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Biomedical subjects

R M Simmons

Publications and source records attributed to R M Simmons.

At least 55 records · Page 3Linked to original sources
PubMed1984

Control of sarcomere length in skinned muscle fibres of Rana temporaria during mechanical transients.

A new technique is described for high-speed measurement of striation spacing of single skinned muscle fibres. A galvanometer mirror directs helium-neon laser light on to the muscle fibre at a variable angle. Light diffracted by the cross-striations is collected by a position-sensitive photodetector. The incident angle necessary to centre the diffracted light beam on to the photodetector is related to sarcomere length. The instrument was tested by comparison with measurements obtained with a compound microscope. Discrepancies of several nanometers per half sarcomere were observed between these two methods. When the incident angle of the laser beam was varied sinusoidally about its mean position the magnitude of the discrepancy was reduced. During steady passive shortening of the muscle fibres the output of the diffraction instrument often displayed pauses and brief periods of rapid shortening. These irregularities were eliminated by averaging the sarcomere length output over a range of illumination angles by oscillating the incident angle of the laser beam. The results suggest that at the spatial resolution of several nanometers per half sarcomere, volume diffraction effects can cause the apparent sarcomere length measured from the angle of coherent light diffraction to differ from the mean striation spacing. With incident-angle oscillation the time and spatial resolution of the equipment were satisfactory for the sarcomere length signal to be fed back to a length controller for a 'sarcomere length clamp'. In active contractions, stiffness was closely related to steady developed tension at sub-saturating calcium concentrations. Skinned fibres are less stiff than intact fibres at a given level of developed tension.

Animals↗
PubMed1984

The dependence of force and shortening velocity on substrate concentration in skinned muscle fibres from Rana temporaria.

The force-velocity relation was determined in fully activated skinned fibres from frog muscle at concentrations of the substrate, magnesium adenosine triphosphate (MgATP), ranging from 10 microM to 10 mM. The ionic strength of the solutions was 200 mM, temperature 0-5 degrees C, pH 7.1. The activation procedure of Moisescu (1976) was used to raise the calcium concentration rapidly in the interior of the fibres. A re-phosphorylating system (creatine kinase and creatine phosphate) was used to maintain the MgATP concentration in the fibres. Isotonic releases were performed using a fast servo-controlled motor and tension transducer. Releases to a pre-determined tension level relative to the isometric tension were made using a novel normalizing circuit. In some of the experiments changes of sarcomere length were recorded using the diffraction device described in the preceding paper (Goldman & Simmons, 1984). There was satisfactory agreement between velocities determined from the total length change and the sarcomere length change. The isometric tension showed a biphasic dependence on MgATP concentration. Tension increased with MgATP concentration from 1 microM to reach a peak at about 30-100 microM and decreased by about 20% from the value at the peak with further increase in the MgATP concentration to 5 mM (about the physiological concentration). At 5 mM-MgATP, the isometric tension was approximately the same as in intact fibres, if allowance is made for the increase in cross-sectional area that occurs when the surface membrane is removed. The maximum velocity of shortening, Vmax, was obtained by fitting the force-velocity relation using Hill's (1938) equation. Vmax showed a roughly hyperbolic dependence on MgATP concentration, with a Km of 0.47 mM. At 5 mM-MgATP, the value of Vmax was 2.16 muscle lengths per second, which is similar to that of intact fibres. a/P0, the parameter of Hill's (1938) equation that is related to the curvature of the force-velocity relation, showed a slight decrease with increasing MgATP concentration. Its value at 5 mM-MgATP of 0.16 is somewhat lower than found for intact fibres. The results are discussed in terms of a simple model based on the biochemical cycle of hydrolysis of ATP by actomyosin in solution. The decrease of tension from about 30 microM to higher concentrations of MgATP can be related to the dissociating effect of MgATP on actomyosin. The increase of isometric tension from 1 to 30 microM-MgATP is discussed in terms of two types of rigor attachment of cross-bridges which support different amounts of tension.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1984

Quantitative studies of the evolution of the thalamus in primates.

