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PubMed1999

Fine-needle aspiration cytology of spindle cell lesions of the breast.

BACKGROUND: Fine-needle aspiration biopsy (FNA) has been successful in diagnosing epithelial lesions of the breast. Its role in the evaluation of spindle cell and mesenchymal lesions of the breast, which include a variety of benign and malignant conditions, is less clear. This article discusses the cytologic features and differential diagnosis of these lesions, as well as the potential diagnostic pitfalls associated with them. METHODS: FNAs of the breast, in which a spindle cell or mesenchymal component was a key or dominant feature, were retrieved. Fibroadenomas without cellular stroma and typical lipomas were excluded. RESULTS: Forty-six aspirates (0.87%) in a series of 5306 breast FNAs contained a significant spindle cell or mesenchymal component. The aspirates were classified into 4 categories: 1) reactive conditions, including 2 diabetic mastopathies, 3 granulation tissue specimens, and 7 granulomatous lesions; 2) benign neoplastic conditions, including 1 mammary hamartoma, 1 dermatofibroma, 1 fibromatosis, 2 granular cell tumors, 2 angiolipomas, and 7 cellular fibroadenomas; 3) low grade malignant neoplastic lesions, including 10 low grade phyllodes tumors; and 4) high grade malignant neoplastic lesions, including 1 metaplastic carcinoma with chondroid stroma, 1 pleomorphic liposarcoma, 2 malignant fibrous histiocytomas, 2 osteosarcomas, and 4 metastatic melanomas. A specific diagnosis was rendered in 38 cases (82.6%). The mammary hamartoma was diagnosed as fibrocystic changes; the dermatofibroma as benign spindle cell lesion, not otherwise specified (NOS); and the primary osteosarcoma as an atypical spindle cell proliferation, NOS. The reactive ductal epithelial cells in one of the granulomatous mastitis specimens, as well as the hyperplastic ductal epithelial cells in one of the phyllodes tumors, were interpreted as atypical ductal proliferation. The marked cytologic atypia displayed by one granular cell tumor was interpreted as low grade adenocarcinoma and the primary liposarcoma as poorly differentiated carcinoma. CONCLUSIONS: Breast lesions with a significant spindle cell or mesenchymal component are rarely encountered in FNA and constitute a heterogeneous group that may pose a diagnostic dilemma. FNA should be the initial diagnostic procedure for investigating these lesions, as a specific diagnosis was rendered in the majority of cases. Cancer (Cancer Cytopathol)

Adult↗

PubMed2001

Transthoracic fine-needle aspiration biopsy of pulmonary spindle cell and mesenchymal lesions: a study of 61 cases.

BACKGROUND: Spindle cell and mesenchymal lesions of the lung encompass a wide variety of benign and malignant conditions. However, to the authors' knowledge, because of their rarity, few reports concerning their cytologic findings are available in the literature. The current review emphasizes the cytomorphologic features, differential diagnosis, and potential pitfalls associated with these lesions. METHODS: Seven hundred seventy-nine percutaneous lung fine-needle aspiration (FNA) specimens were retrieved from the authors' cytopathology files over a period of 5 years. Sixty-one cases (7.8%) in which a spindle cell component was the dominant or key feature were identified. The authors reviewed the cytologic smears, immunocytochemical studies, and corresponding surgical material and clinical information. RESULTS: Of these 61 aspirates, 33 (54%) were reactive processes (31 granulomas, 1 organizing pneumonia, and 1 inflammatory pseudotumor). Five cases (0.8%) were benign neoplasms (2 hamartomas, 2 solitary fibrous tumors, and 1 schwannoma). Twenty-three cases (38%) were malignant neoplasms (8 cases were primary tumors [including 5 carcinomas with spindle cell or sarcomatoid features, 1 spindle cell carcinoid tumor, 1 leiomyosarcoma, and 1 synovial sarcoma] and 15 cases were secondary tumors [including 9 melanomas, 2 leiomyosarcomas, 1 malignant fibrous histiocytoma, 1 meningioma, 1 sarcomatoid renal cell carcinoma, and 1 uterine malignant mixed müllerian tumor]). A specific diagnosis was rendered in 52 cases (85%). No false-positive cases were encountered but there was one false-negative case. One patient who was diagnosed with granulomatous inflammation on FNA was found to have nonsmall cell lung carcinoma on subsequent transbronchial biopsy. No malignant cells were identified in the smears on review. The FNA from the organizing pneumonia was interpreted as a solitary fibrous tumor whereas the inflammatory pseudotumor was diagnosed as granulomatous inflammation. The FNA from one pulmonary hamartoma initially was considered to be nondiagnostic. One solitary fibrous tumor and the schwannoma were diagnosed as smooth muscle tumor and spindle cell tumor, not otherwise specified, respectively. Among the malignant tumors, the primary synovial sarcoma and one of the metastatic malignant melanomas initially were interpreted as primitive neuroectodermal tumor/Ewing sarcoma and poorly differentiated carcinoma, respectively. CONCLUSIONS: Spindle cell lesions of the lung rarely are encountered on transthoracic lung FNA and are comprised of a wide variety of benign and malignant entities. By correlating clinical and radiologic data, cytologic findings, and ancillary studies, a high diagnostic accuracy rate can be achieved with FNA.

