Human perception of horizontal trunk and head rotation in space during vestibular and neck stimulation

Summary The vestibular signal of head motion in space must be complemented by a neck signal of the trunk-to-head excursion in order to provide the individual with information on trunk motion in space. This consideration led us to study psychophysically the role of vestibular-neck interaction for human self-motion perception. Subjects (Ss) were presented with passive horizontal rotations of their trunk and/or head (sinusoidal rotations, f=0.025 –0.4 Hz) in the dark for vestibular and neck stimulation, as well as for combinations of both. Ss' perception was evaluated in terms of gain (veridical perception of stimulus magnitude, G=1), phase, and detection threshold. (1) Perception of trunk rotation in space. During vestibular stimulation (whole-body rotation) and neck stimulation (trunk rotation with the head kept stationary) the frequency-transfer characteristics underlying this perception were very similar. The gain fell short; it was only about 0.7 at 0.4 and 0.2 Hz stimulus frequency and was further attenuated with decreasing frequency. In contrast, the phase was close to that of actual trunk position. The gain attenuation was found to be a function of the peak angular velocity of the stimulus, a fact, which we related to a velocity threshold of the order of 1 deg/s. During the various vestibular-neck combinations used, Ss' perception was again erroneous, reflecting essentially the sum of its two non-ideal constituents. However, there was one noticeable exception; during the combination head rotation on stationary trunk, Ss veridically perceived their trunk as stationary (compatible with the notion that the sum yielded zero). (2) Perception of head rotation in space. During vestibular stimulation, Ss' estimates showed the same non-ideal gain-vs.-frequency characteristics as described above for the trunk. Neck stimulation induced an illusion as if the head had been rotated in space. This neck contribution was such that, when it was combined with its vestibular counterpart during head rotation on stationary trunk, the perception became almost veridical. On closer inspection, however, this neck contribution was found to reflect the sum of two components; one was the non-ideal neck signal contributing to the perception of trunk in space, the other was an almost ideal neck signal of head-on-trunk rotation. (3) The results could be described by a simple model. In this model, the erroneous vestibular signal head in space is primarily used to create an internal representation of trunk in space. To this end, it is combined with the closely matching neck signal of trunk to head. The perception of head rotation in space is achieved by summing this trunk in space signal with the almost ideal head on trunk signal, again of nuchal origin. These seeming complex interactions have two implications: (i) the head is referred to trunk coordinates, whereas the trunk is referred to space coordinates; (ii) there is at least one condition in the dark where orientation is correct (despite an erroneous vestibular signal), i.e., during head rotation on stationary trunk.Supported by Deutsche Forschungsgemeinschaft, SFB 325     

Canal-neck interaction in vestibular nuclear neurons of the cat

Summary The convergence and interaction of horizontal semicircular canal and neck proprioceptive inputs were studied in neurons of the caudal two thirds of the vestibular nuclear complex. Extracellular neuron activity was recorded under muscle relaxation and slight anesthesia in chronically prepared cats. The following stimulations were applied: horizontal rotations of (a) the whole body (labyrinth stimulation), (b) the trunk vs. the stationary head (neck stimulation), and (c) the head vs. the stationary trunk (combined labyrinth and neck stimulation).Of 152 neurons investigated, 83 (55%) showed convergence of the two inputs. In about half of these neurons, the neck input was very weak and hardly affected the labyrinthine response during head rotation. Judged from the response pattern, several of these neurons presumably were related to vestibulo-oculomotor function (i.e., vestibular nystagmus). In the other half (i.e., 27% of all neurons), sensitivity of the two inputs was similar. Both labyrinthine and neck responses contained a dynamic (velocity) component; neck responses of more than half of these neurons had, in addition, a static (position) component. The dynamic components were either antagonistic or synergistic as to their convergence during head rotation. When applying this combined stimulation, the dynamic components summed linearly, yielding subtraction in case of antagonistic convergence and addition in case of synergistic convergence. In contrast, the static components of the neck responses remained largely unchanged during head rotation. However, the static head-to-trunk deflection determined the tonic discharge level in such neurons and thus facilitated or disfacilitated the dynamic responses to superimposed labyrinth stimulation.We suggest that the two patterns of labyrinthine-neck interaction observed in vestibular nuclear neurons, i.e., subtraction and addition, may be involved in the postural control of the trunk and head, respectively. In contrast, interference of the neck input with vestibule-oculomotor function appears to be almost negligible in the intact cat.Supported by Deutsche Forschungsgemeinschaft, SFB 70     