A quantitative study of the thalamus and metathalamus has been carried out on brains of six different primate species. The allometric formula devised by Stephan, Bauchot and Andy (1970) has been slightly modified as two steps have been utilized in order to attain the required magnification of the final photomicrograph (a positive print, as opposed to Stephan et al's negative print). The thalamic and metathalamic structures are divided on the basis of their developmental stages into two groups--paleothalamus and neothalamus, so that their proportions to each other in primate phylogeny can be estimated. The results show that the neothalamus extends the paleothalamus by two-thirds (2/3rds) in Tupaia and by more than three-quarters (3/4ths) in Cercopithecus. Of all the thalamic groups, the dorsolateral thalamic nuclear group is most dominant in all primate species, except Tupaia, where the ventrolateral thalamic nuclei are larger than all other nuclei. The pulvinar is the most dominant nucleus in all species except Tupaia. These quantitative results conform, in most places, with the observations of other researchers, while they do not agree much with the qualitative observations of the thalamus in the same species (Simmons 1974). How this study has a bearing on the phylogenetic positions of the Tupaioidea and the Tarsioidea in the Primate Order, is briefly discussed.

Animals↗
PubMed1983

Changes in the X-ray reflections from contracting muscle during rapid mechanical transients and their structural implications.

During normal contractions of vertebrate striated muscle, it is believed that the cross-bridges which produce the sliding force undergo asynchronous cyclical changes in their structure. Thus, an X-ray diffraction diagram from a muscle under these conditions will give structural information averaged over the whole range of cross-bridge states. Such diagrams show characteristic and informative differences from those given by relaxed muscle, but can give little information about changes in the configuration of the cross-bridges at different stages of their working stroke. However, it is possible to effect a partial synchronization of these changes by applying very rapid changes in length, completed in less than one millisecond to an otherwise isometrically contracting muscle. If the amplitude of these length changes is comparable to the length of the cross-bridge stroke (say 100 A per half-sarcomere), then it should bring about a transient but significant redistribution of cross-bridge states, which would show up in the X-ray diagram. We have made use of synchrotron radiation as a high intensity X-ray source in order to record such patterns with the necessary time resolution (1 ms or less) and have found major changes in the intensity of the 143 A meridional reflection accompanying the rapid length changes of the muscle. These changes appear to arise from specific configurational changes in the cross-bridges during the working stroke. A model is suggested in which the 143 A meridional intensity in a contracting muscle arises mainly from attached cross-bridges and is generated by the part of the myosin head near the S1-S2 junction. During normal contraction, cross-bridges go through their structural cycle asynchronously with each other, since they start at different times, but if the S2 changes in length rather little, then the configurational changes in the myosin heads are synchronized with the actin filament movement in such a way that the S1-S2 junction remains relatively fixed in its axial position. In a quick release, it is suggested that bringing many S1 heads simultaneously to the end of their working strokes on actin disrupts the 143 A axial repeat of their distal ends near S2, and brings about the large decrease of the 143 A meridional reflection. This model therefore involves a large change in the position of part of the myosin head structure relative to actin during the working stroke of the cross-bridge.

Animals↗
PubMed1982

Branched skeletal muscle fibers not associated with dysfunction.

We report the occurrence of large clefts and branches in some amphibian vertebrate skeletal muscle fibers. Such fibers can be isolated intact from various skeletal muscles of fully mature animals and apparently are normal in other respects. Electron micrographs showed no signs of degeneration in most fibers. Electrical and mechanical studies revealed that all branches were excitable and able to contract. Branches evidently can arise in the absence of abnormal influences such as experimentally induced overload. The apparent cause may be either fusion or splitting of fibers.

Animals↗
PubMed1982

The results of 100 operations for velopharyngeal incompetence--selected on the findings of endoscopic and radiological examination.

