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Biomedical subjects

J T Murphy

Publications and source records attributed to J T Murphy.

At least 73 records · Page 4Linked to original sources

Transcription of a gene for human U1 small nuclear RNA.

Transcription of U1 small nuclear RNA from a 592 bp fragment of human DNA was analyzed in vivo and in vitro. When injected into Xenopus laevis oocyte nuclei, the cloned DNA is transcribed by RNA polymerase II to make human U1 snRNA. Thus the sequences of this fragment are sufficient for expression of the U1 snRNA gene. Moreover, injection of templates carrying deletions of flanking sequences demonstrates that the DNA sequences required for in vivo transcription are located at least 100 nucleotides upstream from the point corresponding to the 5' end of mature U1 snRNA. In vitro transcription in a HeLa cell extract leads to synthesis not of mature U1 snRNA, but of a larger molecule starting 183 nucleotides upstream from the site corresponding to the 5' end of mature U1 snRNA. Transcription from this upstream promoter also is catalyzed by RNA polymerase II, and is comparable in efficiency with the very strong major late promoter of adenovirus 2. We propose that U1 snRNA is synthesized in vivo as a precursor that is processed by an enzyme or enzymes missing from our extracts.

Cloning, Molecular↗

Distribution of responses to visual cues for movement in precentral cortex or awake primates.

Unit recordings were made from areas 4 and 6 monkeys after they were trained to align a cursor over a vertical target line on a video screen by control of a manipulandum with wrist flexion or extension movement. The appearance of the cursor and line on the screen was the visual cue for movement. Responses were observed 150 (+/- 40) msec after cue presentation. The responses were found only in the forelimb area of precentral cortex, which was most immediately involved in the control of the task, and the majority of them were uncorrelated with either the specific details of the visual cue, or with the direction of the subsequent wrist movement.

Animals↗

The role of the basal ganglia in controlling a movement initiated by a visually presented cue.

This study examines the effects on single neurons in caudate nucleus and globus pallidus of a visual stimulus, which is a cue to begin a tracking movement involving the forelimb on the side contralateral to the recording site. The experiments were designed to examine the relationship between activity of single neurons in these structures and movement initiation. Four monkeys were prepared for chronic recording of single neurons. The animals were trained to perform a tracking task that involved flexion and extension of the wrist at the onset of visual cue. The activities of a large proportion of neurons examined were correlated with the task, the proportion being greater in globus pallidus than in caudate nucleus. The majority of correlated neurons were activated after the onset of muscle activity and subsequent movement. It is thus unlikely that these cells were involved in movement initiation. However a role in movement execution is not excluded by the results. The fact that many cells were responsive only to certain specific conditions of the visual cue trial suggests an influence on these cells by highly processed visual information from other brain areas.

Animals↗

The value of aspiration cytology in the evaluation of dysplastic breasts.

Sixteen consecutive patients who had carcinoma of the breast and who had preoperative xeromammography were evaluated and classified according to Wolfe's classification. Five of the patients had correct preoperative evaluation by mammography, and 11 had false negatives. Eight of these were in patients who had Wolfe's classification "DY", suggesting that this is an extremely difficult group to diagnose by mammography alone. The value of aspiration cytology in this group and in all patients having breast masses is discussed. Aspiration cytology as a cellular technique for diagnosing the group with dysplastic breast is strongly recommended.

Adult↗

Sensory-motor processing in the caudate nucleus and globus pallidus: a single-unit study in behaving primates.

Monkeys were prepared for chronic recording of single neurons in the caudate nucleus (Cd) or globus pallidus (GP) during learned wrist flexion-extension movements triggered by visual and somatic sensory inputs. Almost two-thirds of GP cells and more than one-third of Cd cells modified their discharge during these tasks. Three categories of response types were observed. The first was movement related. The second type was event related, in which the cells responded to either the onset or offset of the sensory inputs regardless of the correcting movement direction. A third type combined elements of the first two categories and was termed complex. These cells responded to complex abstractions of the sensory-motor event. A latency analysis indicated that the majority of cells was not involved in initiating movements but may have participated in movement execution. The results of this experiment suggest that during voluntary movement the basal ganglia activity is correlated with motor outputs, sensory inputs, and perceptual abstractions of these sensory-motor events. As such the results are compatible with an influence by diverse regions of cerebral cortex on basal ganglia neurons during the movement control process.

Animals↗

Function of caudate neurons during limb movements in awake primates.

Recordings from single neurons were made in the head of the contralateral caudate nucleus in awake primates during performance of visually and somatically guided hand movements. Populations of cells showed temporal correlation of discharge patterns with visual or somatic disturbances or both. However these discharges occurred about or after the onset of the compensating movement triggered by the disturbances. These findings indicate that the observed cells do not participate in the initiation of these compensating movements, and may instead act as part of an internal feedback loop whose function is unrelated to movement onset.

Animals↗

Differential effects of reciprocal wrist torques on responses of somatotopically identified neurons of precentral cortex in awake primates.

The present study was undertaken to investigate the functional significance of previous observations that both reciprocal and bidirectional responses are found in the forelimb area of precentral cortex following oppositely directed torques delivered about a single forelimb joint. Extracellular unit recordings were made in the contralateral precentral cortex of awake monkeys. These units were classified, according to their responses to passive somatosensory stimulation and to the effects of local intracortical microstimulation (ICMS), as being functionally coupled to single joints. Both joint- and cutaneous-sensitive neurons were included. The responses of such classified neurons to oppositely directed torques were then studied. All of the joint-sensitive wrist (flexion-extension) units responded reciprocally to the oppositely directed torques. In contrast reciprocally and bidirectionally responsive neurons were found in the cutaneous-sensitive wrist population and in both the joint- and cutaneous-sensitive non-wrist (F-E) populations. These results are discussed in terms of the expected receptor actions of the applied torques, and are consistent with other evidence that a correlation exists between activities of precentral neurons which respond to sensory events at or about a single forelimb joint, and voluntary movement about the same joint.

