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Effects of apomorphine and (+/-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine, injected into the striatum, on the caudate spindle in the rat.

The caudate spindle in rats was observed following bilateral application of apomorphine (1.5-50 micrograms) and (+/-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP, 0.3-3 micrograms) into the striatum. The smallest dose (1.5 micrograms) of apomorphine enhanced the spindle whereas with a larger dose (50 micrograms), suppression occurred. The preferential dopamine (DA) autoreceptor (inhibitory-receptor) agonist, (+/-)-3-PPP, enhanced the spindle, in a dose-dependent manner. The enhancing effect of apomorphine (1.5 micrograms) and (+/-)-3-PPP (3 micrograms) was prevented by neuroleptics, such as haloperidol (20 micrograms/kg, i.v.) and sulpiride (2 mg/kg, i.v.) at doses which, per se, did not affect the spindle. Small doses of neuroleptics are thought to block DA autoreceptors, suggesting that the enhancing effects of the DA agonists are mediated by autoreceptors. These results lend further support to the assumption that the development of the caudate spindle involves activation or DA receptors. Enhancement of the spindle, induced by injections of apomorphine into the striatum (small dose) and (+/-)-3-PPP, may be mediated by DA autoreceptors (inhibitory-receptors) located at presynaptic elements of the nigro-striatal DA system, while suppression may be due to stimulation of the postsynaptic DA receptors.

Animals↗

Pseudomalignant spindle cell proliferations of the urinary bladder.

Twelve cases of polypoid, nonrecurrent, pseudomalignant spindle cell proliferations of the urinary bladder (eight women and four men) were analyzed. Two patients had a simultaneous urinary bladder carcinoma. The lesions were characterized by proliferating spindle- or strap-shaped cells, which on electron microscopic examination (performed in all 12 cases) revealed characteristics of fibroblasts and myofibroblasts. The cells showed immunoreactivity for vimentin in all cases, for alpha-smooth muscle-specific and muscle-specific actin in six cases, for cytokeratins in five cases, and for CD 34 in one case. No immunoreactivity was observed for desmin, myoglobin, epithelial membrane antigen, S-100 protein, endothelial cell antigen (H and Y), CD 68, or factor VIII RAG. Immunoreactivity for Ki-67 and proliferating cell nuclear antigen was detected in up to 30% of the spindle cell nuclei. The static cytometric DNA analysis revealed a diploid, or in two cases a hyperdiploid, stem cell line. An awareness of this type of spindle cell lesion and its immunophenotypic characteristics and diversity is of importance to avoid an erroneous diagnosis of spindle cell sarcoma (in particular leiomyosarcoma and embryonal rhabdomyosarcoma) or spindle cell carcinoma.

Actins↗

Effects on the caudate spindle in rats of dopamine microinjected into the caudate nucleus.

We examined the caudate spindle in control and pargyline-pretreated rats following bilateral application of 3 doses (15, 50 and 150 micrograms/site) of dopamine (DA) into the caudate nucleus. The highest dose of DA (150 micrograms) suppressed the spindle, whereas lower doses (15, 50 micrograms) enhanced the spindle in control rats. Haloperidol given into the bilateral caudate nucleus increased the spindle in control rats. In pargyline-pretreated rats, 50 and 150 micrograms DA caused marked suppression, but 15 micrograms DA caused enhancement. These findings indicate that the DA system may mediate the development of the caudate spindle. Suppression of the caudate spindle induced by intracaudate DA injection may be due to stimulation of postsynaptic DA receptors and enhancement mediated by DA autoreceptors on the DA nerve terminals in the caudate nucleus with a subsequent inhibition of DA neurotransmission.

Animals↗

Muscle spindles form in paralyzed but not in aneural hindlimbs of fetal rats.