Adult↗

PubMed2003

Accuracy of cytological grading of spindle-cell sarcomas.

Spindle-cell sarcomas constitute an important component of soft-tissue sarcomas, where accurate grading may be more important than histologic subtype in order to plan treatment strategies and determine prognosis. To evaluate the applicability and accuracy of grading spindle-cell sarcomas on fine-needle aspiration cytology (FNAC) smears, 54 cases of histologically documented spindle-cell sarcomas, consisting of synovial sarcomas (20 cases), neurofibrosarcomas (12 cases), leiomyosarcomas (9 cases), dermatofibrosarcoma protuberans (DFSP; 6 cases), fibrosarcomas (3 cases), hemangiopericytomas (2 cases), and spindle-cell sarcomas, unclassified (2 cases), were graded according to a three-tier system proposed earlier for FNAC smears, while the histological sections were graded using the French Federation of National Cancer Centers (FNCLCC) grading system. The cytological grading was correlated with the histological grade. There was an overall cytologic and histologic concordance in 40/54 (74%) cases, and concordance in 9/13 (69%) grade I, 19/25 (76%) grade II, and 12/16 (75%) grade III cases. Analysis of grading of individual sarcomas revealed a concordance in 92% of neurofibrosarcomas, 78% of leiomyosarcomas, 70% of synovial sarcomas, 67% of dermatofibrosarcoma protuberans, 67% of fibrosarcomas, 50% of hemangiopericytomas, and 50% of cases of malignant mesenchymal tumors, spindle-cell type unclassified. Major noncorrelation was seen in 10/54 (18.5%) cases. Minor noncorrelation was seen in 4/54 (7.4%) cases. Thus it is possible to accurately predict the grade in 74% of cases of spindle-cell sarcomas. The cytological and histological concordance was better (75%) in high-grade (grades II and III) as compared to grade I sarcomas (69%). Sampling errors due to morphologic heterogeneity in sarcomas may cause noncorrelation in a few cases.

Adult↗

PubMed1992

Fine-needle aspiration cytology of spindle cell neoplasms of the adrenal gland.

Three spindle cell neoplasms were encountered in a series of 46 FNA of the adrenal performed between 1984 and 1991. These neoplasms included a recurrent undifferentiated adrenal cortical carcinoma (ACC) with a predominant spindle cell pattern, a pheochromocytoma (PC), and a metastatic desmoplastic malignant melanoma (DMM). Cytologically, the ACC was characterized by the presence of numerous microtissue fragments composed of spindle-shaped malignant cells with oval to spindle-shaped nuclei, one or more nucleoli, and bipolar cytoplasmic processes. In some areas the tumor cells were dissected by vascular channels. The background contained abundant metachromatic stroma as well as individually scattered tumor cells. The PC was composed predominantly of loosely cohesive spindle-shaped cells along with more polygonal shaped cells with delicate faintly staining granular cytoplasm. The tumor cells exhibited mild anisonucleosis. The tumor fragments were well vascularized by arborizing delicate capillary channels. The DMM was composed of microtissue fragments, interlacing fascicles and loose aggregates of spindle-shaped malignant cells with hyperchromatic nuclei, small nucleoli, and an absence of cytoplasmic pigment. In each case ancillary studies including immunocytochemistry and electron microscopy (EM) were helpful in the differential diagnosis. The ACC was negative for cytokeratins, neuron-specific enolase (NSE), and muscle-specific actin (HHF), but displayed strong positivity for vimentin as well as characteristic whorls of smooth endoplasmic reticulum by EM. The PC was positive for NSE and chromogranin with no EM performed. The DMM stained for S-100 and vimentin but was negative for HMB-45, cytokeratin, and HHF. EM examination revealed rare atypical premelanosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

PubMed1995

Expression of beta 1 integrin receptors in transformed mouse epidermal keratinocytes: upregulation of alpha 5 beta 1 in spindle carcinoma cells.

