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Network mechanisms of spindle-burst oscillations in the neonatal rat barrel cortex in vivo.

Early in development, cortical networks generate particular patterns of activity that participate in cortical development. The dominant pattern of electrical activity in the neonatal rat neocortex in vivo is a spatially confined spindle-burst. Here, we studied network mechanisms of generation of spindle-bursts in the barrel cortex of neonatal rats using a superfused cortex preparation in vivo. Both spontaneous and sensory-evoked spindle-bursts were present in the superfused barrel cortex. Pharmacological analysis revealed that spindle-bursts are driven by glutamatergic synapses with a major contribution of AMPA/kainate receptors, but slight participation of NMDA receptors and gap junctions. Although GABAergic synapses contributed minimally to the pacing the rhythm of spindle-burst oscillations, surround GABAergic inhibition appeared to be crucial for their compartmentalization. We propose that local spindle-burst oscillations, driven by glutamatergic synapses and spatially confined by GABAergic synapses, contribute to the development of barrel cortex during the critical period of developmental plasticity.

Action Potentials↗

Morphology and distribution of muscle spindles in dorsal muscles of the cat neck.

Silver-stained sections have been examined from the five dorsal neck muscles splenius, biventer, cervicis, complexus, rectus capitis major, and occipitoscapularis. Every serial section was examined for at least one muscle of each type so that a complete description of the spindle distribution and morphology could be made. With the exception of occipitoscapularis (whose prime function is probably in scapula rotation and not in head movement), neck muscles have a remarkably high spindle density. Occipitoscapularis has a spindle density similar to that of hindleg locomotor muscles (13-19 per gram), but splenius has a density of 46-66 per gram, biventer cervicis 74-96 per gram, complexus 71-107 per gram, and rectus capitis major 48-84 per gram. Such high densities have only previously been seen in small muscles whose total spindle population is not large. Because of the relatively large size of some neck muscles, individual muscles with a spindle content of up to 254 spindles have been found.

Animals↗

High incidence of long-chain fibers in spindles of cat superficial lumbrical muscles.

Forty-two complete spindle poles of cat superficial lumbrical muscles were analyzed with particular regard to the length and the diameter of intrafusal fiber types. Poles were reconstructed from serial transverse sections of fresh-frozen muscles. The staining module, which was repeated throughout the whole muscle, comprised sections treated for glycogen detection and sections treated for detecting myofibrillar ATPase activity after preincubation at three different pH's (see METHODS). The identification of intrafusal fiber types was essentially based on the ATPase activity of the B region of the intrafusal fibers. Long-chain fibers, i.e., chain fibers that have at least one pole that extends by more than one millimeter beyond the end of the spindle capsule (6), were very commonly observed. Of 42 spindle poles analyzed, 30 (71%) contained at least one long-chain fiber (one in 17 spindle poles, 2 in 11 poles, and 3 in 2 poles). Of 246 poles of chain fibers, 45 (18%) were "long". In four spindles, in which both poles could be completely examined, 10 long-chain fibers were observed. In eight of these, only one pole was long; the opposite pole ended either intracapsularly or at a short distance outside the capsule. Since long-chain fiber poles, presently considered to be among the effectors of static skeletofusimotor (beta) axons, are present in a large proportion of muscle spindles of lumbrical muscles, it would be of particular interest to reevaluate the beta-supply of these muscles by physiological methods.

Adenosine Triphosphatases↗

Cyclic nucleotide hydrolysis in bovine aortic endothelial cells in culture: differential regulation in cobblestone and spindle phenotypes.

Cyclic nucleotide phosphodiesterases (PDEs) were investigated in cultured bovine aortic endothelial cells having two phenotypes, cobblestone and spindle, representing, respectively, the resting and angiogenic phenotypes in vivo. Spindle cell homogenates displayed higher hydrolytic activities towards cAMP (52%) and cGMP (10-fold). These increases were due to: (1) increased number of spindle PDE isozymes in the cytosolic fraction (for cAMP: PDE1, PDE2, PDE3 and PDE4 compared to PDE2 and PDE4 in cobblestone; for cGMP: PDE2 and PDE5 compared to PDE2 in cobblestone); (2) increased spindle-specific activities of cytosolic and particulate PDE2, cytosolic PDE3 and particulate PDE4. These changes were associated with an increase in spindle transcripts: 7.5 kb PDE3A (6-fold) and 7.0 kb PDE4D (3-fold). Moreover, cAMP hydrolysis in the two phenotypes was differently regulated by 5 microM cGMP: 60% increase in total cAMP-PDE activity in cobblestone homogenate related to PDE2 stimulation; 30% decrease in spindle homogenate related to PDE3 inhibition. This underlines the roles played by PDE2, PDE3 and PDE5 in the cross-talk involving the two cyclic nucleotides. These changes in PDE isozyme expression along with the cross-talk between cAMP and cGMP may well modulate NO production and consequently might participate in angiogenesis, making PDEs potential targets to modulate angiogenesis.

