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M Schoenberg

Publications and source records attributed to M Schoenberg.

69 records · Page 4Linked to original sources

Geometrical factors influencing muscle force development. I. The effect of filament spacing upon axial forces.

The influence of geometry on the force and stiffness measured during muscle contraction at different sarcomere lengths is examined by using three specific models of muscle cross-bridge geometry which are based upon the double-hinge model of H. E. Huxley (Science [Wash. D.C.]. 1969, 164:1356-1366) extended to three dimensions. The force generated during muscle contraction depends upon the orientation of the individual cross-bridge force vectors and the distribution of the cross-bridges between various states. For the simplest models, in which filament separation has no effect upon cross-bridge distribution, it is shown that changes in force vectors accompanying changes in myofilament separation between sarcomere lengths 2.0 and 3.65 microgram in an intact frog skeletal muscle fiber have only a small effect upon axial force. The simplest models, therefore, produce a total axial force proportional to the overlap between the actin and myosin filaments and independent of filament separation. However, the analysis shows that it is possible to find assumptions that produce a cross-bridge model in which the axial force is not independent of filament spacing. It is also shown that for some modes of attachment of subfragment-1 (S1) to actin the azimuthal location of the actin site is important in determining the axial force. A mode of S1 attachment to actin similar to that deduced by Moore et al. (J. Mol. Biol., 1970, 50:279-294), however, exhibits rather constant cross-bridge behavior over a wide range of actin site location.

Actins↗

Geometrical factors influencing muscle force development. II. Radial forces.

If the subfragment-2 (S2) portion of the myosin cross-bridge to actin does not lie parallel to the myofilament axes then when a muscle fiber contracts, there will be a radial component to the cross-bridge force. When the subfragment-1 (S1) portion of the cross-bridge attaches to actin with its long axis projecting through the filament axis, the magnitude of the radial force depends upon the azimuthal location of the actin site, but when the attachment of the S1 to actin is slewed, as in the reconstruction of Moore et al. (J. Mol. Biol., 1970, 50:279-294), then for a single cross-bridge the radial component of the cross-bridge force is not quite so sensitive to actin site location and is approximately 0.1 the axial component. In both cases, the ratio of the radial to axial force decreases with decreasing filament separation. If the radial-axial force ratio for each cross-bridge is approximately 0.1, then at full overlap in a frog skeletal muscle fiber the radial component of the cross-bridge force accompanying full activation will exert a compressive pressure of approximately 5 X 10(-3) atm. This would have little effect upon an intact muscle fiber where the volume constraints are likely osmotic, but it might produce a 1-2% change in filament spacing in a "skinned" muscle fiber from which the sarcolemma had been removed. These computations assume that the S2 link between the S1 head and the myosin filament does not support a bending moment of shear. If it does, then the radial component of the cross-bridge will be either greater or less, depending on the specific cross-bridge geometry.

Actins↗

Schedule-dependent cytotoxicity of methotrexate and 5-fluorouracil in human colon and breast tumor cell lines.

The effect of sequential methotrexate and 5-fluorouracil on the clonal growth of the human colon adenocarcinoma cell, HCT-8, and the hormone-dependent human breast carcinoma cell, 47-DN, was examined. In both cell lines, when 5-fluorouracil was given during the last 6 h of a 24 h methotrexate exposure period, there was marked synergistic inhibition of clonal growth. Shorter intervals or the reverse sequence of drugs were either additive or antagonistic. These results indicate the importance of the drug sequence and time interval between drug administration for optimal cytotoxicity in these human cell lines. This information suggests that the administration of methotrexate 18 h before 5-fluorouracil may have potential application in the design of clinical trials for these malignancies.

Adenocarcinoma↗

The influence of intercellular clefts on the electrical properties of sheep cardiac Purkinje fibers.

