Biomedical subjects

N Robbins

Publications and source records attributed to N Robbins.

At least 37 records · Page 2Linked to original sources

PubMed1986

Comparison of the effects of pancuronium and tubocurarine on different muscles of young and old mice.

In order to evaluate the sensitivity of different muscle types to neuromuscular blocking drugs, a system using mouse muscles in vitro was developed and applied to detect changes in drug sensitivity in relation to age. The effect of pancuronium and tubocurarine on initial twitch and on the ratio of fourth twitch to first twitch (T4/T1) of a train-of-four at 2 Hz were compared in fast-twitch, slow-twitch and respiratory muscles in the mouse. The muscles used were: extensor digitorum longus (EDL), soleus (SOL) and diaphragm (DIA). For both drugs the order of decreasing sensitivity was EDL greater than SOL greater than DIA. This result was the same whether first twitch or T4/T1 was used, although the latter was a more sensitive indicator. The sensitivity of neuromuscular block was less in muscles from old (30-33 month) animals than in the equivalent muscles from young (8-12 month) animals.

Aging↗

PubMed1986

Vertebral osteomyelitis caused by Streptococcus bovis.

The association of Streptococcus bovis septicemia with abnominal neoplasms has been well-documented. The case of a man who presented with vertebral osteomyelitis due to S. bovis is reported; he was subsequently found to have bacteremia and colonic polyps. It is recommended that patients who present with localized as well as generalized S. bovis infections undergo yearly colonoscopy.

Aged↗

PubMed1986

Sustained transmitter output by increased transmitter turnover in limb muscles of old mice.

The ability of neuromuscular junctions in old animals to maintain tetanic output was tested in phasic and tonic limb muscles and the physiologic mechanism of maintenance was elucidated by analysis of the turnover of a false transmitter during prolonged tetani. Transmitter release during and after tetani was compared in limb muscles of young (8-9 month) and old (28-30 month) male CBF-1 mice. Amplitudes of end-plate potentials (epp's) in curarized preparations and of spontaneous miniature end-plate potentials (mepp's) were measured in vitro at 30 degrees C in soleus and extensor digitorum longus (edl) muscles. In both young and old soleus muscles, epp amplitude was maintained at about 45% of resting level during the latter part of trains of 1,200 stimuli at 10 Hz but recovered to about 90% control within a few seconds after stimulation ceased. In edl muscles of young mice, epp amplitudes during a 20 Hz train of 1,200 impulses steadily declined to about 20% of control and gradually recovered over 2 min after the tetanus. In old edl muscles, tetanic decay of the epp's was greater and recovery slower than in young muscles, but absolute epp amplitudes were invariably greater. During trains of 6,000 impulses at 10 Hz, plateau epp amplitude decayed to 40-50% in young soleus muscle and 30-40% control in old muscle, but recovery was similar and absolute epp amplitudes were greater in old soleus muscle. A false transmitter precursor, homocholine (HoCh), was used to investigate the mechanism of this prolonged output, and, therefore, the use of HoCh in this system was first validated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1985

Fluorescent staining of living mouse neuromuscular junctions.

A technique for staining living neuromuscular junctions is described and used for electrophysiological recording with both intra- and extra-cellular microelectrodes. This technique may be used on thicker muscles (eg. mouse soleus), has no effect on any of several physiological parameters tested, and should have several useful applications.

Animals↗

PubMed1985

Progression of age changes in mature mouse motor nerve terminals and its relation to locomotor activity.

There is indirect evidence for morphologic 'turnover' of motor nerve terminals, but the consequences in terms of changing nerve terminal structure throughout mature lifetime are unknown. Therefore, quantitative morphometry of nerve terminals stained with zinc iodide-osmium was carried out in soleus and extensor digitorum longus (EDL) muscles of CBF-1 mice at various ages from 5 to 32 months. Because of previous questions as to the role of disuse in producing age changes in nerve terminal structure, locomotor activity was recorded for an average of 20 days continuously in mice spanning the same ages. The length, area, perimeter and tortuosity of nerve terminals increased either early in maturity (soleus) or progressively with age (EDL). Another prominent change, i.e. increased numbers of nerve terminal 'regions' (branches or boutons that are spatially separate or only connected by fine nerve filaments) per junction, only appeared late in life (at or after 25 months). This regionalization was characteristic of all terminals and involved a redistribution rather than an accretion of nerve terminal area. None of the morphological changes with age sufficiently account for previously reported physiologic findings in the same muscles. Locomotor activity (including peaks and troughs of daily activity and circadian rhythm) was not significantly altered over the period of mature lifetime in which nerve terminals were remodelling; therefore, disuse was not a factor in this process. However, slightly retarded and smaller age changes in soleus than in EDL nerve terminals may reflect a modifying effect of activity. It is inferred that two major processes account for morphologic alterations in nerve terminals of mature mice: changes that are simple continuations of normal development and late changes that reflect newly arising age-dependent extrinsic or intrinsic factors.

