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Biomedical subjects

M Lacour

Publications and source records attributed to M Lacour.

At least 73 records · Page 4Linked to original sources

Type II collagen-specific human T cell lines established from healthy donors.

Four type II collagen-specific T cell lines established from the peripheral blood of a healthy donor were studied in detail. These CD4+ T cell lines with an alpha/beta T cell receptor proliferated in response to native and denatured human and chicken type II collagen and human type I collagen, but not to human type IV collagen or other potentially arthritogenic antigens. The T cell response showed typical dose response characteristics, peaked between 30 and 48 h, was major histocompatibility complex class II restricted and not due to a mitogenic effect. Type II collagen-reactive T cells could hardly be detected in freshly isolated peripheral blood mononuclear cells from healthy donors, as revealed by limiting dilution analysis (frequency less than 1/100,000). By prestimulation in bulk cultures for 10 days, type II collagen-reactive T cells could be approximately 1000-fold enriched. However, in these limiting dilution cultures, collagen-reactive T cells could only be observed in a narrow window of cell concentrations, suggesting that type II collagen-reactive T cells may be controlled by suppressive mechanisms in healthy persons.

Adult↗

Spontaneous production of anti-mouse red blood cell autoantibodies is independent of the polyclonal activation in NZB mice.

New Zealand Black (NZB) mice spontaneously develop an autoimmune hemolytic anemia together with a markedly increased production of polyclonal antibodies. The spontaneous generation of anti-mouse red blood cells (MRBC), anti-bromelain-treated MRBC (BrMRBC) and anti-DNA autoantibodies was compared to the polyclonal antibody formation in irradiated (800 rad) 2-month-old NZB mice reconstituted with bone marrow cells (BMC) from 2- or 10-month-old NZB mice. The injection of 10-month-old NZB BMC markedly accelerated the mortality rate in parallel with the progressive increase of anti-MRBC and anti-BrMRBC autoantibody production, but the spontaneous production of polyclonal IgM antibodies and anti-DNA autoantibodies was completely abolished down to the levels of non-autoimmune mice. In contrast, mice reconstituted with 2-month-old NZB BMC exhibited neither the acceleration of anemia nor the lack of polyclonal antibody production. These results strongly suggest that the spontaneous production of anti-MRBC autoantibodies, including anti-BrMRBC autoantibodies, in the NZB mouse occurs independently of the polyclonal B cell activation, and that they result from a specific immune stimulation, while the anti-DNA autoantibody production is a consequence of polyclonal antibody formation.

Anemia, Hemolytic, Autoimmune↗

Functional coupling of the stabilizing gaze reflexes during vertical linear motion in the alert cat.

Eye-head coordination is mainly achieved by means of stabilizing reflexes (VOR, VCR, OKR) and orienting movements (eye-neck surgery) underlying the close cooperation of the visual and vestibular systems in gaze stabilization. The functional coupling of these different sensorimotor subsystems has been principally analysed using rotatory stimulation of the whole body and/or of the visual surround. The aim of the present study was to investigate the dynamic properties of these stabilizing gaze reflexes and their coupling during linear motion in the vertical plane. These investigations were performed in the alert cat under open-loop conditions (head fixed). Otolith stimulation consisted of vertically translating the cat in total darkness using sinusoidal linear motion (0.025 Hz-1.39 Hz; 290 mm peak-to-peak amplitude). Optokinetic stimulation was provided by sinusoidally moving a pseudo-random visual pattern in front of the cat and in the vertical plane, with identical kinematic parameters. Normal visual-otolith interaction was performed by translating the cat in front of the stationary visual surround while conflicting interaction was provided by moving the animal and the visual pattern in phase and at the same velocity (visual stabilization). Results showed that the vertical otolith-neck reflex is very poorly developed or absent in the low frequency range of motion (0.025 Hz-0.25 Hz) while consistent EMG activity is found during pure optokinetic stimulation. EMG responses are in phase with the visual surround velocity in the upward direction and with the upward OKR velocity. A close correlation is observed between the EMG gain and the OKR gain, which both decrease in this low frequency range, indicating that gaze stabilization would be mainly ensured by the OKR and a functional oculo-collic coupling or eye-neck surgery in the vertical plane. On the contrary, gaze stabilization is principally achieved by way of the otolith-neck reflex in the higher frequency range of motion (above 0.25 Hz). EMG responses recorded during otolith stimulation exhibit a relatively constant gain and a phase lead with respect to motion velocity which progressively reduces as the stimulus frequency increases up to 1.39 Hz. When present, EMG responses evoked during the optokinetic stimulation show strong gain attenuation and phase lag. Normal visual-otolith interaction induces neck muscle activity which parallels the optokinetic and the otolith responses in the low and high frequency ranges, respectively. The motor responses are however improved in terms of gain and phase values in the whole frequency range when both sensory inputs are combined.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Autoantibody repertoire analysis in normal and lupus-prone mice.

