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N Robbins

Publications and source records attributed to N Robbins.

At least 55 records · Page 3Linked to original sources
PubMed1982

Cell proliferation in denervated muscle: time course, distribution and relation to disuse.

The effects of denervation on skeletal muscle fibers have been intensively investigated, but the effects on other cell types within muscle tissue are not well understood. In the present experiments, cell proliferation was analyzed in mouse extensor digitorum longus muscles denervated for periods of one day to six weeks. Incorporation of tritiated thymidine into DNA increased 36 h after denervation, reached a maximum at a level twenty times control at 4 days, and returned towards control values by 7 days. Incorporation first increased in the endplate area, but 12 h later involved the entire muscle. Six weeks after denervation, muscles labeled at 4 days had lost 90% of the total label. Muscle disuse, produced by tetrodotoxin block of the nerve for up to 4 days, did not result in a proliferative response. Thus, cell proliferation after denervation is not a response to simple disuse, but rather to a nerve- or muscle-related mitogen. Since the response is mostly distributed throughout the entire muscle, the mitogen probably emanates from muscle fibers.

Animals↗
PubMed1982

Cell proliferation in denervated muscle: identity and origin of dividing cells.

DNA synthesis in skeletal muscle increases dramatically during the first week after denervation. In the present study, we have characterized the dividing cells in order to assess the specificity and significance of this response to denervation. Autoradiography of [3H]thymidine-labeled denervated muscles revealed that many classes of cells were dividing, including fibroblasts (the most numerous of the labeled cells), macrophages, vascular cells, muscle satellite cells, spindle capsule cells, perineurial cells and Schwann cells. The number of labeled satellite cells accounted for no more than 10% of the dividing cells. Labeling indices of spindle capsule, perineurial and Schwann cells reached a maximum 3 days after denervation, while those of fibroblasts and macrophages peaked at 4 days. The former group of cells, which are in close contact with nerve trunks, accounted for 28% of cell division on day 3 (but only 5% on day 4) and were apparently responding to a local influence from degenerating axons. Connective tissue cells, making up the largest class of dividing cells (80% on day 4) were found throughout the muscle and appeared to proliferate in response to changes occurring along the entire length of the muscle fibers. Macrophages involved in the response were mostly resident histiocytes, since prior labeling of blood cells showed that leukocytes did not enter the muscle in substantial number after denervation. Both muscle satellite cells and connective tissue cells are essential for the functional regeneration of muscle. Thus, on the basis of overall cytologic characterization, cell division after denervation seems to represent a limited regenerative response.

Animals↗
PubMed1981

Neurotrophic regulation of rat muscle glucose-6-phosphate dehydrogenase in vitro.

In organ culture of rat diaphragm, the presence of a 2-2.5 cm phrenic nerve stump delays the time of failure of miniature endplate potentials and eliminates the increase in glucose-6-phosphate dehydrogenase (G6PD) activity which otherwise occurs at 16.5 h in muscles cultured without nerve stumps. The nerve stump effect persists in the presence of blocking doses of D-tubocurarine but is eliminated by nerve crush. As shown by studies of amino acid incorporation into protein, the effect does not involved an overall change in protein synthesis. Effluents collected over 1-2 h from unstimulated or stimulated phrenic nerve-muscle preparations had no effect on G6PD activity when applied to muscles cultured without nerve stumps. However, medium conditioned by use in organ cultures with long nerve stumps partially countered the denervation-like effect in host cultures. Thus, the nerve maintains muscle G6PD by a humoral mechanism probably unrelated to impulse activity or nicotinic receptor activation.

Animals↗
PubMed1981

A transient increase in junctional acetylcholine receptors after denervation.

An improved method for assaying acetylcholine (ACh) receptors at the neuromuscular junction has been used to examine the effects of denervation in the rat diaphragm. An early increase of junctional ACh receptors occurred after two days of denervation followed by a decline at 14 days. Possible mechanisms responsible for this transient increase in junctional ACh receptors are discussed.