Age Factors↗

PubMed1985

Is a nicotinic influence involved in denervation-induced depolarization of muscle?

The neurotrophic role of acetylcholine (ACh) in the denervation-dependent decline of muscle resting membrane potential (RMP) was evaluated. Freshly dissected rat hemidiaphragms with short or long (2 cm) nerve stumps attached ("-N" and "+N" preparations, respectively) were incubated in organ culture in the presence or absence of the nicotinic blockers, alpha-bungarotoxin (alpha-BTX) or d-tubocurarine (curare). Subsequently, RMPs and miniature endplate potentials (MEPPs) of the junctional region were measured. Spontaneous MEPPs disappeared with a half-life of 12 and 20 hr in -N and +N preparations, respectively. A 10- to 15-mV depolarization of RMP was observed between 15 and 20 hr in -N muscles and between 24 and 28 hr in +N muscles. This time course of disappearance of spontaneous potentials and of membrane depolarization agrees well with that observed in vivo. Although nicotinic transmission was blocked from the initiation of the incubation period in alpha-BTX- or curare-treated muscles, no acceleration of RMP decline in -N muscles in vitro was observed. Moreover, in +N preparations the effect of the nerve stump in delaying RMP depolarization persisted despite the continuous presence of alpha-BTX or curare. Since excess ACh triggers a lysosomal proteolytic response at the nerve-muscle junction and since this may occur early in denervation, the possible role of a nicotinic-induced proteolytic mechanism was tested in vitro with the potent protease inhibitor leupeptin. This inhibitor did not delay or prevent the denervation-dependent alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

The effects of chronic muscular activity on age-related changes in single fiber electromyography.

Single fiber electromyography ( SFEMG ) of the extensor digitorum communis (EDC) muscle and nerve conduction studies were performed on healthy, active elderly men (66-77 years old) to assess age-related changes in neuromuscular physiology and the effect of long-term increased muscular activity on these changes. The following two groups were studied: a control group and a group composed of men with occupationally greater usage of hand extensors. Fiber density and mean jitter were essentially the same in both groups; however, in the hand-user group there was greater variability in mean jitter and a significant increase in the prevalence of potential pairs with increased jitter or blocking. In both groups, slower nerve conduction velocities and lower amplitudes of sensory and motor evoked potentials tended to correlate with increased jitter and fiber density. These electrophysiological changes in healthy aged men are consistent with an extremely mild process of nerve terminal denervation and reinnervation. Although long-term increased synaptic activity did not greatly alter the rate or extent of this process, it did produce a higher incidence of abnormal potential pairs and greater variability in mean jitter.

Aged↗

PubMed1984

Endplate topography of denervated and disused rat neuromuscular junctions: comparison by scanning and light microscopy.

The effect of denervation and tetrodotoxin-induced muscle disuse on endplate structure was investigated in rat hind-limb muscles. The endplate was visualized by light microscopic cholinesterase staining and by scanning electron microscopy. Denervation resulted in a reduction in histochemically determined endplate dimensions proportionate to the decrease in muscle fiber circumference. Scanning electron microscopy, on the other hand, revealed a flattening or more often collapse of primary grooves with a reduction in the width of the endplate but no longitudinal shrinkage. Primary groove area per se was not measurable due to the loss of primary groove structural integrity. Thus, the apparent histochemical diminution of endplate length after denervation was artefactual, probably due to loss of cholinesterase activity and impeded access of substrate. In disuse, cholinesterase staining revealed a similar reduction in endplate girth with fiber atrophy but with a corresponding increase in endplate length. Scanning electron microscopy of disused muscle fibers confirmed these histochemical findings and the overall preservation of primary groove area. Disuse also resulted in an increase in the number of intrasynaptic primary groove branches as visualized by scanning electron microscopy. Finally, a specialized endplate "raised area", prominent in soleus muscle, was greatly reduced after disuse but much less so after denervation. Thus, after denervation, primary groove structural integrity is lost and the shape of the endplate passively follows that dictated by circumferential loss of surface membrane. In disused muscle, presence of an intact axon preserves the structure and area but not the orientation of the primary grooves which are distorted by fiber atrophy. Disuse also strongly affects other endplate surface structures visualized by scanning electron microscopy.

Animals↗

PubMed1984

Topographic comparison of neuromuscular junctions in mouse slow and fast twitch muscles.