Of one hundred patients with velopharyngeal incompetence subjected to a pharyngoplasty selected on the results of endoscopic and radiological examination 97% were cured of unacceptable nasal escape and 93% of unacceptable nasal resonance on the criteria described. It was considered that this provided a vindication of the system of treatment. Critical examination of the morbidity revealed an unacceptably high proportion of hyponasality. This appeared to be due to ignoring the criteria for selection for pharyngoplasty and opting for the more radical operation resulting in over-treatment in some cases. With the numbers available in the smaller treatment groups it was not possible to state that there was no significant difference in the results between the different pharyngoplasties in the groups for which they were selected. It is expected that there will be a larger proportion of patients receiving less radical treatment without detriment to the success rate, but with a lower morbidity. Assuming that it is accepted that as much accurate information as possible prior to operation is needed for the correct selection of operation, simultaneous endoscopic and radiological examination provide a time- and cost-efficient system the benefit of which becomes overwhelming for revision of the failed pharyngoplasty.

Adolescent↗
PubMed1981

Millisecond time-resolved changes in x-ray reflections from contracting muscle during rapid mechanical transients, recorded using synchrotron radiation.

Low-angle x-ray diffraction diagrams have been recorded from frog sartorius muscles by using synchrotron radiation as a high-intensity x-ray source. This has enabled changes in some of the principal reflections of interest to be followed with a time resolution of 1 ms, during small but very rapid length changes imposed on a contracting muscle. The 143-A meridional reflection, which is believed to arise from a repeating pattern of myosin cross-bridges along the length of the muscle, shows large changes in intensity in these circumstances. During both rapid releases and rapid stretches, by amounts that produce a translation of actin and myosin filaments past each other by about 100 A and that are completed in about a millisecond (i.e., before significant cross-bridge detachment would be expected), an almost synchronous decrease in 143-A intensity occurs, by 50% or more. This is followed, in the case of quick releases, by a rapid partial recovery of intensity lasting 5--6 ms (which may represent cross-bridge release and reattachment) and then by a more gradual return to the normal isometric value. Quick stretches show only the slower return of intensity. Immediately after the length change, the initial drop in 143-A intensity can be reversed if the release (or stretch) is reversed. These changes provide evidence of a more direct kind than has hitherto been available that the active sliding of actin filaments past myosin filaments during contraction is produced by longitudinal movement of attached cross-bridges.

Actins↗
PubMed1981

The relation between stiffness and filament overlap in stimulated frog muscle fibres.

1. Tension transients were recorded at sarcomere lengths from 2.0 to 3.2 mum in isolated fibres from the tibialis anterior muscle of frogs during tetanic stimulation at 0-1 degrees C. 2. The length of a selected portion of the fibre was controlled by feed-back from a spot-follower device. The step was complete in 0.2 ms and the natural frequency of the force transducer was 10.8 kHz. 3. The transients were analysed by comparing the tension record with the output of an analogue circuit (delay line) which contained components representing (a) force transducer response, (b) fibre inertia, (c) viscosity and inertia of surrounding fluid, (d) passive stiffness and viscosity of the fibre, (e) tendon compliance and (f) stiffness and early tension recovery of the contractile apparatus. 4. In releases at different sarcomere lengths, the instantaneous stiffness and the early tension recovery attributed to the contractile apparatus varied almost exactly in proportion to the developed tension. In the later phases of the transient there were minor deviations from proportionality. 5. The results confirm that the entire transient represents events in the cross-bridges. 6. At full overlap, the compliance attributable to the cross-bridges is at least 80%, and probably well over 90% of the measured instantaneous compliance of the fibre. Stiffness can therefore be used as a measure of the number of attached cross-bridges. 7. The amount of instantaneous sliding movement of thick relative to thin filaments required to bring tension in a cross-bridge from the isometric value to zero is about 3.9 nm if filament and Z-line compliance are negligible, as suggested by the results. It is not however excluded that filament compliance, though small, may be sufficient to reduce this figure to 3.5 nm or possibly 3.1 nm. 8. The responses to quick stretch, unlike those to release, could not be satisfactorily matched with the delay line. The deviations suggest that the instantaneous elasticity is non-linear in stretches. 9. In resting fibres at all sarcomere lengths, the first peak of the tension response was determined chiefly by fibre inertia and viscosity, rather than elasticity.

Animals↗
PubMed1980

Control of tension development in scallop muscle fibres with foreign regulatory light chains.

