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PubMed2004

Laser microsurgery in fission yeast; role of the mitotic spindle midzone in anaphase B.

INTRODUCTION: During anaphase B in mitosis, polymerization and sliding of overlapping spindle microtubules (MTs) contribute to the outward movement the spindle pole bodies (SPBs). To probe the mechanism of spindle elongation, we combine fluorescence microscopy, photobleaching, and laser microsurgery in the fission yeast Schizosaccharomyces pombe. RESULTS: We demonstrate that a green laser cuts intracellular structures in yeast cells with high spatial specificity. By using laser microsurgery, we cut mitotic spindles labeled with GFP-tubulin at various stages of anaphase B. Although cutting generally caused early anaphase spindles to disassemble, midanaphase spindle fragments continued to elongate. In particular, when the spindle was cut near a SPB, the larger spindle fragment continued to elongate in the direction of the cut. Photobleach marks showed that sliding of overlapping midzone MTs was responsible for the elongation of the spindle fragment. Spindle midzone fragments not connected to either of the two spindle poles also elongated. Equatorial microtubule organizing center (eMTOC) activity was not affected in cells with one detached pole but was delayed or absent in cells with two detached poles. CONCLUSIONS: These studies reveal that the spindle midzone is necessary and sufficient for the stabilization of MT ends and for spindle elongation. By contrast, SPBs are not required for elongation, but they contribute to the attachment of the nuclear envelope and chromosomes to the spindle, and to cell cycle progression. Laser microsurgery provides a means by which to dissect the mechanics of the spindle in yeast.

Anaphase↗

PubMed1999

Structure, distribution and innervation of muscle spindles in avian fast and slow skeletal muscle.

Muscle spindles in 2 synergistic avian skeletal muscles, the anterior (ALD) and posterior (PLD) latissimus dorsi, were studied by light and electron microscopy to determine whether morphological or quantitative differences existed between these sensory receptors. Differences were found in the density, distribution and location of muscle spindles in the 2 muscles. They also differed with respect to the morphology of their capsules and intracapsular components. The slow ALD possessed muscle spindles which were evenly distributed throughout the muscle, whereas in the fast PLD they were mainly concentrated around the single nerve entry point into the muscle. The muscle spindle index (number of spindles per gram wet muscle weight) in the ALD was more than double that of its fast-twitch PLD counterpart (130.5+/-2.0 vs 55.4+/-2.0 respectively, n = 6). The number of intrafusal fibres per spindle ranged from 1 to 8 in the ALD and 2 to 9 in the PLD, and their diameters varied from 5.0 to 16.0 microm and 4.5 to 18.5 microm, respectively. Large diameter intrafusal fibres were more frequently encountered in spindles of the PLD. Unique to the ALD was the presence of monofibre muscle spindles (12.7% of total spindles observed in ALD) which contained a solitary intrafusal fibre. In muscle spindles of both the ALD and PLD, sensory nerve endings terminated in a spiral fashion on the intrafusal fibres in their equatorial regions. Motor innervation was restricted to either juxtaequatorial or polar regions of the intrafusal fibres. Outer capsule components were extensive in polar and juxtaequatorial regions of ALD spindles, whereas inner capsule cells of PLD spindles were more numerous in juxtaequatorial and equatorial regions. Overall, muscle spindles of the PLD exhibited greater complexity with respect to the number of intrafusal fibres per spindle, range of intrafusal fibre diameters and development of their inner capsules. It is postulated that the differences in muscle spindle density and structure observed in this study reflect the function of the muscles in which they reside.

Animals↗

PubMed2000

Skeletor, a novel chromosomal protein that redistributes during mitosis provides evidence for the formation of a spindle matrix.