The neuromuscular junctions of mammalian slow and fast twitch muscles are activated differently in vivo and show corresponding physiological differences in vitro, but the structural basis or consequences of these differences are relatively unexplored. Therefore, neuromuscular junctions of mouse fast (extensor digitorum longus) and slow (soleus) twitch muscles were compared by use of new scanning and light microscopy techniques. In both muscles, the endplate appeared as an elliptical area raised to a variable extent above the surrounding sarcolemma and containing the primary clefts. In most soleus endplates, this raised surface area was considerably higher and wider and about three times larger than in extensor digitorum longus. In addition, the primary cleft area was about two-fold greater in soleus than in extensor digitorum longus, even though cleft length was the same. The primary clefts formed either an elliptical shape along the outer margin of the endplate with inward-directed branches or a group of relatively rectilinear dendritic branches orthogonally oriented to one another. The latter type was most frequent in soleus and the elliptical type in extensor digitorum longus. Corresponding patterns of nerve terminal arborizations were seen by light microscopy. Although nerve terminal areas were the same in fast and slow muscles, in the former, numerous diverticulae significantly increased the length of the nerve terminal outline. The possible physiological significance of the different synaptic structure of slow and fast muscle is discussed.

Animals↗

PubMed1984

Bimodal miniature and evoked end-plate potentials in adult mouse neuromuscular junctions.

Intracellular recordings of spontaneous miniature end-plate potentials (m.e.p.p.s) in muscles from adult CBF-1 mice revealed a population of muscle fibres in which the amplitude distribution of m.e.p.p.s was bimodal. The large mode m.e.p.p.s were similar to those from fibres having unimodal amplitude distributions and the small mode m.e.p.p.s were about one-half to one-quarter the amplitude of the large mode. In five diverse muscle groups (extensor digitorum communis, gluteus maximus, diaphragm, extensor digitorum longus, and soleus) from mice 10-12 or 31 months of age, bimodal m.e.p.p. amplitude distributions were present in about 20% of fibres sampled. In the common bimodal distribution (type 1), the rise times of small mode m.e.p.p.s were similar to those of large mode m.e.p.p.s. A rare class of small mode m.e.p.p.s (type 2) having long rise times was also observed. Amplitudes and half-decay times of type 1 small mode m.e.p.p.s increased in the presence of an anticholinesterase (edrophonium). Increasing extracellular potassium concentration led to an increase in large mode m.e.p.p. frequency but had more variable effects on small mode frequency. In the few cases available for study, type 2 small mode m.e.p.p.s disappeared after addition of edrophonium or increased potassium. When the extracellular calcium/magnesium ratio was reduced, large mode but not small mode m.e.p.p. frequency decreased. In almost all muscle fibres in which end-plate potentials (e.p.p.s) were evoked by nerve stimulation at 20 Hz in low calcium/high magnesium solution, small mode e.p.p.s similar to small mode m.e.p.p.s appeared during 'failures' of large mode m.e.p.p.s. Also, in twelve out of fifteen fibres which had unimodal m.e.p.p. amplitude distributions, small mode e.p.p.s appeared which were similar in amplitude to small mode m.e.p.p.s in fibres with type 1 bimodal m.e.p.p.s. Thus, if both spontaneous and evoked potentials are included, small mode m.e.p.p.s are present at most CBF-1 mouse adult neuromuscular junctions independent of muscle type or animal age. Small and large mode m.e.p.p.s differ in certain responses but both are evoked by nerve stimulation at physiological frequencies and therefore participate in normal neuromuscular synaptic activity. The possible origin of small mode m.e.p.p.s is discussed.

Aging↗

PubMed1984

Pyomyositis caused by Yersinia enterocolitica.

Yersinia enterocolitica is known to be associated with gastroenteritis in children and Reiter's syndrome in adults, but it has only rarely been the cause of primary soft tissue infections. A patient with diabetes mellitus developed a calf abscess, from which Y. enterocolitica was isolated in pure culture. Incision, drainage, and intravenous gentamicin therapy resulted in cure.

Abscess↗

PubMed1983

A maturational increase in rat neuromuscular junctional acetylcholine receptors despite disuse or denervation.

Junctional acetylcholine receptors (AChR) of rat skeletal muscles were microassayed 4-7 days after denervation or total disuse. The normal growth-related increase in AChR number occurred despite denervation or muscle atrophy, but in disused muscles, this increase was less. Thus, at least for short periods, the developmental addition of junctional AChR is independent of muscle fiber size or innervation and partly independent of usage.

Acetylcholine↗

PubMed1983

Scanning and light microscopic study of age changes at a neuromuscular junction in the mouse.