3',5'-Cyclic-AMP Phosphodiesterases↗

A study on gender and age differences in sleep spindles.

In the present work, gender differences in sleep spindle topography were examined in 40 subjects. Their median age was 32 years (range 22-49 years). Spindles were detected from 3,306,060 s of visually scored stage 2 sleep EEG by a previously validated automatic fuzzy detector at 1-second intervals. A total of 271,168 spindles were found from the six EEG channels analyzed. Females showed a significantly higher percentage of spindles in the left frontal channel than males (Fp1-A2; p = 0.026). To confirm that this difference was gender and not age related, the subjects were divided into two age groups. No significant differences in spindle activity of the frontal channels were found between the groups. However, the interindividual spindle variability seemed to be at least as large as that stemming from gender.

Adult↗

Expression of E- or P-cadherin is not sufficient to modify the morphology and the tumorigenic behavior of murine spindle carcinoma cells. Possible involvement of plakoglobin.

Transfection of E- and P-cadherin cDNA has been carried out in murine spindle carcinoma cells previously shown to be deficient in both cadherins (Navarro et al., J. Cell Biol. 115, 517-533, 1991). High levels of expression of E- or P-cadherin do not significantly affect the fibroblastic morphology of the parental spindle cells. In addition, the tumorigenic behavior of these highly malignant cells is not influenced by the ectopic expression of either cadherin. Nevertheless, a fraction of the exogenous cadherins is able to associate to detergent-insoluble components of the transfectant cells, and the expression of the exogenous E-cadherin confers Ca(2+)-dependent aggregation on the spindle transfectants in an in vitro assay. Immunoprecipitation analysis of the cadherin-catenin complex of the transfectants revealed that the ectopic E-cadherin associates with the alpha- and beta-catenin proteins. However, the gamma-catenin/plakoglobin component could not be detected in the E-cadherin immunocomplexes of the spindle transfectant cells, in contrast to the epithelial cells where the three catenins appeared to be associated with E-cadherin. The lack of association of gamma-catenin is correlated with very low levels of plakoglobin in whole cell extracts of the parental spindle cells. These results indicate that the association of E-cadherin with the alpha- and beta-catenin components is not sufficient to promote a fibroblastoid-epithelial conversion of highly malignant spindle cells. The presence of plakoglobin could be required for the proper organization of E-cadherin in the transfectant cells in order to acquire an epithelioid phenotype.

Animals↗

Variation in cytoplasmic microtubule organization and spindle length between the two forms of the dimorphic fungus Candida albicans.

Candida albicans is a dimorphic fungus capable of growing as a budding yeast and as a filamentous hypha. We have used the technique of immunofluorescence to study the changes in the microtubule cytoskeleton during the cell cycle in both growth forms. This approach has revealed the presence of an extensive system of microtubules, including cytoplasmic microtubules and a rod-like intranuclear spindle. We have provided a complete description of the arrangement of cytoplasmic and spindle microtubules at each phase of the yeast cell cycle. A novel and characteristic feature of the yeast phase of Candida is the presence of an array of short microtubules at the neck of the doublet cell. This neck-associated array (NAA), is apparently organized independently of the main microtubule-organizing centre, the spindle pole bodies, at late anaphase. Analysis of microtubule patterns in the hyphal state reveals that the general arrangements of microtubules are similar to those seen in the yeast phase. These patterns suggest a role for the cytoplasmic microtubules in the nuclear migration that occurs during hyphal growth. A major finding is that the mitotic spindle in hyphae is considerably longer (12-20 microns) than the spindle in yeast cells (7-8 microns). This may reflect the role of the hyphal mitotic spindle not only in nuclear division but also in the positioning of the daughter nuclei at the centres of hyphal compartments.