A spindle matrix has been proposed to help organize and stabilize the microtubule spindle during mitosis, though molecular evidence corroborating its existence has been elusive. In Drosophila, we have cloned and characterized a novel nuclear protein, skeletor, that we propose is part of a macromolecular complex forming such a spindle matrix. Skeletor antibody staining shows that skeletor is associated with the chromosomes at interphase, but redistributes into a true fusiform spindle structure at prophase, which precedes microtubule spindle formation. During metaphase, the spindle, defined by skeletor antibody labeling, and the microtubule spindles are coaligned. We find that the skeletor-defined spindle maintains its fusiform spindle structure from end to end across the metaphase plate during anaphase when the chromosomes segregate. Consequently, the properties of the skeletor-defined spindle make it an ideal substrate for providing structural support stabilizing microtubules and counterbalancing force production. Furthermore, skeletor metaphase spindles persist in the absence of microtubule spindles, strongly implying that the existence of the skeletor-defined spindle does not require polymerized microtubules. Thus, the identification and characterization of skeletor represents the first direct molecular evidence for the existence of a complete spindle matrix that forms within the nucleus before microtubule spindle formation.

Active Transport, Cell Nucleus↗

PubMed1997

Three-dimensional analysis and ultrastructural design of mitotic spindles from the cdc20 mutant of Saccharomyces cerevisiae.

The three-dimensional organization of mitotic microtubules in a mutant strain of Saccharomyces cerevisiae has been studied by computer-assisted serial reconstruction. At the nonpermissive temperature, cdc20 cells arrested with a spindle length of approximately 2.5 microns. These spindles contained a mean of 81 microtubules (range, 56-100) compared with 23 in wild-type spindles of comparable length. This increase in spindle microtubule number resulted in a total polymer length up to four times that of wild-type spindles. The spindle pole bodies in the cdc20 cells were approximately 2.3 times the size of wild-type, thereby accommodating the abnormally large number of spindle microtubules. The cdc20 spindles contained a large number of interpolar microtubules organized in a "core bundle." A neighbor density analysis of this bundle at the spindle midzone showed a preferred spacing of approximately 35 nm center-to-center between microtubules of opposite polarity. Although this is evidence of specific interaction between antiparallel microtubules, mutant spindles were less ordered than the spindle of wild-type cells. The number of noncore microtubules was significantly higher than that reported for wild-type, and these microtubules did not display a characteristic metaphase configuration. cdc20 spindles showed significantly more cross-bridges between spindle microtubules than were seen in the wild type. The cross-bridge density was highest between antiparallel microtubules. These data suggest that spindle microtubules are stabilized in cdc20 cells and that the CDC20 gene product may be involved in cell cycle processes that promote spindle microtubule disassembly.

Cdc20 Proteins↗

PubMed2000

Spindle formation and dynamics of gamma-tubulin and nuclear mitotic apparatus protein distribution during meiosis in pig and mouse oocytes.

This work focuses on the assembly and transformation of the spindle during the progression through the meiotic cell cycle. For this purpose, immunofluorescent confocal microscopy was used in comparative studies to determine the spatial distribution of alpha- and gamma-tubulin and nuclear mitotic apparatus protein (NuMA) from late G2 to the end of M phase in both meiosis and mitosis. In pig endothelial cells, consistent with previous reports, gamma-tubulin was localized at the centrosomes in both interphase and M phase, and NuMA was localized in the interphase nucleus and at mitotic spindle poles. During meiotic progression in pig oocytes, gamma-tubulin and NuMA were initially detected in a uniform distribution across the nucleus. In early diakinesis and just before germinal vesicle breakdown, microtubules were first detected around the periphery of the germinal vesicle and cell cortex. At late diakinesis, a mass of multi-arrayed microtubules was formed around chromosomes. In parallel, NuMA localization changed from an amorphous to a highly aggregated form in the vicinity of the chromosomes, but gamma-tubulin localization remained in an amorphous form surrounding the chromosomes. Then the NuMA foci moved away from the condensed chromosomes and aligned at both poles of a barrel-shaped metaphase I spindle while gamma-tubulin was localized along the spindle microtubules, suggesting that pig meiotic spindle poles are formed by the bundling of microtubules at the minus ends by NuMA. Interestingly, in mouse oocytes, the meiotic spindle pole was composed of several gamma-tubulin foci rather than NuMA. Further, nocodazole, an inhibitor of microtubule polymerization, induced disappearance of the pole staining of NuMA in pig metaphase II oocytes, whereas the mouse meiotic spindle pole has been reported to be resistant to the treatment. These results suggest that the nature of the meiotic spindle differs between species. The axis of the pig meiotic spindle rotated from a perpendicular to a parallel position relative to the cell surface during telophase I. Further, in contrast to the stable localization of NuMA and gamma-tubulin at the spindle poles in mitosis, NuMA and gamma-tubulin became relocalized to the spindle midzone during anaphase I and telophase I in pig oocytes. We postulate that in the centrosome-free meiotic spindle, NuMA aggregates the spindle microtubules at the midzone during anaphase and telophase and that the polarity of meiotic spindle microtubules might become inverted during spindle elongation.