Firing characteristics of vestibular nuclei neurons in the alert monkey after bilateral vestibular neurectomy

Summary After destruction of the peripheral vestibular system which is not activated by moving large-field visual stimulation, not only labyrinthine-ocular reflexes but also optokinetic-ocular responses related to the velocity storage mechanism are abolished. In the normal monkey optokinetic-ocular responses are reflected in sustained activity changes of central vestibular neurons within the vestibular nuclei. To account for the loss of optokinetic responses after labyrinthectomy, inactivation of central vestibular neurons consequent on the loss of primary vestibular activity is assumed to be of major importance. To test this hypothesis we recorded the neural activity within the vestibular nuclear complex in two chronically prepared Rhesus monkeys during a period from one up to 9 and 12 months after both vestibular nerves had been cut. The discharge characteristics of 829 cells were studied in relation to eye fixation, and to a moving small and large (optokinetic) visual stimulus producing smooth pursuit (SP) eye movements and optokinetic nystagmus (OKN). Units were grouped into different subclasses.After chronic bilateral vestibular neurectomy (BVN) we have found: (1) a rich variety of spontaneously active cells within the vestibular nuclear complex, which — as far as comparison before and after BVN is possible — belong to all subclasses of neurons functionally defined in normal monkey; and (2) no sustained activity changes which are related to the activation of the velocity storage mechanism; this is especially true for pure-vestibular, vestibular-pause and tonic-vestibular-pause cells in normal monkey which show a pure, pause and tonic-pause firing pattern after BVN. Neurons which are modulated by eye position are, however, modulated with the velocity of slow eye movements with comparable sensitivity during SP and OKN. Retinal slip is extremely rarely encoded. The results of the present study do not directly answer the question why the velocity storage mechanism is abolished after BVN but they suggest that only a small number of central vestibular cells may be inactivated by neurectomy.Supported by SNF grant no. 3.510-0.86     

Canal-neck interaction in vestibular neurons of the cat's cerebral cortex

Summary Interaction of semicircular canal and neck proprioceptive inputs was studied in the cerebral cortex of awake, intact cats. Neuronal responses were recorded extracellularly in the anterior suprasylvian gyrus of the left hemisphere. Stimulations consisted of horizontal rotations in the dark applied as sinusoids or position ramps. There were three stimulus conditions: (1) Pure canal stimulation; rotation of whole body. (2) Pure neck stimulation; rotation of trunk about stationary head. (3) Canalneck interaction; rotation of head about stationary trunk.(1) We recorded 105 neurons with either Type I or Type II canal response. These showed often pronounced non-linearities such as a clear firing increase upon rotation in the on-direction and hardly any decrease in the opposite direction. The responses reflected mostly angular velocity, but angular position signals were also obtained. (2) In 79 neurons, either Type I or Type II neck responses were obtained. They coded either angular velocity, velocity plus position, or position. (3) Canal-neck convergence was found in 67 of 88 neurons tested. In the majority of neurons, interaction was dantagonistic in the sense that the canal and neck responses tended to cancel each other during rotation of the head about the stationary trunk. These neurons could signal trunk rotation in space rather than head in space or head relative to trunk. Most of the remaining neurons showed a synergistic interaction such that the response upon head rotation was enhanced as compared to whole body or trunk rotation. These neurons might be involved in the dual task of monitoring head rotation in space and relative to trunk. Interaction was compatible with linear summation of canal and neck inputs in 70% of the neurons. In part of these, however, the assumption had to be made that the interaction had taken place already at some stage prior to the cortical neurons investigated. The response characteristics of cortical canal neurons are discussed in comparison to vestibular nuclear neurons. Furthermore, parallels are drawn between the observed canal-neck interactions in the cortical neurons and (i) interactions of canal and neck dependent postural reflexes in the decerebrate cat, and (ii) interactions of canal and neck induced turning sensations in man.     

