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Biomedical subjects

D Burke

Publications and source records attributed to D Burke.

At least 307 records · Page 17Linked to original sources

Simultaneous high-performance liquid chromatographic determination of chlordiazepoxide and amitriptyline hydrochloride in two-component tablet formulations.

A rapid, precise, and accurate high-performance liquid chromatographic procedure is presented for the stimultaneous determination of amitriptyline hydrochloride and chlordiazepoxide in two-component tablet formulations. The impurities and decomposition products of both components were separated, making the determination specific for amitriptyline hydrochloride and chlordiazepoxide. The method was used for the assay, content uniformity, and dissolution testing of dosage forms containing 5--30 mg of chlordiazepoxide and 12.5--75 mg of amitriptyline.

Amitriptyline↗

Cell-cell recognition in yeast: purification of Hansenula wingei 21-cell sexual agglutination factor and comparison of the factors from three genera.

Trypsin digestion of Hansenula wingei 21-cells releases a protein (21-factor-T) that inhibits the agglutination of 21-cells by purified 5-agglutinin obtained from 5-cells by subtilisin digestion [Crandall, M. A. & Brock, T. D. (1968) Bacteriol. Rev. 32, 139-163]. We have purified this inhibitor 415-fold by ion-exchange chromatography, affinity adsorption to 5-cells, and gel permeation chromatography. The material shows a diffuse band, on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, with an apparent M(r) of 27,000. It has a pI of 3.8, is rich in acidic amino acids, contains 5% mannose and a trace of glucosamine, and is stable to reducing agents but is inactivated by heat. Zymolyase (beta1-->3-glucanase) digestion of 21-cells releases a similar inhibitor that, after purification, has a larger size than 21-factor-T. This 21-factor-Z appears to contain an additional portion that may serve to anchor 21-factor in the cell wall. Haploid cells of the yeasts Pichia amethionina and Saccharomyces kluyveri also show a constitutive sexual agglutination, and little or no crossreactivity is observed in heterologous mixtures. The agglutination factors in all three genera, however, have parallel properties; one cell type of each pair is heat stable and is inactivated by reducing agents (H. wingei 5-cells, P. amethionina alpha-cells, and S. kluyveri 16-cells), and the other is heat labile and is unaffected by reducing agents H. wingei 21-cells, P. amethionina a-cells, and S. kluyveri 17-cells). Because S. kluyveri 16-cells respond to Saccharomyces cerevisiae alpha-factor with the typical morphogenetic change of a mating half-reaction, the heat-stable agglutinin appears related to the S. cerevisiae a mating type and the heat-labile factor to the S. cerevisiae alpha mating type.

Ascomycota↗

Induced changes in the thresholds for voluntary activation of human spindle endings.

1. Recordings were made from forty-two muscle spindle afferents from the pre-tibial muscles of human subjects. For each afferent, the contraction level at which its discharge accelerated (its 'threshold for activation') was defined using isometric voluntary contractions of the receptor-bearing muscle. The effects on these thresholds of various manoeuvres designed to activate descending pathways or segmental sensory inputs were studied to determine whether the balance between the skeletomotor and fusimotor drives to the contracting muscle could be altered. 2. The Jendrassik reinforcement manoeuvre raised the threshold for voluntary activation of one spindle ending slightly but had no significant effect with seven other endings. It is concluded that the Jendrassik manoeuvre does not excite fusimotor neurons selectively or even preferentially. 3. Caloric vestibular stimulation altered the thresholds for voluntary activation of eight of eleven spindle endings, the most common effect being lowering of the threshold during the irrigation and for 1--1 . 5 min after its cessation. 4. Cutaneous stimulation by vibration lowered the thresholds for voluntary activation of some spindle endings when applied to the dorsum of the foot, and raised thresholds when applied to the lateral plantar surface. 5. Passive stretch of the receptor-bearing muscle by plantar flexion of the ankle and passive stretch of synergistic muscles in isolation raised thresholds for spindle activation; passive stretch or vibration of triceps surae lowered thresholds. 6. These studies suggest that the relationship between the skeletomotor and fusimotor drives to a muscle during a voluntary contraction is not rigidly fixed, but can be varied appropriately with the changing motor role demanded of the muscle by supraspinal drives and with the changes in sensory feed-back generated by the movement itself. 7. It is concluded that, provided the skeletomotor effects of a stimulus are known, changes in the threshold for spindle activation in a voluntary contraction can provide a means of determining the effects of that stimulus on fusimotor neurons even when the stimulus alone is not adequate to alter fusimotor drive.