Animals↗

PubMed2001

Male meiotic spindle lengths in normal and mutant arabidopsis cells.

Spindle elongation is crucial to normal chromosome separation in eukaryotes; in particular, it is required for or associated with the extension of distance between spindle poles and the further moving apart of the already separated chromosomes. However, little is known about the relationship between spindle elongation and the status of chromosome separation, and it is unknown whether spindle elongation in different organisms shares any quantitative feature. The Arabidopsis ask1-1 mutant might be a unique material for addressing these questions because it appears to have functional spindles, but a severe defect in homolog separation at male anaphase I (M. Yang, Y. Hu, M. Lodhi, W.R. McCombie, H Ma [1999] Proc Natl Acad Sci USA 96: 11416-11421). We have characterized male meiotic spindle lengths in wild-type and the ask1-1 mutant plants. We observed that during meiosis I some ask1-1 cells had spindles that were similar in length to fully elongated normal spindles, but the chromosomes in these cells did not show appreciable movement from the equator. Furthermore, greater movement of chromosomes from the equator was usually found in the ask1-1 cells that had longer than normal spindles. These results suggest that additional elongation of ask1-1 spindles occurred; one possible reason for the extra-long spindles may be that it is a consequence of chromosome non-separation. We also found that normal and ask1-1 spindle lengths are clustered at discrete values, and their differences are of multiples of 0.7 microm. A search of the literature revealed that in each of several organisms, spindle lengths also differ by multiples of 0.7 microm. These findings strongly suggest that the spindle elongates in response to status of chromosome separation, and perhaps there are conserved mechanisms controlling the extent of spindle elongation.

Arabidopsis↗

PubMed1975

Barbiturate spindle activity in the thalamic lateral ventro-posterior nucleus and the second somato-sensory area of the cortex.

(1) Barbiturate spindles recorded from the second somato-sensory cortical area (SII) were similar to spindles in the primary somato-sensory area (SI) both with respect to incidence, duration of each spindle and per cent spindle time. The spindle wave amplitude was smaller in SII. The highest spindle wave amplitude was observed in the anterior part of SII which receives input from nucleus ventralis postero-lateralis (VPL). No spindle activity was observed in the posterior part of SII which receives input from the posterior nuclear group (PO) of the thalamus. (2) Barbiturate spindles recorded from a locus in VPL and its projection area in SII were cross-correlated. The analysis resulted in high cross-correlation factors, indicating that a considerable degree of spindle wave synchrony existed between the spindles. This wave synchrony was reduced by moving the cortical electrode a short distance. (3) Cortical spindles recorded from corresponding sites in SI and SII were cross-correlated, and gave a high cross-correlation coefficient. This synchrony was markedly reduced if one of the electrodes was moved a few millimetres away from the optimal point. (4) Spindles started simultaneously in corresponding sites of SI and SII. A high degree of coincidence was found also between spindles in a VPL locus and the corresponding projection site in SII. Local anaesthesia applied to or total removal of SI failed to influence the spindle activity in SII and vice versa. Similarly, the SI-SII synchrony survived a deep incision cutting all connections between the two areas. (6) It is suggested that spindles in corresponding sites of SII and SI have a common thalamic pacemaker which probably projects to both areas by axonal branching.

