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Biomedical subjects

B W Festoff

Publications and source records attributed to B W Festoff.

125 records · Page 7Linked to original sources
PubMed1977

In vitro studies of skeletal muscle membranes. Effects of denervation on the macromolecular components of cation transport in red and white skeletal muscle.

The effects of denervation on the macromolecular components of active monovalent cation transport in skeletal muscle have been studied using purified sarcolemma membranes. A comparison of membrane activities of fast-twitch, slow-twitch, and mixed-fiber muscles was made to determine what role, if any, the motor nerve has in regulating this important aspect of muscle metabolism. A dramatic increase in the basal sarcolemmal Mg++ ATPase activity (three- to fourfold) was found for both major muscle types. An increase in the ouabain-inhibitable (Na+ + K+)-stimulated enzyme was also found, but the effect was substantially less (1.5- to twofold). [3H]-ouabain binding, as an index of glycoside receptor sites, also increased (two- to threefold) midway in the course of denervation. On the other hand, the phosphorylated intermediate activity, a functional component of the transport system, clearly decreased over the same time course and remained below control values for the remainder of the course. This resulted in a two- to threefold increase in the turnover number, suggesting that active transport of cations should increase dramatically with denervation. The membrane protein patterns on SDS gels were less obvious than the changes observed in the functional components. The major effects appeared after only one week and seemed to be restricted to high molecular weight membrane proteins, especially in the 100,000 to 250,000 daltons range. This effect was more prominent in slow-twitch membranes with an apparent semiquantitative decrease in stain at 240,000 daltons. In gels of membranes from fast-twitch muscles a decreased stain in the range of 100,000 to 110,000 daltons occurred, and this became more obvious with longer periods of denervation. The results suggest that considerable influence on the macromolecular components of active cation transport in skeletal muscle is exerted by the motor nerve. No appreciable difference was found in this effect when the two major types of skeletal muscle, fast-twitch and slow-twitch, were compared, suggesting that motor nerve regulation of this membrane property is qualitatively the same.

Adenosine Triphosphatases↗
PubMed1977

Neurotrophic control of cyclic nucleotide levels during muscle differentiation in cell culture.

The effects of chick brain-spinal cord extract on morphological development and cyclic nucleotide levels of cultured chick embryo skeletal muscle cells were determined. It had previously been shown that the extract stimulated morphological differentiation, protein synthesis, and choliniesterase activity of muscle cells. Myoblasts fused earlier and an increase in number as well as diameter of myotubes were seen in the extract treated cultures. Cyclic nucleotides levels were higher (almost twice the controls for both adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate) and preceded their occurrence in the control cultures. It was suggested that factor(s) in the extract interact with membrane receptor(s) to alter nucleotide levels which, in turn, allow the effects to be expressed.

Animals↗
PubMed1977

Neuromuscular blockade with anti-axoplasmic antibodies.

In the process of developing an immunopharmacologic method for identifying a "trophic" protein released from motor nerve terminals, a soluble fraction of peripheral nerve axoplasm was prepared. An attempt was made to eliminate contaminating myelin and basic protein. Antibodies were produced to soluble nerve proteins in all sheep immunized. On boosting, after a 6-week interval, the animals became weak, and some could not stand on the fifth day after injection. A distinct component of neuromuscular blockade was demonstrated electrically and in response to edrophonium. Because this syndrome was (1) in the broadest sense, an experimental allergic neuropathy but produced by a distinctly different antigen than has been utilized previously (the soluble nerve proteins represented the axoplasmic compartment) and (2) a clinical condition associated with a defect in neuromuscular transmission, this may represent a new and potentially important model in the study of neuromuscular and other neurologic diseases.

Animals↗
PubMed1974

In vitro analysis of the general properties and junctional receptor characteristics of skeletal muscle membranes. Isolation, purification, and partial characterization of sarcolemmal fragments.

