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Biomedical subjects

R Roll

Publications and source records attributed to R Roll.

At least 19 recordsLinked to original sources

Foot sole and ankle muscle inputs contribute jointly to human erect posture regulation.

In order to assess the relative contribution and the interactions of the plantar cutaneous and muscle proprioceptive feedback in controlling human erect posture, single or combined vibratory stimuli were applied to the forefoot areas and to the tendons of the tibialis anterior muscles of nine standing subjects using various vibration frequency patterns (ranging from 20 to 80 Hz). The variations in the centre of foot pressure, ankle angle and the EMG activities of the soleus and tibialis anterior muscles of each subject were recorded and analysed. Separate stimulation of the plantar forefoot zones or the tibialis anterior muscles always resulted in whole-body tilts oppositely directed backwards and forwards, respectively, the amplitude of which was proportional to the vibration frequency. EMG activity of ankle muscles also varied according to the direction of the postural responses. However, the same vibration frequency did not elicit equivalent postural responses: in the low frequency range, tactile stimulation induced stronger postural effects than proprioceptive stimulation, and the converse was the case for the higher frequency range. Under sensory conflict conditions, i.e. foot sole-flexor ankle muscle co-stimulation, the direction of the body tilts also varied according to the difference and the absolute levels of the vibration frequencies. In all cases, the resulting postural shifts always corresponded to the theoretical sum of the isolated effects observed upon vibrating each of these two sensory channels. We proposed that tactile and proprioceptive information from the foot soles and flexor ankle muscles might be co-processed following a vector addition mode to subserve the maintenance of erect stance in a complementary way.

Adult↗

Enantiomer separation of hydrocarbons in preparation for ROSETTA's "chirality-experiment".

Until now the favored method for separating racemic pairs of underivatized alcohols, diols, and phenylsubstituted amines has been gas chromatography on cyclodextrin phases. However, certain enantiomers of saturated chiral hydrocarbons could not be resolved in this way because they lack the functional groups necessary to undergo "intensive" diastereomeric interactions with the cyclodextrins. The present study describes a gas-chromatographic technique for resolution of saturated aliphatic hydrocarbons into their enantiomers and presents a brief discussion of the possible applications. The (enantiomer) separations were performed in preparation for the Cometary Sampling and Composition Experiment on board the cometary lander RoLand, part of ESA's cornerstone mission ROSETTA. This experiment has been designed to investigate the hypotheses that biomolecular asymmetry has an interstellar origin and to separate and identify a wide range of organic enantiomers in situ on the surface of a comet's nucleus.

Alkanes↗

Construction of a new multi-turn time-of-flight mass spectrometer.

A new type of multi-turn time-of-flight mass spectrometer was constructed, consisting of four cylindrical electric sectors and 28 electric quadrupole lenses, the size of the vacuum chamber being 60 x 70 x 20 cm. It was demonstrated that the mass resolution can be increased according to the number of cycles of the ions through the ion optical system.

Mass Spectrometry↗

Specific whole-body shifts induced by frequency-modulated vibrations of human plantar soles.

This study sought to analyze the postural responses induced by separately or simultaneously vibrating with different frequencies the forefoot and rear foot zones of both soles in standing subjects. Stimulating each zone separately resulted in spatially oriented body tilts; their amplitude and velocity varied linearly according to the frequency, and their direction was always opposite to the plantar site vibrated. When the two zones were each co-stimulated at different frequencies, the parameters of the postural responses depended on the frequency difference. When this frequency difference was zero, no clearly oriented body tilts occurred. We concluded that the change in the relative pressures evoked by differently co-vibrating these zones gave rise to regulative postural adjustments able to cancel the simulated body deviation.

Adult↗

From balance regulation to body orientation: two goals for muscle proprioceptive information processing?

This study was based on the assumption that the central processing of proprioceptive inputs that arise from numerous muscles contributes to both awareness and control of body posture. The muscle-spindle inputs form a "proprioceptive chain" which functionally links the eye muscles to the foot muscles. Here, we focused on the specific contribution of two links in the control of human erect posture by investigating how proprioceptive messages arising from ankle and neck muscles may be integrated by the central nervous system. Single or combined mechanical vibrations were applied to different muscle tendons at either one (ankle or neck) or both (ankle plus neck) body levels. The amplitude and the specific direction of the resulting oriented body tilts were analyzed by recording the center of foot pressure (CoP) through a force platform with four strain gauges. The results can be summarized as follows: (1) the vibration-induced whole-body tilts were oriented according to the muscles stimulated; furthermore, the tilts were in opposite directions when neck or ankle muscles on the same side of the body were stimulated; (2) except for the ankle antagonist muscles, co-vibrating adjacent or antagonist muscles at the same body level (ankle or neck) resulted in body sways, whose orientation was a combination of those obtained by stimulating these muscles separately; and (3) likewise, co-vibrating ankle and neck muscles induced whole-body postural responses, whose direction and amplitude were a combination of those obtained by separate vibration. We conclude that the multiple proprioceptive inputs originating from either one or both body levels may be co-processed in terms of vector-addition laws. Moreover, we propose that proprioceptive information from ankle and neck muscles may be used for two tasks: balance control and body orientation, with central integration of both tasks.