Acetylcholine↗
PubMed1980

Quantitative study of motor endplates in muscle fibres dissociated by a simple procedure.

Large numbers of single muscle fibres can be obtained reproducibly from glutaraldehyde-fixed skeletal muscle by the method described here. With suitable modifications, one can estimate acetylcholine receptor number (alpha-bungarotoxin binding sites) and endplate area in parallel portions produced from the same muscle sample, so that small differences (e.g. with growth or between muscle types) become detectable. Microdissection further increases the precision of evaluation of junctional, perijunctional and extrajunctional binding sites. Other applications are illustrated.

Acetylcholinesterase↗
PubMed1980

Infective endocarditis in the elderly.

We reviewed 56 cases of infective endocarditis (IE) in patients 65 years of age and older. The clinical features, laboratory manifestations, and bacterial etiology of IE in our patients were similar to those in younger patients. Ninety-three percent were febrile, 86% had heart murmurs, and 36% had peripheral stigmas. Streptococci were predominant in community-acquired cases and staphylococci in nosocomial infections; most patients (89%) had persistent bacteremia. Preexisting valvulitis was present in only 23% of patients; 34% had evidence of atherosclerotic heart disease. Complications included congestive heart failure (CHF) in 64%, neurologic sequelae in 36%, and myocardial infarction in 13%. The mortality rate was 45%. A significantly increased mortality was associated with neurologic sequelae, myocardial infarction, or IE with Staphylococcus aureus. The diagnosis of IE should be considered in any elderly patient with a fever, heart murmur, worsening CHF, or an acute cerebrovascular insult.

Aged↗
PubMed1979

Early changes in muscle glucose-6-phosphate dehydrogenase activity after denervation: locus and dependence on nerve stump length.

Glucose-6-phosphate dehydrogenase (G6PD) activity of rat diaphragm muscle increased significantly 12 h after intrathoracic ('distal') denervation. Since this change represented one of the earliest known events after loss of innervation, the mechanism of neuronal regulation and the nature of the muscle response were further investigated. When, instead of distal denervation, the motor nerve was cut about 3.5 cm from the diaphragm, G6PD activity slightly decreased 12 h later. Denervations in which part of the same hemidiaphragm had a short nerve stump and another part, a long nerve stump, also showed a differential increase of G6PD activity dependent on length of nerve stump. In biochemical studies of the locus of the early post-denervation elevation of G6PD, enzyme activity was increased both in endplate and non-endplate regions of the muscle. Finally, the histochemical reaction for G6PD was more intense in both muscle fibers and interstitial elements, although the former made the major contribution to the biochemical results. In sum, muscle G6PD enzyme activity is closely regulated by a neurotrophic mechanism partly independent of nerve or muscle electrical activity.

Animals↗
PubMed1978

On the appearance of acetylcholine receptors in denervated rat diaphragm, and its dependence on nerve stump length.

Acetylcholine (ACh) sensitivity and extrajunctional receptor distribution of the rat diaphragm were closely monitored during the early period following denervation. Both contracture in response to 10 microgram/ml of ACh and extrajunctional binding of [125I]alpha-bungarotoxin ([125I]alpha-BTX)) were first detectable 30 h after cutting the phrenic nerve in the thorax. If the nerve were cut more proximally, leaving a 3.5 cm distal nerve stump, the same level of ACh contracture and [125I]alpha-BTX binding did not appear until 40 h after operation. This 10-h delay was far longer than the 3-h delay in transmission failure reportedly dependent on stump length. The earliest detectable extrajunctional [125I]alpha-BTX binding appeared throughout the entire muscle fiber, and was not localized to the endplate region as would be expected if degeneration in the nerve terminal induced new receptors. However, later significant increases in [125I]alpha-BTX binding at the endplate region could have resulted from such degeneration. All these results are consistent with neurotrophic regulation of muscle ACh receptors, working via a mechanism involving axonal transport.