The interactive contribution of neck muscle proprioception and vestibular stimulation to subjective “straight ahead” orientation in man

Seventeen normal subjects were asked to direct a laser point to the position they felt to lie exactly straight ahead of their body. Subjects were seated in complete darkness in an approximately spherical cabin in an upright position with the orientation of the trunk and head aligned. For both the horizontal and vertical plane, straight ahead judgements were closely scattered around the objective straight ahead body position. Posterior neck muscle vibration as well as caloric vestibular stimulation with ice water led to (1) an apparent motion and horizontal displacement of a stationary visual target to the side opposite to stimulation and (2) a horizontal deviation of subjective straight ahead perception toward the side of stimulation. Only those subjects who experienced an illusion of target motion also showed a deviation of their subjective body orientation. No systematic effect of a displacement of subjective body orientation in the vertical plane was detected. When vestibular stimulation and neck muscle vibration were combined their effects were additive, i.e. the horizontal deviation of subjective body orientation observed when either type of stimulation was applied in isolation, was linearly combined either by summation or by cancellation. The present results clearly support the assumption that afferent visual, vestibular and proprioceptive input converge to the neural generation of an egocentric, body-centred coordinate system that allows us to determine our body position with respect to visual space.     

Lability in the responses of cells in the auditory cortex of squirrel monkeys to species-specific vocalizations

Summary The activity of 28 cells located mainly in the secondary auditory cortex (A II) of awake squirrel-monkeys, was extracellularly recorded for periods of up to 6 h. Seven different species-specific vocalizations, which were repeatedly presented to the monkey, were used as auditory stimuli. Twenty-six cells responded, at least once, to one or more vocalizations; 22 cells revealed some change in their response (pattern or strength) to at least one vocalization (change in response). Twenty-one cells exhibited a change in the number and/or type of vocalization to which they responded during the recording period (change in selectivity). At some time during the recording period all the responding cells exhibited a change in response and/or a change in selectivity (change in responsiveness). A change in response of a cell to a vocalization did not necessarily exclude a change in selectivity, associated with the same vocalization, later in time and vice-versa. A change in responsiveness to one vocalization was not necessarily correlated with changes in responsiveness to other vocalizations.     

GABA<Subscript>A</Subscript> receptor subunit expression in the guinea pig vestibular nucleus complex during the development of vestibular compensation

The aim of this experiment was to investigate whether vestibular compensation following unilateral vestibular deafferentation (UVD) is associated with changes in the expression of GABA_A receptor subunits in the guinea pig vestibular nuclear complex (VNC) at 2, 10, and 30 h post-surgery. Using Western blotting, the ₁ and ₂ subunits (but not the ₂ subunit) were detected in the VNC of labyrinthine-intact animals. However, there were no significant differences in the protein expression of the ₁ and ₂ subunits within the ipsilateral or contralateral VNC at any time post-UVD compared to sham and anesthetic controls. Furthermore, UVD did not induce the expression of the ₂ protein. These results suggest that vestibular compensation in guinea pig, as in the rat, is not associated with changes in the protein levels of the GABA_A receptor subunits ₁, ₂, and ₂ in the VNC. However, a limitation of this study is that the Western blotting technique can detect only changes that are larger than 30% and therefore small changes cannot be excluded.     