Anesthesia, General↗

PubMed2004

Physiological and pathological spindling phenomena have similar regional EEG power distributions.

Sleep spindles in human and in rat are known to have a thalamocortical substrate. It has also been suggested that absence epilepsy spike and wave discharges may be generated by a similar mechanism. In addition, we have previously reported a possible thalamocortical origin of the EEG spindling rhythmic discharges associated with myoclonic jerks in the picrotoxin rat model of primary generalised epilepsy. To investigate whether pathological and physiological brain rhythms have common mechanisms of generation, we analysed four electroencephalographic (EEG) spindling activities in the rat. These were the non-convulsive spindle discharges induced by picrotoxin (picrotoxin spindles), naturally occurring absence epilepsy spike and wave discharges (absence spindles), spindle discharges during natural sleep (sleep spindles) and spindling activity that occurs under barbiturate anaesthesia (barbiturate spindles). We used power spectral analysis to define and compare the strength and brain distribution of EEG power during the spindling activities in 12 forebrain and 7 brainstem regions. There were brain-wide differences in power for each of the different spindle types with the pathological rhythms of the epilepsies containing more power than the physiological rhythms. There were also similar differences in the expression of spindles related to the region examined and no thalamic emphasis. These results provide evidence for a similar regional EEG power distribution for all four types of spindling activity and thus for the different spindles being expressions of a single phenomenon.

Analysis of Variance↗

PubMed2000

Sleep spindle asymmetry in epileptic patients.

OBJECTIVE: To investigate sleep spindle asymmetry in patients with idiopathic generalized epilepsy (IGE), cryptogenic partial epilepsy (CPE), and symptomatic partial epilepsy (SPE). METHODS: Post-sleep deprivation EEG records of the patients were investigated. Fast Fourier transform was applied to 200 s of stage-2 activity (without spikes, spike-waves and artefacts). Individual spindle frequency and topography was identified in each patient. Spindle intensity was computed and expressed in microvolts. In order to calculate spindle asymmetry the site of maximum spindle intensity within one hemisphere was compared to the mirror site in the other hemisphere. Asymmetry was expressed by the asymmetry index (AI). In the PE group AI was defined as [AI=(P-N)/(P+N)x100], where P and N were spindle intensity in the pathological and normal hemisphere, respectively. In the IGE group P and N were substituted for L and R (spindle intensity in the left and right hemisphere, respectively). RESULTS: In IGE patients spindle asymmetry was in the range of -13 to +12%. No significant lateralization to the left or right hemisphere was observed. In PE patients, spindle asymmetry ranged from -23 to+29%. As compared to spindle intensity in the unaffected hemisphere, spindling was enhanced in the 'epileptic' hemisphere in most PE patients (15/20 in the CPE and 5/7 in the SPE group). CONCLUSION: In IGEs (where the epileptic condition involved both hemispheres to the same extent) spindle intensity did not show significant asymmetry. In PE patients (where the epileptic process was clearly lateralized to one hemisphere while the other hemisphere was unaffected) enhanced spindling usually was related to the side of the epileptic process. The generally held notion that the pathological hemisphere displays less spindling than the healthy one might be misleading in cases of focal epilepsy. The results suggest that epileptogenic cortex slightly facilitates spindle generation.

Adolescent↗

PubMed2003

Human sleep spindle characteristics after sleep deprivation.