A model of a 100 micrometers diameter Purkinje fiber with intercellular clefts was studied under voltage clamp conditions to examine the consequences of radial nonuniformity. Sodium and potassium conductances were distributed so that the surface and cleft membranes had similar channel density. Assuming that the model is appropriate, sodium current (and conductance) measured in the voltage clamp is grossly underestimated because of loss of voltage control of the cleft membrane. Under these conditions a value for g Na of about 15-20 mmho/cm2 of actual membrane is consistent with the experimental measurements of Dudel and Rüdel (1970. Pfluegers Arch. Eur. J. Physiol. 315:136-158.). Intermediate and slow currents (slow inward current and potassium current) appear to be accurately measured under the model conditions, despite some voltage nonuniformity within the cleft. This result depended on the presence of a residual sodium current, and experimental removal of sodium may alter this result. All effects of nonuniformity would be accentuated in fibers of larger diameter.

Animals↗

Graves' disease manifesting after maintenance lithium.

A 36-year-old woman with no prior history of thyroid dysfunction developed Graves' disease (hyperthyroidism with exophthalmos) 4 months after her maintenance lithium therapy was stopped. Although a causal relationship between these events cannot be established, several hypotheses are presented. The possibility that lithium may mask the hyperthyroidism of Graves' disease but allow the exophthalmos to develop cryptically is discussed. Hyperthyroidism and mania have similar symptoms, but in the case presented two psychiatrists were able to distinguish between these two conditions by careful examination.

Adult↗

Tissue PO2 during reanimation with hemoglobin solutions.

Solutions of conventional stoma-free hemoglobin (SFH) and of pyridoxylated stoma-free hemoglobin (SFH-PLP) were compared in a dog model of reanimation from severe arterial blood loss. SFH and SFH-PLP restored central hemodynamics after infusion without yielding significant differences between the experimental groups. To cope with the developing hypovolemia, Ringer's lactate load amounted to about 120 ml/kg, edema formation was not encountered. Skeletal muscle oxygenation was studied by means of a multiwire platin electrode. The infusion of SFH-PLP was associated with a shift to the right of the cumulative PO2-distribution curve, indicating better tissue oxygenation. Oxygen was not unloaded from SFH in plasma unless the oxygen extraction from red cell hemoglobin exceeded 40%. Oxygen unloading was, however, improved when SFH-PLP with low oxygen affinity was used. Thus, SFH-PLP merits further consideration as a short-term oxygen-carrying blood substitute.

Animals↗

The mind-body dichotomy reified: an illustrative case.

Cartesian dualism, the splitting of human existence into mind versus body, is at times reified with unfortunate consequences. The authors report a case in which a social policy formulation based on such diagnostic dualism resulted in the denial of health-related facility placement to a patient. They argue that this denial was prejudicial and illogical and that benefits should be related to a functional disability rather than to diagnosis.

Adolescent↗

Effect of diameter on membrane capacity and conductance of sheep cardiac Purkinje fibers.

Membrane electrical properties were measured in sheep cardiac Purkinje fibers, having diameters ranging from 50 to 300 mum. Both membrane capacitance and conductance per unit area of apparent fiber surface varied fourfold over this range. Membrane time constant, and capacitance per unit apparent surface area calculated from the foot of the action potential were independent of fiber diameter, having average values of 18.8 +/- 0.7 ms, and 3.4 +/- 0.25 muF/cm2, respectively (mean +/- SEM). The conduction velocity and time constant of the foot of the action potential also appeared independent of diameter, having values of 3.0 +/- 0.1 m/s and 0.10 +/- 0.007 ms. These findings are consistent with earlier suggestions that in addition to membrane on the surface of the fiber, there exists a large fraction of membrane in continuity with the extracellular space but not directly on the surface of the fiber. Combining the electrical and morphological information, it was possible to predict a passive length constant for the internal membranes of about 100 mum and a time constant for chaning these membranes in a passive 100-mum fiber of 1.7 ms.

Action Potentials↗

The devil-priest syndrome.

Men frequently relate to women as either "sanctified" and hence, asexual, or as sexual, and therefore "degraded." A case is presented demonstrating a similar finding in a woman. The uncovering of the "Devil-Priest Syndrome" during psychotherapy is described. Some speculations as to the significance of this finding in the understanding of the psychodynamics of sexuality are included.

