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Biomedical subjects

D L Morgan

Publications and source records attributed to D L Morgan.

At least 181 records · Page 10Linked to original sources

Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells.

Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with 51Cr were exposed to the following antitumor drugs alone or with O3: carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K3 (Vit K). Release of 51Cr (cell injury) was greater for F-cells than WRC-cells with any single treatment. Pretreatment with any drug (400 microM), except for Vit K with WRC-cells, did not significantly increase O3-induced loss of 51Cr. Co-exposure of F-cells to drugs and O3 resulted in a marked potentiation of O3-induced injury with Vit K, and an inhibition with Dox.

Animals↗

A quantitative model of intersarcomere dynamics during fixed-end contractions of single frog muscle fibers.

A numerical model of a muscle fiber as 400 sarcomeres, identical except for their initial lengths, was used to simulate fixed-end tetanic contractions of frog single fibers at sarcomere lengths above the optimum. The sarcomeres were represented by a lumped model, constructed from the passive and active sarcomere length-tension curves, the force-velocity curve, and the observed active elasticity of a single frog muscle fiber. An intersarcomere force was included to prevent large disparities in lengths of neighboring sarcomeres. The model duplicated the fast rise, slow creep rise, peak, and slow decline of tension seen in tetanic contractions of stretched living fibers. Decreasing the initial non-uniformity of sarcomere length reduced the rate of rise of tension during the creep phase, but did not decrease the peak tension reached. Limitations of the model, and other processes that might contribute to the shape of the fixed end tetanic tension record are discussed. Taking account of model and experimental results, it is concluded that the distinctive features of the tension records of fixed end tetanic contraction at lengths beyond optimum can be explained by internal motion within the fiber.

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Role of in vitro factors in ozone toxicity for cultured rat lung fibroblasts.

Ozone toxicity for cultured rat lung fibroblasts was concentration dependent and was affected by the manner in which ozone was delivered to the cells, i.e. cultures were either rotated with a thin moving overlay of medium or were stationary with a fixed layer of medium between the cells and the gas phase. The influence of culture medium components and culture dish composition on the toxicity of ozone were also investigated. Cell viability, used to measure ozone toxicity, was quantified by the chromium-51 release assay, and by a viability index calculated from the percentage of cells stained with a vital dye combined with the decrease in cell number as determined by DNA measurements. During stationary ozone exposure, toxicity appeared to be mediated primarily by hydrogen peroxide and could be inhibited by catalase or fetal bovine serum when measured by the viability index. During rotated exposure, catalase and fetal bovine serum provided no protection when measured by the viability index, however, when measured by the chromium-51 release assay, fetal bovine serum was partially protective. The effect of ozone on the fibroblasts was not influenced by whether culture dishes were glass or plastic, or whether the culture medium was balanced salt solution or complete chemically-defined medium.

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Variation of muscle stiffness with tension during tension transients and constant velocity shortening in the frog.

1. The length changes of a central segment of a frog muscle fibre were measured during and after a quick shortening was applied to the end of the fibre, by attaching two markers an using a spot follower apparatus. In this way it was shown that the stiffness of tetanized single frog fibres as mounted in our apparatus was located predominantly in the sarcomeres, and that the ends were comparatively stiff. 2. The stiffness of tetanized frog single fibres at 0 degrees was measured by applying a small 4 kHz sinusoidal length change, and measuring the resultant tension change. This was done during the first few milliseconds after a quick release, and while the fibre was shortening at constant velocity. 3. The stiffness during the fast tension transient after a quick release was always less than the stiffness before release, supporting the idea that the fast recovery is not due to attachment of extra cross-bridges. 4. The stiffness during the steady shortening was always less than when isometric. A line fitted to this stiffness-tension plot, when extended, intercepted the stiffness axis at less than half the isometric value. 5. The slope of the stiffness-force plot during the fast tension transient was consistently and significantly less than the slope of the stiffness-force plot during steady shortening, further supporting the conclusion that only a small part of the decrease seen during shortening could be due to non-linear end compliance. 6. Possible ways of reconciling these results with recent reports of X-ray diffraction suggesting little if any change in the position of myosin heads during steady shortening are discussed.

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Tension, stiffness, unloaded shortening speed and potentiation of frog muscle fibres at sarcomere lengths below optimum.