Adult↗

[Errors in targeted movements of the hand under the conditions of orbital space flight].

Three crew members of the Russian-French MIR mission were tested to determine errors in pointing to memorized visual targets. In the laboratory, all test-subjects consistently used to point to the spot below the actual target presentation. The mean Y-error (the vertical error) made up -31.6 +/- 21.8 mm. In microgravity, the Y-error moved "upward" so that the mean Y-error was -16.8 +/- 37.0 mm. The data demonstrate adaptation of the central program of aiming arm movement to the microgravity conditions.

Adaptation, Physiological↗

The plantar sole is a 'dynamometric map' for human balance control.

This study investigated the role of the plantar cutaneous information in controlling human balance. We hypothesized that the cutaneous afferent messages from the main supporting zones of the feet have sufficient spatial relevance to inform the CNS about the body position with respect to the vertical reference and consequently to induce adapted regulative postural responses. Skin mechanoreceptors of anterior and/or posterior areas of one or both soles of 10 standing subjects were activated by superficial mechanical vibration with high frequency and low amplitude. Variations of the subject's center of pressure (CoP) were recorded. Spatially oriented whole-body tilts were observed for every subject. Their direction depended on the foot areas stimulated and was always opposite to the vibration-simulated pressure increase. These responses are found to subserve a postural regulative function and we suggest that co-processing of the various cutaneous messages followed a vector addition mode.

Adult↗

A chicken c-Rel-estrogen receptor chimeric protein shows conditional nuclear localization, DNA binding, transformation and transcriptional activation.

In this report, we characterize the biological and biochemical properties of a conditional protein containing chicken c-Rel fused to the hormone-binding domain of the human estrogen receptor. This chimeric c-RelER protein causes estrogen-dependent, but otherwise c-Rel-specific, transformation of avian fibroblasts in vitro. Our results demonstrate that c-RelER heterodimerizes with wild-type c-Rel and forms specific complexes with IkappaB-alpha. Estrogen causes translocation of c-RelER to the nucleus and stabilizes its binding to DNA. Hormone-activated c-RelER induces transcription of at least four cellular genes that are constitutively active in wild-type c-Rel-transformed fibroblasts. Two distinct cell populations were examined that differed with respect to their growth phenotypes. The growth of fibroblasts with moderate expression levels of c-RelER was stimulated by estrogen. In contrast, the addition of estrogen to cells with high cRelER expression levels resulted in inhibition of cytokinesis and the arrest of growth. The carboxy terminal transactivation domain of c-Rel was required for the induction of these effects since neither v-Rel nor c-Rel deletion mutants were able to induce similar changes. Taken together, our results demonstrate that high levels of c-Rel expression can affect cell cycle control and/or cytokinesis. Furthermore, they also indicate that the biological properties of c-Rel in cell growth and differentiation will potentially differ depending on the level of expression.

Animals↗

Proprioceptive information processing in weightlessness.

The "illusions" experiment carried out on five astronauts during the last two French-Russian flights (Antarès in 1992 and Altaïr in 1993) and in the Russian Post-Antarès mission (1993) was designed to investigate the adaptive changes in human proprioceptive functions occurring in weightlessness at both the sensorimotor and cognitive levels, focusing on two kinds of responses: (1) whole-body postural reflexes, and (2) whole-body movement perception. These kinesthetic and motor responses were induced using the tendon-vibration method, which is known to selectively activate the proprioceptive muscular sensory channel and to elicit either motor reactions or illusory movement sensations. Vibration (70 Hz) was therefore applied to ankle (soleus or tibialis) and neck (splenii) muscles. The subject's whole-body motor responses were analyzed from EMG and goniometric recordings. The perceived vibration-induced kinesthetic sensations were mimicked by the subjects with a joystick. The main results show that a parallel in-flight attenuation of the vibration-induced postural responses and kinesthetic illusions occurred, which seems to indicate that the proprioceptive system adapts to the microgravity context, where standing posture and conscious coding of anteroposterior body movements are no longer relevant. The same sensory messages are used at the same time in different sensory motor loops and in the coding of newly developed behavioral movements under microgravity. These results suggest that the human proprioceptive system has a high degree of adaptive functional plasticity, at least as far as the perceptual and motor aspects are concerned.