OBJECTIVE: Sleep spindles (12-15 Hz oscillations) are one of the hallmarks of the electroencephalogram (EEG) during human non-rapid eye movement (non-REM) sleep. The effect of a 40 h sleep deprivation (SD) on spindle characteristics along the antero-posterior axis was investigated. METHODS: EEGs during non-REM sleep in healthy young volunteers were analyzed with a new method for instantaneous spectral analysis, based on the fast time frequency transform (FTFT), which yields high-resolution spindle parameters in the combined time and frequency domain. RESULTS: FTFT revealed that after SD, mean spindle amplitude was enhanced, while spindle density was reduced. The reduction in spindle density was most prominent in the frontal derivation (Fz), while spindle amplitude was increased in all derivations except in Fz. Mean spindle frequency and its variability within a spindle were reduced after SD. When analyzed per 0.25 Hz frequency bin, amplitude was increased in the lower spindle frequency range (12-13.75 Hz), whereas density was reduced in the high spindle frequency range (13.5-14.75 Hz). CONCLUSIONS: The observed reduction in spindle density after SD confirms the inverse homeostatic relationship between sleep spindles and slow waves whereas the increase in spindle amplitude and the reduction in intra-spindle frequency variability support the hypothesis of a higher level of synchronization in thalamocortical cells when homeostatic sleep pressure is enhanced.

Adult↗

PubMed1985

Sleep spindles.

Sleep spindles are discussed from various viewpoints. The definition of this pattern has been debated and requires clarification. There is evidence of two spindle types around 14 c/s and 12 c/s. The existence of a third spindle type (around 10 c/s) is controversial. The relationship of spindles to vertex waves and K complexes and the role of spindles in sleep staging are other topics that are covered. As "transient nonstationarities," spindles may escape methods of EEG computer analysis; special methods of spindle detection have been designed. Spindle activity may be influenced by various sedative drugs. An exceptional coexistence of spindles and waking patterns may occur in patients with 5-HIAA-hypersomnia. Sleep spindles change with age and show a typical configuration in early childhood; their decline in old age is also discussed. In monkeys and apes, "natural" spindle activity declines after adolescence. The distinction between natural and experimentally induced (barbiturate) spindles in animals must be stressed. After a discussion of spindle anomalies in neurological diseases, depth EEG data are presented. Spindles are found in the frontal cortex, whereas the scalp EEG indicates light drowsiness or even wakefulness. Attempts are made at an integrated view of these findings. A "shock-absorbing" function is attributed to spindles.

Adolescent↗

PubMed2006

[Spindle cell carcinoma of breast with neuroendocrine differentiation].

OBJECTIVE: To describe the morphologic features and immunohistochemistry of spindle cell carcinoma of breast with neuroendocrine differentiation. METHODS: Retrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2 represented intraductal spindle cell carcinoma and 3 represented invasive spindle cell carcinoma. The paraffin sections were stained with hematoxylin and eosin, alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up information was available in 4 of the 5 cases. RESULTS: The mean age of the patients was 68 years. Histologically, all tumors were predominantly composed of elongated spindle cells. Three of these cases also contained tumor cells with vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases. Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3, CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3 cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4 cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type, while the remaining 2 cases of invasive spindle cell carcinoma were considered as metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients with follow-up information available, 3 were still alive 24 to 58 months after the initial diagnosis. One patient died within 27 months of diagnosis. CONCLUSIONS: The presence of spindle tumor cells and sometimes intracytoplasmic mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle cell carcinoma needs to be distinguished from usual ductal hyperplasia and intraductal papilloma. On the other hand, invasive spindle cell carcinoma with neuroendocrine differentiation needs to be distinguished from spindle cell myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.

Aged↗

PubMed2006

Phosphoproteome analysis of the human mitotic spindle.

