to serve no useful purpose. Why dynamic overshoot is monocular and coincides with the eye having less post-saccadic drift is unclear.

Biomechanical Phenomena↗

A model of the smooth pursuit eye movement system.

Human, horizontal, smooth-pursuit eye movements were recorded by the search coil method in response to Rashbass step-ramp stimuli of 5 to 30 deg/s. Eye velocity records were analyzed by measuring features such as the time, velocity and acceleration of the point of peak acceleration, the time and velocity of the peaks and troughs of ringing and steady-state velocity. These values were averaged and mean responses reconstructed. Three normal subjects were studied and their responses averaged. All showed a peak acceleration-velocity saturation. All had ringing frequencies near 3.8 Hz and the mean steady-state gain was 0.95. It is argued that a single, linear forward path with any transfer function G(s) and a 100 ms delay (latency) cannot simultaneously simulate the initial rise of acceleration and ring at 3.8 Hz based on a Bode analysis. Also such a simple negative feedback model cannot have a steady-state gain greater than 1.0; a situation that occurs frequently experimentally. L.R. Young's model, which employs internal positive feedback to eliminate the built-in unity negative feedback, was felt necessary to resolve this problem and a modification of that model is proposed which simulates the data base. Acceleration saturation is achieved by borrowing the idea of the local feedback model for saccades so that one nonlinearity can account for the acceleration-velocity saturation: the main sequence for pursuit. Motor plasticity or motor learning, recently demonstrated for pursuit, is also incorporated and simulated. It was noticed that the offset of pursuit did not show the ringing seen in the onset so this was quantified in one subject. Offset velocity could be characterized by a single exponential with a time constant of about 90 ms. This observation suggests that fixation is not pursuit at zero velocity and that the pursuit system is turned on when needed and off during fixation.

Eye Movements↗

The systems approach to the oculomotor system.

Recent progress in understanding the oculomotor system is briefly reviewed. This progress is largely due to technological advances such as the ability to record from neurons in behaving animals. Furthermore, parts of the oculomotor system are now well-enough understood that the techniques of exact science, such as quantitation and mathematical description, are becoming useful. This, in turn, leads to the use of the language of systems analysis, and the vestibulo-ocular reflex is examined as an example of such a description. Systems analysis not only organizes current knowledge but leads to predictions by way of hypotheses known as models. A model of time integration by neurons is given as an example. It is put forward to illustrate that our biggest problem at the moment is an inability to test such models at the neuronal network level.

Animals↗

Saccadic undershoot is not inevitable: saccades can be accurate.

Saccades normally take the eye 90% of the way to a target, followed by a 10% corrective saccade. An exception to this rule occurs with the range effect. When targets appear in a set of positions, saccades overshoot the near positions and undershoot the far. This phenomenon, previously reported, was confirmed with more accurate methods. The range effect increases if a visual discrimination task is added. It is established rapidly in only a few trials. Latencies of corrective saccades from overshoots and undershoots were the same. Centripetal saccades were more accurate than centrifugal. Thus, undershooting is not inevitable.

Eye Movements↗

The vestibulo-ocular reflex during human saccadic eye movements.

Eye and head movements were recorded in normal humans during rapid refixations with the head still (saccades) or moving (gaze saccades) to determine if the vestibulo-ocular reflex was operating at such times. Subjects made self-electrooculogram for large saccades and with the eyecoil/magnetic field method for smaller movements. The putative function of the vestibulo-ocular reflex during a gaze saccade is to adjust the movement of the eye for the movement of the head by adding the saccadic command and the vestibular signal. This action, referred to here as linear summation, would maintain gaze-saccade accuracy by making gaze velocity (eye in space) independent of head velocity. It would also preserve the duration of the eye saccades of about 200 deg. When a subject increased his head velocity voluntarily, for example, from 420 to 805 deg/s, mean gaze velocity rose from 540 to 820 deg/s and duration dropped from 380 to 250 ms. Linear summation did not occur. By means of a yoke clenched in the teeth, the subject's head could be momentarily and unexpectedly slowed by collision of the yoke with a lead weight during a 180 deg gaze saccade. The perturbation decreased head velocity by about 150-200 deg/s, decreased gaze velocity by about the same amount and did not change eye velocity (in the head); another indication that the vestibulo-ocular reflex was not working. Nevertheless, gaze-saccade duration was automatically increased so that the over-all accuracy of the movement was not changed. Subjects made saccades between targets at +/- 20 deg without attempted head movements. Simultaneously the experimenter struck the yoke, clenched in the subject's teeth, with a rubber hammer. The hammer blow caused a transient head velocity of about 70 deg/s. Gaze velocity transiently rose or fell, depending on the direction of the blow, by similar amounts and a quantitative analysis suggested that the vestibulo-ocular reflex was essentially absent. Again, duration was automatically altered so that saccade accuracy was not changed. Subjects looked back and forth between targets 20, 40 and 60 deg apart as their head turned through the straight ahead position, actively or passively, at velocities up to 600 deg/s (active) or 300 deg/s (passive).(ABSTRACT TRUNCATED AT 400 WORDS)

Eye Movements↗

Hysteresis and slow drift in abducens unit activity.