We have analyzed at the clonal level (limiting dilution assay) the repertoire of lipopolysaccharide (LPS)-responsive murine B cells committed to the production of autoantibodies characteristic of systemic lupus erythematous (SLE), i.e. anti-single-stranded DNA (ssDNA), anti-double-stranded DNA, anti-Sm and rheumatoid factors (RF). Our results demonstrated that: (1) the frequency of precursor B cells producing each lupus autoantibody (approximately 1 in every 100-400 LPS-responding B cell) was similar in two non-autoimmune (C57BL/6 and BALB/c) and four SLE-prone (NZB, (NZB x NZW)F1, MRL/MpJ and BXSB/MpJ) mice despite the marked differences in autoimmune responses in the different SLE-prone mice, and (2) the relative frequency of autoantibody-secreting precursor B cells was constant throughout life, and equally distributed among activated and resting B-cell populations and among B cells from the peritoneal cavity and spleen. The lack of association of anti-ssDNA secretion with anti-Sm or RF secretion in cultures set up with a smaller number of B cells ruled out the possibility that the similar frequency of different autoantibody-secreting cell precursors is due to the poly-specificity of IgM autoantibodies. Notably, the frequencies of autoantibody-secreting precursor cells were significantly lower, approximately 4 and 10 times, than those of anti-tetanus toxoid and anti-dinitrophenyl antibody-producing precursor B cells, respectively. The similar frequency of precursor B cells producing four different lupus autoantibodies on the one hand and the considerable variation in each autoimmune response among SLE-prone mice on the other, support the hypothesis that specific stimulatory mechanisms may govern each autoimmune response in different SLE strains of mice.

Animals↗

Neuronal coding of linear motion in the vestibular nuclei of the alert cat. II. Response characteristics to vertical optokinetic stimulation.

Extracellular activity from vestibular nuclei neurons and vertical eye movements were recorded in the alert cat during sinusoidal optokinetic stimulation in the vertical plane at frequencies varying from 0.0125 Hz to 0.75 Hz. Among a population of 96 vestibular units located in and around Deiters' nucleus, 73 neurons (76%) displayed a firing rate modulation which followed the input at the standard parameters of visual stimulation (0.05 Hz; 10.1 deg/s or 9.1 cm/s peak to peak velocity). Two different patterns of modulation were found. In 42 cells (57%) an increase in the firing rate was observed during motion of the visual scene in the downward direction, while 31 neurons (43%) showed the opposite behavior, with an enhanced firing rate during upward movement. The phase of the neuronal responses was close (+/- 45 degrees) to the velocity peaks (+90 degrees: downward and -90 degrees: upward) of visual scene motion for 65 among the 73 neurons. Mean values of phase was -6.1 +/- 19.5 degrees (SD) and -3.2 +/- 15.5 degrees (SD) with respect to the +90 degrees and -90 degrees velocity peaks, respectively. In the frequency range 0.0125-0.75 Hz, the phase of the neuronal responses remained almost stable, with only a slight lag which reaches -22 degrees at the 0.25 Hz visual stimulation. The firing rate modulation was found to be predominant at low frequencies (0.0125 Hz-0.25 Hz), with three distinct peaks of modulation occurring either at 0.025 Hz, 0.10 Hz or 0.25 Hz, depending on the recorded cells. Above 0.5 Hz, the cell modulation was very poorly developed or even absent. A gain attenuation was observed in all units, which was more important in cells showing a peak of modulation at 0.025 Hz as compared with the others (-20.7 dB vs -9.6 dB, respectively, in the 0.025 Hz-0.25 Hz decade). The gain of the optokinetic reflex (OKR) progressively decreased from mean values of 0.78 +/- 0.15 to 0.05 +/- 0.06 in the 0.025 Hz-0.5 Hz frequency range. A close correlation was observed between the OKR slow phase velocity and the modulation of the neuronal responses in the two cell populations with maximal modulations at 0.10 Hz or 0.25 Hz. No correlations were noticed in the third population characterized by a peak of modulation at 0.025 Hz. In all units, the phase of eye movement velocity and of neuronal responses were both related to the velocity of the visual surround motion. These correlations were also found when varying the amplitude of the visual stimulation at a fixed frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Neuronal coding of linear motion in the vestibular nuclei of the alert cat. III. Dynamic characteristics of visual-otolith interactions.