The necessity of innervation and/or neural activity for the formation of muscle spindles was investigated by treating fetal rats with neurotoxins on embryonic day 16 or 17 (E16-17), one or two days prior to the onset of spindle assembly. The neurotoxin-treated soleus muscles were examined on E21 for the presence of spindles and immunocytochemical expression of the slow-tonic myosin heavy-chain (MHC) isoform, which is characteristic of intrafusal fibers. Irreversible destruction of sensory and motor nerves by beta-bungarotoxin prevented the formation of spindles and expression of the slow-tonic MHC. Abolishment of nerve and muscle activity by tetrodotoxin did not block the spindle assembly or expression of the slow-tonic MHC. Thus, the formation and differentiation of spindles is dependent on innervation, but is independent of activity in nerve fibers or muscle cells.

Animals↗

Movement-dependent after-effects in the firing of the spindle endings from the de-efferented muscles of the cat hindlimb.

The muscle spindle reactions evoked by the servo-controlled changes in the muscle length or external load were studied on the de-efferented muscles in experiments on cats under Nembutal anaesthesia. The activity of 39 primary and 10 secondary endings of the muscle spindles from four hindlimb extensor muscles: soleus, plantaris, lateral and medial heads of gastrocnemius has been recorded during servo-controlled changes in muscle length (L-control) or external load (P-control). Slow linear reciprocating (triangular) signals and their modification with fixation of the controlled parameter at the same level at forward and reverse phases were used as commands for the muscle stretcher. The steady firing rates in primary and secondary endings during fixation of muscle length or external load were shown to be strongly dependent on the direction of previous changes in these parameters. The firing rates were always higher after preceding lengthening (loading) and lower after shortening (unloading). These rate uncertainties in the steady firing of spindle endings at the same level of controlled parameter could be as much as 15-20 p.p.s. The revealed dependence of the spindle ending firing on the past history of the muscle movement was denoted as movement-dependent after-effects. Two kinds of movement-dependent after-effects in the firing of the spindle endings can be observed: (1) the movement-dependent ones being studied in the present work, and (2) those connected with the conditioning fusimotor stimulation and described elsewhere. Their common origin is supposed to be connected with the hysterical (thixotropic) properties of the intrafusal muscle fibres. Similarity of the movement-dependent after-effects in L- and P-control conditions was shown to be connected with a resemblance of the length-firing rate [F(L)] and load-firing rate [F(P)] hysterical loops registered during reciprocating movements. Both kinds of loops were in a clock-wise direction, their comparison in normalized form showed that F(L) loops were always broader than F(P) ones. Isotonic and isometric uncertainty vectors were introduced to analyse quantitatively the hysterical effects in the spindle firing and their relation to the muscle hysteresis proper. Uncertainty vectors connect the points of equal load (isotonic uncertainty vectors) and equal length (isometric uncertainty vectors) on F(L) and F(P) loops correspondingly. The projections of both uncertainty vectors onto the Y-axis give the rate uncertainty coinciding in sign for both cases, whereas their projections onto the X-axis differ in sign, being positive for isometric uncertainty vectors (the tension uncertainty) and negative for isotonic uncertainty vectors (the length uncertainty).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Development of the sensory innervation of muscle spindles in the kitten.

This is a report of the changes observed in the pattern of sensory innervation of muscle spindles in hindlimb muscles of kittens during the first four weeks of life. The structural analysis, made on teased, silver-stained preparations, was complemented by a series of recordings of afferent responses of kitten spindles during ramp-and-hold stretches of the muscle. The primary endings of spindles from newborn animals showed a large degree of variability in their branching pattern and branches formed a network across the intrafusal fibres. In older animals there was less variability and lateral branches of stem axons began to encircle the intrafusal fibres. The process of maturation was characterized by a more uniform shape of the endings and more complete, evenly spaced, annulospiral terminals. Recordings of the responses of primary endings of spindles during muscle stretch showed that several features of the adult response were already present in the newborn, although the overall rate of discharge was very much lower. It was concluded that the changes observed in the structure of the sensory endings of kitten spindles did not have clearly identifiable physiological correlates. It appears that an annulospiral shape of the sensory terminals is not a necessary prerequisite for the generation of stretch responses. The predominant factor which appears to determine the responses of spindles to stretch is the maturity of the intrafusal fibres, in particular, the bag2 fibre.

