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Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

At least 289 records · Page 16Linked to original sources

Protein synthesis in human lymphoblastoid cells (Namalwa) after treatment with butyrate and 5'-bromodeoxyuridine.

The pattern of protein synthesis has been compared in Namalwa cells following treatment with butyrate and 5'-bromodeoxyuridine (BrdUrd). Although these treatments cause a substantial increase in Sendai virus-induced interferon synthesis (up to 300-fold) we observed no comparable effect on the synthesis of other cellular proteins. Using two-dimensional gel electrophoresis we have investigated the proteins synthesised before and 8 h after Sendai virus infection of treated cells. Only 2 of the 300 most abundant cellular proteins were reproducibly affected, these always showed increased rates of synthesis in butyrate-treated cells. The most significant was a 3-4-fold enhancement in synthesis of a 35,000 molecular weight protein which we have called BEP35. On individual occasions treatment caused changes in the rates of synthesis of other proteins, these were not reproducible and involved less than 4% of the proteins investigated. None of the Sendai virus structural proteins or virus-induced cellular proteins were affected by the treatment. We conclude that butyrate and BrdUrd treatments have a relatively specific effect on the synthesis of interferon in Namalwa cells, as the majority of protein synthesis remains unaffected.

Bromodeoxyuridine↗

Sexual agglutination factors from the yeast Pichia amethionina.

Pichia amethionina is a heterothallic yeast isolated from necrotic cactus tissue. Haploid cells of opposite mating type, designated alpha and alpha, agglutinate strongly when mixed. The agglutination factors of the two cell types have been solubilized from the cell walls by beta-glucanase digestion and then partially purified by affinity adsorption to the opposite cell type and by gel filtration. From alpha-cells was obtained a large, heat-stable glycoprotein with the ability to agglutinate alpha-cells. This alpha-agglutinin was inactivated by mercaptoethanol, probably because the recognition sites are linked to the glycoprotein core by disulfide bonds. Digestion of alpha-cells with beta-glucanase released a large heat-labile glycoprotein that did not agglutinate alpha-cells but did inhibit agglutination of alpha-cells by alpha-agglutinin. Subtilisin digestion of this alpha-factor released a carbohydrate-free protein of 27,000 daltons that retained the biological activity of the factor. These agglutination factors are sex- and species-specific and are not found on the surface of heterozygous diploid cells.

Agglutinins↗

Interactions between cutaneous and muscle afferent projections to cerebral cortex in man.

In order to demonstrate interactions between cutaneous and muscle afferent volleys in the ascending somatosensory pathways, different nerves of the lower limb were stimulated together in a conditioning-test paradigm, the changes in the earliest component of the cerebral potential evoked by the test stimulus being taken to indicate such an interaction. It was first confirmed that the cerebral potential evoked by stimulation of the posterior tibial nerve at the ankle is derived from muscle afferents in the mixed nerve and has shorter latencies than the cerebral potential evoked by purely cutaneous volleys in the sural nerve (see Burke et al. 1981). Complete suppression of the cerebral potential evoked by stimulation of muscle or cutaneous afferents was produced by conditioning volleys in a different nerve or in a different fascicle of the same nerve. The major factors determining the degree of suppression were found to be the relative sizes of the conditioning and test volleys and their timing, rather than whether the volleys were of cutaneous or muscular origin. It is concluded that the transmission of cutaneous or muscle afferent volleys to cortex can be profoundly altered in normal subjects by conditioning activity. The possibility that normal background afferent activity can similarly modify afferent transmission has implications for diagnostic studies, particularly when they are performed under non-standard conditions, such as in the operating theatre or intensive care unit. It is also concluded that, although a subject may perceive cutaneous paraesthesiae when the posterior tibial nerve is stimulated at the ankle, there may be no cutaneous component to the evoked cerebral potential.

Adult↗

The relationship between the size of a muscle afferent volley and the cerebral potential it produces.

This study examined the relationship between the size of an afferent neural input produced by electrical stimulation of the posterior tibial nerve at the ankle and the size of the early components of the evoked cerebral potential. For five of six subjects the first peak of the afferent neural volley recorded in the popliteal fossa was uncontaminated by either motor efferents or cutaneous afferents. This was established by measuring the conduction times of motor fibres in the posterior tibial nerve and cutaneous fibres in the sural and posterior tibial nerves over the ankle to popliteal fossa segment. It is likely therefore that the first peak of the afferent volley contained predominantly, if not exclusively, activity in rapidly conducting afferents from the small muscles of the foot. The size of the two earliest components of the cerebral potential did not increase in direct proportion to the size of the afferent volley which produced it. The early components of the cerebral potential reached a maximum when the responsible muscle afferent volley was less than 50% of its maximum.