Ankle Joint↗

Anticipation and fusimotor activity in preparation for a voluntary contraction.

1. Multi-unit and single-unit recordings were made of muscle spindle afferent activity from the pretibial muscles of human subjects who were initially relaxed. The muscles were subjected to a stretching perturbation of 1 s duration, occurring irregularly, on average once every 5 s. In test sequences, an auditory or visual warning was provided 1 . 06 s before some of the perturbations. Subjects were required to oppose every perturbation by contracting the receptor-bearing muscle as rapidly as possible. 2. Following the warning all subjects sometimes tensed the receptor-bearing muscle unintentionally in preparation for the perturbation. In these contractions, the discharge of a spindle ending accelerated only if the contraction strength exceeded the ending's threshold for activation, established in control voluntary contractions performed under isometric conditions. 3. When the receptor-bearing muscle did not contract in the interval between warning and perturbation, there was no detectable change in the multi-unit recordings of spindle activity or in recordings from twelve of thirteen single spindle afferents. The thirteenth spindle afferent discharged prior to the perturbation in the absence of detectable e.m.g. in response to (only) three of twenty-three warning stimuli. However, this ending had been so responsive during isometric voluntary contractions that a contraction level at which it did not respond could not be established, and it is suggested that the findings with this ending resulted from its low threshold rather than from selective activation of the fusimotor system. 4. When subjects were warned of the perturbations, the dynamic response of spindle endings to the perturbations was not increased in size or altered in latency. 5. The motor response to perturbations without warning generally contained only long-latency (volitional) e.m.g. activity occurring 107--200 ms after the onset of the perturbation. When a warning was given, short-latency (reflex) e.m.g. activity was also recorded, beginning 46--76 ms after the onset of the perturbation. 6. It is concluded that anticipation of the need to contract a muscle does not result in selective activation of fusimotor neurones in preparation for the contraction. The change in stretch reflex gain that occurs as a result of 'anticipation' occurs through a central process which does not involve the fusimotor system.

Acoustic Stimulation↗

Hyperexcitability of motor and sensory neurons in neuromyotonia.

Two members of a family with a neuropathy resembling Charcot-Marie-Tooth disease were unable to relax their muscles after voluntary contraction. Muscle spasm often outlasted voluntary contraction by 30 seconds or more before subsiding into myokymia and fasciculations. The posture of the hand during muscle spasm resembled that of tetany, and Trousseau's and Chvostek's signs were present although no abnormality of calcium or magnesium metabolism could be demonstrated. Muscle spasms ceased during medication with carbamazepine, 600 mg daily. Nerve stimulation, electromyography, and regional neuromuscular blockade with curare indicated that the condition originated in peripheral nerve, while microneurographic recordings showed that sensory as well as motor fibers were hyperexcitable. Sural nerve biopsy revealed axonal degeneration involving myelinated and unmyelinated fibers. It was concluded that the neural hyperexcitability is caused by a membrane defect resulting in a low threshold for excitation throughout the length of the axon.

Adult↗

Voluntary activation of spindle endings in human muscles temporarily paralysed by nerve pressure.