Candida albicans↗

Spindle cell metaplasia in follicular adenoma of the thyroid gland: case report and review of the literature.

Spindle cell tumors and reactive proliferations of the thyroid gland are rarely reported. In this report, we described a case of follicular adenoma with spindle cell component. The spindle cell proliferation constituted more than 90% of the 4.0 cm lesion and showed fascicular pattern with focal areas of collagenous stroma and hyalinized blood vessels. There was a transition from follicle like glandular structure to fascicular pattern. There was no mitosis and necrosis. Immunoreactivity with thyroglobulin proved that the spindle cell proliferation is of follicular origin. Also strong thyroglobulin and cytokeratin positivity of glandular areas and the gradual decrease in positivity of spindle cells showed epithelial-mesenchymal transformation/spindle cell metaplasia of the thyroid. We thought that it is important to differentiate spindle cell metaplasia in follicular lesions, especially follicular adenoma, from malignant thyroid neoplasms.

Adenoma↗

Head and neck spindle cell carcinoma: an evaluation of current management.

Spindle cell carcinoma is an unusual variant of squamous cell carcinoma. The histogenesis of these tumors is controversial, as is the prognosis for patients with spindle cell carcinoma of the head and neck when compared with all squamous cell carcinomas of these sites. Fifteen consecutive nondermal cases of spindle cell carcinoma of the head and neck were reviewed. Six patients had spindle cell carcinoma either in recurrent tumor or in neck metastases following treatment for squamous cell carcinoma where a spindle cell component was not initially noted. Despite aggressive management, 13 patients have died from their disease. The histogenesis and management of spindle cell carcinoma of the head and neck are discussed.

Adult↗

Learning-dependent increases in sleep spindle density.

Declarative memory consolidation is enhanced by sleep. In the investigation of underlying mechanisms, mainly rapid eye movement (REM) sleep and slow-wave sleep have been considered. More recently, sleep stage 2 with sleep spindles as a most prominent feature has received increasing attention. Specifically, in rats hippocampal ripples were found to occur in temporal proximity to cortical sleep spindles, indicating an information transfer between the hippocampus and neocortex, which is supposed to underlie the consolidation of declarative memories during sleep. This study in humans looks at the changes in EEG activity during nocturnal sleep after extensive training on a declarative learning task, as compared with a nonlearning control task of equal visual stimulation and subjectively rated cognitive strain. Time spent in each sleep stage, spindle density, and EEG power spectra for 28 electrode locations were determined. During sleep after training, the density of sleep spindles was significantly higher after the learning task as compared with the nonlearning control task. This effect was largest during the first 90 min of sleep (p < 0.01). Additionally, spindle density was correlated to recall performance both before and after sleep (r = 0.56; p < 0.05). Power spectra and time spent in sleep stages did not differ between learning and nonlearning conditions. Results indicate that spindle activity during non-REM sleep is sensitive to previous learning experience.

Adolescent↗

Bilateral Synchronous Spindle Cell, Apocrine and Scirrhous Carcinoma Breast Cancer in a Case of Malignant Lymphoma.

An unusual case of synchronous bilateral breast cancer occurring during combination chemotherapy and radiation to the outside of the breast for malignant lymphoma is reported. Two histologically rare carcinomas, spindle cell carcinoma and apocrine carcinoma, were observed in this case. A 77-year-old woman, who had been treated for stage IIIA non-Hodgkin's lymphoma, developed bilateral breast tumors. Aspiration biopsy cytology findings of the tumor in the left breast showed several clusters of adenocarcinoma cells and some large atypical spindle shaped cells, which suggested spindle cell carcinoma. The cytologic findings of the right breast tumor were highly suggestive of scirrhous carcinoma. A modified radical mastectomy was performed on both breasts. Pathological examination disclosed two separate cancer lesions in the left breast. The lesion which had been detected before the operation, was a spindle cell carcinoma. Another lesion, detected for the first time by pathological examination, was an apocrine carcinoma. The lesion in the right breast was a scirrhous carcinoma. Since non-invasive fociwere detected in these three cancer lesions, each lesion was thought to be a primary cancer. All dissected bilateral axillary lymph nodes showed malignant lymphoma. Immuno-histochemistry of the spindle cell carcinoma revealed positive immunoreactivity for cytokeratin, which suggested the epithelial as well as mesenchymal nature of this tumor. Synchronous existence of malignant lymphoma and three independent breast cancers including spindle cell carcinoma and apocrine carcinoma is very rare.