Adult↗

Muscle compliance and the longitudinal transmission of mechanical impulses.

The time required for a mechanical impulse to propagate from one end to the other was measured directly in frog sartorius muscles and in fiber bundles from the semitendinosus muscle. When the fibers were fully activated, the transmission velocity was 170 mm/ms. In resting fibers the transmission time was three to four times greater than in activated fibers. Control experiments indicated that the transmission time across the tendons was negligible. A muscle compliance of 55-80 A per half sarcomere was estimated from these data. The "measurement time" of the method was calculated to be about 15 micros. This relatively short measurement time makes the method potentially useful for detecting changes in cross-bridge compliance.

Animals↗

Length-force relation of calcium activated muscle fibers.

Calcium activated skinned frog muscle fibers develop a large relative force at a sarcomere length of 1.0 micrometer. Since the normal myofilament lattice is perturbed at this length, regularity of the lattice does not appear to be an important factor in the contraction mechanism.

Animals↗

Strength-duration curves in cardiac Purkinje fibres: effects of liminal length and charge distribution.

1. Strength-duration curves for excitation in long point-stimulated sheep cardiac Purkinje fibres, where the charge distribution varies along the length of the fibre, are characterized by (a) a time constant which is short relative to the membrane time constant, (b) an apparent fall in charge threshold for short duration stimuli, (c) an apparent rise in voltage threshold as measured by an electrode at the point of current passage (see Dominguez & Fozzard, 1970).2. Strength-duration curves obtained from shortened segments of Purkinje fibres, where the charge distribution along the segment is fairly uniform after 2-3 msec, have much larger time constants.3. For stimulus durations longer than the 2-3 msec necessary to establish charge uniformity, strength-duration curves obtained from shortened segments of Purkinje fibres were well fitted by the Lapicque-Hill equation, I/I(rh) = [1 - exp (-t/tau)](-1).4. The differences in the time constants and apparent voltage thresholds for point-stimulated long fibres and uniformly charged short fibre segments could be explained by the liminal length concept of Rushton (1937). The liminal length concept, in its simplest form, states that a liminal length of fibre must be raised above a given voltage threshold in order for a propagated action potential to be generated.5. This concept predicts that the shorter the liminal length, the shorter the time constant of strength-duration curves in point-stimulated long fibres.6. Another conclusion of the model is that only those point-stimulated long fibres with longer liminal lengths would have a constant charge threshold for stimuli of the order of 0.2 tau.7. Liminal length was found by experiment and calculation to be about 0.1-0.2 lambda(m) in cardiac Purkinje fibres.8. The differences in behaviour with regards to excitation between the point-stimulated theoretical squid axon and the point-stimulated Purkinje fibre may be explained by assuming that the liminal length of the theoretical squid axon is several times larger than that of the Purkinje fibre.

Action Potentials↗

Pulse wave propagation in elastic tubes having longitudinal changes in area and stiffness.

The behavior of both step waves and sinusoidal waves in fluid-filled elastic vessels whose area and distensibility vary with distance is explored theoretically. It is shown that the behavior of these waves may be explained, to a large extent, by considering the effect of the continuous stream of infinitesimal reflections that is set up whenever any wave travels in a region of vessel where the local impedance, (that is, the ratio of elastic wavespeed to tube area) is not constant. It is found that in such vessels the behavior of sinusoidal waves over distances which are a fraction of a wavelength can be quite different from their average behavior over several wavelengths. Both behaviors are described analytically. The results are applied to the mammalian circulatory system, one of the most interesting results being that a longitudinal variation in the pressure and velocity amplitudes which has a wavelength roughly one-half that of standing waves is predicted. The treatment is essentially a linearized quasi-one-dimensional one, the major assumptions being that the fluid is inviscid, the mean flow is zero, and the vessel is perfectly elastic and constrained from motion in the longitudinal direction. As in the physiological situation, the ratio of fluid velocity to pulse propagation speed is assumed small. For comparison with the analytical results, the linearized equations are also solved numerically by computer.

Blood Flow Velocity↗