Age changes in cross striated muscle of the rat

1. Senile muscle atrophy is characterized by a marked reduction in the frequency of spontaneous transmitter release with no electrophysiological evidence of denervation.2. In spite of the reduced number of muscle fibres, there is no ultrastructural evidence for denervation at the end-plates. There is agglutination of synaptic vesicles, neurotubules and filaments, thickening of the basement membrane, widening of the primary synaptic cleft, and irregular branching of the junctional infoldings, but no axonal degeneration.3. The contractile process in senile muscles is slowed down as is indicated by a prolongation of contraction time, latency period, maximum rate of twitch tension and relaxation time.4. The muscle fibres show proliferation of the T system and increased SR but no fragmentation as is observed in denervation atrophy.5. Senile muscle atrophy thus presents some specific features affecting both pre- and post-synaptic structures, related to a very slow process of deterioration of the neuromuscular contact.     

Fibre type changes in striated muscle of alcoholics

Striated muscle from patients taking more than 80 g of alcohol each day shows selective atrophy of the type II fibres which are dependent on glycogenolytic pathways. This atrophy is associated with an excess of glycogen and lipid within the fibres and may represent a selective metabolic insult.     

Functional outcomes of structural peculiarities of striated muscle tropomyosin

Tropomyosin is a dimer coiled-coil actin-binding protein. Adjacent tropomyosin molecules connect each other ‘head-to-tail’ via an overlap junction and form a continuous strand that winds around an actin filament and controls the actin–myosin interaction. High cooperativity of muscle contraction largely depends on tropomyosin characteristics. Here we summarise experimental evidence that local peculiarities of tropomyosin structure have long-range effects and determine functional properties of the strand, including changes in its bending stiffness and interaction with actin and myosin. Point mutations and posttranslational modifications help to probe the roles of the conserved ‘non-canonical’ residues, clusters of stabilising and destabilising core residues, and core gap in tropomyosin function. The data suggest that tropomyosin structural lability including a diversity of homo- and heterodimers of different isoforms provide a balance of stiffness, flexibility, and strength of interaction with partner sarcomere proteins necessary for fine-tuning of Ca²⁺ regulation in various types of striated muscles.

     

Histochemical changes in striated muscle in patients with intermittent claudication

Biopsy specimens from the gastrocnemius or rectus femoris muscle of 20 patients with intermittent claudication were studied using fresh frozen cryostat sections and histochemical reactions for adenosine triphosphatase, nicotinamide adenine nucleotide dehydrogenase reductase and phosphorylase and modified Gomori trichrome staining. Neuropathic changes, such as fibertype grouping and small group atrophy, were present to some extent in all of the biopsy specimens. Myogenic muscle changes such as necrosis and phagocytosis were seen in approximately one third and various forms of myofibrillar disorganization in approximately two thirds of the specimens. The amount and size of the type I aerobic fibers increased with the increasing severity of the ischemic disease.     

Nonrandom chromosome changes in multiple sclerosis

In order to study the role of genetic factors in multiple sclerosis, cytogenetic analysis was performed on 48 patients with the clinically defined disease. We found a high incidence of subjects (50%) with abnormal chromosomes, showing premature centromere division of the X chromosome and structural aberrations, translocations, or deletions that could suggest preferential breakpoints. Correlation between clinical and cytogenetic data showed that cytogenetic abnormalities were more common in patients with high frequency of relapse or with a progressive form of the disease.     

Nonrandom chromosome changes in multiple sclerosis

We report on two brothers with renal hypophosphatemia, intracerebral calcifications, minor facial anomalies, and short distal phalanges. The children presented with recurrent dental abscesses; one had premature closure of the anterior fontanelle. Biochemical findings included hypophosphatemia and elevated serum alkaline phosphatase with normocalcemia. Blood levels of parathyroid hormone, 1,25(OH)₂ and 25(OH) vitamin D levels were normal; TRP (the fractional tubular reabsorption of PO₄) and TmP/GFR (the tubular maximum rate of PO₄ reabsorption in relation to GFR) were low. Both parents had a normal serum phosphate and brain CT scan without evidence of calcifications. This apparently new syndrome of renal hypophosphatemia associated with intracerebral calcifications appears to be inherited as either an autosomal recessive or an X-linked trait.     