Journal Article↗

Sleep spindles and arousal: the effects of age and sensory stimulation.

This study assessed a proposed sleep-preserving role for sleep spindles by evaluating variations in this activity as a function of factors, both naturally occurring and experimentally induced, known to affect and effect arousal from sleep. These factors included age, auditory stimulation, and experimentally induced arousal from sleep. Analyses were based on data from 84 males (5-49 yrs. old) from normal and clinical (hyperactive, enuretic, and chronic pain) populations who had participated in sleep auditory arousal threshold studies involving adaptation and 1-2 experimental nights. Spindles on experimental nights were visually analyzed and incidence determined for the two minutes preceding and throughout all Stage 2 arousal attempts. Prestimulation spindle occurrence in 39 preadolescent subjects with two experimental nights did not vary significantly from night-to-night, and prestimulation period comparisons between clinical groups and their respective controls were also non-significant. Anticipated relationships between spindle activity and indices of arousal-either inverse with respect to known variations in arousal threshold, i.e., decreases with age and across the night, or direct with respect to stimulus intensity particularly on trials when arousal did not occur-were not observed. Instead, all age groups showed significant decreases in spindle density as an increasing negative function of stimulus intensity. These findings suggest that to the extent to which sleep spindles can be considered to play a role in sleep preservation by inhibiting or attenuating potentially arousing stimuli, these effects appear to be restricted to endogenously generated stimuli and are passive rather than reactive in nature.

Acoustic Stimulation↗

Topographical distribution of spindles: variations between and within nrem sleep cycles.

Spindle density, visually scored in the 12-15 Hz range over antero-posterior midline derivations, was assessed during a baseline night in ten normal subjects. Sleep spindles were found to be highly variable between subjects and more abundant during Stage 2. Topographical distribution of spindle density showed a centroparietal prevalence, stable between NREM sleep stages. Intra-night variations of spindle density exhibited a linear increase across consecutive NREM episodes, suggesting an inverse relation with the time course of slow wave sleep. Except for occipital leads reaching a maximum during the third NREM cycle and then decreasing, changes in spindle density across sleep cycles were similar over different derivations. Intra-cycle variations fit a fourth-order polynomial curve with a minimum in the middle part of each sleep episode (when most slow wave sleep is expressed); this intra-cycle trend also seems stable between derivations and consecutive sleep cycles. These results confirm and extend, to the level of macroscopic EEG, the reciprocal relationship between sigma and delta waves previously shown by spectral analysis of EEG frequencies and, at a neuronal level in the thalamocortical network, by changes of membrane potentials that oscillate in the frequency range of spindles or delta at different levels of hyperpolarization.

Adult↗

[Spindle cell lipoma and 13q deletion: diagnostic utility of cytogenetic analysis].

AIM: Spindle cell lipomas are rare adipose tissues tumors. Histologically, these lesions are composed of mature adipocytes and spindle cells associated with collagen bundles. Spindle cell lipomas are benign tumors that can be difficult to distinguish from malignant tumors such as spindle cell liposarcomas, myxoid liposarcomas or well-differentiated liposarcomas. RESULTS: We report herein the description of two new cases. The first case was a deeply situated and infiltrating tumor located in the retromastoidian area. The karyotype showed the presence of two chromosomal abnormalities, a partial deletion of the long arm of chromosome 13, del(13)(q12) and a balanced reciprocal translocation t(2;6)(p16~21;p21). The second case was a subcutaneous tumor of posterior cervical localization. The karyotype showed a 13q deletion associated with a complex rearrangement of chromosomes 5, 6 and 10. The presence of the 13q deletion allowed us to confirm the diagnosis of spindle cell lipoma in both cases. This deletion has been previously described in six out the eleven published karyotype reports. The 13q deletion is usually associated with partial monosomy 16. The present case confirms that it can occur independently. The 6p21 rearrangement may also play a role in the pathobiology of this tumor, as suggested by the positive HMGIY expression detected by immunohistochemistry. CONCLUSION: Our study further illustrates that spindle cell lipomas can infiltrate the surrounding muscle and emphasizes the usefulness of cytogenetic analysis in the differential diagnosis of soft tissue tumors.