Muscle membranes were partially purified from rat leg muscles. Externally oriented membrane functions were used to monitor and characterize the resulting membrane fractions. Na(+)K(+)-stimulated Mg(++)-adenosinetriphosphatase, acetylcholinesterase, and cholinergic receptor activities are present and enriched in the density-gradient subfractions of crude sarcolemma when compared with the first pellet. The physical separation of the cholinesterase and receptor activities on the gradient subfractions is demonstrated. Receptor activity, determined by specific (125)I-labeled alpha-bungarotoxin binding, appears in fractions with densities similar to other plasma membranes (D(4) (20) 1.1015-1.1520). Acetylcholinesterase, on the other hand, is preferentially distributed in lighter density fractions (D(4) (20) 1.0507-1.0780) and parallels the gradient distribution of the ATPase. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a high-molecular-weight glycoprotein sediments with the higher density fractions only. The data suggest a molecular dissection of the layers of the sarcolemma. The receptor is tentatively felt to be an integral component of the junctional plasma membrane. Acetylcholinesterase is felt to be superficially located on the ectolamina of the junctional sarcolemma, and may be woven within the matrix of the intersynaptic basement membrane.

Acetylcholinesterase↗
PubMed1968

Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase.

Previous studies have demonstrated that electrically induced seizures in rat result in an increased brain intracellular sodium which can be decreased by treatment with sodium diphenylhydantoin (DPH). The correlation of cation transport with membrane-oriented sodium-potassium-adenosine triphosphatase (Na-K-ATPase) prompted an investigation of the effect of DPH upon ATPase enzyme activity.Rat cerebral cortical synaptosomes isolated in Ficoll gradients were employed as the source for Na-K-ATPase. With 50 mM Na, 10 mM K, 7.5 mM Mg, and 1.8 mM ATP, the specific activity of the preparation was 70 mumoles P(i) released/mg synaptosomal protein per 30 min. The ionic and substrate concentrations yielding one-half maximal velocity were 0.5 mM K, 5 mM Na, and 8.5 x 10(-5) M ATP, respectively. At 50 mM Na and 0.2 mM K, DPH produced an average of 92% stimulation of P(i) release above control. The ratio of Na:K rather than the absolute levels of the ions was critical in determining the effect of DPH. DPH produced significant stimulation of enzyme activity under conditions of a high Na:K ratio (25-50:1). At ratios of 5-10:1, DPH produced little or no effect, and at low Na:K ratios (less than 5:1), DPH was inhibitory. Under all ionic conditions examined, DPH produced no apparent change in enzyme affinity for ATP. Assuming the proposed association of Na-K-ATPase with cation transport in brain, the data suggest the possibility that DPH may control seizures by its stimulation of Na-K-ATPase activity.

Adenosine Triphosphatases↗
PubMedDate not supplied

Neurotrophic control of skeletal muscle phospholipids.

The phospholipid composition of rat gastrocnemius muscles was assessed one to nine days after sciatic nerve transection was performed either close to the muscle (5-8 mm from the point of entrance of the nerve into the muscle for short-stump nerve sections) or far from it (30-35 mm central to the nerve's point of entrance for long-stump nerve sections). In both instances, denervation did not cause striking changes in total phospholipid content but resulted in a selective loss of 1,2-diacyl-sn-glycero-3-phosphorylethanolamine (phosphatidyl ethanolamine, GPE). The quantity of GPE in denervated muscles was found to be significantly less than that it controls (p less than 0.01) within one day for short-stump preparations, as compared to three days for long-stump preparations. Also, direct comparison of short- and long-stump GPE values showed significant differences (p less than 0.01) at all times from the first to the fifth day following denervation, with no difference detected thereafter. These results imply that maintenance of skeletal muscle GPE involves a neurogenic influence which is independent of nerve-evoked muscle activity. This conclusion may help us understand neuromuscular diseases in which perturbation of phospholipid components has been implicated.