Two trained monkeys made saccadic eye movements to a small visual target. The activity of 39 isolated abducens units, presumed to be motoneurons or abducens internuclear neurons, was recorded in relation to these eye movements. After a calibration trial, a test trial repeatedly elicited 20 degrees horizontal saccades to primary position from either the left or right. On average, the steady-state firing rate at primary position depended on the direction of the saccade. For saccades where the neuron showed a burst in activity during the saccade (on-saccades) the steady-state firing rates were usually higher than for those saccades that showed a pause in activity during the saccade (off-saccades). For the population of units this hysteresis measured 5.4 spikes/s, which may be compared with an average primary-position rate of 97 spikes/s. The average hysteresis for individual units ranged from -2.1 to 18.5 spikes/s. The steady-state firing rate after equal saccades in the same direction and ending at the same position (primary) varied slowly over time. Across all units the variability (standard deviation) ranged from 0.5 to 11.8 spikes/s with a mean of 4.7 spikes/s. Furthermore, for any one unit the variations following on-saccades generally correlated with the variations following the off-saccades. Hysteresis, doubted by many, does exist. Fortunately, it is small enough, 5.5% of typical primary-position rate, that it can be neglected for many purposes. Nevertheless, it poses the interesting theoretical question of how the oculomotor system compensates for hysteresis. The simplest explanation of slow variations in background rate is cocontractive noise: a slow fluctuation in all abducens neurons so that these variations do not result in fluctuations of eye position.

Abducens Nerve↗

Effects of electrical stimulation and reversible lesions of the olivocerebellar pathway on Purkinje cell activity in the flocculus of the cat.

The activity of Purkinje cells (P-cells) in the flocculus of 8 lightly anesthetized cats and one alert cat was recorded for periods of up to several hours each. The resting simple spike (SS) rate in the anesthetized cats was 37 +/- 21 Hz (mean +/- standard deviation), similar to that observed in the alert cat. Complex spikes (CSs) were evoked by an electrode placed in the climbing fiber (CF) decussation or inferior olive (IO). For each P-cell, SS activity was suppressed completely at or above a cut-off frequency of evoked CSs; median cut-off rate was 5 Hz (range 1-10 Hz, 15 cells). Reversible lesions of the CF pathway were made by microinjection of 1-10 microliter of saturated lidocaine into the IO or CF decussation. This abolished spontaneous CS activity and produced two reversible effects on SS discharge: (1) an increase in mean SS rate of 98%, from 23 +/- 13 to 40 +/- 18 Hz (11 cells); and (2) a decrease of 50% in the variability of SS firing rate. Similar effects were observed in two P-cells whose CF axons were lesioned mechanically. These results show that electrical stimulation and reversible lesions in areas previously shown to alter the gain of the vestibulo-ocular reflex (VOR) also alter CF input to the flocculus, suggesting that the gain changes were caused by changes in CS rate. This study confirms and extends the observation that a reciprocal relationship exists between CS rate and SS background rate, and therefore further suggests that the changes in the gain of the VOR might be due to changes in SS background rate.

Animals↗

An improved neural-network model for the neural integrator of the oculomotor system: more realistic neuron behavior.

The discharge rates of premotor, brain-stem neurons that create eye movements modulate in relation to eye velocity yet firing rates of extraocular motoneurons contain both eye-position and eye-velocity signals. The eye-position signal is derived from the eye-velocity command by means of a neural network which functions as a temporal integrator. We have previously proposed a network of lateral-inhibitory neurons that is capable of performing the required integration. That analysis centered on the temporal aspects of the signal processing for a limited class of idealized inputs. All of its cells were identical and carried only the integrated signal. Recordings in the brain stem, however, show that neurons in the region of the neural integrator have a variety of background firing rates, all carry some eye-velocity signal as well as the eye-position signal, and carry the former with different strengths depending on the type of eye movement being made. It was necessary to see if the proposed model could be modified to make its neurons more realistic. By modifying the spatial distribution of afferents to the network, we demonstrate that the same basic model functions properly in spite of afferents with nonuniform background firing rates. To introduce the eye-velocity signal a double-layer network, consisting of inhibitory and excitatory cells, was necessary. By presenting the velocity input to only local regions of this network it was shown that all cells in the network still carried the integrated signal and that its cells could carry different eye-velocity signals for different types of eye movements. Thus, this model stimulates quantitatively and qualitatively, the behavior of neurons seen in the region of the neural integrator.

Brain Stem↗

Bielschowsky head-tilt test--II. Quantitative mechanics of the Bielschowsky head-tilt test.

In ten recent cases of superior oblique (SO) palsy the involved eye elevated by 8.2 +/- 3.8 deg (standard deviation) on 45 deg ipsilateral head tilt. A computer model predicted a rise to only 4.1 deg but could easily achieve 8.2 deg by including reactions in the other cyclovertical muscles, notably on overaction of the superior rectus (SR). In 17 older cases the elevation on tilt rose to an average of 15 deg. The model shows that these deviations must be due to SR overaction. The analysis suggests that SR overaction is the main cause of the rapid increase in eye elevation in recent cases and further increases in older cases.

Eye Movements↗

The upper limit of human smooth pursuit velocity.

The maximum smooth pursuit eye velocity was determined in five human subjects. Eye movements were recorded with the d.c.-coupled EOG. On each trial the target moved in a ramp, at a constant velocity between 10 and 200 deg/sec. In four subjects eye velocity was approximately 90% of target velocity up to a target velocity of 100 deg/sec. Eye velocity then saturated with a large variability from trial to trial (standard deviation 16 deg/sec). The fifth subject had eye velocities only 60% of these values.

Adult↗