During cell division, the mitotic spindle segregates the sister chromatids into two nascent cells, such that each daughter cell inherits one complete set of chromosomes. Errors in spindle formation can result in both chromosome missegregation and cytokinesis defects and hence lead to genomic instability. To ensure the correct function of the spindle, the activity and localization of spindle associated proteins has to be tightly regulated in time and space. Reversible phosphorylation has been shown to be one of the key regulatory mechanisms for the organization of the mitotic spindle. The relatively low number of identified in vivo phosphorylation sites of spindle components, however, has hampered functional analysis of regulatory spindle networks. A more complete inventory of the phosphorylation sites of spindle-associated proteins would therefore constitute an important advance. Here, we describe the mass spectrometry-based identification of in vivo phosphorylation sites from purified human mitotic spindles. In total, 736 phosphorylation sites were identified, of which 312 could be attributed to known spindle proteins. Among these are phosphorylation sites that were previously shown to be important for the regulation of spindle-associated proteins. Importantly, this data set also comprises 279 novel phosphorylation sites of known spindle proteins for future functional studies. This inventory of spindle phosphorylation sites should thus make an important contribution to a better understanding of the molecular mechanisms that regulate the formation, function, and integrity of the mitotic spindle.

Electrophoresis, Polyacrylamide Gel↗

PubMed1997

Mitosis in vertebrate somatic cells with two spindles: implications for the metaphase/anaphase transition checkpoint and cleavage.

During mitosis an inhibitory activity associated with unattached kinetochores prevents PtK1 cells from entering anaphase until all kinetochores become attached to the spindle. To gain a better understanding of how unattached kinetochores block the metaphase/anaphase transition we followed mitosis in PtK1 cells containing two independent spindles in a common cytoplasm. We found that unattached kinetochores on one spindle did not block anaphase onset in a neighboring mature metaphase spindle 20 microm away that lacked unattached kinetochores. As in cells containing a single spindle, anaphase onset occurred in the mature spindles x = 24 min after the last kinetochore attached regardless of whether the adjacent immature spindle contained one or more unattached kinetochores. These findings reveal that the inhibitory activity associated with an unattached kinetochore is functionally limited to the vicinity of the spindle containing the unattached kinetochore. We also found that once a mature spindle entered anaphase the neighboring spindle also entered anaphase x = 9 min later regardless of whether it contained monooriented chromosomes. Thus, anaphase onset in the mature spindle catalyzes a "start anaphase" reaction that spreads globally throughout the cytoplasm and overrides the inhibitory signal produced by unattached kinetochores in an adjacent spindle. Finally, we found that cleavage furrows often formed between the two independent spindles. This reveals that the presence of chromosomes and/or a spindle between two centrosomes is not a prerequisite for cleavage in vertebrate somatic cells.

Animals↗

PubMed2002

Muscle spindle distribution, morphology, and density in longus colli and multifidus muscles of the cervical spine.

STUDY DESIGN: Tissue blocks comprising muscle and bone from C5 to C7 segments were harvested at autopsy from 16 individuals ranging in age from 4 to 77 years. The prevertebral longus colli and postvertebral multifidus muscle pairs from one side in each individual were randomly selected for this study of muscle spindles. OBJECTIVES: To determine muscle spindle distribution, morphology, and density for the longus colli and multifidus in caudal segments of the human cervical spine, and to assess whether changes are evident from infancy to old age. SUMMARY OF BACKGROUND DATA: Age-related changes to the osteoligamentous framework of the cervical spine have been well documented. Postural modification accompanies these structural alterations, but there have been limited attempts to document whether muscle sustains a comparable level of morphologic alteration. Previous studies have examined muscle spindles in the neck muscles of various animal models and in a variety of isolated human muscles. However, most of these studies incurred bias through sampling and methodologic assumptions. METHODS: The longus colli and multifidus were resected between C5 and C7, and between left and right pairs selected randomly for spindle analysis. These vertebral segments were selected deliberately because they form the apex of the cervical lordosis and the site at which the greatest age-related modification occurs. The tissue was processed in paraffin, sectioned, and then stained by Masson's trichrome. Spindle characteristics were examined using light microscopy and analyzed by unbiased stereologic methods. A one-sample paired t test was used to ascertain whether the differences in spindle density between the two muscles were statistically significant. RESULTS: The longus colli has a high density of muscle spindles, which appear clustered and concentrated anterolaterally, away from the vertebral body. The multifidus has a low density of muscle spindles, which are found predominantly as single units concentrated closely to the vertebral lamina. No change in spindle distribution, morphology, and density were observed with age. CONCLUSIONS: The current study examined spindle characteristics for an intrinsic neck muscle pair whose coactivation contributes to segmental stability of the cervical spine. The distribution and morphology of muscle spindles differ between the longus colli and the multifidus. In addition, these muscles have significant differences in terms of mean spindle density. Spindle characteristics represent one of many factors that govern proprioceptive regulation in skeletal muscle, and in neck muscles, the central connectivity of these receptors remains undefined. Therefore, although there are anatomic differences between the neck flexor and extensor, the functional implications of these differences are not clear. It is also of interest that spindle characteristics remain unchanged in these intrinsic muscles whose underlying segments are subject to age-related osteoligamentous changes.

