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Sleep spindles in twins.

Sleep spindle characteristics and spindle power periodicity were studied in 4 identical and 3 fraternal twin pairs (mean age, 16 years). There were no significant genetic effects such as concordance between the identical twins and discordance between the fraternal twins for mean duration, mean amplitude and mean frequency of spindles. Spindle periodicity, which is correspondent to the sleep cycle, was visually more similar between the identical twins than between the fraternal twins. These observations suggest that the sleep cycle which is expressed by periodic appearance of spindle powers is genetically determined. On the other hand, some spindle characteristics and some physical measures had significant relationships. These relationships may suggest that some spindle characteristics are influenced by the individual development rather than by a genetic trait.

Adolescent↗

Development of sleep spindles in the first year of life.

Spindles develop in a man at 6 weeks conceptional age, at first at a low amplitude, gradually increasing in amplitude but especially in duration to a maximum at 13 weeks (mean, 6 sec; longest, 21 sec), rapidly decreasing in duration with age to 23 weeks (mean, 2.5 sec) and then slowly decreasing to the end of the first year (mean, 1.5 sec). The pause between the spindles is usually inversely related to the spindle duration and stabilizes after 23 weeks at 7 sec. The complex of spindle and pause is the longest at 10 weeks (12.5 sec), decreasing with age and stabilizing at 17 weeks at 8.1 sec. Thus, from 17 weeks until the end of the first year, spindles tend to recur every 8-9 sec, although variability is evident, especially in the duration of the pause. Synchronous spindles develop from a low value of 10% to around a 30% value until the end of the year, and asynchronous ones tend to have the same value (30%) for most of the year, except in the youngest patients. The reticular nucleus of the thalamus is known to be the generator of spindles and an increase in some size may be related to the great increase in duration, peaking at 13 weeks, and an increase in the development of the dendritic tree of this nucleus may be related to the many changes that stabilize at 23 weeks of age.

Child Development↗

Electron-microscopic study of the spindle and chromosome movement in the yeast Saccharomyces cerevisiae.

Mitosis in yeast Saccharomyces cerevisiae was investigated in thick (0-25-I mum) serial sections with a high voltage electron microscope and in preparations of spheroplasts spread on a water surface. Spindle microtubules originate from a plaque-like structure called the spindle pole bosis the SPB duplicates and a set of long and short microtubules develops on each SPB. The spindle arises as the SPBs separate on the nuclear membrane adense and are not individually visible. Genetic studies, however, have indicated that there are 17 linkage groups. The number of microtubules was determined in diploid and haploid spindles on serial stereo micrographs. In diploid mitosis about 40 microtubules issue from a SPB. Most are non-continuous and often they are visibly associated with a chromatin fibre. The spindle in haploid cells is similar except that the number of microtubules is about half that in diploid cells and the SPB is smaller. The pole-to-pole microtubules vary in number from spindle to spindle, but in each case enough microtubules are present to account for each linkage group being associated with a single non-continuous microtubule. We conclude that mitosis in yeast is comparable in its general aspect to that observed in typical eukaryotes.

Chromatin↗

Actin in spindles of Haemanthus katherinae endosperm. I. General results using various glycerination methods.

We have studied actin-containing filaments in spindles in Haemanthus endosperm cells glycerinated by various methods; the actin-containing filaments were identified by their reaction with rabbit skeletal muscle heavy meromyosin (HMM) to form 'decorated' filaments. Actin-containing filaments in the spindle were seen in amongst microtubules in bundles (both non-kinetochore microtubule bundles and kinetochore microtuble bundles) and were also seen not associated with microtubules. There were very few extra-spindle actin-containing filaments in these cells. Actin-containing filaments seemed to interact with microtubules, because the filaments remained close to and parallel to microtubules even when the microtubules were sharply curved. Because of the close association between microtubules and actin-containing filaments we could not identify all the actin-containing filaments present in microtubule bundles: microtubules obscured actin-containing filaments. We studied Haemanthus endosperm cells as they were glycerinated. For some of these observations we used phase-contrast microscopy. Glycerination caused the cells to shrink, initially, and this was followed by rapid expansion, but the cells did not expand to as large a volume as before glycerination. Spindle structure was maintained despite these changes in cell size. Evidences for this are that relative chromosome positions were maintained during glycerination, that spindle birefringence was maintained during glycerination, and that individual chromosomal spindle fibres remained birefringent during glycerination. Electron-microscopic observations supported this in that kinetochore microtubule bundles and non-kinetochore microtubule bundle were maintained during glycerination, as was the helical arrangement of spindle ribosomes into polyribosomes. One-step glycerination procedures were used (cells were treated with mixtures containing 25% glycerol, Triton-X-100 and HMM), and such procedures might be of general use. Living cells were embedded in fibrin clots in making light-microscopic observations; this procedure, too, might be of general use.