1. Unloaded shortening velocity, stiffness, and the effects of potentiators were studied to understand the basis for the shallow ascending limb (1.65-2.0 micrometers sarcomere length) of the sarcomere length-tension diagram of from single fibres. 2. The velocity of externally unloaded shortening was found to be constant over most of the range. It is therefore unlikely that this part of the sarcomere length-tension diagram results from an internal force opposing shortening. 3. Stiffness was found not to vary in proportion with tension between sarcomere lengths 1.65 and 2.0 micrometers, nor to be constant between 2.0 and 2.2 micrometers, where tension is constant. By assuming a small filament compliance, the observations could be adequately modelled on the hypothesis that the variation in tension in the range of sarcomere lengths 1.65-20 micrometers was caused by variations in the number of attached cross-bridges. 4. The twitch potentiators Zn2+, tetraethylammonium (TEA), nitrate and caffeine were found not to change the shape of the sarcomere length-tension diagram. Potentiation in a tetanus was less than 3% in all experiments. 5. Contractures induced by raised [K+] in the bathing solution were found to produce more tension than a tetanus beyond optimum length, insignificantly different tension near optimum length, and less tension at sarcomere lengths near 1.7 micrometer. An explanation is proposed for these results in terms of inhomogeneous activation and internal motion. 6. It is concluded that there is no evidence from this work that a tetanized fibre is other than maximally activated over the range of sarcomere lengths spanned by the shallow ascending limb.

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Myocyte growth without physiological impairment in gradually induced rat cardiac hypertrophy.

A surgical technique was developed to place sutures around the pulmonary arteries of young rats (about 1 month old and 100 g body weight). As the operated rats grew, the pulmonary arteries were gradually constricted, leading after 4-6 weeks to the development of severe right ventricular hypertrophy with free wall weights about twice those from control rats. There were no signs of heart failure or cardiac decompensation. Collagen concentrations were the same in operated and control rats. Myocytes were isolated from right ventricles by enzymatic digestion. Autoradiographic studies showed considerable uptake in non-myocyte nuclei. Myocyte sarcomere lengths were unchanged. However, myocyte lengths and areas increased sufficiently to account for the increase in free wall weights observed. Physiological studies were done on isolated papillary muscles and ventricular strands, which were subsequently fixed. The force-generating capability at optimum length, magnitude of active compliance, and maximum speed of shortening (using four different techniques) were measured in each isolated muscle. There were no significant changes observed between operated and control rats. Microscopic examination of the muscle cross-sections confirmed that average myocyte area in the muscles obtained from operated rats was significantly increased. The results show that it is possible to obtain considerable increases in average myocyte size (by about a factor of 2) while still maintaining normal physiological function.

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Derivation of reliable electromyograms and their relation to tension in mammalian skeletal muscles during synchronous stimulation.

There exists a good correlation between the measured electrical activities and isometric twitch tension in the cat soleus muscle during synchronous stimulation. For an unbiased sampling of electrical activities by averaging a number of electromyograms over the muscle concerned, a relation of the form E = 0.98T + 5.35 has been established. It is hoped that this relation will prove valuable in clinical application where EMGs are used. Electrode types for EMG pick-up differ in terms of the signal recorded due to the difference in the spatial and temporal addition of individual motor unit firing and the constructional difference of the electrodes. Fine wire pairs are the best for linearity and ease of application. Whe surface electrodes are used because of their non-invasive nature, care must be exercised to established the exact relation between EMG and tension. EMG recordings from different sites within a muscle show considerable variation. A more reliable measure can be obtained by external averaging of multiple pairs of electrodes.

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Intersarcomere dynamics during fixed-end tetanic contractions of frog muscle fibres.

1. The stability of sarcomere lengths along single twitch fibres from frog muscles was examined during fixed-end tetani, using a spot follower apparatus to monitor the length of a central segment. 2. Internal movement, with most of the fibre lengthening and small regions at the ends shortening as the contraction proceeded, was always seen at fibre lengths beyond those corresponding to a sarcomere length of 2.3 micrometer. 3. The rate of lengthening of the central region was fastest during the slow phase of tension rise (creep) but continued at a slower rate throughout the tetanus. These observations are in accord with the idea that progressive development of sarcomere non-uniformity is responsible for the creep phase. 4. Observations at various muscle lengths of the rate of decay of tension and the duration of the slow phase of relaxation suggest that movement during relaxation is due to sarcomere length non-uniformities and variations of decay rate with sarcomere length. 5. The rate of tension fall after stimulation ceases in an isometric sarcomere, and the factors which determine that rate, are discussed in view of evidence from fixed-end and length-clamped tetani, and recently reported experiments using aequorin.

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The effect on tension of non-uniform distribution of length changes applied to frog muscle fibres.