Adolescent↗

PubMed1986

Two types of static gamma-axon in cat muscle spindles.

The action of single static gamma-axons in 'single fibre' ventral root filaments was tested on the responses of from two to eight spindles in the same tenuissimus muscle in anaesthetized cats. The type of intrafusal fibre activated in each spindle by a particular axon was diagnosed from its effect on the discharge of primary and secondary sensory endings, frequently in the same spindle. One or two spindles were subsequently isolated in most experiments and the type of intrafusal fibre activated by the axon was observed directly. Except in the case of a few weak actions which could not be interpreted, the diagnosis made from the afferent recordings was always correct. Twenty-four static gamma-axons activated the chain fibres in every spindle they supplied on which their action was tested; the static bag2 fibre was also involved in about 20% of the spindles though its contraction was quite often weak. Eleven static gamma-axons activated the static bag2 fibre in every spindle they supplied on which their action was tested; some chain fibres were activated as well in about 20% of the spindles. There were only two possible exceptions to the general rule that a static gamma-axon activates either the chain fibres or the static bag2 fibre in every spindle it supplies and never activates only the chain fibres in one spindle, and only the static bag2 fibre in another spindle. Direct observation of isolated spindles provided preliminary evidence that some non-selective connexions of static gamma-axons have a pronounced physiological action by way of their terminals on one type of intrafusal fibre while the terminal(s) on the other type of fibre produce such a weak contraction that the sensory endings are not affected. Other non-selective connexions do, however, have a significant physiological effect by way of their terminals on both the static bag2 fibre and the chain fibres. It is proposed that there are two types of static gamma-motoneurone. 'Static bag gamma-motoneurones', through their terminals on the static bag2 fibre in every spindle, bias the discharge from primary endings (and to a lesser extent from some secondary endings) but leave their length sensitivity largely unaltered; connexions to chain fibres in some spindles have a weak action on primary endings but may greatly increase the length sensitivity of secondary endings.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Regeneration and recovery of cat muscle spindles after devascularization.

