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M Lacour

Publications and source records attributed to M Lacour.

At least 19 recordsLinked to original sources
PubMed1992

H-2-linked control of the Yaa gene-induced acceleration of lupus-like autoimmune disease in BXSB mice.

The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.

Animals↗
PubMed1992

Functional coupling of the stabilizing eye and head reflexes during horizontal and vertical linear motion in the cat.

The otolith contribution and otolith-visual interaction in eye and head stabilization were investigated in alert cats submitted to sinusoidal linear accelerations in three defined directions of space: up-down (Z motion), left-right (Y motion), and forward-back (X motion). Otolith stimulation alone was performed in total darkness with stimulus frequency varying from 0.05 to 1.39 Hz at a constant half peak-to-peak amplitude of 0.145 m (corresponding acceleration range 0.0014-1.13 g). Optokinetic stimuli were provided by sinusoidally moving a pseudorandom visual pattern in the Z and Y directions, using a similar half peak-to-peak amplitude (0.145 m, i.e., 16.1 degrees) in the 0.025-1.39 Hz frequency domain (corresponding velocity range 2.5 degrees-141 degrees/s). Congruent otolith-visual interaction (costimulation, CS) was produced by moving the cat in front of the earth-stationary visual pattern, while conflicting interaction was obtained by suppressing all visual motion cues during linear motion (visual stabilization method, VS, with cat and visual pattern moving together, in phase). Electromyographic (EMG) activity of antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles as well as horizontal and vertical eye movements (electro-oculography, EOG) were recorded in these different experimental conditions. Results showed that otolith-neck (ONR) and otolith-ocular (OOR) responses were produced during pure otolith stimulation with relatively weak stimuli (0.036 g) in all directions tested. Both EMG and EOG response gain slightly increased, while response phase lead decreased (with respect to stimulus velocity) as stimulus frequency increased in the range 0.25-1.39 Hz. Otolith contribution to compensatory eye and neck responses increased with stimulus frequency, leading to EMG and EOG responses, which oppose the imposed displacement more and more. But the otolith system alone remained unable to produce perfect compensatory responses, even at the highest frequency tested. In contrast, optokinetic stimuli in the Z and Y directions evoked consistent and compensatory eye movement responses (OKR) in a lower frequency range (0.025-0.25 Hz). Increasing stimulus frequency induced strong gain reduction and phase lag. Oculo-neck coupling or eye-head synergy was found during optokinetic stimulation in the Z and Y directions. It was characterized by bilateral activation of neck extensors and flexors during upward and downward eye movements, respectively, and by ipsilateral activation of neck muscles during horizontal eye movements. These visually-induced neck responses seemed related to eye velocity signals. Dynamic properties of neck and eye responses were significantly improved when both inputs were combined (CS).(ABSTRACT TRUNCATED AT 400 WORDS)

Acceleration↗
PubMed1991

Selective autoantibody production by Yaa+ B cells in autoimmune Yaa(+)-Yaa- bone marrow chimeric mice.

The accelerated autoimmune syndrome observed in BXSB/MpJ male mice is associated with the presence on the Y chromosome of an as yet unidentified mutant gene, designated Y chromosome-linked autoimmune acceleration (Yaa). To study the mechanisms by which the Yaa gene accelerates and/or induces the production of autoantibodies, we have developed double-congenic bone marrow chimeras containing B cells from autoimmune males carrying the Yaa gene, and from nonautoimmune male or female mice lacking it and differing by the Igh allotype. The analysis of the allotype of total immunoglobulins and anti-DNA antibodies in Yaa+ male-normal female (Yaa-) chimeric mice revealed that the selective activation of B cells from autoimmune Yaa+ male mice was responsible for the hypergammaglobulinemia and autoantibody production. This phenomenon was not due to an anti-HY interaction between female T helper cells and male B cells, because first, Yaa+ B cells were selectively stimulated to produce autoantibodies in Yaa+ male-Yaa- male chimeric mice; and second, normal male and female chimeras failed to develop an autoimmune syndrome. In addition, the fact that both B cell populations in Yaa(+)-Yaa- chimeras similarly responded to a foreign antigen, human IgG, argues against the possibility that the selective activation of Yaa+ B cells may be due to their hyper-responsiveness to T helper signals. We propose that a cognate interaction of T helper cells with Yaa+ B cells, because of possible T cell recognition of a Yaa-related molecule expressed on Yaa+ B cells, may be responsible for the acceleration and/or induction of autoantibodies in BXSB/MpJ mice.