Animals↗

Activity of precentral neurons during torque-triggered hand movements in awake primates.

In monkeys performing a handle-repositioning task involving primarily wrist flexion-extension (F-E) movements after a torque perturbation was delivered to the handle, single units were recorded extracellularly in the contralateral precentral cortex. Precentral neurons were identified by passive somatosensory stimulation, and were classified into five somatotopically organized populations. Based on electromyographic recordings, it was observed that flexors and extensors about the wrist joint were specifically involved in the repositioning of the handle, while many other muscles which act at the wrist and other forelimb joints were involved in the task in a supportive role. In precentral cortex, all neuronal responses observed were temporally correlated to both the sensory stimuli and the motor responses. Visual stimuli, presented simultaneously with torque perturbations, did not affect the early portion of cortical responses to such torque perturbations. In each of the five somatotopically organized neuronal populations, task-related neurons as well as task-unrelated ones were observed. A significantly larger proportion of wrist (F-E) neurons was related to the task, as compared with the other, nonwrist (F-E) populations. The above findings were discussed in the context of a hypothesis for the function of precentral cortex during voluntary limb movement in awake primates. This hypothesis incorporates a relationship between activities of populations of precentral neurons, defined with respect to their responses to peripheral events at or about single joints, and movements about the same joint.

Animals↗

Control of stiffness by the medium latency electromyographic response to limb perturbation.

It is hypothesized that the medium latency electromyographic (EMG) response (ML) to limb perturbation functions to preset limb stiffness to a constant initial level. Three predictions are derived from this hypothesis: Firstly, in the presence of an instruction calling for opposition to limb perturbation, a control signal, ML, will be observed and will lead to the establishment of a constant level of limb stiffness. Secondly, in the absence of an instruction to oppose, no control signal will be observed and correspondingly a constant stiffness will not be generated. Thirdly, the latency of onset of stiffness control will covary with the latency of onset of ML. These predictions were tested in experiments involving perturbation of the human forearm about the elbow joint, with surface EMG measurements and computation of the limb stiffness function. The results are in accord with these predictions, and support the hypothesis that ML functions in the feedforward control of limb stiffness.

Adult↗

Patterns of early and late discharges in somatotopically identified precentral neurons in awake monkeys in response to somatic inputs.

Extracellular recordings were made of single neurons in precentral cortex of awake monkeys. These neurons were somatotopically identified with respect to their responses to inputs from single joints or their somatic surround. Many of these neurons exhibited early (less than 50 ms) and late (greater than 50 ms) discharges in response to flexion or extension torques delivered about the wrist. With the monkey in a mode requiring opposition to the injected torque, all responsive neurons showed a parallel excitatory or inhibitory modification in the early and late discharges. This was true both for cells identified as wrist (flexion-extension) neurons and those identified as nonwrist (flexion-extension) neurons. These findings indicate that the reflex and voluntary components of percentral discharge invariably show a congruent functional response to a torque disturbance, for this particular instruction set.

Action Potentials↗

Withdrawal from long-term high-dose desipramine therapy. Clinical and biological changes.

Investigation was undertaken on a patient whose long-term intake of desipramine hydrochloride was amongst the highest reported. Desipramine treatment instituted at a daily dosage of 75 mg for depressive equivalents of head, chest, and abdominal pain was increased to 1,000 mg daily over a 12-year interval with minimal side effects. Plasma desipramine level dropped immediately on withdrawal, and urinary metabolite values dropped over the subsequent five days. The electrocardiographic abnormalities of first-degree atrioventricular block and incomplete left bundle branch block rapidly disappeared on cessation of medication. Electroencephalographic changes with symmetrical generalized irregular 5- to 7-cps theta activity and 18- to 28-cps beta activity also improved. Longitudinal polygraphic sleep studies showed prolonged rapid eye movement rebound and increased delta sleep coincident with withdrawal. It took ten days after cessation of desipramine for urinary 3-methoxy-4-hydroxyphenylglycol concentration to increase substantially. Although catecholamines are involved in growth hormone (GH) and cortisol regulation, no abnormalities were found in GH or cortisol levels.

Adult↗

The influence of a visual cue on muscle stretch reflexes.

Evidence has recently been presented indicating that muscle stretch reflexes have a large supraspinal component. The finding introduces the possibility that stretch reflex parameters may be modifiable by stimuli involving other modalities besides stretch. In this investigation, the effects of a visual cue on the reflex portions of the EMG activity following a sudden muscle stretch were examined. The results, obtained from the flexor carpi radialis muscles of six normal awake subjects, failed to show any significant change in the EMG parameters as a result of visual cues occurring at the instant of onset of muscle stretch. This was interpreted as indicating that visual inputs do not reach the areas of brain involved in the supraspinal reflex in sufficient time to modify the reflex.

Adult↗

The electromyographic response to sudden stretches of limb muscles in normal human subjects.

The electromyographic (EMG) activity following a sudden stretch applied to wrist flexor or extensor muscles was investigated using a method which enabled the individual records and cumulative results of 30 trials to be observed simultaneously. The results showed that in each case the spinal reflex EMG burst was followed by one or two additional reflex bursts. The second of these latter bursts, when present, occurred in one of two distinct latency ranges. Thus, three distinct latency ranges were observed for reflex bursts following the spinal reflex burst. A possible explanation for these results is that there are three distinct long-loop reflexes, one or two of which may be active following a muscle stretch. The present results do not distinguish whether any or all of these long-loop reflexes are segmental or supraspinal in origin.

Adult↗