In the present study we have investigated in the awake cat the response dynamics of vestibular nuclei neurons to visual or/and otolith stimulation elicited by vertical linear motion. Of the 53 units tested during sinusoidal motion at 0.05 Hz (9.1 cm/s), 1 (1.9%) was responsive to the otolith input only, 13 (24.5%) were influenced by the visual input only and 23 (43.4%) responded to both modalities. Neurons were excited either during upward or downward animal or visual surround movement. Most units displayed a firing rate modulation very close to motion velocity. All the neurons receiving convergent visual and otolith inputs (0.05 Hz, 9.1 cm/s) exhibited synergistic patterns of response. Motion velocity coding was improved in terms of input-output phase relationship and response sensitivity when visual and otolith signals were combined. Depending on the units, visual-otolith interactions in single neurons could follow a linear or a nonlinear mode of summation. The dynamic characteristics of visual-otolith interactions were examined in the 0.05 Hz-0.50 Hz frequency bandwidth. Visual signals seemed to predominate over otolith signals at low stimulus frequencies (up to 0.25 Hz), while the contrary was found in the higher frequency range of movement (above 0.25 Hz). The effects of visual stabilization (VS: suppression of visual motion cues) was observed in a small sample of units. As a rule, VS induced a reduction in the amplitude of unit response as compared to visual + otolith stimulation, the lower the motion frequency, the more pronounced the attenuation. VS also decreased the amplitude of the otolith-dependent component of response. The possible modes of visual-vestibular interactions in single cells are discussed. The present study supports the hypothesis that visual and vestibular motion cues are weighted according to their internal relevance.

Action Potentials↗

Dynamic properties of the vertical otolith neck reflexes in the alert cat.

Electromyographic activity of dorsal neck muscles elicited by sinusoidal vertical linear accelerations was studied in alert cats over a wide range of frequencies. Experiments were performed in head-fixed cats and total darkness in order to activate selectively the otolith system. The polyunitary EMG activity was recorded from splenius capitis muscles in normal and labyrinthectomized cats during vertical translations varying from 0.05-1 Hz with a fixed 290 mm peak-to-peak amplitude. The corresponding accelerations ranged from 0.003-1.2 g. In normal cats, the results showed a bilateral and sinusoidal modulation of the EMG activity characterized by two typical EMG patterns depending on the stimulus frequency. In the low-frequency range (0.05-0.25 Hz), the neck muscles responses were composed of a second harmonic (frequency double that of the input signal: H2 responses). The H2 pattern was characterized by an increase in EMG activity during both the upward and downward parts of translation. These two components of the H2 response were closely related to the two peak velocities (+90 degrees and -90 degrees) of the animal motion. Only slight decreases in amplitude and shifts in phase were observed when increasing the frequency. In the higher frequency range (0.25-1 Hz), the neck muscles response was composed of a fundamental frequency corresponding to the input signal (H1 response). The H1 pattern was in phase with the peak of downward acceleration at 0.25 Hz. A phase lag (up to 45 degrees) and a gain attenuation (16.5 dB) were observed when increasing the frequency. The two H1 and H2 EMG patterns were totally absent in bilateral vestibular neurectomized cats. In unilateral vestibular neurectomized cats, a strong drop in gain and phase advance was noted, which mainly affected the H1 pattern. The present results describe some characteristics of otolith-spinal reflexes acting on the head musculature during vertical motion. They are compared with the neuronal responses that we have recorded within the vestibular nuclei complex in the same experimental conditions. The functional role of the vertical otolith-neck reflexes in stabilizing the head in space during many real-life situations is discussed.

Acceleration↗

Neuronal coding of linear motion in the vestibular nuclei of the alert cat. I. Response characteristics to vertical otolith stimulation.