Animals↗
PubMedDate not supplied

Plasma and red blood cell acetylcholinesterase in amyotrophic lateral sclerosis.

Red blood cell and plasma cholinesterases were evaluated in control subjects and patients with the major forms of adult, sporadic motor neuron disease. For the purposes of this communication, the patients were considered as having amyotrophic lateral sclerosis (ALS) or its subtypes. Cholinesterase and acetylcholinesterase activities were evaluated and separated by dose response to their respective inhibitors. No kinetic differences were observed comparing red blood cell or plasma enzyme activities using either inhibitor. As found in previous studies, acetylcholinesterase accounted for more than 90% of acetylcholine hydrolysis in red blood cells. The plasma data were more complicated to evaluate, but at least 20% of total activity could be attributed to acetylcholinesterase. When red blood cell acetylcholinesterase activities of patients and controls were compared, no statistically significant difference was found. However, when plasma acetylcholinesterase activity was compared between the 2 groups, a statistically significant increase, almost twice the control value, was found in the ALS patients. These data may ultimately be important in the prognosis of this disease and, conceivably, could aid in understanding its pathogenesis.

Acetylcholine↗
PubMedDate not supplied

Zeroing in on amyloid proteins in Alzheimer disease therapy.

The authors have provided us with a complete review of the approaches to the amyloid proteins of Alzheimer's disease in regards to targets for drug therapy. Sufficient information is now available concerning systemic amyloidogenesis, genes for familial Alzheimer's disease and the beta amyloid precursor protein, as well as the posttranslational processing requirements for amyloidogenesis and its prevention. Recent excitement concerning the roles for serine proteases and their inhibitors, both in the production and prevention of amyloidogenesis, make this review and its publication in the Neurobiology of Aging extremely timely.

Alzheimer Disease↗
PubMedDate not supplied

The influence of denervation on beta-amyloid protein precursor and alpha 1-antichymotrypsin in mouse skeletal muscle.

A serpin, alpha 1-antichymotrypsin (alpha 1-ACT), and Kunitz inhibitor containing forms of the beta-amyloid precursor protein (beta APP) may be important components of the balance between serine proteases and inhibitors in the nervous system. In the current report we studied whether axotomy affected the localization of beta APP and alpha 1-ACT in adult mouse muscle. Immunocytochemical experiments indicated that beta APP was present in normal muscle both at neuromuscular junctions and within intramuscular nerves. alpha 1-ACT was also present at neuromuscular junctions, on the perineurium of nerves and endothelial cell surfaces. Following axotomy, both beta APP and alpha 1-ACT disappeared from intramuscular nerves simultaneously. However, at the neuromuscular junction alpha 1-ACT decreased more rapidly with beta APP lingering before disappearing.

Amyloid beta-Protein Precursor↗
PubMedDate not supplied

Mechanism of action of neurotoxins.

This paper is a summary of studies over the past few years that pertain to animal neurotoxins. These toxins are found throughout the animal kingdom. Homologies exist in the structures of these poisons within classes and point to conservation of active sites throughout evolution. In the case of the peptides, invariant amino acids may be involved in the active site, be essential for maintaining the shape and conformation of the molecule or serve as a fulcrum for folding of the peptide chain after synthesis. At the nuclear or DNA-level, a constant base sequence may regulate gene operation so that only a specific amino acid is coded. Physiologically, and with ultrastructural and biochemical correlation, the predominant mode of action of neurotoxins relate to one or the other of the major activities of the excitable cell,--on conductile activity affecting Na+ or K+ permeabilities, on output or secretory activities affecting the release of neurotransmitter or on in put generator activities affecting the receptor molecules for transmitter themselves. The future of these animal neurotoxins in neurobiological research is secure. The elucidation of molecular mechanisms, by which these various physiological activities of excitable tissue are expressed, will surely involve one or more of these fascinating, naturally-occurring compounds.

Animals↗