Acetylcholine↗
PubMed1977

Cation movements in normal and short-term denervated rat fast twitch muscle.

1. The earliest known change in rat fast muscle following denervation is a fall in resting membrane potential unaccompanied by change in membrane resistance. The present study tested the hypothesis that increased Na permeability (P(Na)) accounted for this early depolarization.2. In all experiments, rat extensor digitorum longus muscles were studied in vitro at 25 degrees C. Li uptake in vitro, used as a measure of P(Na), was greater in 1- and 2-day denervated muscles (and in 2-day denervated diaphragm) than in paired controls.3. The extra Li taken up by denervated muscle was not sequestered in an extracellular or freely exchangeable compartment, nor was it irreversibly bound.4. Measurements of resting membrane potential and of internal Na, K, and Li in Krebs solution before and 2 hr after replacement of NaCl by LiCl, were used to compute the ratios P(Na)/P(K) and P(Li)/P(K) for normal or denervated muscles. P(Na) and P(Li) were similar relative to P(K) within each class of muscle.5. Both P(Na)/P(K) and P(Li)/P(K) ratios were elevated more than twofold in denervated muscle, as were most estimates of relative P(Li) approximated by the flux equation.6. These data, and measurement of resting membrane potential of normal muscle in 1 mM external K-Krebs solution, support the view that an electrogenic Na-K pump does not substantially contribute to this potential of normal or denervated muscle, and that the early depolarization after denervation results from increased P(Na).7. The Na-K pump of denervated muscle was as sensitive to ouabain as normal muscle. An effect of ouabain on P(Na) may explain previously noted differential effects of ouabain on normal and denervated muscle.

Animals↗
PubMed1977

Neurotrophic regulation of insulin-sensitive amino acid uptake in rat fast muscle.

Our object was to determine how innervation regulates muscle insulin sensitivity. Insulin-stimulated uptake of the nonmetabolized amino acid, 2-amino-isobutyric acid, was used as a measure of insulin sensitivity in denervated rat extensor digitorum longus muscles retaining either a similar 2.5-cm (""proximal denervation'') or a similar to 0.5-cm (""distal denervation'') length of distal nerve stump. Because both muscles were inactive in the first 24 h, any difference in insulin sensitivity could be due only to some trophic influence of the distal nerve stump. Fifteen hours after either type of denervation, 2-aminoisobutyric acid uptake was refractory to insulin. However, at 24 h, insulin sensitivity of distally denervated muscles (with or without a second ipsilateral proximal denervation) was normal, whereas that of proximally denervated muscles was still relatively insensitive. In the absence of insulin, the two types of denervated muscles at 24 h showed no difference in 2-aminoisobutyric acid uptake. Finally, organ culture of paired muscles with or without long nerve stumps showed corresponding differences in insulin-stimulated 2-aminoisobutyric acid uptake after 48 h in vitro. Thus, a neurotrophic factor, independent of impulse activity, stretch, or changes in blood flow, regulates one type of muscle insulin sensitivity.

Amino Acids↗
PubMed1977

Infective endocarditis caused by Streptococcus mutans. A complication of idiopathic hypertrophic subaortic stenosis.

Three patients with endocarditis caused by Streptococcus mutans were seen during a six-month period. All had clinical features of subacute bacterial endocarditis, including fever, heart murmurs, and positive blood cultures. One had underlying aortic insufficiency and two had idiopathic hypertrophic subaortic stenosis. All patients were treated with parenteral antibiotics and were cured. Streptococcus mutans is a pleomorphic, microaerophilic organism that is associated with dental caries and plaque. Differentiation of S mutans from enterococcal endocarditis is important because the former condition can be treated for a shorter period of time with penicillin alone, without the addition of aminoglycoside antibiotics.

Cardiomyopathy, Hypertrophic↗