Actins↗

Retinal waves trigger spindle bursts in the neonatal rat visual cortex.

During visual system development, the light-insensitive retina spontaneously generates waves of activity, which are transmitted to the lateral geniculate nucleus. The crucial question is whether retinal waves are further transmitted to the cortex and influence the early cortical patterns of activity. Using simultaneous recordings from the rat retina and visual cortex during the first postnatal week in vivo, we found that spontaneous retinal bursts are correlated with spindle bursts (intermittent network bursts associated with spindle-shape field oscillations) in the contralateral visual cortex (V1). V1 spindle bursts could be evoked by electrical stimulation of the optic nerve. Intraocular injection of forskolin, which augments retinal waves, increased the occurrence of V1 spindle bursts. Blocking propagation of retinal activity, or removal of the retina reduced the frequency, but did not completely eliminate the cortical spindle bursts. These results indicate that spontaneous retinal waves are transmitted to the visual cortex and trigger endogenous spindle bursts. We propose that the interaction between retinal waves and spindle bursts contributes to the development of visual pathways to the cortex.

Action Potentials↗

Hyalinizing spindle cell tumor with giant rosettes--a soft tissue tumor with mesenchymal and neuroendocrine features. An immunohistochemical, ultrastructural, and cytogenetic analysis.

CONTEXT: Hyalinizing spindle cell tumor with giant rosettes is a recently described biphasic neoplasm of soft tissues that shares mesenchymal and neuroendocrine features. Its morphologic structure is distinctive, with the presence of hyalinized paucicellular foci that are termed rosettes. The cells around the latter display positive immunoreactivity for neuroendocrine markers. The small number of cases described to date indicates that they tend to be localized in the extremities. OBJECTIVE: To describe the clinicopathologic features of 2 unusual cases of hyalinizing spindle cell tumor with giant rosettes. METHODS AND RESULTS: One tumor was located in the prestyloid parapharyngeal space and the second in the left thigh. Both tumors were well circumscribed and surrounded by a thin capsule-like fibrous band without infiltrating projections. The rosettes were embedded in a spindle cell proliferation. Immunohistochemical stains showed positive results for S100 protein, synaptophysin, CD57, protein gene product 9.5, and neuron-specific enolase exclusively in the cells palisading the rosettes. These markers were negative in the spindle cell portions of the tumor. The latter were immunoreactive for factor XIIIa, vimentin, HAM56, collagen IV, and CD68. Vimentin was the only marker shared by the rosette-forming cells and the spindle cells. Ultrastructurally, the rosette-forming cells contained neurosecretory granules. This study describes the first cytogenetic analysis in this type of tumor revealing 2 cell lines, both containing a balanced translocation between chromosomes 7 and 16. Follow-up of the patients at 16 and 8 months did not disclose evidence of recurrence. CONCLUSIONS: These 2 new cases increase the awareness of hyalinizing spindle cell tumor with giant rosettes and demonstrate that it is a spindle cell neoplasm of unique cytogenetic rearrangements composed of dendritic, histiocytic, and fibroblastic cells admixed with cells that have neuroendocrine differentiation.

Adult↗

[Morphology and immunohistochemical characteristics of hepatic primary and metastatic malignant spindle cell tumors].