1. The stability of sarcomere lengths along single frog twitch fibres was examined, during lengthening and shortening, using a spot follower appparatus to monitor or control the length of a central segment. 2. During active shortening from sarcomere lengths beyond 2.2 micrometer the end sarcomeres shortened dramatically, while much of the fibre did not shorten at all. It is proposed that this is the cause of the tension failing to recover, after the shortening ceased, to the value of isometric tension at the shorter length. 3. During active lenghtening from sarcomere lengths beyond 2.2 micrometer, non-uniformity of stretch was seen, with the middle stretching more than the ends. Some maintained extra tension after stretch above that appropriate to the longer length was found, as were consistent changes in internal movement, and in the shape of the tension record during relaxation. 4. Measurements of stiffness during and after a lengthening suggest that no increased activation is involved. Observation of internal movement during the raised tension after a lengthening contradicts theories involving 'locked on' bridges. 5. From these and other observations, an explanation for the extra tension in terms of non-uniformity of sarcomeres is proposed. The explanation is in accord with that previously suggested for the creep phase of tension rise seen at these lengths.

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The stiffness of amphibian slow and twitch muscle during high speed stretches.

Experiments were carried out to compare the stiffness of cross-bridges in amphibian slow and twitch muscle. An isolated iliofibularis muscle was subjected to rapid, small stretches during contraction of either slow or twitch fibres at a number of different isometric tensions. The method of analysis allowed the compliance of the cross-bridges to be distinguished from other sources of compliance. Provided that the muscle was stretched sufficinetly rapidly to obtain limiting values of stiffness, little difference was found between the mechanical properties of the cross-bridges in slow and twitch muscle. It is concluded that the difference in observed stiffness of the two muscle types is due to a lower turnover rate of cross-bridges and a smaller number of sarcomeres in slow fibres.

Animals↗

Measurements of muscle stiffness and the mechanism of elastic storage of energy in hopping kangaroos.

1. A kangaroo hopping above a certain speed appears to consume less oxygen than a quadrupedal mammal, of similar weight, running at the same speed (Dawson & Taylor, 1973). This is thought to be achieved by storage of elastic energy in tendons and ligaments. 2. Energy can be stored in a tendon by stretching it, but only if the muscle fibres in series with it are stiff enough to resist most of the length change. We have measured length and tension changes in the contracting gastrocnemius muscle of the wallaby Thylogale during rapid, controlled stretches, and from this determined the amount of movement in muscle fibres and tendon (method of Morgan, 1977). 3. When the muscle was developing close to its maximum isometric tension, up to eight times as much movement occurred in the tendon as in the muscle fibres. This is made possible by the wallaby having a long and compliant tendon. 4. Measurement of work absorption by the muscle with a full length of free tendon and when the tendon had been shortened, showed that with the shortened tendon a larger proportion of movement occurred in the muscle fibres, producing a steep rise in work absorption by the muscle and a consequent increase in energy loss.

Animals↗

Left heart myxomas.

Separate left ventricular and left atrial myxomas were detected with echocardiography in an asymptomatic young adult with a systolic murmur. Successful surgical removal of both tumors was performed without complications. The value of echocardiography in evaluating heart murmurs of uncertain origin is demonstrated by this unique case.

Adult↗

Intra-ocular pressure during retrobulbar injection.

It was found that the use of retrobulbar injections can cause quite large transient rises in intra-ocular pressure which can be significantly reduced by using local anaesthetic in the injected saline, and by injecting in small steps, typically 0.2 to 0.3 mls/kg body weight at 1 minute intervals for a total of not more than ten steps. After a moderate retrobulbar injection, the intra-ocular pressure was found to return to near normal in a few minutes, but with some decrease in anterior chamber volume.

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Separation of active and passive components of short-range stiffness of muscle.

The short-range stiffness of smoothly but submaximally contracting isometric soleus muscles of anesthetised cats was measured by applying small fast stretches. The ratio of isometric tension to stiffness was plotted against tension over a wide range of muscle lengths and stimulus rates. The results fitted a straight line well, as predicted from crossbridge theory, showing the stiffness to be a function of tension only, independent of the combination of length and stimulus rate used to generate the tension. The major deviation from this line was attributed to incomplete fusion at low frequencies of stimulation. Values believed to be tendon compliance and crossbridge tension per unit of stiffness were found from the graph, and the tendon compliance correlated with the maximum muscle tension. Shortening the tendon by attaching nearer to the muscle changed the results in a manner consistent with the theory, provided that appropriate precautions were taken against slippage.

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