Aging↗

Sleep spindle detection using artificial neural networks trained with filtered time-domain EEG: a feasibility study.

An artificial neural network (ANN) based on the Multi-Layer Perceptron (MLP) architecture is used for detecting sleep spindles in band-pass filtered electroencephalograms (EEG), without feature extraction. Following optimum classification schemes, the sensitivity of the network ranges from 79.2% to 87.5%, while the false positive rate ranges from 3.8% to 15.5%. Furthermore, due to the operation of the ANN on time-domain EEG data, there is agreement with visual assessment concerning temporal resolution. Specifically, the total inter-spindle interval duration and the total duration of spindles are calculated with 99% and 92% accuracy, respectively. Therefore, the present method may be suitable for investigations of the dynamics among successive inter-spindle intervals, which could provide information on the role of spindles in the sleep process, and for studies of pharmacological effects on sleep structure, as revealed by the modification of total spindle duration.

Alpha Rhythm↗

Effects of cryopreservation on the meiotic spindle of human oocytes.

The microtubular meiotic spindle of most mammals, including humans, is very sensitive to cooling [Hum. Reprod. 16 (2001) 2374; Fertil. Steril. 54 (1990) 102; Fertil. Steril. 75 (2001) 769; Zygote 3 (1995) 357] and is rapidly depolymerised even after a slight reduction in temperature to 33 degrees C. Spindle disassembly is dependent on the extent of temperature decrease and its duration. After rewarming, the recovery is far from complete. Cryoprotectants themselves may alter the spindle structure, depending on the duration and temperature of exposure, the duration of recovery at 37 degrees C and the species [Hum. Reprod. Update 2 (1996) 193]. Damage to the meiotic spindle is considered to be the cause of aneuploid embryos, by inducing chromatid non-disjunction and chromosome scattering and by disturbing the sequence of events leading to the completion of meiosis and fertilisation. Nevertheless, a consensus arose from all the studies: appropriate exposure to cryoprotectants and appropriate rates of cooling and thawing allow the cryopreservation of mature oocytes without any significant changes in their second meiotic spindle organisation and without any increase in the rate of aneuploid embryos [Mol. Hum. Reprod. 2 (1996) 445; Hum. Reprod. 8 (1993) 1101; Hum. Reprod. 9 (1994) 684; Microsc. Res. Technol. 27 (1994) 165; Fertil. Steril. 75 (2001) 354]. These fundamental studies in humans, showing good preservation of cell structures after freeze-thaw procedures opened the way to new successful clinical trials with embryos derived from cryopreserved mature oocytes [Fertil. Steril. 68 (1997) 724]. Considering immature oocyte freezing at prophase I (germinal vesicle (GV) stage), a stage which was thought to be less sensitive to cryoinjury, pooled data from the literature showed no advantage in terms of survival rates, fertilisation rates of in vitro matured oocytes and developmental ability of the resulting embryos, especially in unstimulated cycles. Moreover, conflicting results are reported on the effects of freezing on the spindle-chromosome configuration of immature oocytes or in vitro matured oocytes, highlighting the need for large scale studies [Hum. Reprod. 10 (1995) 1816; Hum. Reprod. 13 (Suppl. 3) (1998) 161; Hum. Reprod. 17 (2002) 1885; Microsc. Res. Technol. 27 (1994) 165; Fertil. Steril. 68 (1997) 920]. One child has been born after the use of cryopreserved immature oocytes at GV stage, matured in vitro and fertilised by ICSI [Hum. Reprod. 13 (1998) 3156], demonstrating at least the feasibility of this technique. Improvements are required so as to make mature and immature oocyte cryopreservation an established and safe technique for ART.

Cold Temperature↗

Choice of rotation speed (rpm) for bio-relevant drug dissolution testing using a crescent-shaped spindle.