The aim of the present study was to investigate some aspects of the central processing of otolith information during linear motion. For this purpose, the response characteristics of 69 vestibular nuclei units to sinusoidal otolith stimulation in the vertical Z axis were analysed in the alert cat. Among this population of neurons which responded to a 0.05 Hz, 290 mm translation, 47 units (70%) displayed a firing rate modulation which followed the input frequency (H1 units). The majority of these neurons exhibited an increase in discharge rate during upward displacement, with a response phase close to the motion velocity or slightly leading downward acceleration. The acceleration related units were divided into two groups according to whether they showed clear increases or only a slight change in discharge rate when the stimulus frequency was increased. The former group was characterized by an average -16.3 dB drop in gain (from 43.9 +/- 1.8 dB, S.D. to 27.6 +/- 7 dB, S.D.) within the 0.05 Hz-0.5 Hz frequency range, while the latter group displayed an average -31.2 dB gain attenuation (from 45.1 +/- 1.1 dB, S.D. to 13.9 +/- 0 dB) within the same decade. In contrast to differences in response gain, all the units tested exhibited a relatively stable phase lead of about 20 degrees with respect to downward peak acceleration. Conversely, units whose response was close to motion velocity in the lower frequency range (0.05 Hz-0.10 Hz) displayed a strong phase lead of about 100 degrees when the stimulus frequency was increased (up to 0.50 Hz). These neurons were thus characterized by an acceleration related response in the higher frequency range. At the same time, an average -24.8 dB gain attenuation (from 47.7 +/- 3.4 dB to 22.9 +/- 3.7 dB) was found in the 0.05 Hz-0.5 Hz decade. The remaining 22 neurons (30%) were called H2 units since they displayed a response waveform double that of the input frequency, a response already described during sinusoidal rotation. Unit discharge reached a peak approximately in phase with maximum upward and downward velocity. Asymmetrical change in unit firing rate about the resting discharge level and different dynamic behavior of the upward and downward response components were usually found. These response characteristics suggest that the H2 patterns are centrally constructed and could result from convergence of otolith afferents having opposite polarization vectors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Treatment,in girls, of ectopic ureters, due to duplication, using reimplantation of the single pathological ureter into the bladder].

Mostly the ectopic ureter belongs to the upper pole in urinary tract duplications. In the pelvis, the two ureters are clearly separated. The only dissection of the ectopic ureter is in no case dangerous for the ureter of the lower pole. Therefore the reimplantation of the ectopic ureter can be performed separately. This only reimplantation of the ectopic ureter has been performed 9 times, without any mortality nor morbidity. The scar is almost invisible and the child is cured without any risk for the upper pole and saving the whole of the renal parenchyma. If the upper pole is functional, which happened in 1/4 of the cases, this technique is the best way and the less dangerous to recovery.

Adolescent↗

Excimer laser surgery of the cornea: qualitative and quantitative aspects of photoablation according to the energy density.

Using an excimer laser working in the far ultraviolet and cutting fresh corneas of human cadaver eyes, we were able to demonstrate that there is an ideal fluence (joule/cm2/pulse) that allows a maximum tissue ablation depth per shot. Above the threshold of 1 J/cm2/pulse the depth of tissue ablated does not increase and both thermal and mechanical damage appears at the cut edges.

Cornea↗

Central compensation of vestibular deficits. III. Response characteristics of lateral vestibular neurons to roll tilt after contralateral labyrinth deafferentation.