Contraction kinetics of striated muscle fibres following quick changes in load

1. The contraction kinetics of single striated muscle fibres and small fibre bundles from the frog and the toad were measured when the load was changed from P(0) to L < P(0). Simultaneous recordings were made of displacement at one end and force at the other end of the preparation.2. After the load was changed, the contractile force generally reached a steady value before the contraction velocity became steady. The amount of time required for isotonic contraction to become steady depended on the change in fractional load and on the temperature; it did not depend on sarcomere length in the range 2.2-3.0 mu or on the number of fibres in the preparation. The characteristics of the non-steady state are described in terms of the displacement deviation (the difference between the actual displacement at a given time and the back extrapolation of the steady phase of the displacement record) and the null times (the times at which the displacement deviation became zero, measured relative to the time at which the contractile force first reached the value of the load).3. The time average of the transient velocity was approximately equal to the final steady velocity.4. The product of the null time following a given relative force step and V(max), the steady velocity of unloaded contraction, was found to be independent of temperature. This is taken as evidence that the isotonic velocity transients originate in the contractile mechanism.5. The non-steady state following step changes in load is identified with the motion of cyclic contraction mechanisms. The motion of the specific model formulated by A. F. Huxley (1957) was compared with that of frog muscle fibres and, although the transients in the two systems differ in detail, the characteristic dimensions are of the same order.     

Longitudinal neuropsychological assessment in pediatric multiple sclerosis

Although Multiple Sclerosis (MS) occurring in childhood and adolescence has received increasing attention in recent years, the impact of the disease on cognitive function in this subgroup remains poorly understood. It has been posited that children and adolescents with MS may be particularly susceptible to cognitive dysfunction because the pathological processes, including inflammation, blood brain barrier breakdown, and demyelination, occur concurrently with ongoing myelination. Early work has documented that a number of these children present with cognitive deficits. However, there is no available information on the progression of these deficits, or on what clinical factors may predict further decline. The current article reviews what is currently known about pediatric MS and follows a cohort of pediatric MS patients and assesses cognitive function longitudinally. Participants were evaluated with a brief neuropsychological test battery on two separate occasions and correlational analyses assessed the relations between changes in cognition and several clinical variables including level of neurologic impairment, number of relapses prior to baseline assessment, number of interim relapses, age of disease onset, and disease length. The results indicate that a number of these patients experience further cognitive decline over time, or decline from previously normal functioning. Baseline level of neurologic disability was significantly correlated with changes in cognition. The number of interim relapses (i.e., relapses occurring between baseline assessment and re-evaluation) showed a modest relationship to changes in cognitive function, but this did not reach statistical significance.     

X-ray diffraction study of the structural changes accompanying phosphorylation of tarantula muscle

Summary Electron microscopy of negatively stained isolated thick filaments of tarantula muscle has revealed that phosphorylation of myosin regulatory light chains is accompanied by a loss of the helical order of myosin heads. From equatorial X-ray diffraction patterns of tarantula muscles in the phosphorylated state we have detected a mass movement in the myosin filaments that supports this finding.     

Experimental light-optical and electron-microscopic study of changes induced by sea water and thymogen in striated muscle tissue

Department of Naval and General Surgery, S. M. Kirov Military Medical Academy, Leningrad (Presented by Academician of the Academy of Medical Sciences of the USSR D. S. Sarkisov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 94–96, January, 1992     

Morphological and certain histochemical changes in striated muscle in various forms of denervation

Summary A study was made on the cat tongue tissues, in particular the striated muscles, in various types of denervation. The material was examined by histological and some other histochemical methods in terms ranging from 2 to 60 days. The sensory denervation was characterized by the development in the deafferentated region of an inflammatory process accompanied by a decrease in the degree of maturity of highly differentiated tissue structures. The motor denervation caused atrophy of the striated muscles, their destruction and replacement by connective tissue. Desympathization had no effect on the structure of the straited muscles, but caused the destruction of the smooth muscles of the walls of certain vessels.(Presented by Active Member of USSR Academy of Medical Sciences, V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 60, No. 8, pp. 115–117, August, 1965     

Red cell and hemorheological changes in multiple sclerosis

Blood rheology in multiple sclerosis (MS) was investigated in 15 subjects with varying degrees of locomotor difficulties who were members of the local MS Society. Control data were obtained from blood samples from 25 male and 25 female normal blood donors. Whole blood viscosity was measured and blood filterability was assessed. Six MS females provided blood samples for scanning electron microscopy. Erythrocyte membrane fatty acids and phospholipids were assayed. Whole blood viscosity in MS females was higher than controls at 3 of 4 shear rates (p less than 0.001) but in MS males blood viscosity was higher only at shear rate of 1.0 s-1 (p less than 0.05). MS erythrocyte filtration rates were significantly lower than controls (p less than 0.001). Leucocyte counts in MS were greater than controls both in males (p less than 0.01) and females (p less than 0.001). MS erythrocyte morphology was greatly different from controls (p less than 0.0001) and erythrocyte membranes contained less sphingomyelin than controls (p less than 0.01) but more phosphatidylinositol plus phosphatidylserine (p less than 0.02). We conclude that, because our findings indicate an identifiable and potentially correctable abnormality, it is possible to envisage an inhibition of the progressive nature of MS, with the hope of a better prognosis for patients.     