We have shown previously that chemically skinned fibre bundles from scallop muscle can be desensitized to the action of calcium by the removal of the regulatory light chains of myosin and that sensitivity can be restored by the re-addition of scallop light chains. We have now confirmed these results and extended our observations to fibre bundles from which one or both of the regulatory light chains per myosin have been removed (by treatment with EDTA at 7 and 25 degrees C, respectively) and replaced by the corresponding light chains from other species. In the case of a double substitution--where both light chains were replaced--sensitivity was restored completely by light chains from other molluscs and from gizzard muscle; for a single substitution there was restoration of sensitivity by all the light chains tested.

Animals↗
PubMed1980

The morphology of the diencephalon in the Prosimii. II. The Lemuroidea and Lorisoidea. Part II. Epithalamus, subthalamus and hypothalamus.

This study (Part II) deals with the comparative structure of the epithalamus, subthalamus and hypothalamus. The same prosimian species used in the study of the thalamus and metathalamus (Part I) are used here. The epithalamus does not show any remarkable change in the phylogeny of the prosimian diencephalon. In the subthalamus, the nucleus subthalamicus enlarges progressively in size, and shows a very close relationship to the zona incerta, the fields of Forel and the pregeniculate body. The zona incerta is observed to consist of two parts the ventral part relating to the nucleus subthalamicus and the dorsal part ot the nucleus reticularis. The fields of Forel is well differentiated into fields H1 and H2. The hypothalamus is described here having four regions--preoptic, suraoptic, infundibular and mamillary. The preoptic and supraoptic regions appear to be indivisible in all prosimian species, for the constituent nuclei of both regions extend rostrally and caudally in the anterior part of the hypothalamus. The nucleus supraopticus is evidently complicated in structure, as it appears not only to have two separate parts, but also an isthmus that connects these parts. This interlinking strand of cells is termed not the nucleus supraopticus diffuses but the nucleus/area commissuralis postopticus. The nucleus paraventricularis is a massive nucleus, and appears to have a non-neurosecretory part and a neurosecretory part. An interesting feature has been observed in certain prisimian species such as Galago demidovii, Lepilemur and Loris gracilis, the nucleus paraventricularis accessorius which may be regarded as an erratic derivative of either nucleus paraventricularis or nucleus supraopticus. The nucleus tuberalis lateralis makes its first definitive appearance in the Prosimii. The nucleus ventromedialis hypothalami appears to be larger and more clearly defined than the nucleus dorsomedialis hypothalami. From the latter nucleus, a cellular condensation has been observed to stretch lateralwards--nucleus dorsolateralis hypothalami. The hypothalamic areas--anterior, dorsal, lateral and posterior--are not very much different among the prosimian species, although the anterior and posterior hypothalamic areas appear to have more attributes of a nucleus than an area. The mamillary region is very well developed in all prosimian species. The medial mamillary nucleus is clearly divided into several parts. The nucleus mamillaris lateralis is poorly developed, but can be identified lying between the lateral part of the medial mamillary nucleus and the nucleus intercalatus. In regard to the latter nucleus, there is some topographical confusion, but the nucleus intercalatus is easily identified as the bed nucleus of the supramamillary commissure.

Animals↗
PubMed1980

The morphology of the diencephalon in the Prosimii. II. The Lemuroidea and Lorisoidea. Part I. Thalamus and metathalamus.