The adhesive properties and the expression of extracellular matrix receptors of the beta 1-integrin subfamily were analyzed in transformed epidermal keratinocyte cell lines of different stages of mouse skin carcinogenesis. One- and two-dimensional analyses of the immunoprecipitates obtained with anti-beta 1- and specific anti-alpha-integrin subunits showed qualitative and quantitative changes in the expression of beta 1 integrins by the different cell lines. The polyvalent alpha 3 beta 1 integrin was expressed by all analyzed cell lines, although the levels detected in undifferentiated spindle CarC cells were lower than those present in the rest of keratinocyte cell lines. In contrast, spindle cells expressed high levels of the specific fibronectin receptor alpha 5 beta 1, whereas this integrin was absent or expressed at very reduced levels in the other epithelial cell lines. Expression of alpha 5 beta 1 integrin in spindle cells appeared organized in cell-substratum contact areas on spread cells. In addition, high and homogenous expression of alpha 5 beta 1 was detected in fully undifferentiated tumors induced in nude mice by three independent spindle cell lines. These results suggest that the expression of alpha 5 beta 1 integrin is upregulated during the development of spindle cell carcinomas that occur in the last stages of mouse skin carcinogenesis and can be associated with the acquisition of the fibroblastoid phenotype of spindle cells. On the other hand, expression of the collagen receptor alpha 2 beta 1 was demonstrated in a transformed cell line (PDV), and it was apparently also expressed in two other malignant keratinocyte cell lines (PDVC57 and HaCa4). The expression of alpha 2 beta 1 was correlated with the increased adhesion to collagen type I and collagen type IV exhibited by the tumorigenic cell lines.

Animals↗

PubMed1988

Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast.

Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase-antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.

Adult↗

PubMed1986

An interpretation of retinopathy of prematurity in terms of spindle cells: relationship to vitamin E prophylaxis and cryotherapy.

Spindle cells in the hyperoxygenated, avascular, vanguard retina are proposed to be the peripheral inducers of the neovascularization associated with retinopathy of prematurity (ROP). The induction of ROP is conceptualized in terms of three basic events. First, activation of spindle cells results initially in the increase in gap junctions between adjacent spindle cells, secondarily in the increase in cytoplasmic volume of rough endoplasmic reticulum, and ultimately in the synthesis and secretion of angiogenic factors Second, maturation of spindle cells is associated with a decrease in gap junctions, a diminished cytoplasmic volume of rough endoplasmic reticulum, and a cessation of synthesis and secretion of angiogenic factors. Third, myofibroblasts invade the vitreous concomitantly with spindle cell maturation and provide the tractional force that can produce retinal separation. The extent of interstitial retinol binding protein within the subretinal space explains the gestational-age-dependent efficacy of vitamin E in suppressing the development of severe ROP. The kinetics of both spindle cell activation/maturation and myofibroblast invasion predict the efficacy of appropriately timed and placed transretinal cryotherapy.

Cell Movement↗

PubMed2003

Automatic analysis of electro-encephalogram sleep spindle frequency throughout the night.

A fully automatic method to analyse electro-encephalogram (EEG) sleep spindle frequency evolution during the night was developed and tested. Twenty all-night recordings were studied from ten healthy control subjects and ten sleep apnoea patients. A total of 22,868 spindles were detected. The overall mean spindle frequency was significantly higher in the control subjects than in the apnoea patients (12.5 Hz against 11.7 Hz, respectively; p<0.004). The proposed method further identified the sleep depth cycles, and the mean spindle frequency was automatically determined inside each sleep depth cycle. In control subjects, the mean spindle frequency increased from 12.0 Hz in the first sleep depth cycle to 12.6 Hz in the fifth cycle. No such increase was observed in the sleep apnoea patients. This difference in the spindle frequency evolution was statistically significant (p<0.004). The advantage of the method is that no EEG amplitude thresholds are needed.

Adult↗

PubMed1999

Physiological evidence for caudal brainstem projections of jaw muscle spindle afferents.