From previous work, it appears that synaptic transmission is well preserved at aging mouse neuromuscular junctions despite profound ultrastructural changes. Scanning and light microscopy have been used to determine whether expansion or sprouting of nerve terminals or postsynaptic reorganization play a role in this apparent compensatory mechanism. The number and length of nerve terminal branches in the extensor digitorum longus of young (7 months) and old (29 months) mice were studied with a combined silver-cholinesterase method. In aged animals, there were increases in nerve terminal length and number of intrasynaptic branches, with no change in muscle fibre diameter or numbers of axons entering the junction. Neither collateral sprouting nor collateral innervation, hallmarks of partial denervation, were present. Motor endplates visualized by scanning electron microscopy appeared as slightly elevated, elliptical plateaux ('raised areas') with smooth surfaces into which the synaptic clefts were etched. In the aged endplates more than in young endplates, the primary clefts were often interrupted by narrow short outpouchings approximately perpendicular to the long axis of the primary cleft. In addition, oval primary cleft islets were more frequent and there was increased randomness and branching of secondary clefts. Both light and scanning microscopy gave concordant quantitative evidence that nerve terminals and the underlying postsynaptic cleft are longer and more branched in aged mice. The increased length of synaptic nerve terminal approximately balances the loss of girth previously reported leaving nerve terminal volume unchanged. The observed expansion of the synaptic area in the aged neuromuscular junction may be compensatory, preserving neuromuscular function. The data also point to plasticity of adult neuromuscular synaptic structure.

Aging↗

PubMed1983

Properties of junctional acetylcholine receptors that appear rapidly after denervation.

It was previously found that the number of junctional acetylcholine receptors of rat diaphragm, as measured with [125I]alphabungarotoxin binding, suddenly increased 2 days after denervation in vivo or in vitro. Organ culture was used here to characterize further this unusual class of junctional receptors. The 'new' acetylcholine receptors were physiologically functional and were functionally located only in the junctional region. The rate of degradation of new receptors was slower than that of extrajunctional receptors and similar (in the first 24 h) to that of typical junctional receptors. In addition, the appearance of new junctional receptors was inhibited by cycloheximide and actinomycin D given at critical periods, implicating a protein synthetic step. Finally, nerve stimulation in the presence of a post-synaptic blocker (pancuronium) advanced the time of appearance of new junctional receptors. This last finding coupled with our previous report of nerve stump length effects on junctional acetylcholine receptors reinforces the suggestion that under certain conditions the level of junctional receptors can be regulated by the motor neuron.

Animals↗

PubMed1983

Neuromuscular transmission and correlative morphology in young and old mice.

1. Age changes in spontaneous and evoked transmitter release, in receptor number and in ultrastructure at the neuromuscular junction were studied in the CBF-1 mouse strain, which stays physically active and relatively free of organ pathology into advanced age.2. Spontaneous miniature end-plate potentials (m.e.p.p.s) were recorded in the following young (8-12 months) and old (29-33 months) mouse muscles: extensor digitorum longus (e.d.l.), soleus (sol.), gluteus maximus (g.m.), diaphragm (diaph.) and extensor digitorum communis (e.d.c.).3. M.e.p.p. amplitudes were unchanged with age in four muscle groups despite increases in input resistance (in e.d.l., sol. and g.m.). M.e.p.p. amplitude in old diaph. increased 54% with no change in input resistance. Bimodal distributions of m.e.p.p. amplitudes were observed in 6-23% of muscle fibres but were not more prevalent in old mice. There was little or no change in resting membrane potential with age.4. Numbers of junctional acetylcholine receptors (measured with (125)I-alpha-bungarotoxin) were the same in all young and old muscles except e.d.l., where a 30% decrease was noted. Extrajunctional receptors and other indicators of denervation (decreases in resting potential, twitch tension or muscle fibre diameter) were absent or minimal.5. M.e.p.p. frequency decreased in e.d.l., sol. and e.d.c. but not in g.m. or diaph. There was no correlated change in the cholinesterase-positive end-plate area.6. It is concluded that m.e.p.p. amplitude is maintained in old muscles by a combination of compensatory changes. The decline in m.e.p.p. frequency varies between muscle groups and is independent of the length of the motoneurone axon or level of innervation.7. Evoked end-plate potentials (e.p.p.s) were recorded in e.d.l., sol. and diaph. from young (11-13 months) and old (29-30 or 34-35 months) male CBF-1 mice in curarized preparations stimulated at 2 or 20 Hz. The amplitude of the initial e.p.p. of the trains was increased by 122% in old e.d.l. and 93% in old sol., and plateau e.p.p. amplitudes were also increased by about 100% (e.d.l.) and 67% (sol.). This, combined with the absence of change in m.e.p.p. amplitude with age, suggests that the number of quanta released per nerve impulse was increased. In diaph. there was no change with age.8. In all muscle groups, the threshold for initiation of the muscle action potential was unchanged with age. Thus, the relative safety factor of transmission was increased in curarized old e.d.l. and sol. (but not diaph.).9. Depression of the indirect twitch in solutions with a decreased calcium: magnesium ratio was also used as a relative measure of synaptic efficacy. Old sol. and e.d.l. but not diaph. muscles showed less depression of indirect twitch amplitude than did young muscle under these conditions.10. In cut-fibre preparations of sol. and diaph. stimulated at 20 Hz, there was no age-dependent difference in e.p.p. amplitude, in directly measured quantal content, or in curare sensitivity. In view of other results, these findings require careful interpretation.11. Ultrastructural morphometry was carried out in e.d.l. The nerve terminals in old (30 and 34 months) e.d.l. muscles exhibited pronounced loss of synaptic vesicles. In 34-month animals, decreased nerve terminal area and post-synaptic folds devoid of nerve terminals were often observed. Since no evidence of denervation was found by physiological criteria, it is concluded that in 34-month mice, nerve terminals withdraw from some synaptic gutters but do not abandon any junction entirely. The large presynaptic ultrastructural changes contrast with the physiological data showing no deficit and even increases in transmitter release. Therefore, under these conditions, these profound structural changes are either not functionally significant or are well compensated.