1. In normal human subjects, the afferent activity from muscle spindle endings in the pretibial muscles was recorded while a pressure block was applied to the peroneal nerve proximally in the popliteal fossa. 2. In five of ten blocks, spindle activity increased in attempted isometric voluntary contractions when the receptor-bearing muscles were completely paralysed. In the remaining five blocks, voluntary effort still increased spindle activity when maximum voluntary power was reduced by more than 90%, but the ability to activate spindles voluntarily was lost with or slightly before block of the last motor units. When the ability to activate spindle endings in an attempted voluntary contraction was lost sympathetic efferent fibres remained unblocked. 3. It is concluded that the fusimotor effects seen during a voluntary contraction are mediated by myelinated fibres of small calibre which probably innervate intrafusal structures exclusively (gamma fusimotor fibres). There is no necessity to postulate that skeleto-fusimotor (beta) fibres are responsible for the tight 'alpha-gamma co-activation' seen in man during voluntary contractions.

Humans↗

The regularity of muscle spindle discharge in man.

1. The variability of discharge of thirty-nine muscle spindle afferents from the pretibial muscles of normal human subjects was determined for spike train sequences recorded with the ankle joint fixed in 25 degrees plantar flexion, during further stretch and during graded voluntary contractions of the receptor-bearing muscle. 2. In non-contracting muscles with the ankle joint in 25 degrees plantar flexion, a sustained discharge was maintained by twenty-four of the thirty-nine endings. The mean discharge frequency for the active endings was 11.1 Hz (range 4.8--22.1 Hz), the mean coefficient of variation 0.073 (range 0.021--0.183). With further stretch, the discharge of endings maintaining frequencies below 10--12 Hz became more regular. For endings maintaining higher frequencies, changes in the coefficient of variation were small and occurred in either direction. All secondary endings maintained a highly regular discharge, but, at these frequencies, there was no statistically significant difference in the variability of primary and secondary endings. 3. It is considered that these findings are comparable to those of Matthews & Stein (1969) for de-efferented feline spindle endings, and support the view that there is no functionally effective background fusimotor drive to non-contracting muscles of normal human subjects. 4. A voluntary contraction sufficient to accelerate a spindle ending invariably decreased the regularity of its afferent discharge. During voluntary contractions, coefficients of variation up to 0.345 were recorded. However, coefficients as low as 0.1 were not uncommon, and thus the absence of fusimotor drive cannot necessarily be inferred from a regular afferent discharge pattern. 5. With contractions of different strength, the increase in the coefficient of variation did not parallel the increase in discharge frequency. It is concluded that not all fusimotor influences acting on a spindle ending are translated into variability, and that measurements of the variability of discharge do not accurately reflect the level of fusimotor drive. 6. The discharge frequency of some spindle endings decreased slightly in some contractions and this was accompanied by an increase in the variability of discharge. It is suggested that contracting extrafusal muscle fibres can modulate the discharge pattern of spindle endings and contribute to the variability of discharge during a voluntary contraction. 7. In contracting muscles the irregular fusimotor-driven spindle discharge contained a 'hidden' periodicity, but this was not as extensive as has been reported for the cat. No such periodicity could be demonstrated for spindle endings in non-contracting human muscles.

Action Potentials↗

Carbohydrate structure of Sindbis virus glycoprotein E2 from virus grown in hamster and chicken cells.