Chromosome Aberrations↗

Mycobacterial spindle cell pseudotumor of skin.

Spindle cell pseudotumors may occur due to mycobacterial infection in immunocompromised hosts, particularly those with acquired immunodeficiency syndrome (AIDS). Most of the reported mycobacterial spindle cell pseudotumors were found in the lymph nodes. We report a case of spindle cell pseudotumor in a 37-year-old man with AIDS who presented with a firm nodule over his right arm. Histologically, the tumor was composed of proliferative spindle cells admixed with histiocytes and inflammatory cells. Ziehl-Neelsen stain revealed many acid-fast bacilli in the spindle cells and histiocytes. The acid-fast bacilli were shown to be Mycobacterium avium intracellulare by culture and sequencing of the polymerase chain reaction product of mycobacterial 65-kDa heat shock protein gene. Immunohistochemically, the spindle cells were reactive to CD68, suggesting macrophage differentiation of these cells. It is important for pathologists to recognize this unusual manifestation of mycobacterial infection in immunocompromised patients and avoid mistaking the lesion for a mesenchymal neoplasm.

AIDS-Related Opportunistic Infections↗

[A case of spindle cell carcinoma of the penis].

Spindle cell carcinoma of the penis is extremely rare. The present case report is the nineth case in the world literature. A 71-year-old man was referred to our institution for examination of a penile tumor that showed non-specific granuloma histopathologically. We performed biopsy and total tumor resection. The histopathological finding showed squamous cell carcinoma with spindle type cells constituting the majority of the tumor, and the switching over from squamous cell carcinoma to spindle cell carcinoma was clearly visible in the histopathological examination. Therefore, we diagnosed this as spindle cell carcinoma of penis and performed partial penectomy with inguinal lymph node dissection. Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma. We report the histopathological findings including the data of p53 immunohistochemical study, and reviewed the eight previous reports of spindle cell carcinoma of the penis.

Aged↗

Chordomas with malignant spindle cell components. A DNA flow cytometric and immunohistochemical study with histogenetic implications.

The authors studied four chordomas with malignant spindle cell components (SCs) and 12 conventional chordomas (CCs) by DNA flow cytometry using paraffin-embedded tissue. In addition, immunohistochemical stains for a variety of epithelial and mesenchymal markers were performed. The four SCs contained areas histologically identical to conventional chordomas, as well as a high-grade malignant spindle cell component. All four (100%) SCs had an aneuploid-multiploid DNA content. Of interest, the conventional chordoma areas in these tumors had DNA contents different from those containing the high-grade malignant spindle cells. In contrast, only three (27%) of the 11 conventional chordomas with analyzable histograms had an aneuploid-multiploid DNA content. Immunohistochemical studies performed on the four SCs showed the high-grade malignant spindle cells to stain strongly for vimentin and weakly for cytokeratin, S-100 protein, and epithelial membrane antigen (EMA), whereas the areas of conventional chordoma in these same neoplasms stained moderately for vimentin and S-100 protein, and strongly for cytokeratin and EMA. In two cases, the staining for EMA and cytokeratin highlighted a gradual transition between the areas of conventional chordoma and the spindle cell areas. The immunohistochemical staining pattern of the 12 conventional chordomas was similar to that seen in the conventional chordoma components of the four chordomas with malignant spindle cell components. These results suggest that: 1) aneuploidy is more common in SCs than in CCs, and 2) some SCs are multipotential neoplasms in which the neoplastic cells are capable of differentiation along both epithelial and mesenchymal pathways.

Adult↗

Keratin subsets in spindle cell sarcomas. Keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins.

The presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone-fixed frozen sections. Results revealed that keratins 8 and 18 were present in a high number of tumors: 9 of 9 synovial sarcomas, 5 of 7 leiomyosarcomas, 5 of 5 malignant schwannomas, and 1 of 4 undifferentiated spindle cell sarcomas. In addition to keratins 8 and 18, the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19. Also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution, but desmoplakin was absent in other spindle cell sarcomas. Furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas. In contrast, keratins 7, 13, and 19 were practically absent in leiomyosarcomas, malignant schwannomas, and undifferentiated spindle cell sarcomas. The widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells, previously described in cultured transformed fibroblasts. The presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas.

Cytoskeletal Proteins↗