Animals↗
PubMed1991

Lack of anti-DNA precursors in lambda chain-bearing B lymphocytes in (NZB x NZW)F1 mice. Evidence for the contribution of V kappa genes to anti-DNA specificity.

We have analyzed by the limiting dilution assay on spleen cells from (NZB x NZW)F1 hybrid mice the repertoire of lipopolysaccharide-responsive murine kappa- and lambda 1-secreting B cells committed to the production of anti-DNA autoantibodies to determine the contribution of the heavy and light chains to anti-DNA specificities. Our results demonstrated that anti-DNA precursors were predominantly found in the kappa-secreting B cell population, but not in lambda 1-secreting B cells, while anti-hapten, dinitrophenyl, and anti-tetanus toxoid activities were distributed fairly well in both populations of B cells. This suggests that the V kappa gene segments are critically involved in the generation of anti-DNA specificities, and that at least at the germ-line gene level, the heavy chain V region genes by themselves are not able to confer the anti-DNA autoreactivity.

Animals↗
PubMed1991

Osteoarticular infections due to Kingella kingae in children.

By the description of two cases of osteoarticular infections due to Kingella kingae in two young children we wish to draw the attention of clinicians to invasive infections due to this micro-organism. Since its biological characterization in 1976, K. kingae has been increasingly reported as a human pathogen. Most common presentations are endocarditis, bacteraemia, septic arthritis, osteomyelitis and spondylodiscitis. Interestingly, osteorticular involvement is largely predominant in previously healthy children. From the literature, we reviewed 51 cases of K. kingae bone and joint infections, representing 23 cases of septic arthritis, 17 of osteomyelitis and 11 spondylodiscitis. Of the cases 88% occurred in children below 5 years of age and in all cases only one bone or joint was involved. An underlying disorder could be found in only 4 patients. Since these infections have a favourable outcome with intravenous antibiotic treatment, proper isolation and identification of K. kingae is essential.

Arthritis, Infectious↗
PubMed1991

Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of Ginkgo biloba (EGb 761).

The effects of administration of an extract of Ginkgo biloba (EGb 761) on vestibular compensation was studied in unilateral vestibular neurectomized cats. This experimental model of CNS plasticity was investigated by using behavioral tests (postural disorders compensation, locomotor balance recovery), electrophysiological (spontaneous and evoked neck muscle activity) and neurophysiological (spontaneous firing rate recovery of deafferented vestibular cells) recordings, and immunocytochemical methods (synaptic loss and synaptic reoccupation within the deafferented vestibular nuclei). In all experiments, EGb 761 was administered over 30 days at daily doses of 50 mg/kg IP. The results showed a faster recovery in the EGb-treated group of cats as compared to an untreated control group. EGb administration strongly accelerated postural and locomotor balance recovery. Concomitantly, spontaneous neck muscle activity, vestibulo-collic reflexes and spontaneous firing rate of vestibular units located on the lesioned side were restored earlier. Morphological correlates characterized by a more rapid synaptic reoccupation were found in the deafferented medial vestibular nucleus by means of immunoreactive labelling using an antibody against a synaptic vesicle-associated protein (synaptophysin), but they displayed a longer time-constant in comparison with the behavioral and neurophysiological data. These results clearly demonstrate that EGb 761 acts on recovery mechanisms considered as key processes in vestibular compensation. They suggest that this substance would possess neurotrophic and/or neuritogenic properties improving functional recovery after CNS injury.

Animals↗
PubMed1991

Spray-induced frostbite in a child: a new hazard with novel aerosol propellants.

A case of deep frostbite occurred in an 8.5-year-old child. The lesion was due to the improper use of a toilet air freshener and was severe enough to require a skin graft. The propellants contained in the spray were propane and butane. We measured the temperature of this aerosol during spraying (-40 degrees) in comparison with an ethyl chloride spray (-3 degrees) widely used for local skin anesthesia. This difference is mainly due to the much lower evaporation temperature of propane (-42.2 degrees) and butane (-0.6 degrees) compared with ethyl chloride (12.5 degrees). This child aimed the spray directly toward his skin, thus producing a deep frostbite. We wish to draw the attention of clinicians to this potential hazard with new propellants, since they should soon replace chlorohydrofluorocarbons throughout the world for ecologic reasons.

Aerosol Propellants↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