Adult↗

Thrombin-induced secretion of serotonin from platelets can occur in seconds.

The platelet release reaction was studied by a new quenched-flow approach. Platelets labeled with 14C-serotonin were reacted for short times (up to 5 sec) with thrombin and then quenched with glutaraldehyde or paraformaldehyde. Serotonin secretion began within 1 sec and was nearly complete by 4 sec. Aggregation recorded by a resistive-particle counter was similarly fast. Therefore, the quenched-flow system reveals that serotonin secretion can occur more rapidly than estimated in earlier studies.

Blood Platelets↗

New metabolites in isovaleric acidemia.

Two metabolites, 4-hydroxyisovaleric acid and mesaconic acid, have been identified and quantified in the urine of a patient with isovaleric acidemia. These compounds do not appear to have been reported previously as being components of human metabolism. In addition, large quantities of 3-methylbutyrolactone, the lactone of 4-hydroxyisovaleric acid, were observed in the volatile profile obtained by headspace chromatography. The demonstration of 4-hydroxyisovaleric acid supports the contention that urinary methylsuccinic acid seen in patients with isovaleric acidemia has arisen by omega-oxidation of isovaleric acid. The identification of mesaconic acid may indicate that the methylsuccinic acid formed in these patients is subject to further metabolism.

4-Butyrolactone↗

The irrelevance of fusimotor activity to the Achilles tendon jerk of relaxed humans.

In two normal subjects the sciatic nerve was blocked completely using concentrated lidocaine. The muscle afferent and reflex electromyographic responses to reproducible percussion of the Achilles tendon were recorded while the blocks developed. The intensity of percussion was sufficient to produce an Achilles tendon jerk in one subject when at rest and in the other during reinforcement. The block did not alter the muscle afferent response to tendon percussion in either subject. It is concluded that background fusimotor activity is not a prerequisite for the tendon jerk and that, during complete relaxation, there may be no significant fusimotor drive directed to the triceps surae. The varying ease with which tendon jerks can be elicited in different normal subjects or in different muscles of the same subject appears to be related not to fusimotor activity but to differences in the "central excitability state."

Achilles Tendon↗

Dependence of the Achilles tendon reflex on the excitability of spinal reflex pathways.

Muscle afferent activity from the triceps surae was recorded during experimentally induced alterations in amplitude of the Achilles tendon jerk. No changes in the neural afferent response to tendon percussion or in the background level of neural activity occurred when the reflex response was altered by discomfort, distraction, changes in attention, or changes in the rate of tendon percussion. Reinforcement of the Achilles tendon jerk by forceful contraction of the forearm muscles did not alter the relationship between intensity of the tendon tap and amplitude of the evoked neural afferent volley. Nevertheless, such maneuvers lowered the reflex threshold and raised reflex sensitivity so that a smaller afferent volley was required to produce a tendon jerk, and an increase in the afferent volley produced a disproportionately greater increase in reflex electromyographic activity than would have occurred at rest. Reinforcement maneuvers potentiated the H-reflex but did not alter the electrically induced afferent volley or the background level of neural activity. It is concluded that these changes in reflex responsiveness occurred through intrinsic spinal mechanisms independent of the fusimotor system.

Achilles Tendon↗

Repositioning of fast and slow skeletal muscle.

The origins of the rat fast plantaris and slow soleus muscles were surgically reversed and their fibre types and contractile properties examined in vitro up to 12 weeks post surgery. Muscles in which the origins had been severed and then immediately sutured back in place served as one control group. Unoperated animals served as a second control group. As compared to these groups, no significant differences in the histochemical or mechanical properties of the repositioned muscles were detected. Under the conditions of the experiments, no evidence was obtained to indicate that the intrinsic properties of a muscle could be altered by changing its site of origin and thus its functional environment.

Animals↗

Cerebral potentials evoked by muscle stretch in man.