1. We have assessed the sensory reinnervation and recovery of regenerated muscle spindles in extensor digitorum longus (EDL) 6, 8 and 13 weeks after the muscle, with its nerve left intact, had been devascularized. Recordings were made from the dorsal roots of the responses of single afferent fibres to ramp-and-hold stretch of the regenerated spindles whose sensory reinnervation was subsequently examined in teased, silver preparations. 2. The spindle population in four normal EDL muscles ranged from 53 to 83 (mean 69); analysis of the afferent innervation of 166 normal b1b2c spindles showed that 23% had primary endings supplied by two Ia afferents. Regenerated spindles were identified as belonging to one of four groups in which afferents establish sensory endings on intrafusal muscle fibres in groups 1-3, but not in group 4. Sensory reinnervation was complete after 6 weeks recovery and similar proportions of group 1-3 spindles occurred after each recovery period, i.e. 58% after 6 weeks, 65% after 8 weeks and 62% after 13 weeks. We estimate that about half the original spindle population was lost owing to persistent ischaemic necrosis; that 30% regenerated and acquired functional afferent connections (group 1-3 spindles); and that the total loss of spindle afferents was over 60%. 3. The conduction velocities of the regenerated spindle afferents were very similar to those of normal EDL spindle afferents. The proportions that responded normally to ramp-and-hold stretch at the end of each recovery period increased from 58% after 6 weeks to 61% after 8 and 88% after 13. Other responsive spindle afferents were either predominantly phasic or only responded to supramaximal stretch. The proportions of these decreased as recovery progressed reducing from 19% after 6 weeks to 9% after 13 weeks in the case of those giving predominantly phasic responses and from 23% after 6 weeks to 3% after 13 weeks in the case of those unresponsive to physiological stretch. 4. The mean peak and held firing rates of regenerated spindle afferents responsive to 10 mms-1 ramp-and-hold stretches were all significantly lower than normal. There was no marked trend towards higher firing rates after longer periods of recovery through, considered separately, the mean peak firing rates of the normally responding afferents did show a distinct improvement. The mean dynamic and velocity indexes were not significantly different from normal. 5. The ratio of Ia:spindle II afferents, as identified by their responses to stretch, was 1:1.22 in the control animals and 1:1.26 in the experimental series.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1998

Multiple spindle cell lipomas: a report of 7 familial and 11 nonfamilial cases.

Spindle cell lipoma, a variant of a benign lipoma, usually occurs as a solitary, subcutaneous, circumscribed lesion in the posterior back, neck, or shoulders of older men. Multiple lesions are exceedingly rare. To our knowledge, there have been no previous series reported of patients with multiple subcutaneous spindle cell lipomas. We examine the clinicopathologic findings of a group of patients with multiple spindle cell lipomas, including seven with a familial occurrence of this disease. The Soft Tissue Registry of the Armed Forces Institute of Pathology and the consultation files of one of the authors (S.W.W.) from the Department of Pathology at the University of Michigan were searched for patients with multiple spindle cell lipomas. All patients' records, clinical history, and pathology were reviewed. All patients had a minimum of two tumors that met strict morphologic criteria for spindle cell lipoma. Pleomorphic cells, typical of pleomorphic lipoma, were observed in some cases and were acceptable as part of the spectrum of spindle cell lipomas. Associated lesions, family history, ethnic background, daily habits, and natural progression of disease were recorded and compared. Eighteen patients in our files met the criteria for multiple spindle cell lipomas; 4 of the 18 patients were from the same family. Three additional patients had a family history of multiple spindle cell lipomas. The ratio of patients with multiple spindle cell lipomas to all patients with spindle cell lipoma in the two consultation files was 0.5 and 3%, respectively. All of the patients in our study were male; three had a family history of females with less severe disease (fewer and smaller spindle cell lipomas); however, no material from these female patients was available for review. All but four patients presented in their sixth through eighth decades of life; yet, several older patients stated that their first lesion occurred in their fifth decade. Patients had between 2 and >220 lesions, which usually commenced on the posterior neck or back, commonly followed by additional bilateral lesions on the shoulders and upper torso. The natural history of this disease revealed development of multicentric lesions over several years, for both familial and nonfamilial cases. The tumors became more cellular as the disease progressed, often with features of pleomorphic lipoma; however, no patients developed spindle cell liposarcoma. Multiple spindle cell lipomas are rare. The clinical presentation may mimic Madelung's disease (symmetrical lipomatosis). As mentioned above, some cases are familial. Genetic predisposition must be further examined. There appears to be no common ethnic background, environmental exposure, medical condition, or syndrome of associated lesions with multiple spindle cell lipomas.

Adult↗