OBJECTIVE: To investigate the morphology and immunohistochemical characteristics of hepatic primary and metastatic malignant spindle cell tumors, and to conclude the diagnostic and differential diagnostic criteria for these morphologically similar tumors. METHODS: Forty-six specimens of hepatic spindle cell tumors. 20 primary tumors (43.4%), including 3 cases of sarcomatoid carcinoma (6.5%), 11 of angiosarcoma (23.9%), 2 of epithelioid hemangioendothelioma (5%), 1 of spindle cell carcinoid (2.2%), and 3 of undifferentiated sarcoma (6.5%). and 26 metastatic malignant tumors (56.5%), including 20 cases of gastrointestinal stromal tumors (GIST, 43.4%), 3 of leiomyosarcoma (6.5%), 2 of malignant peripheral never sheath tumor (4.3%), and 1 of meningeal hemangiopericytoma (2.2%), resected during operation or collected during imaging-mediated liver puncture underwent hematoxylin-eosin staining, SP staining, and EnVision immunohistochemical staining. RESULTS: Either primary or metastatic tumors showed extensive overlapping in histopathologic appearance, and hemangiopericytoma-like structure was the predominant pattern, which could be seen in nearly every kind of hepatic spindle cell tumors. The morphology of GIST was the most complex. Two or three entirely different kinds of structure could be seen in one specimen of GIST, especially in the resected ones. Most stromal tumor cases were CD117 positive, and existed the condition that the primary tumor was positive and the metastatic tumor was negative or vice versa or one part of specimen was positive but other part was negative. Leiomyosarcoma was immunoreactive to smooth muscle specific antigen (SMA), malignant peripheral nerve sheath tumor was immunoreactive to S-100 protein and neurofilament (NF), and both were CD117 negative. Angiosarcoma and epithelioid hemangioendothelioma expressed different immunoreactivity to CD31, CD34 and factor VIII related antigen. Sarcomatoid carcinoma was positive for CK and vimentin. Spindle cell carcinoid was positive for CK and neuroendocrine markers, such as synaptophysin and chromogranin A. CONCLUSION: Primary angiosarcoma is the most common form of primary spindle cell tumor in liver, and metastatic GIST is predominant in hepatic metastatic spindle cell tumors. A penal of immunohistochemical markers is necessary for the final diagnosis of these tumors because of the complexity and similarity of different tumors of this kind.

Adolescent↗

[Pathological study of pulmonary carcinomas with spindle and/or giant cells].

OBJECTIVE: To study the pathologic features of pulmonary carcinomas with spindle and/or giant cells. METHODS: Twenty cases of pulmonary carcinomas with spindle and/or giant cells were studied by using lightmicroscopy and immunohistochemical staining. RESULTS: Of 20 cases, 15 cases were pleomorphic carcinoma (10 cases with adenocarcinoma, 3 cases with large cell carcinoma, 1 case with squamous cell carcinoma and 1 case with giant cell carcinoma) , 4 cases were spindle cell carcinoma, and 1 case was giant cell carcinoma. Immunohistochemical results showed AE1/AE3 was positive in the spindle and/or giant cell component of 19 cases, Vimentin was positive in the spindle and/or giant cell component of 20 cases, P53 was positive in 10 cases and thyoid transcription factor-1 (TTF-1) was negtive in all cases. CONCLUSIONS: Pulmonary carcinomas with spindle and/or giant cells is definded as a group of poorly differentiated non-small cell carcinoma that contains a component of spindle and/or giant cells. The diagnosis is based on histopathology and immunohistochemical staining of AE1/AE3 and Vimentin.

Adenocarcinoma↗

[Sleep spindles and physical parameters].