Synoviocytes in chronic synovitis in situ and cytokine stimulated synovial cells in vitro neo-express α1, α3 and α5 chains of β1 integrins

The expression of the 1 integrins was examined immunohistochemically in synoviocytes from normal synovial membrane and from chronic synovitis of different aetiology and intensity. Normal synoviocytes were 61-positive but lacked 1 through 5. In mild inflammation type A synoviocytes neo-expressed 1, 3, and 5 chains. In severe inflammation both type A and B synoviocytes expressed 3, 4, 5, and 6 chains. The effects of inflammatory cytokines, as single agents or in combination, on the 1 integrin expression in cultured normal synoviocytes was determined by immunocytochemistry and flow cytometry. The 1 chain, while absent in unstimulated synoviocytes, was induced by interleukin-1 (IL-1), tumour necrosis factor- (TNF-), and interferon- (INF-). This effect was enhanced by combining IL-1 and TNF-. Expression of the 3 chain was up-regulated by IL-1 and, more intensely, by IFN-. Transforming growth factor (TGF-) inhibited the up-regulating effect of IL-1 and antagonized the effect of IFN- on 3 chain expression. Expression of the 5 chain was up-regulated significantly by co-stimulation through IL-1 together with TGF- or TNF-. Thus, the 1 integrin profile of cytokine activated synoviocytes in vitro resembled that of synoviocytes in synovitis in situ. These data suggest that IL-1, TNF-, IFN-, and TGF- are likely to be among the effectors regulating 1 integrin expression in synoviocytes in vivo.     

Auditory cortex neurons sensitive to correlates of auditory motion: underlying mechanisms

Summary Neuronal response properties such as phasic vs. tonic, onset vs. offset, monotonicity vs. non-monotonicity, and E/E vs. E/I, can be shown to act synergistically suggesting underlying mechanisms for selectivity to binaural intensity correlates of auditory sound source motion. Both identical (diotic), and oppositely directed dichotic AM ramps were used as stimuli in the lightly anesthetized cat, simulating motion in four canonical directions in 3-dimensional space. Motion in either azimuthal direction evokes selective activity in cells which respond best to the onset of monaural sound in one ear and show a decreased response to binaural stimulation (E/I or I/E). In some cells specificity is increased by off components in the non-dominant ear. Although these cells fire only at the onset of stationary sound, they fire throughout oppositely directed AM ramps. Motion toward or away from the head evokes responses from EE cells; strong binaural facilitation increases selectivity for motion in depth. The sharpness of direction of tuning was related to the degree of binaural facilitation in E/E cells. Selectivity for sound moving away from the head is correlated with off responses, while on responses correlate with preference for motion toward the head. Most units showed a monotonic rate function as AM ramp excursion and rate was increased. One third were selective for slower rates of intensity change and may therefore encode slower rates of stimulus motion, as well as direction of movement. The findings suggest that neural processing of auditory motion involves neural mechanisms distinct from those involved in processing stationary sound location and that these mechanisms arise from interactions between the more traditionally studied response properties of auditory cortex neurons.This research was supported by MRC of Canada grant no MA-9856 to M.S.C., and a MRC studentship to E.S.     

Activation of atrial muscarinic K+ channels by low concentrations ofβγ subunits of rat brain G protein

Effects of G protein subunits from rat brain on cardiac K⁺ channel was examined in single atrial cells of guinea-pig, using patch clamp techniques. We found that 10 pM concentration of rat brain subunits preparation could activate the atrial muscarine receptor-gated K⁺ channel (I_K.ACh). Neither the detergent, CHAPS, used to suspend nor the boiled preparation activated I_K.ACh. Furthermore, preincubation of subunits preparation in Mg²⁺-free solution, which easily inactivated -GTP-S, did not affect -activation of I_K.ACh. We concluded, therefore, that subunits themselves can activate I_K.ACh.Supported by the grants from the Ministry of Education, Culture and Science of Japan and from the Calcium Signal Workshop on Cardiovascular Systems     