Retrograde transport and intra-axonal labeling studies provide convincing evidence that jaw-muscle spindle afferents project to the caudal medulla by way of Probst's tract. However, functional properties of this caudal projection are not well understood. Extracellular recordings were made in cats at the level of the subnucleus interpolaris (Vi) to identify single units that showed consistent responses to ramp-and-hold stretches of the jaw. In this report, we present data from 20 central units with properties indicating that they received input from trigeminal muscle spindle afferents. All units were activated by gentle palpation of jaw muscles, and none had superficial receptive fields. Two groups of neurons could be defined based on their responses to passive jaw movements. One group (n=12) showed an obvious dynamic response (i.e., a higher level of activity at the onset of stretch than during the hold period). Activity was maintained during the hold phase, and the units stopped firing (unloaded) for a brief period upon jaw closure. The other group (n=8) lacked a dynamic response. Instead, they showed an increase in firing with onset of stretch that was maintained during the hold phase. Thirteen units, which were tested with more than three different jaw stretch speeds and/or amplitudes, were further characterized by analyzing dynamic index (DI) and mean firing rate (MFR) during each phase of the ramp-and-hold movement as well as interspike interval (ISI) variability. All but one unit with a dynamic response showed a speed-sensitivity. In all cases, the MFR was a more sensitive indicator of changes in jaw speed than DI. Neurons in the other group (5/5 tested) showed a high position-sensitivity, i.e., their firing rates varied as a function of amplitude of jaw opening. The percent change in ISI variability for all neurons ranged from 37-84%. The response characteristics of these central neurons were compared to known physiological properties of muscle spindle afferents. The results provided compelling evidence for jaw-muscle-spindle afferent projection onto these neurons. Reconstruction of recording sites showed that medial Vi, and the adjacent reticular formation, are likely recipients for the caudal projections from jaw-muscle-spindle afferents. We suggest that muscle spindle input to this region is well suited for influencing the coordination of motor behavior during feeding and for the integration and processing of kinesthetic information.

Afferent Pathways↗

PubMed2006

Primary hepatic lymphoma with spindle cell components: a case report.

Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of primary DLBCL with spindle cell components arising in the liver, for which a preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70-year-old man with a continuous cough. Thoracic computed tomography incidentally detected a mass of 5 cm in diameter in his liver. The initial and second needle biopsies from the liver mass were pathologically diagnosed as suspicious for sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy. Histological examination revealed a diffuse or epithelioid arrangement of round and polygonal cells, mixed with the fascicles of spindle-shaped cells. Immunohistochemically, all the morphological types of tumor cells showed positive reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a). Double-immunostaining revealed that the spindle-shaped tumor cells expressed CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a spindle cell morphology is quite uncommon, and this variant can be a diagnostic pitfall, especially in tiny biopsy specimens. We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors.

Aged↗

PubMed2000

Lipomatous myofibroblastoma: a potential diagnostic pitfall in the spectrum of the spindle cell lesions of the breast.

We report on two cases of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately three quarters of the entire tumour area. Both tumours consisted of a well-circumscribed lipomatous tumour mass containing dispersed nodular or irregularly shaped spindled cellular areas. The fatty component was represented exclusively by mature adipocytes, uniform in size and shape, lacking nuclear pleomorphism. The cellular areas contained spindly to oval cells with morphological and immunophenotypical features typical of MFB. The two components were so intimately admixed that a finger-like infiltrating growth pattern was apparent. The cases reported here as "lipomatous MFB" aim to clarify further the morphological spectrum of MFB of the breast. Lipomatous MFB may potentially mimic other benign or aggressive tumour-like lesions or even bland-looking malignant spindle cell tumours such as fibromatosis, nodular fasciitis, spindle cell lipoma, spindle cell liposarcoma, spindle cell variant of metaplastic carcinoma, spindle cell malignant myoepithelioma, and low-grade fibrosarcoma/malignant fibrous histiocytoma. The histogenesis of the present bimorphic mesenchymal tumours could be explained as the result of a dual, myofibroblastic and lipomatous, differentiation from a common pluripotential mesenchymal precursor cell, probably represented by the vimentin+/CD34+ fibroblast of the mammary stroma.

Aged↗

PubMed2006

Undifferentiated spindle-cell carcinoma of the gallbladder: an immunohistochemical study.