Adaptation, Physiological↗

Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization.

BACKGROUND: Activation of phospholipase D (PLD) is an important but poorly understood component of receptor-mediated signal transduction responses and regulated secretion. We recently reported the cloning of the human gene encoding PLD1; this enzyme has low basal activity and is activated by protein kinase C and the small GTP-binding proteins, ADP-ribosylation factor (ARF), Rho, Rac and Cdc42. Biochemical and cell biological studies suggest, however, that additional and distinct PLD activities exist in cells, so a search was carried out for novel mammalian genes related to PLD1. RESULTS: We have cloned the gene for a second PLD family member and characterized the protein product, which appears to be regulated differently from PLD1: PLD2 is constitutively active and may be modulated in vivo by inhibition. Unexpectedly, PLD2 localizes primarily to the plasma membrane, in contrast to PLD1 which localizes solely to peri-nuclear regions (the endoplasmic reticulum, Golgi apparatus and late endosomes), where PLD activity has been shown to promote ARF-mediated coated-vesicle formation. PLD2 provokes cortical reorganization and undergoes redistribution in serum-stimulated cells, suggesting that it may have a role in signal-induced cytoskeletal regulation and/or endocytosis. CONCLUSIONS: PLD2 is a newly identified mammalian PLD isoform with novel regulatory properties. Our findings suggest that regulated secretion and morphological reorganization, the two most frequently proposed biological roles for PLD, are likely to be effected separately by PLD1 and PLD2.

Amino Acid Sequence↗

Eye proprioception and visual localization in humans: influence of ocular dominance and visual context.

It has been previously established that the application of low amplitude mechanical vibrations to the inferior rectus muscle of human subjects results in an illusory upward movement of a luminous spot fixated in total darkness, and in a corresponding overshooting of the target when the subject is asked to point to this spot. In the first experiment described here, we compared the effects of applying vibrations to each eye separately and to both eyes simultaneously, under monocular and binocular viewing conditions, in left- and right-eyed subjects. The results confirmed that proprioceptive signals arising from both eyes are involved in egocentric visual localization. A proprioceptive dominance was observed however since vibration of the dominant eye gave rise to larger pointing displacements. In addition, whichever eye was stimulated, the pointing shift induced by vibrating a covered eye was of smaller amplitude than that which occurred when vibrations were applied to the viewing eye. The second experiment showed that both the vibration induced illusions and the pointing shifts disappeared in a structured visual context, which suggests that the processes involved when the target is viewed in darkness might differ from those occurring in structured surroundings.

Eye Movements↗

RB1 protein in normal and malignant human colorectal tissue and colon cancer cell lines.

The pattern of human retinoblastoma (RB1) gene protein expression was directly examined in normal and malignant human colorectal tissues and in seven colorectal carcinoma cell lines by immunohistochemistry using the mouse monoclonal antibody (RB-MAb-1) directed against the retinoblastoma protein (RB). This is the first demonstration of RB immunostaining in adult human colonic epithelium and colorectal carcinomas. Specificity using RB-MAb-1 was confirmed by western blot analysis, which showed bands of 110-116 kDa corresponding to the sizes of unphosphorylated and phosphorylated RB. RB staining of normal adult colonic epithelium was confined to the nucleus and was most intense in the transitional zone of the crypt, whereas lumenal cells (fully differentiated) were RB negative. Primary colorectal carcinomas and all the colon cancer cell lines stained positively for nuclear RB, but the expression was heterogeneous with varying fractions of RB negative cells present. Because we and others have previously shown that loss or inactivation of the RB1 gene is infrequent in colorectal carcinomas, reduced RB expression in such cells is probably due to a cellular regulatory mechanism. For example, RB negative cells may be those in early-G1 phase (known to have reduced RB levels) or growth-arrested cells that have differentiated. The ability to directly detect RB in primary colorectal carcinomas will permit assessment of whether heterogeneous expression of the RB1 gene product has prognostic significance for survival of patients with this cancer.

Antibodies, Monoclonal↗

A national validation study of the acute-toxic-class method--an alternative to the LD50 test.

In a national collaborative study an alternative to the classical LD50 test--the acute-toxic-class method--was validated. With this testing procedure mortality ranges are determined between defined dose levels that are used for classification and labelling in the European Community. The results were compared with LD50 data obtained from the literature which were categorized according to the defined dose levels. The results of this collaborative study have shown that the acute-toxic-class method allows allocation to the toxicity classes of very toxic, toxic, harmful and unclassified in the same manner as on the basis of the classical LD50 tests. The acute-toxic-class method uses fewer animals and subjects fewer animals to pain and distress than the LD50 test and yields the same information on toxic signs in the treated animals. Identical classifications were obtained by the six participating laboratories in 86% of the tests. This demonstrates that the acute-toxic-class method results in excellent reproducibility in comparison to the classical LD50 test and that this new method is a reliable alternative to the LD50 test.