Modulation of Nav1.5 by β1- and β3-subunit co-expression in mammalian cells

Cardiac sodium channels (Na_v1.5) comprise a pore-forming -subunit and auxiliary -subunits that modulate channel function. In the heart, 1 is expressed throughout the atria and ventricles, whilst 3 is present only in the ventricles and Purkinje fibers. In view of this expression pattern, we determined the effects of 3 and 1 co-expression alone, and in combination, on Na_v1.5 stably expressed in Chinese hamster ovary cells. The current/voltage relationship was shifted –5 mV with either 1 or 3 co-expression alone and –10 mV with co-expression of both 1 and 3. In addition, 3 and 1/3 co-expression accelerated macroscopic current decay. There were significant hyperpolarizing shifts in equilibrium gating relationships with co-expression of 1 and 3 alone and in combination. Co-expression of 1/3 together resulted in a greater hyperpolarizing shift in channel availability, and an increase in the slopes of equilibrium gating relationships. Co-expression of 3 and 1/3, but not 1, slowed recovery from inactivation at –90 mV. Development of inactivation at –70 and –50 mV was accelerated by -subunit co-expression alone and in combination. -Subunit co-expression also reduced the late Na current measured at 200 ms. In conclusion, -subunits modulate Na_v1.5 gating with important differences between co-expression of 1 and 3 alone and 1/3 together.     

Influences of object weight and instruction on grip force adjustments

Summary This study investigated the influence of object weight and instructions on grip force responses in humans. Using a precision grip, subjects lifted a small instrumented test object to a predetermined height. Prior to each set of 40 trials, subjects were verbally instructed to either hold or let go of the object in response to any change in weight. Unpredictably on some trials (< 20%), a sudden sustained increase (load) or decrease (unload) in vertical load was applied to the object. Grip responses to these induced weight changes were evaluated by measuring grip force, object position, and associated electromyographic (EMG) activity. Grip force changes for a load were over three times greater than those for an unload. Such asymmetry may reflect everyday grasp and manipulation in a gravity-influenced world. Grip force adjustments to loads following hold instructions were on the average somewhat larger than those following let go instructions, but there was no influence of instructions on responses to unloads. These findings contrast with more robust influences of verbal instruction on automatic postural and proximal upper limb responses and also may suggest that grip force adjustments are influenced to a greater extent by intrinsic task variables than by extrinsic volitional intent. Such organization appears tailored to functional task requirements in natural environmental contexts.     

Effects of sleep deprivation on the activity of selected metabolic enzymes in skeletal muscle

Summary The present study gives the results of a comparison of the recorded and true tibia-calcaneal angles in 17 normal subjects and in 14 patients with abnormally hypoextensible non contracting triceps. 1. For a minimal passive torque, the difference between true and recorded angles varied considerably from one individual to another. The means and ranges for the two groups were respectively: –8 (+7, –21) and –7 (+5, –20). 2. When the passive torque increased as a result of slow passive lengthening of the muscle, the true curve was steeper than the recorded one, owing to differences between the two angle measurements. For each of the two groups the differences in means and ranges were respectively: 6 (0, +13.5) and 8 (3, 12). 3. Subjects made isometric voluntary contractions of the triceps surae at fixed angles which corresponded to step by step muscle lengthening. The resulting true curve was much steeper than the recorded curve. The differences in means and ranges were: 7 (1.5, +15) in children of the two groups and respectively 3 (0, +9) and 12 (10, 14) in adults of the two groups. The present results show that this methodology was the only reliable way of correctly obtaining passive and active torque-angle curves, measuring differences between subjects, appreciating the effects of treatments and these by ascertaining whether or not trophic muscle regulation was defective.     