The cerebral potentials evoked by passive plantar flexion movements of the ankle were recorded by scalp electrodes in normal human subjects. The potential consisted of a biphasic positive wave (P45, P65), a prominent negative wave (N90), and a subsequent positive-negative-positive complex (P120, N145, P190). The components of the potential were of largest amplitude at the vertex, small displacements of the active recording electrode resulting in a marked decrease in amplitudes. The amplitudes of the components were also profoundly affected by changes in the repetition rate of the stimulus and by changes in the acceleration of the stretching movements; they were little affected by changes in the extent or peak velocity of stretch provided that acceleration remained constant. Potentials of similar morphology but of slightly shorter latency could be evoked by percussion of the tendon of tibialis anterior and by electrical simuli delivered through a microelectrode inserted into a pure muscle nerve fascicle of the peroneal nerve innervating one of the pretibial flexor muscles. The results of nerve block experiments (ischaemic/pressure block above the ankle; pressure block and local anaesthetic block of the peroneal nerve at the fibular head) suggest that the afferents responsible for evoking the cerebral potential arose from muscle mechanoreceptors. It is concluded that information about muscle stretch arising from muscle mechanoreceptors (probably muscle spindle endings) reaches the cerebral hemispheres of man at short latency and that the resulting potentials can be readily detected using scalp electrodes.

Adult↗

Rupture of diaphragm associated with spinal cord injury.

A review of 1,007 patients treated a spinal injuries unit revealed 11 instances of rupture of the diaphragm. In five patients it took more than 48 hours before the ruptured diaphragm was diagnosed. The hazards of delay in diagnosis and treatment were highlighted by three instances of gastric perforation--two due to attempted pleural aspiration and one spontaneous. There is a need for the greater use of contrast radiology in the assessment of these patients.

Adult↗

Mechanical properties of tenotomized and denervated-tenotomized muscles.

Mechanical properties of rat soleus and plantaris muscles were studied in vitro following tenotomy, denervation, or tenotomy plus denervation, all of 3 wk duration. Controls included muscles from sham-operated animals and from animals with muscle tendons severed but immediately resutured. Results of twitch times, times to peak tension, and times to half-relaxation for 145 muscles clearly showed that the slight increase in muscle speed that occurs in the soleus muscles only is due to severance of the muscle tendon per se and not related to muscle shortening and possible related alterations in muscle spindle activity that occurs in simple tenotomy. Furthermore, any demonstrable mechanical changes that occur with tenotomy or with section and resuturing of the tendon requires the presence of intact innervation. We conclude that, contrary to published opinion, tenotomy does not transform slow contracting muscles into fast contracting muscles and that comments concerning the role of stretch receptors in this postulated transformation are pure conjecture, unsupported by experimental data.

Animals↗

Component of muscle spindle discharge related to arterial pulse.

1. In human subjects microelectrode recordings were made from 25 muscle spindle afferents from the pretibial muscles. 2. The spike discharges of three endings were locked in time to the arterial pulse. With 17 of the remaining endings, there was a significant pulse-related modulation of discharge rate. For these 20 endings the latency to the onset of the pulse-related influence was 200-310 ms. 3. The time course of the modulation of discharge rate was similar to that of arterial blood flow, as estimated using a Doppler flowmeter. With four endings occlusion of blood flow using a sphygmomanometer cuff reduced any modulation. 4. For five endings the contribution by the arterial modulation to the variance of discharge of the ending was 3-54%. For the population of endings there was no significant relationship between the depth of modulation and coefficient of variation. 5. It is concluded that the arterial pulse can be significant contributor to the variability of muscle spindle discharge. The pulsatile effects seen in the responses of single afferents are unlikely to be eliminated in the summed activity forming the population response. This could constitute a limitation of the information capacity of the population of muscle spindle afferents.

Adult↗

The activity of human muscle spindle endings in normal motor behavior.

In none of the above instances has the fusimotor system been found to be responsible for the described changes in stretch reflex gain. These findings do not prove that the fusimotor system is incapable of altering the gain of the stretch reflex; they do, however, establish that there are quite adequate mechanisms of gain control completely independent of the fusimotor system. One could reasonably question whether the fusimotor system ever operates primarily as a gain-controlling mechanism. That "more in" would probably result in "more out" cannot be disputed, but this may be of little real functional importance when compared with other possible sources of adaptive control of reflex activity. This conclusion has been reached by others in this department, working independently and using a quite different approach (79). Given that there are other adequate mechanisms of controlling reflex gain, one should question whether the fusimotor system plays any primary role in the disorders of stretch reflex gain that characterize spinal shock and cerebellar hypotonia on the one hand, and spasticity and Parkinsonian rigidity on the other hand.

Afferent Pathways↗