In 4 identical (Nos. 1-4) and 3 fraternal (Nos. 5-7) male twin pairs (mean age, 16 years), sleep spindles were analysed during sleep. The height, body weight, plantar length and chest circumference were measured, and the correlations between sleep spindles and these physical parameters were examined. The physical parameters showed concordance between identical twin pairs except one pair (No. 4) and one fraternal pair (No. 5) but discordance between two fraternal twin pairs (Nos. 6 and 7). Number of sleep spindles and sleep spindle density showed almost concordance between identical twin pairs and one fraternal pair (No. 5), while discordance between two fraternal ones (Nos. 6 and 7). Both number of sleep spindles and sleep spindle density were inversely correlated with body weight (r = -0.61, p less than 0.02; r = -0.62, p less than 0.02). These facts would suggest that sleep spindles rather reflect the individual development than genetic trait.

Adolescent↗

[Spindle activity during sleep in subjects with a deficit in pallesthetic sensibility].

Sleep spindle activity was studied on four subjects affected by pallesthesic deficit due to injury the posterior funiculi of the cord. The spindle activity was studied as density (number of spindles min.), duration and percent of sleep time utilized in spindle activity. The polygraph sleep records included EOG, EMG and 6 monopolar EEG recordings, 3 for each side, on the frontal, parietal and occipital regions. The records showed a spindle activity which was similar in different subjects and that was significantly higher than the physiological values. In fact, the spindle density was about 250%, the duration was about 130% and the spindle percent was about 280%, with respect to the physiological values assumed to be 100%.

Aged↗

The organization of microtubules during anaphase and telophase spindle elongation in the rust fungus Puccinia.

The entire framework of microtubules (MTs) in the meiotic spindle of the rust fungus Puccinia has been reconstructed during the later stages of meiosis I, by tracking MTs through transverse serial sections. This spindle is of special interest because it elongates considerably during anaphase spindle elongation, from 5 microns at metaphase to 15 microns at telophase. The spindle is composed mainly of MTs from opposite poles which interdigitate or overlap in the middle of the spindle. In the overlap region, MTs from one pole seek out as near neighbors, MTs from the opposite pole at a preferred spacing of 43 to 55 nm. During anaphase elongation three changes in spindle structure occur: 1) the region of overlap decreases, but this reduction in overlap cannot account for all the increase in spindle length; 2) interdigitated MTs (MTs from one pole that are within 80 nm of a MT from the opposite pole) dramatically increase in length by MT polymerization and; 3) kinetochore MTs, free MTs (those unattached to the poles) and non-interdigitated polar MTs shorten and disappear. The mechanism of anaphase elongation and the control over MT polymerization and depolymerization during anaphase are discussed.

Anaphase↗

Spindle epithelial tumor with thymus-like differentiation: a case report with cytologic, histologic, immunohistologic, and ultrastructural findings.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare and distinctive low-grade neoplasm of thymic or related branchial pouch differentiation. The tumor usually presents in the thyroid or lateral neck of children and adolescents and could mimic spindle-cell carcinoma, synovial sarcoma, or malignant teratoma. We report the clinical, cytologic, histologic, immunohistochemical, and ultrastructural features of a SETTLE present for 10 years in a 15-year-old boy. The fine-needle aspirate, initially interpreted as synovial sarcoma, contained numerous clusters of bland spindle cells, with a few detached sheets of columnar mucous cells in a homogeneous background of dissociated spindle cells. Mitoses, necrosis, and atypia were not present. The excised tumor was a well-circumscribed, white-tan mass, with occasional microcysts. Microscopically, the mass consisted of a lobulated, highly cellular, spindle-cell neoplasm arranged in intersecting, whorled, and storiform fascicles separated by fibrous bands. Entrapped within the fibrous bands were squamous-lined cysts and benign-appearing glands lined by columnar epithelium with goblet cells or ciliated pseudostratified epithelium. Immunohistochemically, the spindle cells showed diffuse reactivity for cytokeratins, smooth muscle actin, muscle-specific actin, and MIC-2, and they were negative for epithelial membrane antigen, calcitonin, and thyroglobulin. Ultrastructurally, numerous perinuclear tonofilaments, some aligned with mature desmosomes, were identified in the spindle cells. Occasional cells showed thin filaments with fusiform dense bodies occupying the peripheral cytoplasm. These findings distinguish SETTLE from ectopic thymoma, synovial sarcoma, medullary carcinoma, and teratoma, and they support a thymic epithelial origin for SETTLE, possibly with myoepithelial differentiation.