The importance of peripheral changes in determining the sensitivity of striated muscle to depolarizing drugs

1. The sensitivity of the flexor digitorum longus and soleus muscles to depolarizing drugs was tested after cross-union of their respective motor nerves.2. The alien innervation did not affect the sensitivity of either the flexor digitorum longus (FDL) or soleus muscles, which retained their normal characteristic responses to decamethonium and suxamethonium. The time course of muscle contractions was, however, altered by the cross-union operation.3. A considerable increase in sensitivity to depolarizing drugs was shown after de-afferentation and after tenotomy of the soleus muscles. Both these conditions are associated with muscle atrophy.4. It is suggested that hypersensitivity to depolarizing drugs can be expected in any situation where the muscle is undergoing atrophy.     

Phosphorylation of tropomyosin in striated muscle

An historical perspective of the phosphorylation of tropomyosin is provided. The effects of this covalent modification on the properties of striated muscle tropomyosin are summarised. Technical hurdles and findings in other systems are also discussed.     

Regulation of contraction in striated muscle

Ca(2+) regulation of contraction in vertebrate striated muscle is exerted primarily through effects on the thin filament, which regulate strong cross-bridge binding to actin. Structural and biochemical studies suggest that the position of tropomyosin (Tm) and troponin (Tn) on the thin filament determines the interaction of myosin with the binding sites on actin. These binding sites can be characterized as blocked (unable to bind to cross bridges), closed (able to weakly bind cross bridges), or open (able to bind cross bridges so that they subsequently isomerize to become strongly bound and release ATP hydrolysis products). Flexibility of the Tm may allow variability in actin (A) affinity for myosin along the thin filament other than through a single 7 actin:1 tropomyosin:1 troponin (A(7)TmTn) regulatory unit. Tm position on the actin filament is regulated by the occupancy of NH-terminal Ca(2+) binding sites on TnC, conformational changes resulting from Ca(2+) binding, and changes in the interactions among Tn, Tm, and actin and as well as by strong S1 binding to actin. Ca(2+) binding to TnC enhances TnC-TnI interaction, weakens TnI attachment to its binding sites on 1-2 actins of the regulatory unit, increases Tm movement over the actin surface, and exposes myosin-binding sites on actin previously blocked by Tm. Adjacent Tm are coupled in their overlap regions where Tm movement is also controlled by interactions with TnT. TnT also interacts with TnC-TnI in a Ca(2+)-dependent manner. All these interactions may vary with the different protein isoforms. The movement of Tm over the actin surface increases the "open" probability of myosin binding sites on actins so that some are in the open configuration available for myosin binding and cross-bridge isomerization to strong binding, force-producing states. In skeletal muscle, strong binding of cycling cross bridges promotes additional Tm movement. This movement effectively stabilizes Tm in the open position and allows cooperative activation of additional actins in that and possibly neighboring A(7)TmTn regulatory units. The structural and biochemical findings support the physiological observations of steady-state and transient mechanical behavior. Physiological studies suggest the following. 1) Ca(2+) binding to Tn/Tm exposes sites on actin to which myosin can bind. 2) Ca(2+) regulates the strong binding of M.ADP.P(i) to actin, which precedes the production of force (and/or shortening) and release of hydrolysis products. 3) The initial rate of force development depends mostly on the extent of Ca(2+) activation of the thin filament and myosin kinetic properties but depends little on the initial force level. 4) A small number of strongly attached cross bridges within an A(7)TmTn regulatory unit can activate the actins in one unit and perhaps those in neighboring units. This results in additional myosin binding and isomerization to strongly bound states and force production. 5) The rates of the product release steps per se (as indicated by the unloaded shortening velocity) early in shortening are largely independent of the extent of thin filament activation ([Ca(2+)]) beyond a given baseline level. However, with a greater extent of shortening, the rates depend on the activation level. 6) The cooperativity between neighboring regulatory units contributes to the activation by strong cross bridges of steady-state force but does not affect the rate of force development. 7) Strongly attached, cycling cross bridges can delay relaxation in skeletal muscle in a cooperative manner. 8) Strongly attached and cycling cross bridges can enhance Ca(2+) binding to cardiac TnC, but influence skeletal TnC to a lesser extent. 9) Different Tn subunit isoforms can modulate the cross-bridge detachment rate as shown by studies with mutant regulatory proteins in myotubes and in in vitro motility assays. (ABSTRACT TRUNCATED)     

Age-related changes in multiple sclerosis and experimental autoimmune encephalomyelitis

A better understanding of the pathological mechanisms that drive neurodegeneration in people living with multiple sclerosis (MS) is needed to design effective therapies to treat and/or prevent disease progression. We propose that CNS-intrinsic inflammation and re-modelling of the sub-arachnoid space of the leptomeninges sets the stage for neurodegeneration from the earliest stages of MS. While neurodegenerative processes are clinically silent early in disease, ageing results in neurodegenerative changes that become clinically manifest as progressive disability. Here we review pathological correlates of MS disease progression, highlight emerging mouse models that mimic key progressive changes in MS, and provide new perspectives on therapeutic approaches to protect against MS-associated neurodegeneration.