Recently a new crescent-shaped spindle has been proposed to address the issues related to poor hydrodynamics of the USP paddle apparatus and its associated artifacts of high variability and lack of bio-relevant results. For improved comparison of drug dissolution characterization, it is highly desirable to conduct testing using common experimental conditions such as spindle rotation speed. A study was conducted in which different products were tested using the crescent-shaped spindle to propose a common rpm speed for improved comparative drug dissolution testing. Conventional- (200 mg) and extended-release (200 and 400 mg) carbamazepine tablets of multiple brands and amoxicillin capsules (250 and 500 mg) were analysed using the crescent- shaped spindle at 25, 50 and/or 75 rpm. Drug release was evaluated for 1.5h for amoxicillin and for 3.0 and 24h for conventional- and extended-release carbamazepine tablets products respectively. The dissolution media used were 0.05 M phosphate buffer for amoxicillin capsules and water containing 0.5% sodium lauryl sulphate for carbamazepine tablet products. All products showed characteristic drug release profiles, reflecting the fast and slow drug release natures of the products tested with complete drug release within expected time durations. Based on an expected maximum drug release criterion of 85% in a reasonable time, at a relatively slow drug release rate and within a dosing interval, a spindle speed of 25 rpm was found to be the most appropriate. Thus, it is concluded that drug products can be analysed using a single spindle type (crescent) with a single rpm (25) which would, not only result in simpler dissolution procedures, but also provide enhanced efficiencies from economical and regulatory aspects.

Amoxicillin↗

Twenty-four hours retention of visuospatial memory correlates with the number of parietal sleep spindles.

Recent evidence suggests that the sleep-dependent consolidation of declarative memories relies on the non-rapid eye movement (NREM) rather than the rapid eye movement (REM) phase of sleep. Moreover, a few studies both at the cellular and the behavioural levels have suggested the involvement of sleep spindles, the most synchronous oscillatory waveforms during NREM sleep stage 2, in this process. Our previous study showed that overnight verbal memory retention correlates with the total number of sleep spindles in left frontocentral areas, while spindling in other regions did not correlate with mnemonic retention. In the present study, we show that retention of visuospatial memories over a 24-h period correlates with the total number of sleep spindles detected over parietal regions during the intervening night-time sleep. This result provides further evidence for the association between sleep spindle activity and declarative memory consolidation, and suggests that visuospatial and verbal memory retention differ in the topographic distribution of the NREM spindle activity with which they are associated.

Adult↗

Dual control of the brainstem on the spindle oscillation in humans.

In human subjects, the excitability change of the brainstem was investigated over the course of the spindle oscillation. The investigation was carried out by a sequential analysis of brainstem auditory evoked potentials (BAEPs) with reference to one sequence of spindle oscillation. The method was based on the characteristics of BAEPs, i.e. far-field evoked potential. The brainstem revealed two types of excitability change: one in the lower ventral brainstem (wave-III components), and the other in the upper dorsal brainstem (wave-V components). The excitability in the dorsal brainstem showed an oscillation with one cycle period of about 1.5 s, whereas in the ventral brainstem, the excitability showed a long-range biphasic (decaying-growing) fluctuation. Both excitability changes in the brainstem preceded the spindle oscillation, and the phase was reversed during the emerging period of spindle oscillation. The results suggest a primary triggering mechanism of the brainstem for the spindle oscillation, which is independent of preceding cortical drives (K-complexes) upon the thalamus. The difference of the excitability change between the spindle oscillation and the paroxysmal discharge (spike-and-wave complex) was also discussed.

Adult↗

A light microscopical, ultrastructural and immunohistochemical study of spindle-cell adrenocortical tumours of ferrets.