Adolescent↗

Immunohistochemistry of unclassified sex cord-stromal tumors of the testis with a predominance of spindle cells.

Unclassified sex cord-stromal tumors (SCSTs) of the testis comprised predominantly of spindle cells can be difficult to classify. To achieve better definition of these tumors, we examined the histologic, histochemical, and ultrastructural features of four unclassified SCSTs with spindle-cell features, and compared their immunohistochemical features with those of 24 other SCSTs of the testis and ovary. Three of the spindle-cell tumors were composed of relatively short spindled cells with prominent nuclear grooves and intermixed epithelioid cells. All of the three were located adjacent to the rete testis. The fourth case consisted of elongate spindle cells that were reminiscent of smooth muscle. In all of the four cases, reticulin enveloped aggregates of cells of various sizes but not individual cells. Ultrastructural analysis of two of the spindle-cell tumors revealed desmosomes, numerous thin filaments, and focal dense-bodies. Immunohistochemically, all of the four tumors were reactive for S-100 protein and smooth muscle actin. Staining for S-100 protein and smooth muscle actin was also observed in three of six granulosa cell tumors and both juvenile granulosa cell tumors. Although variable staining for S-100 protein was found in 5 of the 12 other SCSTs (4 Leydig cell, 6 Sertoli-Leydig cell, and 2 unclassifiable ovarian SCSTs), reactivity for smooth muscle actin was present in only 1 Sertoli-Leydig cell tumor. In contrast, all of the four ovarian fibromas/thecomas were reactive for smooth muscle actin but failed to stain for S-100 protein. Taken together, the histologic, histochemical, immunohistochemical, and ultrastructural features of the spindle-cell tumors are similar to those of granulosa cell tumors. Reactivity for S-100 protein and smooth muscle actin is characteristic of these tumors. These tumors should be distinguished from other unclassified SCSTs.

Actins↗

Microvasculature of rabbit muscle spindles.

The microvasculature of the muscle spindle and its relationship to the microcirculation of teniussimus extrafusal muscle is described. Muscle spindles lie in close proximity and parallel to the central artery, vein, and nerve. The arterioles to spindle capillaries are third to fourth order branches of the central artery, whereas most arterioles to extrafusal capillaries are sixth to eighth order. Two or three capillaries enter each spindle. At least one entry consistently was encountered in the equatorial area near the sensory endings. Branches of intrafusal capillaries run longitudinally, anastomose with each other, and cradle the sensory zone in a longitudinal capillary loop. Capillaries in muscle spindles are larger than those in extrafusal muscle. These characteristic features are presumed to enhance the capability of these capillaries to provide sufficient circulation to the spindle, particularly to the region of the sensory endings.

Animals↗

Relationships between the central spindle and the contractile ring during cytokinesis in animal cells.

During late anaphase and telophase, animal cells develop a bundle of antiparallel, interdigitating microtubules between the two daughter nuclei. Recent data indicate that this structure, called the central spindle, plays an essential role during cytokinesis. Studies in Drosophila and on vertebrate cells strongly suggest that the molecular signals for cytokinesis specifically emanate from the central spindle midzone. Moreover, the analysis of Drosophila mutants defective in cytokinesis has revealed a cooperative interaction between the central spindle microtubules and the contractile ring: when either of these structures is perturbed, the proper assembly of the other is disrupted. Based on these results we propose a model for the role of the central spindle during cytokinesis. We suggest that the interaction between central spindle microtubules and cortical actin filaments leads to two early events crucial for cytokinesis: the positioning of the contractile ring, and the stabilization of the plus ends of the interdigitating microtubules that comprise the central spindle. The latter event would provide the cell with a specialized microtubule scaffold that could mediate the translocation of plus-end-directed molecular motors to the cell's equator. Among the cargoes transported by these motors could be proteins involved in the regulation and execution of cytokinesis.

Actins↗

Factors affecting the role of the spindle during early response of mouse oocytes to ethanol stimulation.