Acetylcholine↗

PubMed1983

Progression of age changes in synaptic transmission at mouse neuromuscular junctions.

The progression of age-related changes in neuromuscular function was investigated in muscles from CBF-1 mice between 7 and 32 months of age. End-plate potentials (e.p.p.s) were recorded in extensor digitorum longus (e.d.l.), soleus, and diaphragm muscles after neuromuscular transmission was blocked with either (+)-tubocurarine chloride (curare) or high-Mg/low-Ca Krebs solutions. Between 10 and 31 months of age in e.d.l. and soleus but not in diaphragm, there was an increase in e.p.p. amplitude with age. In soleus this increase was approximately two-fold in curare and three-fold in high-Mg solution. Increase in e.p.p. amplitude in curarized preparations took place between 20 and 28 months of age in e.d.l. and between 28 and 31 months of age in soleus. Indirectly elicited twitch responses were used to determine the time course of age-related changes in sensitivity to Mg block. Increased resistance to block appeared between 15 and 19 months of age in both e.d.l. and soleus (in which the increase was more gradual). E.d.l. muscles from 25-month-old CFW mice also showed an increased resistance to Mg block compared to those from 7-8-month-old animals. In Mg-blocked preparations, increased quantum content (measured directly) accounted for the increased e.p.p. amplitude. Spontaneous miniature end-plate potential (m.e.p.p.) frequency in old soleus muscles was not sensitive to low-Ca/high-Mg solutions although frequency in young soleus and young and old diaphragm was significantly reduced. It is concluded that age-related changes in evoked transmitter release begin in mid life and take place more rapidly in e.d.l. than in soleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1983

Carcinoma of the colon 2 years after endocarditis due to Streptococcus bovis.

A patient with Streptococcus bovis endocarditis, on complete gastrointestinal evaluation had only an adenomatous polyp of the sigmoid colon. Twenty-eight months later she was found to have invasive cecal carcinoma. Periodic evaluation of the gastrointestinal tract is therefore recommended for all patients with a history of S. bovis septicemia.

Adenocarcinoma↗

PubMed1982

Ultrastructural studies of young and old mouse neuromuscular junctions.

The ultrastructure of the neuromuscular junction of young and old male CBF-1 mice was analysed both qualitatively and quantitatively. The age-related findings were similar in both the phasic extensor digitorum longus muscle and the tonic soleus muscle but more pronounced in the latter. Presynaptic terminals of old mice compared to young showed decreases in nerve terminal area, mitochondria and synaptic vesicles, but increases in smooth endoplasmic reticulum, coated vesicles, cisternae, microtubules and probably neurofilaments. On the postsynaptic side there were increases in complexity of junctional folds and subsarcolemmal vesicles, and the appearance of lipofuscin deposits. Occasional denervated postsynaptic regions were encountered in old neuromuscular junctions, but the predominant characteristics of aging changes were not those of denervation. Rather, a unique and uniform process involving most of the population of nerve terminals, possibly of physiologically adaptive significance, appears to occur with age in both phasic and tonic limb muscles.

Animals↗