This study (Part I) covers the comparative structure of the thalamus and metathalamus in the prosimian superfamilies, Lorisoidea and Lemuroidea. Several lemuroid specimens, namely Lemus, Cheirogaleus, Microcebus, Avahi and Daubentonia, and lorisoid specimens such as Galago, Perodicticus and Loris have been used in this extensive study. The anterior nuclear group does not show much difference among these species, although attention is focussed on the differentiation of the principal anterior nucleus into anteromedial and anteroventral parts; the latter increases in structural complexity. The anterodorsal nucleus has regressed into a small, flattened cap-line structure covering the dorsal surface of the anteroventral nucleus. The midline thalamic nuclei are more or less the same throughout the entire prosimian primate scale, though the gradual fusion of the nucleus rhomboidalis with the nucleus centralis medialis is observed from Microcebus to Daubentonia. The medial thalamic nuclear region is dominated by the nucleus mediodorsalis which is clearly differentiated into dorsomedial magnocellular and ventrolateral parvocellular protions. A third division consisting of rather large, darkly staining cells have been observed in the caudal region of the nucleus mediodorsalis. The nuclei centrum medianum and parafascicularis are both large in size, but is not completely demarcated from each other. The dorsolateral thalamic nuclei--the nuclei laterales dorsalis, intermedius and posterior, are well developed, but cannot be distinguished from one another. The pulvinar shows a remarkable phylogenetic development; it does not only enlarge, but is differentiated into several distinct parts. The ventrolateral thalamic nuclear group is comparably larger in structural size than the dorsolateral thalamic nuclei. The nuclei ventrales anterior and lateralis are not clearly demarcated from each other, but on both cyto- and myelo-architectonic grounds, are separate entities. The nucleus ventralis posterior is differentiated into lateral, medial and inferior parts. The posterior thalamic nuclei show the beginnings of regression. The nucleus pretectalis remains comparatively large in size and divided into medial and lateral parts. The nucleus posterior thalamicus is either absent or involuted into other nuclei. The nucleus limitans makes its first appearance in the Prosimii. The lateral geniculate body is very variable in size in all respects among the prosimian species, that is, in the dorsoventral shift along the lateral surface of the thalamus, the cellular differentiation of the lateral geniculate nucleus into 5 or 6 layers, the topographical position of the pregeniculate nucleus and the degree of inversion. The medial geniculate body is shown to be clearly subdivided on cyto-architectonic grounds into dorsomedial and ventrolateral parts; a magnocellular protion can be seen on the dorsal region of this nucleus, and appears to be closely related to the nucleus suprageniculatus.

Animals↗
PubMed1979

"The diencephalon of Ptilocercus lowii (pen-tailed tree-shrew)".

The pen-tailed tree-shrew (Ptilocercus lowii) has been regarded by Le Gros Clark (1926), and Martin (1968) to possess more primitive morphological and to a certain extent, neuro-anatomical characteristics than the other tree-shrew species belonging to the sub-family Tupaiinae. Investigations have been carried out on the diencephalon of Ptilocercus lowii which has not been completely done by Le Gros Clark and other workers since 1926, to find out whether the diencephalon has actually undegone any phylogenetic changes that should be more advanced than those of the Insectivora or remain more primitive than that of the Tupaiinae. The diencephalic structure that show the most significant phylogenetic features which differe Ptilocerecus from Tupaia are observed in the anterior, dorsolateral and ventrolateral thalamic groups, and the geniculate bodies. The nucleus anteroventralis is, by comparison, much smaller and poorly differentiated from the nucleus anteromedialis. The nucleus anterodorsalis is also comparably large and does not reach the dorsal surface of the thalamus as it does in the primates. The midline nuclei do not show any significant differences, except the notably larger size of nucleus parataenialis in Ptilocercus. The nucleus mediodoralis is small and indifferentiated although it does show some incipient signs of cellular differentiation. The nucleus centralis lateralis is well developed; its inferior (ventral) part is larger than its superior part which is the better developed of the two parts in the tupaiids and primates. The nucleus centrum medianum appears to be very small and forms only a lateral extension of the nucleus parafascicularis. The ventrolateral thalamic group basically consists of nuclei ventrales anterior, lateralis and posterior without intermediate or transitional zones as found in Tupaia and Primates. The nucleus pretectalis is the largest and the best developed of all the elements of the posterior thalamic nuclear group. The lateral geniculate nucleus is not differentiated into laminae like that in Tupaia and Primates; it is merely a homogeneous structure that appears to be smaller in size that the pregeniculate and medial geniculate nuclei. The medial geniculate nucleus is large in proportional size of the whole thalamus and appears to be well differentiated cellularly into several small parts. No remarkable changes are noted in the epithalamus, subthalamus and hypothalamus. However, the nucleus ventromedialis appears to be the most outstanding structure in the infundibular region of the hypothalamus. The mammillary region is of a simpler construction in Ptilocercus than in Tupaia; it does not protrude from the ventral surface of the hypothalamus. In the light of these findings, the phyletic status of Ptilocercus in the family Tupaiidae is discussed.

Animals↗