Winston et al. ([1995] J. Cell Sci., 108:143-151) have shown recently that short (6 min) exposure of spindle intact oocytes from Swiss mice to 8% ethanol induced activation of most oocytes, while disruption of the spindles in these oocytes by nocodazole, before and during ethanol exposure, completely inhibited oocyte activation. We compared the activation rates (ARs) of nocodazole-treated and intact oocytes recovered from SJL and B6D2 F1 hybrid mice under the same experimental conditions. The difference between the ARs of nocodazole-treated and intact SLJ oocytes was about the same as reported for Swiss oocytes (2% vs. 82%, respectively). In contrast, this difference was minor for B6D2 oocytes (87% vs. 100%, respectively). Moreover, 41% of these oocytes underwent activation when the spindle was absent, not only before and during, but also 2 h after ethanol exposure. Shortened exposure (2 min) of B6D2 oocytes to ethanol, however, increased the difference in the ARs of nocodazole-treated and intact oocytes (18% vs. 67%, respectively). We conclude that at least two parameters affect the necessity of the presence of the spindle during ethanol exposure for the activation of mouse oocytes. They are the genotype of the oocytes and the duration of exposure to ethanol. Under one set of these parameters the presence of the spindle is absolutely necessary, while under the other the appearance of the spindle a few hours after ethanol exposure is sufficient to allow the activation of some oocytes.

Animals↗

Minus end-directed kinesin-like motor protein, Kcbp, localizes to anaphase spindle poles in Haemanthus endosperm.

Microtubule-based motor proteins assemble and reorganize acentrosomal mitotic and meiotic spindles in animal cells. The functions of motor proteins in acentrosomal plant spindles are unknown. The cellulosic cell wall and relative small size of most plant cells precludes accurate detection of the spatial distribution of motors in mitosis. Large cell size and absence of a cellulosic cell wall in Haemanthus endosperm make these cells ideally suited for studies of the spatial distribution of motor proteins during cell division. Immunolocalization of a kinesin-like calmodulin-binding protein (KCBP) in Haemanthus endosperm revealed its mitotic distribution. KCBP appears first in association with the prophase spindle. Highly concentrated within the cores of individual kinetochore fibers, KCBP decorates microtubules of kinetochore-fibers through metaphase. By mid-anaphase (when a barrel-shaped spindle becomes convergent), the protein redistributes and accumulates at the spindle polar regions. In telophase, KCBP relocates toward the phragmoplast and cell plate. These data suggest a role for KCBP in anaphase spindle microtubule convergence, which assures coherence of kinetochore-fibers within each sister chromosome group. Increasing coherence of kinetochore-fibers prevents splitting within each sister chromosome group and formation of multinucleated cells.

Anaphase↗

NuMA is a component of an insoluble matrix at mitotic spindle poles.

NuMA associates with microtubule motors during mitosis to perform an essential role in organizing microtubule minus ends at spindle poles. Using immunogold electron microscopy, we show that NuMA is a component of an electron-dense material concentrated at both mitotic spindle poles in PtK1 cells and the core of microtubule asters formed through a centrosome-independent mechanism in cell-free mitotic extracts. This NuMA-containing material is distinct from the peri-centriolar material and forms a matrix that appears to anchor microtubule ends at the spindle pole. In stark contrast to conventional microtubule-associated proteins whose solubility is directly dependent on microtubules, we find that once NuMA is incorporated into this matrix either in vivo or in vitro, it becomes insoluble and this insolubility is no longer dependent on microtubules. NuMA is essential for the formation of this insoluble matrix at the core of mitotic asters assembled in vitro because the matrix is absent from mitotic asters assembled in a cell-free mitotic extract that is specifically depleted of NuMA. These physical properties are consistent with NuMA being a component of the putative mitotic spindle matrix in vertebrate cells. Furthermore, given that NuMA is essential for spindle pole organization in vertebrate systems, it is likely that this insoluble matrix plays an essential structural function in anchoring and/or stabilizing microtubule minus ends at spindle poles in mitotic cells.

Antigens, Nuclear↗