Animal Testing Alternatives↗

Eye and neck proprioceptive messages contribute to the spatial coding of retinal input in visually oriented activities.

The egocentric localization of objects in extrapersonal space requires that the retinal and extraretinal signals specifying the gaze direction be simultaneously processed. The question as to whether the extraretinal signal is of central or peripheral origin is still a matter of controversy, however. Three experiments were carried out to investigate the following hypotheses: 1) that the proprioceptive feedback originating in eye and neck muscles might provide the CNS with some indication about the gaze direction; and 2) that the retinal and proprioceptive extraretinal inputs might be jointly processed depending on whether they are of monocular or binocular origin. Application of low amplitude mechanical vibrations to either the extraocular or neck muscles (or both) of a subject looking monocularly at a small luminous target in darkness resulted in an illusory movement of the target, the direction of which depended on which muscle was stimulated. A slow upward target displacement occurred on vibrating the eye inferior rectus or the neck sterno-cleido-mastoidus muscles, whereas a downward shift was induced when the dorsal neck muscles (trapezius and splenius) were vibrated. The extent of the perceptual effects reported by subjects was measured in an open-loop pointing task in which they were asked to point at the perceived position of the target. These results extend to visually-oriented behavior the role of extraocular and neck proprioceptive inputs previously described in the case of postural regulation, since they clearly show that these messages contribute to specifying the gaze direction. This suggests that the extraretinal signal might include a proprioceptive component.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A differentiated approach to testing skin sensitization. Proposal for a new test guideline skin sensitization.

The present EEC and OECD Guidelines for testing skin sensitization have been reviewed in light of scientific evidence demonstrating that those methods which use Freund's Complete Adjuvant (FCA) are likely to be more accurate in predicting a probable skin-sensitizing effect of a new substance in humans than those methods not employing Freund's Complete Adjuvant. In this new test guideline, therefore, the primary testing of a substance should be carried out using one of the recommended Adjuvant methods. In special cases a non-adjuvant method may be performed in addition. Not all of the seven methods in the EEC Guideline or eight methods in the OECD Guideline have been included, but in a proposal for an updated test protocol two Adjuvant tests (Maximization test by Magnusson and Kligman and Optimization test by Maurer), and two non-Adjuvant tests (Open Epicutaneous test by Klecak and Buehler test) are suggested. The criteria for selecting these methods are based on the fact that they are well validated and widely used on a broad basis by the scientific community. Furthermore, it is considered appropriate to permit the use of a lower number of animals than presently recommended for the testing of skin sensitization. This is also in agreement with aspects of animal welfare.

Animals↗

Eye, head and skeletal muscle spindle feedback in the elaboration of body references.

Evidence is presented to support the notion that the sensory feedback originating in muscles is of major importance in the central elaboration of motor representation. The muscle spindle messages during movement and postural performance may be processed in order to elaborate continuously updated static and dynamic body references. These may then form the basis for the interpretation of retinal information in terms of spatial coordinates. The main arguments supporting this view are as follows. Experimental manipulation of muscle spindle proprioceptive feedback by tendon vibration induced segmental or postural kinaesthetic illusory movements in the direction of stretch of the vibrated muscles. By modifying the spatial distribution (agonists and/or antagonists), the frequency and the duration of the vibratory stimuli it is possible to induce simple or complex kinaesthetic illusions the parameters of which may be predicted. Microneurographic recordings confirmed that vibration rather selectively excited spindle Ia afferents, eliciting 1:1 driving up to 80-100 Hz. Moreover painless vibration, applied at increasing frequency (from 10 to 80 Hz) to either the medial, lateral, superior or inferior rectus of a subject's eye, was found to induce directional perceptual and motor effects which were closely related to the postural context. Likewise, the subjects reported illusory directional shifts of a visually fixed target in darkness during extraocular muscle vibration. These data suggest that extraocular proprioception contributes to the coding of eye, head and body position in relation to postural and environmental conditions. As with eye muscle stimulation, directional visual and postural effects were induced by vibration of neck and/or ankle postural muscles. These effects were found to summate when vibrations were applied simultaneously to the eye, neck and ankle muscles. The likely involvement of extraocular proprioception in interrelating body space with extrapersonal space in oriented behaviour is discussed.

Head↗