Twelve adrenocortical tumours with a variable spindle-cell component in ferrets (six spayed females, three intact females, two castrated males, and one intact male) were examined by light microscopy. One tumour with a moderate spindle-cell component was examined ultrastructurally, and three tumours were studied immunohistochemically. Light microscopy revealed a spindle-cell component in the tumours that varied from a few such cells occupying the stroma between packets of adrenocortical cells to cells in such large numbers that they formed almost the entire substance of the tumour. By light microscopy these spindle cells resembled smooth muscle cells, and the ultrastructural findings, particularly the presence of thin contractile filaments, suggested that the spindle cells were of smooth muscle origin. Immunohistochemical staining revealed that the spindle cells were negative for cytokeratins and S-100 protein but positive for smooth muscle actin. Desmin was readily demonstrated in two tumours but not in the other examined. Vimentin was variable, generally producing a small to moderate amount of reaction product.

Actins↗

Solitary spindle-cell xanthogranuloma of the eyelid.

PURPOSE: To describe a rare presentation of a solitary spindle-cell xanthogranuloma in a 3-year-old boy with a 6-month history of a right upper lid soft tissue lesion. DESIGN: Interventional case report. METHODS: An excisional full-thickness biopsy of the right upper lid was performed. Histologic examination and immunohistochemistry of the specimen were performed. RESULTS: Histopathologic evaluation revealed a well-demarcated nodule arising from the tarsus that contained a storiform array of spindle cells admixed with numerous multinucleated giant cells (some Touton type) and lymphocytes. The spindle cells labeled with antibodies to Factor XIIIa, CD68, lysozyme, Mac 387, and vimentin. The multinucleate giant cells labeled with CD68, lysozyme, and vimentin. Findings were consistent with the diagnosis of solitary spindle-cell xanthogranuloma. CONCLUSIONS: Spindle-cell xanthogranuloma resembles juvenile xanthogranuloma and fibrous histiocytoma (dermatofibroma) and should be considered in the differential diagnosis of spindle-cell tumors of the eyelid and periocular region. If similar lesions are noted elsewhere, the diagnosis of progressive nodular histiocytoma should be considered.

Biomarkers↗

Recurrent conjunctival melanoma with neuroidal spindle cell features.

A 66-year-old white woman had had a 20-year history of flat primary acquired melanosis involving the left inferior forniceal and palpebral conjunctiva. Over the ensuring 12 years, the patient experienced multiple recurrences of invasive malignant melanoma that emerged from the progressive primary acquired melanosis. Two of these recurrences were composed of nonpigmented spindle cells, and in the most florid invasive malignant melanoma that developed, the spindle cells formed a nodule 7.5 mm thick. The spindle cells were organized into fascicles and small bundles, the latter separated by a loose stroma that was devoid of mucopolysaccharides. The fascicular and neuroidal features in this case were sufficiently well developed to suggest the incorrect diagnosis of a neural tumor or a neurofibroma. However, the presence of intraepithelial atypical melanocytes at the edge of the spindle cell lesion, the absence of mucopolysaccharides in the stroma, the mitotic activity, and the absence of intercellular reticulin fibers favored the diagnosis of a spindle cell invasive malignant melanoma. This morphologic variant of conjunctival melanoma is compared with related cutaneous lesions of melanoma featuring a spindle cell population.

Aged↗

Distribution of gamma-tubulin in multipolar spindles and multinucleated cells induced by dimethylarsinic acid, a methylated derivative of inorganic arsenics, in Chinese hamster V79 cells.

Localization of gamma-tubulin, a well-characterized component of microtubule-organizing centers (MTOCs), was investigated because of interest in the mechanism of the induction of aberrant mitotic spindles in Chinese hamster V79 cells exposed to dimethylarsinic acid (DMAA). In control cultures, gamma-tubulin in interphase cells was located as a perinuclear dot on which the microtubules were nucleated. In metaphase cells, the location of gamma-tubulin coincided with that of the mitotic spindle poles. DMAA caused mitotic delay and aberrant spindles, such as tripolar- and quadripolar spindles, in the mitotic cells. Gamma-tubulin was co-localized with the aberrant spindles induced by DMAA. The incidence of gamma-tubulin in the mitotic cells coincided with that of the aberrant spindles and rose with an increasing concentration of DMAA. By contrast, DMAA did not influence the number and location of gamma-tubulin signals in interphase cells. These results suggest that multiple microtubule nucleation sites were induced by DMAA during transition from interphase to mitotic phase. DMAA-induced multiple signals of gamma-tubulin were integrated into one signal at the center of multinucleated cells, surrounded by multiple nuclei as the cell cycle progressed to the next interphase, suggesting the presence of a self-integration mechanism of centrosomal MTOCs during the cell cycle.