Glucocorticoids modulate TGF-beta production by human fetal lung fibroblasts

TGF- is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGF- isoforms affect TGF- production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFLF) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TGF-1, -2, or -3. Post-culture media were collected for ELISA assays of TGF-1, -2, and -3 . TGF- mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TFG-2 and -3 stimulated TGF-1 production significantly (p < 0.01 relative to control). TGF-1 stimulated TGF-2 production (p < 0.01 relative to control). TGF-3 was undetectable. Glucocorticoids significantly inhibited TGF-1 and TGF-2 production and reduced expression of the up-regulated TGF-1 and TGF-2 mRNA induced by exogenous TGF-1, -2, or -3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF--stimulated cells, it was reduced by glucocorticoids. Thus, TGF- isoforms may stimulate production of various TGF- isoforms in the lung. Glucocorticoids then may block TGF- production by modulating mRNA levels and c-Jun.     

Mother-Baby psychiatric units (MBUs): National data collection in France and in Belgium (1999–2000)

Summary The French version of the Marcé checklist was used to collect data for 176 joint admissions to 11 psychiatric mother-baby units in 1999 and 2000. Mean age of the babies at admission ranged from 4 to 16 weeks. Two units also admitted older children. Mothers admitted were diagnosed with schizophrenia or chronic delusional disorders (n=44), acute transitory psychosis Bouffée délirante (n=20), bipolar disorders (n=20), depressive illness (n=38), personality disorders or intellectual disability (n=39), and other disorders (n=15). The mean duration of hospitalisation was 11 weeks. Units that also offered day-care admission in the same or a near-by unit had shorter mean admissions. More than half the womens partners (or babies fathers) had mental health problems. Women with schizophrenia or chronic delusional disorders and personality disorders or intellectual disability remained hospitalised longer, improved less, and were more often separated from their babies, or discharged with supervision, than women admitted with other diagnoses.     

Goal-directed vestibulo-ocular function in man: gaze stabilization by slow-phase and saccadic eye movements

Summary Vestibular function was examined during passive head movements having profiles that approximated the low-to-intermediate range of natural self-generated movements (10–220°/s peak velocity, about 0.5 s duration). A seated subject looked at a point target on the wall, the lights were extinguished and the chair was briefly turned while the subject tried to look at the just-viewed point. The chair was stopped, the lights were turned on again and the target was re-fixated, if necessary. Ocular stabilization was characterized (1) by net stabilization that was due to the combined effects of both slow-phase and rapid (saccadic or quick-phase) eye movements, (2) by cumulative-slow-phase stabilization that was due to slow-phase eye movements, and (3) by cumulative-saccadic stabilization that was due to effects of all rapid eye movements. It was found that both slow-phase and saccadic eye movements tended to keep the eyes on the actual unseen target. During repeatedly applied head movements, net and cumulative-slow-phase stabilization tended to be almost perfect. However, the average magnitude of the error in net stabilization (i.e., deviation from perfection) was always less than the corresponding error in slow-phase stabilization. This occurred because in a given turn, saccadic movements tended to supplement deficient slow-phase movements and to decrement excessive slow-phases. In 4 of 5 subjects, cumulative-saccadic stabilization tended to equal the error in cumulative-slow-phase stabilization. All results were unaffected by head velocities up to ±220°/s. It was concluded that these saccades tended to stabilize gaze (eye + head) in space during head movements in total darkness.     

Acute and chronic inflammatory responses to local administration of recombinant IL-1α, IL-β, TNFα, IL-2 and Ifnγ in mice

The contention that cytokines are important mediators of inflammation prompted the present studies which were designed to compare acute and chronic pathological effects of locally-administered recombinant (r) IL-1, IL-1, TNF, IL-2 and Ifn. Acute (6 hr), resolving (48 hr) inflammation was induced by the following, in order of potency: rIL-1>rIL-1>rTNF>rIfn=BSA (control) following a single sc. injection. However, only rIL-1 and rIL-2 initiated and maintained chronic granulomatous reactions when delivered locally from a sc. ethylene vinyl acetate (EVA) slow-release polymer. The predominance of macrophages in EVA-rIL-1 lesions contrasted with the proliferative lymphoid granulomata induced by EVA-rIL-2 implants. These in vivo observations reinforce, the roles of both IL-1 and IL-2 as potent mediators of chronic immunoinflammatory disease.     