A case of undifferentiated spindle-cell carcinoma of the gallbladder is described. A 72-year-old man presented with right hypochondralgia and fever. Imaging studies revealed a well-demarcated solid tumor (with a necrotic center) in the gallbladder that invaded the liver and transverse colon. On gross examination of the surgical specimen, the cut surface of the polypoid tumor showed nodular invasive growth. Microscopically, the tumor was composed of atypical spindle-shaped tumor cells that proliferated in a whirling or interlacing pattern. The tumor also showed foci with a malignant epithelial component that simulated a carcinosarcoma. Immunohistochemically, the biphasic differentiation of the tumor was highlighted by the different immunoreactivity to antibodies against cytokeratins, epithelial membrane antigen (EMA), and vimentin shown by the malignant epithelial components and the spindle-cell components. However the latter showed faint positivity for cytokeratin antibody. These results suggested that the spindle-cell carcinoma of the gallbladder originated from cholecystic mucosa and showed sarcomatous reaction or dedifferentiation, as indicated by the presence of vimentin-positive cells. The proliferation index, as detected by ki-67, in the spindle-cell component was higher than that in the epithelial component, which may account for the more aggressive biological behavior of the spindle-cell component.

Aged↗

PubMed2003

Spindle cell carcinoma of the intrahepatic bile duct in a patient with primary sclerosing cholangitis.

We present a case of spindle cell carcinoma of the intrahepatic bile duct that developed in a 34-year-old man with primary sclerosing cholangitis. At the time of presentation, the patient had a 10-year history of primary sclerosing cholangitis. A mass was found in the hepatic hilus and was resected surgically. The tumor was composed predominantly of spindle cells, and a small portion of the tumor appeared to be adenocarcinomatous by histology. Histological and immunohistochemical findings suggested that the spindle cells were epithelial in origin; thus, this tumor was identified as a spindle cell carcinoma. Spindle cell carcinomas arising in the bile duct are extremely rare. Furthermore, the coexistence of spindle cell carcinoma and primary sclerosing cholangitis has not been reported thus far. We were able to follow up the entire course of this rare case. In this case report, we describe the clinicopathological findings of this case and review the literature concerning this type of tumor.

Adult↗

PubMed2025

The first case of GOLGA5-RET fusion-positive malignant spindle cell sarcoma of the head and neck responsive to selpercatinib.

Soft-tissue sarcoma (STS) is a rare malignancy that accounts for less than 1% of all cancers, and recent advances in molecular biology have led to its classification based on genomic information. Some RET-rearranged neoplasms have been reported to present pathological features similar to Neurotrophic Tyrosine Kinase Receptor-rearranged spindle cell neoplasms. Here, we report the first case of head and neck spindle cell sarcoma with a GOLGA5-RET fusion that demonstrated a sustained clinical response to selpercatinib, identified through targeted next-generation sequencing (NGS). The patient was a 43 year-old man with a tumor in the arytenoid region that was resected and diagnosed as a malignant spindle cell tumor. Despite initial treatment with surgical resection alone, local recurrence was confirmed, requiring salvage therapy with total laryngectomy and bilateral cervical dissection. Surgical specimen revealed a spindle tumor with a patternless pattern and collagenous stroma. Immunohistochemistry (IHC) with positivity for CD34, bcl-2 (focally), S100, and weak nuclear staining for STAT6, with absence of expression of CK AE1/3, desmin, c-kit, smooth muscle actin, myogenin, synaptophysin, and SOX10. Trk A/B/C were also negative on IHC. Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Targeted NGS identified GOLGA5-RET rearrangement, FGF14 amplification (equivocal), CDKN2B loss, and CDKN2A loss. GOLGA5-RET rearrangements were validated through fluorescence in situ hybridization. The patient subsequently was enrolled in a phase 1/2 trial for the selective RET inhibitor selpercatinib, resulting in a sustained partial response over 5 years. Although solitary fibrous tumor (SFT) was initially considered as a differential diagnosis based on immunohistochemical findings, the lack of strong and diffuse STAT6 expression made this diagnosis unlikely. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of RET-specific inhibitors against RET-altered sarcomas.

Next-generation sequencing↗

PubMed1988

Modification of sensory-terminal responses and membrane structure of frog muscle spindle by collagenase.

A preparation of decapsulated muscle spindles with intact sensory innervation has been developed to allow direct access to the sensory terminal for the application of drugs or to alter the extracellular ionic composition. Muscle spindles were isolated from semitendinosus muscles of the frog Rana catesbeiana, and were incubated in a calcium-free Ringer's solution containing 0.2% collagenase. Following optimal incubation at 34 degrees C for 30 min the response pattern of the spindles during stretch could not be distinguished from that of intact spindles, although the duration of individual afferent spikes was prolonged about 4 times normal. The spikes disappeared immediately after the Ringer's solution was replaced with an isotonic choline chloride solution, in contrast to those of intact spindles which remained for 30 min after the replacement. Electron microscopy showed that the outer and inner capsules were partially disrupted. No significant change was observed in the size or packing density of intramembrane particles in freeze-fracture replicas of spindles decapsulated under optimum conditions. More prolonged treatment with the enzyme resulted in abolition of the static component of the response during stretch, and also in an aggregation of the particles, whose size decreased and packing density increased.