Sindbis virus was used as a probe to examine glycosylation processes in two different species of cultured cells. Parallel studies were carried out analyzing the carbohydrate added to Sindbis glycoprotein E2 when the virus was grown in chicken embryo cells and BHK cells. The Pronase glycopeptides of Sindbis glycoprotein E2 were purified by a combination of ion-exchange and gel filtration chromatography. Four glycopeptides were resolved, ranging in molecular weight from 1,800 to 2,700. Structures are proposed for each of the four glycopeptides, based on data obtained by quantitative composition analyses, methylation analyses, and degradation of the glycopeptides using purified exo- and endoglycosidases. The largest three glycopeptides (S1, S2, and S3) have similar structures but differ in the extent of sialylation. All three contain N-acetylglucosamine, mannose, galactose, and fucose, in a structure similar to oligosaccharides found on other glycoproteins. Glycopeptide S1 has two residues of sialic acid, whereas glycopeptides S2 and S3 contain 1 and 0 residues of sialic acid, respectively. The smallest glycopeptide, S4, contains only N-acetyglucosamine and mannose, and is also similar to mannose-rich oligosaccharides found on other glycoproteins. Each of the complex glycopeptides (S1, S2, or S3) from virus grown in BHK cells is indistinguishable from the corresponding glycopeptides derived from virus grown in chicken cells. Glycopeptide S4 is also very similar in size, composition, and sugar linkages from virus derived from the two hosts. These results suggest that chicken cells and BHK cells have similar glycosylation mechanisms and glycosylate Sindbis glycoprotein E2 in nearly identical ways.

Amino Acids↗

Management of extremity with combined neurovascular and musculoskeletal trauma.

Twenty-five civilians with combined neurovascular and musculo-skeletal trauma to 27 extremities were studied retrospectively. The mechanism of injury was crushing in 16, avulstion in six, and penetrating in three. Autogenous saphenous vein was used to restore arterial circulation in the majority. Nine patients had concurrent repair of venous injuries. Fractures were immobilized by a variety of techniques, the Hoffman external skeletal fixation being preferred. Immediate fasciotomy was performed in five patients and delayed fasciotomy in four. All patients had soft-tissue debridement and initial wound closure with split-skin grafts as biologic dressings. Three immediate amputations were the result of irreversible neurovascular and soft-tissue trauma. Sepsis played a role in three late amputations; delayed primary treatment,, irreversible neurologic injuries and extensive soft-tissue damage contributed. A carefully individualized multidisciplinary approach resulted in salvage of 20 of 27 severely injured extremities.

Adolescent↗

Muscle spindle responses in man to changes in load during accurate position maintenance.

1. Single unit and multi-unit recordings of muscle spindle activity were made from the peroneal nerves of human subjects. While the subjects attempted to maintain a constant ankle joint position, an external load on the receptor-bearing muscle was altered unexpectedly. 2. The spindle discharge produced by a sudden increase in load was of similar strength when the receptor-bearing muscle was relaxed as when it was contracting at the moment of the impact. A motor response at a latency consistent with a spinal reflex mechanism occurred only when the muscle was contracting. It is concluded that the potentiation of the reflex mechanism during contraction was not due primarily to a fusimotor action. 3. Sudden decrease in load produced a pause in spindle discharge followed by a pause in on-going e.m.g. activity at a latency consistent with spinal reflex mechanisms. 4. Slow changes in load produced parallel changes in e.m.g. and spindle discharge. It is suggested that the voluntary effort involved in maintaining joint position in the face of gradually changing loads results in corticospinal activity adjusted in strength to the opposing torque and operating on alpha and gamma motoneurones in parallel.

Action Potentials↗

Muscle spindle activity in man during shortening and lengthening contractions.

1. The responses of forty-one muscle spindle endings, mostly in tibialis anterior, were studied in human subjects during voluntary movements of the ankle joint performed at various speeds against different external loads. 2. During slow shortening contractions, the discharge rates of spindle endings in the contracting muscle accelerated after the appearance of the first e.m.g. potentials but before sufficient force had been generated to move the limb. With some endings, the discharge rate decreased during the shortening movement while the e.m.g. activity was increasing, but it always remained higher than before the onset of contraction. If the speed of the movement was increased fewer spindle discharges were seen during muscle shortening. If the shortening contraction was opposed by an external load, so that greater effort was required to perform the same movement, more discharges were seen and the discharge pattern became less modulated by the change in muscle length. 3. These findings indicate that during shortening contractions the fusimotor system is activated together with the skeletomotor system. However, the fusimotor drive is generally insufficient to maintain a significant spindle discharge unless movement is slow or the muscle is shortening against an external load. 4. During lengthening contractions the spindle responses were greater than to passive stretch of similar amplitude and velocity, suggesting heightened fusimotor outflow. 5. During shortening and lengthening contractions small iregularities in the speed of movement occurred commonly. Unintended acceleration of a shortening movement caused a pause in spindle firing, and unintended acceleration of a lengthening movement caused an increased discharge from spindle endings. These spindle responses were associated with corresponding alterations in the discharge pattern of the voluntarily activated motor units at latencies consistent with the operation of spinal reflex mechanisms. 6. It is suggested that a functional role for the fusimotor activation during slow shortening contractions is to provide spindle endings with a background discharge so that they can detect irregularities in the movement and initiate the appropriate reflex correction.