On the regulation of the expressed L-type calcium channel by cAMP-dependent phosphorylation

The Ca²⁺ channel subunits _1C-a and _1C-b were stably expressed in Chinese hamster ovary (CHO) and human embryonic kidney (HEK) 293 cells. The peak Ba²⁺ current (I _Ba) of these cells was not affected significantly by internal dialysis with 0.1 mM cAMP-dependent protein kinase inhibitor peptide (mPKI), 25 M cAMP-dependent protein kinase catalytic subunit (PKA), or a combination of 25 M PKA and 1 M okadaic acid. The activity of the _1C-b channel subunit expressed stably in HEK 293 cells was depressed by 1 M H 89 and was not increased by superfusion with 5 M forskolin plus 20 M isobutylmethylxanthine (IBMX). The _1C-a·₂·₂/ complex was transiently expressed in HEK 293 cells; it was inhibited by internal dialysis of the cells with 1 M H 89, but was not affected by internal dialysis with mPKI, PKA or microcystin. Internal dialysis of cells expressing the _1C-a·₂·₂/ channel with 10 M PKA did not induce facilitation after a 150-ms prepulse to +50 mV. The Ca²⁺ current (I _Ca) of cardiac myocytes increased threefold during internal dialysis with 5 M PKA or 25 M microcystin and during external superfusion with 0.1 M isoproterenol or 5 M forskolin plus 50 M IBMX. These results indicate that the L-type Ca²⁺ channel expressed is not modulated by cAMP-dependent phosphorylation to the same extent as in native cardiac myocytes.     

Down-regulation of tumor necrosis factor α activity by acute ethanol treatment in human peripheral blood monocytes

As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor (TNF) production in human peripheral blood monocytes (M) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF in M, it was a potent down-regulator of M TNF production whether induced by the combination of interferon- plus muramyl dipeptide (MDP) (P<0.001), lipopolysaccharide (LPS) alone (P<0.01), or interferon- plus LPS. Down-regulation of M TNF by ethanol was dose dependent and statistically significant in the biologically relevant, 25–150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M viability. TNF down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective—though to a lesser extent—if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF production of thein vivo preactivated M of trauma patients, which produce hyperelevated levels of TNF. We have previously shown that the majority of posttrauma elevated M TNF is produced by the M subpopulation expressing high-affinity type I Fc receptors (FcRI). When the FcRI cross-linking-stimulated M subpopulation was treated with acute ethanol, TNF production was suppressed again both inin vivo preactivated M of trauma patients and in M of normal controls. In experiments utilizing cyclooxygenase inhibitor, we also demonstrate that ethanol has a direct, prostaglandin E₂-independent, effect on M TNF production. These results demonstrate that acute ethanol exposure has the potential to down-regulate M production of TNF significantly regardless of the TNF-inducing stimulus. Decreased capacity of M to produce TNF might, therefore, contribute to the immunological and metabolic abnormalities described after ethanol uptake.     

Gaze changing behaviour in head restrained monkey

Summary The electromyographic activity of neck muscles and head torque were recorded in the alert, head-fixed rhesus monkeys together with the horizontal component of eye movements during pursuit movements, scanning movement and vestibular stimulation in darkness. A strong correlation between head torque and the horizontal component of eye position was demonstrated during these three different experimental situations. These conjugate head and eye movements are accompanied by a specific change in the timing of neck neuromuscular activation.Supported by DGRST grant n 80-7-0248 and INSERM PRG grant n 50-7723