Afferent Pathways↗

PubMed1989

Endocytosis and transcytosis by the capsule cell of vertebrate muscle spindles.

The vertebrate muscle spindle has been observed to be ionically and biochemically isolated from the surrounding muscle fibers by the spindle capsule. We have explored the possibility that the capsular cells are endocytically active and can transport both small molecules and macromolecules into the capsular space. Transcytosis (the endocytic transport of extracellular substances across a cell) through the capsule cell layer was examined with muscle spindles of snake, rat, and cat using fluorescent markers for fluorescence microscopy and horseradish peroxidase (HRP) and ferritin for electron microscopic examination. The fluorescent markers were actively taken up by capsule cells, making it easy to locate the spindle capsular region of spindles among extrafusal fibers by their strong fluorescence. Ferritin and HRP were used to identify the pathway of transcytosis by electron microscopy. These markers were found in endocytic vesicles of capsule cells, in the narrow space between capsule layers and in the capsular space, indicating that the marker was transferred to the capsular space by the pinocytic activity of capsule cells. Scattered cells in the capsule of cat muscle spindles appeared to take up fluorescein isothiocyanate (FITC)-coupled beta-glucuronidase by a receptor-mediated process. The uptake was sensitive to temperature and [Ca2+], and specifically inhibited by yeast mannan. By electron microscopy with dilute HRP (10 micrograms/ml) this specific uptake was by isolated cells in the interlamellar space. The functional significance of the above findings is discussed.

Animals↗

PubMed1976

Effect of flurazepam on sleep spindles and K-complexes.

In this research, a quantitative study of the EEG from 5 subjects permitted a detailed analysis of the effect of 30 mg of flurazepam administered over 7 nights. Four placebo baseline nights and 3 placebo withdrawal nights were also recorded. For 4 of the subjects, a nondrug and nonplacebo follow-up record was obtained 4 to 6 weeks later. The subjects were 4 females, 1 male, age range 23-42. All complained of either sleep onset greater than 45 min, sleep length of less than 6 h, or two or more sleep awakenings. Compressed spectral analysis yielded a computer-generated somnogram on each of the 15 nights of sleep, and an automated spindle detector was used to count and measure the duration of spindle bursts with frequencies of 12.25-15.5 c/sec on baseline nights 3 and 4, drug nights 1, 2, 3 and 7, on the 3rd withdrawal night, and on the 4-6 week followup record. K-complexes were scored visually on the 4th baseline and 7th drug nights. There were no significant differences in spindle rate per minute among baseline nights and the follow-up record. By the 2nd drug night, spindle rate had significantly increased over the baseline rate. Linear contrast analysis indicated there was a significant increase of spindle rate over drug nights. All 5 subjects showed this pattern of increase. In contrast to the increase in spindle activity, the rate per minute of K-complexes significantly decreased during drug administration.

Adult↗

PubMed1992

Ontogenesis of nocturnal organization of sleep spindles: a longitudinal study during the first 6 months of life.

Ontogenesis of sleep spindles was studied on overnight longitudinal recordings in 12 full-term infants at 1.5-3-4.5 and 6 months of life. Six parameters (density, duration, frequency, amplitude, asymmetry and asynchrony) were analyzed during both slow wave sleep (SII and delta) and during 5 periods of the night. Results show a significant increase of most parameters between 1.5 and 3 months of age. All spindle patterns developed quite rapidly during the first 3 months of infancy, possibly reflecting developmental changes in thalamo-cortical structures and maturation of the physiological system that produces spindles. The density of 12-14 Hz spindle frequency was higher in stage II when compared to stage delta, as in adults. Our data confirm previous reports on spindle ontogenesis and give a more complete aspect of this ontogenesis in relation to sleep development. Three months of age appeared to be a turning point in maturational processes and might reflect changes in central nervous system activity and behavior which take place during that period. Sleep spindle evolution seems to be an accurate reflection of the slow wave sleep (SWS) development, and our results are discussed in terms of the developmental aspect of SWS production and characterization of sleep stages in young infants. Concordance between quantitative aspects and nocturnal organization leads us to consider that the individualization of slow wave sleep (SWS) in infants occurs from 4.5 months of life.

Aging↗