Action Potentials↗

Recruitment order of human spindle endings in isometric voluntary contractions.

1. The responses of twenty-two spindle endings in the anterior tibial and toe extensor muscles of human subjects were studied during isometric voluntary contractions of the receptor-bearing muscle with the ankle joint fixed in 25 degrees plantar flexion.2. The discharge of eighteen endings accelerated in voluntary contractions when the contraction strength exceeded a threshold level which differed for different endings but was reproducible for the same ending.3. With contractions of slow onset the latency to spindle acceleration varied with the speed of onset of the contraction. Endings with a background discharge were often unloaded by contractions until the contraction strength exceeded the threshold for activation of the ending.4. No correlation was found between the sensitivity of a spindle to external length changes and its ease of activation in a voluntary contraction. For two spindle endings with a background discharge there was no change in either discharge frequency or the regularity of spindle discharge during contractions which were below the threshold for activation of the endings. It is concluded that the threshold for activation of a spindle ending in an isometric voluntary contraction is determined by its fusimotor innervation, and that fusimotor neurones probably have a recruitment order, much as do skeletomotor neurones.5. Once activated, the discharge of spindle endings fluctuated with changes in skeletomotor activity but the relationship for some endings contained non-linearities. Such non-linearities were not as apparent in multi-unit recordings from a number of spindle endings in the contracting muscle. It is concluded that the fusimotor drive to a muscle is proportional to the skeletomotor drive to the muscle, and that skeletomotor and fusimotor neurones are subjected to similar if not identical descending command signals. From the work of Evarts (1968), it seems likely that these command signals are related more to desired muscle force than to desired muscle length.

Action Potentials↗

Coagulation and complement studies in Rocky Mountain spotted fever.

A patient with laboratory-acquired Rocky Mountain spotted fever (RMSF) and concomitant influenza virus infection was studied from the third day of clinical illness. The course of his illness was marked by petechial rash, thrombocytopenia, and elevation of fibrin split products. No evidence of complement activation was observed. Plasma proteins were elevated in a pattern characteristic of the "acute phase reaction." The patient recovered completely, and vascular collapse or clinically important disseminated intravascular coagulation had developed. In febrile patients who had influenza or a clinically similar noninfluenzal respiratory syndrome, no changes in coagulation, complement, or plasma proteins developed. We conclude that aberrations in the patient's laboratory values reflected RMSF, and that complement played no critical role in his illness.

Blood Coagulation↗

Comparison of the carbohydrate of Sinbis virus glycoproteins with the carbohydrate of host glycoproteins.

The carbohydrate portions of the Sindbis virus glycoproteins were compared with the carbohydrate portions of cell surface glycoproteins from uninfected host cells. Comparisons of the size of glycopeptides were made using gel filtrations. Comparisons of sugar linkages were made by methylation analysis. The conclusion was that the Sindbis carbohydrate is similar to a portion of the host carbohydrate. Thus, the Sindbis carbohydrate structures appear to be structures normally made in the uninfected host cell, but which are added to the Sindbis glycoproteins in virus-infected cells.

Animals↗