Animals↗

Attenuated amplitude of circadian and sleep-dependent modulation of electroencephalographic sleep spindle characteristics in elderly human subjects.

Sleep spindles are 12-15 Hz electroencephalographic (EEG) oscillations characteristic of non-rapid eye movement (non-REM) sleep. Sleep EEG recordings (total 252 episodes; duration, 9 h 20 min each) distributed across the circadian cycle were analyzed in eight young and eight elderly human subjects. In the young subjects, sleep spindle amplitude, frequency, duration and incidence displayed significant circadian modulation, with the highest spindle incidence and amplitude and the lowest spindle frequency coincident with circadian phases associated with times of habitual sleep. In the elderly subjects, overall amplitude, duration, and incidence were reduced, and only spindle frequency exhibited a detectable circadian modulation. The results demonstrate that a circadian process modulates sleep spindle characteristics and that the strength of this circadian modulation is reduced with age.

Adult↗

Morphological variability and specializations in bovine extraocular muscle spindles.

Bovine extraocular muscles were examined to determine whether the structure of their muscle spindles was notably different from those commonly encountered in mammalian limb muscles. Extraocular muscle spindles on the whole were shorter, and intrafusal fiber counts/spindle were more variable than in somatic muscles. No pronounced nuclear bags were seen in intrafusal fibers. Based on cross-sectional areas, intrafusal fibers in extraocular muscles could be loosely categorized as small or large types. Small fibers expressed more neonatal/fast myosin heavy chain and less embryonic myosin heavy chain than large fibers. When incubated for myosin ATPase, about 70% of the large fibers and 15% of the small fibers in spindles presented profiles that were characteristic of type I extrafusal fibers, and not of nuclear bag or nuclear chain fibers. The ratio of number of small intrafusal fibers to number of large intrafusal fibers in extraocular spindles was on average greater than the ratio of nuclear chain fibers to nuclear bag fibers that is typical for limb spindles of rodents and cats. Structural modifications at muscle spindle sensory regions, extrafusal-like fibers and intrafusal-like fibers with few equatorial nuclei and many myofibrils, may produce distinct afferent signals that are appropriate for sensorimotor integration in the specialized extraocular muscles.

Animals↗

Topography of muscle spindles and Golgi tendon organs in shoulder muscles of "Monodelphis domestica".

The topography of muscle spindles and Golgi tendon organs in the rotator cuff and surrounding shoulder muscles of a small laboratory marsupial (monodelphis domestica) were studied using light microscopy of serial sections. The shoulder joint of monodelphis has a large degree of freedom of movement allowing this animal to use the upper extremities for a wide range of activities like climbing and manipulating food. Thus, similar to the situation in man the shoulder joint is mainly secured by muscles. Silver stained serial paraffin sections were examined under the light microscope and the distribution of muscle spindles and Golgi tendon organs was reconstructed using three-dimensional image processing. In the two animals examined 113 and 131 muscle spindles respectively were found within the 4 rotator cuff muscles. In addition, 76 and 40 Golgi tendon organs respectively were seen at the musculo-tendinous junctions of these muscles preferentially close to the insertion at the humerus head. Also the surrounding shoulder muscles contain both muscle spindles and Golgi tendon organs in large numbers, but the ratio of Golgi tendon organs per muscle spindle appears to be lower. Number and localization of muscle spindles and Golgi tendon organs suggest, that these receptors are important for both reflex control of shoulder muscle tone as well as monitoring of static position and movement in the shoulder joint.

Animals↗