The responses of lateral vestibular nucleus (LVN) neurons to stimulation of macular labyrinth receptors have been investigated in precollicular decerebrate cats after contralateral acute vestibular neurectomy (aVN). On the whole, 78 LVN neurons were tested during slow sinusoidal tilt of the animal at the standard parameters (0.026 Hz, 10 degrees peak displacement). The neurons were located in both the rostroventral (rvLVN) and the dorsocaudal parts (dcLVN) of Deiters' nucleus, which project mainly to the cervical and the lumbosacral cord, respectively. After contralateral aVN, the proportions of responsive units in rvLVN and dcLVN (100% and 75.4%, respectively) were similar to those obtained in control experiments with intact labyrinths. However, the mean discharge rate of the responsive units slightly decreased with respect to the value obtained in control experiments, the decrease being more prominent within the rvLVN. The average sensitivity (and to a lesser extent the gain) of responses of rvLVN neurons to the labyrinth input was almost twice that of the dcLVN units in preparations with the vestibular nerves intact; these regional differences disappeared after contralateral aVN, particularly due to a decrease in gain and sensitivity of responses in the rvLVN. The proportion of LVN neurons that were maximally excited by animal position increased from 74.0% in the control experiments to 82.8%. However, while in control experiments the proportion of units excited during side-down tilt was twice as high as that of the units excited by side-up tilt, the opposite occurred after contralateral aVN; this finding affected particularly the dcLVN. In addition the average phase lead of responses relative to the extreme animal displacements slightly decreased from +12.3 degrees in control experiments to +9.4 degrees. Among the LVN neurons recorded after contralateral aVN, 35 were antidromically activated by stimulating the spinal cord at T12 L1, while 43 units were not activated. The relation found in control experiments, i.e., that the faster the conduction velocity of vestibulospinal axon the lower was the unit discharge at rest, was lost after contralateral aVN, due to a decrease in resting discharge rate of the slow neurons. This finding, coupled with the observation that slow and fast units did not show any difference in their response gain to tilt, explains why the positive correlation between axonal conduction velocity and response sensitivity occurring in control experiments was lost after contralateral aVN.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

[Relearning and critical postoperative period in the restoration of nerve function. Example of vestibular compensation and clinical implications].

The role of sensorimotor activity in the recovery process after unilateral vestibular neurectomy was studied on cats and monkeys using behavioral and electrophysiological methods. It was analyzed by comparing the time-course of the recovery of posture, locomotion and equilibrium function in animals which remained free after surgery in their usual environment (unrestrained group) to others which were submitted to a postoperative sensorimotor restriction (restrained group). This sensorimotor restriction was applied at different postoperative times; the effects of short and long-lasting restrictions were also studied. Results showed that the functional recovery develops in active animals only, i.e. when they can use all available information elicited by an active sensorimotor exploration. It is blocked and delayed in the restrained group, the postoperative disorders being reduced much later when a long-lasting restriction is used. It is also demonstrated that the functional recovery is better and faster in animals having an early sensorimotor activity. It is concluded that vestibular compensation resembles a sensorimotor relearning process requiring the activity of the subject, and that a postoperative critical period may exist in functional recovery which may be crucial for achieving well-or maladapted behavior. The clinical implications of these findings are presented in the discussion as some general principles able to stimulate reflexions and improve the postoperative training methods.

Animals↗

[A paradoxical orthodontic syndrome].

A particular characteristic of dentomaxillary dysharmony, probably the most frequently encountered anomaly in dentofacial orthopedic practice, is often the result of the presence of physiologic facial asymmetry. Attention is drawn to a syndrome, which could be thought to be paradoxical, and which associates facial asymmetry affecting the left side and dentomaxillary dysharmony that is curiously more marked on this same side.

Adolescent↗

Visual influences on vestibulospinal reflexes during vertical linear motion in normal and hemilabyrinthectomized monkeys.

In the present investigation, we have analysed the visually induced modulations of muscular responses during falls at different rates of acceleration and performed in five different visual conditions: Normal vision (NV), Darkness (D), Stabilized vision (SV), with visual motion cues being enhanced (EV), or reduced (RV). This study was conducted on normal and hemilabyrinthectomized baboons. EMG activities were recorded in the alert monkey from three pairs of muscles (splenius capitis, soleus and tibialis anterior). For testing, the monkey was seated in a special chair unexpectedly dropped by 0.9 m. Five peaks of maximum acceleration were used (8.8, 6.6, 4.4, 3.3, 2.2 m/s2). Conditions EV, SV and RV were tested by way of projector, the input of which consisted of the integral of vertical acceleration and output, the output of which controlled film motion. In the normal baboon the visually induced modulation of EMG responses in the SV, EV, and RV conditions was larger for slow falls than for fast ones. This modulation was direction-specific, at least for slow falls, and depended on the relative speed of the visual scene. Between certain limits, the energy of the responses was roughly proportional to the relative speed of the visual scene. These modifications were most accentuated in the splenius and soleus muscles. Condition D only produced a slight reduction of the EMG response. All these findings eliminate the possibility that the observed effects represents a startle response. Thus, we can conclude that there is a fact directional role of vision in postural control in the normal falling baboon. In the hemilabyrinthectomized animal, greater modulations were recorded only when the visual manipulations were performed during the first two postoperative weeks. This confirms the above results on the normal baboon and previous data on the role of vision in the recovery process.

Animals↗