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Les peptides RFamide ont une extrémité carboxyterminale Arg-Phe-NH2 conservée et indispensable à leur activité. Ils sont impliqués dans la modulation de divers mécanismes biologiques, dont la douleur. Cette revue résume les connaissances sur la localisation de ces neuropeptides et de leurs récepteurs ainsi que leur rôle dans la modulation de la douleur. Les stratégies et outils thérapeutiques innovants en développement pour étudier le rôle respectif de ces récepteurs sont abordés.

International audience; Most studies on the regulation of speed and trajectory during ellipse drawing have used visual feedback. We used on-line auditory feedback (sonification) to induce implicit movement changes independently from vision. The sound was produced by filtering a pink noise with a bandpass filter proportional to movement speed. The first experiment was performed in 2D. Healthy participants were asked to repetitively draw ellipses during 45 second-trials whilst maintaining a constant sonification pattern (involving pitch variations during the cycle). Perturbations were produced by modifying the slope of the mapping without informing the participants. All participants adapted spontaneously their speed: they went faster if the slope decreased and slower if it increased. Higher velocities were achieved by increasing both the frequency of the movements and the perimeter of the ellipses, but slower velocities were achieved only by decreasing the perimeter of the ellipses. The shape and the orientation of the ellipses were not significantly altered. The analysis of the speed-curvature power-law parameters showed consistent modulations of the speed gain factor, while the exponent remained stable. The second experiment was performed in 3D and showed similar results, except that the main orientation of the ellipse also varied with the changes in speed. In conclusion this study demonstrated implicit modulation of movement speed by sonification and robust stability of the ellipse geometry. Participants appeared to limit the decrease in movement frequency during slowing down in order to maintain a rhythmic and not discrete motor regimen.

Le consortium TOURNESOL, regroupant 11 equipes de chercheurs et de cliniciens de trois villes (Marseille, Montpellier et Rouen) et finance par la Fondation de l’Avenir, a pour mission de mener deux essais cliniques destines a reparer des nerfs peripheriques leses–nerfs facials et des membres – grâce a des greffes autologues de cellules souches nasales. Pourquoi la therapie cellulaire ? Environ 100 000 operations de reparation nerveuse sont realisees chaque annee aux Etats-Unis et en Europe. Elles representent 2,8 % des traumatismes et sont le plus souvent responsables d’une perte de fonction voire d’invalidite. Malgre des progres dans le delai de prise en charge et dans la qualite du geste technique chirurgical, il n’y a eu aucun progres majeur depuis une vingtaine d’annees. Une approche de therapie cellulaire pourrait limiter l’inflammation et ameliorer la croissance axonale. Pourquoi les cellules souches olfactives nasales ? Chez le mammifere adulte, y compris chez l’homme, la muqueuse olfactive est le seul tissu nerveux capable d’auto-renouvellement. La plasticite de ce tissu est en partie assuree par des cellules souches qui sont multipotentes. Comme demontre par plusieurs membres du consortium, elles peuvent donner naissance a des cellules neurales (neurones, astrocytes, oligodendrocytes, cellules de Schwann). Leur potentiel therapeutique a ete teste avec succes dans differents modeles animaux de paraplegie, de la maladie de Parkinson, de surdite et d’amnesie. Que disent les etudes menees chez le rat par le consortium. Deux etudes, menees en parallele sur le nerf facial et le nerf peronier ont permis de montrer que la greffe de cellules souches olfactives : ameliore la recuperation fonctionnelle de la mobilite faciale ; diminue les syncinesies œil-bouche ; accroit les capacites locomotrices ; ameliore le seuil tetanique, le temps de contraction et le taux de relaxation musculaire Les cellules souches olfactives, medicament de therapie innovante, agree par l’ANSM. Avant de mener les essais cliniques, il a ete necessaire de cultiver les cellules souches dans un laboratoire de therapie cellulaire, dans des conditions repondant aux normes europeennes. Les essais cliniques multicentriques porteront sur une premiere serie de 10 patients avec des lesions negligees des nerfs collateraux et de la branche sensitive du nerf radial avec une perte de substance. La periode d’evaluation post-greffe s’etalera sur 12 mois. La chirurgie regenerative va representer une revolution dans la reparation des membres. Et les nerfs peripheriques devraient en beneficier.

International audience; The use of continuous auditory feedback for motor control and learning is still understudied and deserves more attention regarding fundamental mechanisms and applications. This paper presents the results of three experiments studying the contribution of task-, error-, and user-related sonification to visuo-manual tracking and assessing its benefits on sensorimotor learning. First results show that sonification can help decreasing the tracking error, as well as increasing the energy in participant’s movement. In the second experiment, when alternating feedback presence, the user-related sonification did not show feedback dependency effects, contrary to the error and task-related feedback. In the third experiment, a reduced exposure of 50% diminished the positive effect of sonification on performance, whereas the increase of the average energy with sound was still significant. In a retention test performed on the next day without auditory feedback, movement energy was still superior for the groups previously trained with the feedback. Although performance was not affected by sound, a learning effect was measurable in both sessions and the user-related group improved its performance also in the retention test. These results confirm that a continuous auditory feedback can be beneficial for movement training and also show an interesting effect of sonification on movement energy. User-related sonification can prevent feedback dependency and increase retention. Consequently, sonification of the user’s own motion appears as a promising solution to support movement learning with interactive feedback.

Nephrotic syndrome (NS) is defined by massive proteinuria and hypoalbuminemia, with resulting hyperlipidemia and edema. The most common cause of NS in children is idiopathic nephrotic syndrome (INS), also called nephrosis. Its annual incidence has been estimated to 1-4 per 100,000 children and varies with age, race, and geography. Many agents or conditions have been reported to be associated with INS such as infectious diseases, drugs, allergy, vaccinations, and malignancies. The disease may occur during the 1st year of life, but it usually starts between the ages of 2 and 7 years. INS is characterized by a sudden onset, edema being the major presenting symptom, but may rarely be discovered during a routine urine analysis. The disease may also be revealed by a complication such as hypovolemia, infection (pneumonia and peritonitis due to Streptococcus pneumoniae), deep-vein or arterial thromboses, and pulmonary embolism. Renal biopsy is usually not indicated in a child aged 1-10 years with typical symptoms and a complete remission with corticosteroids. Conversely, it is indicated in children under 1 year in case of macroscopic hematuria, hypertension, low C3 levels, persistent renal failure, or steroid resistance. Steroid therapy is applied in all children whatever the histopathology. Initial prednisone therapy in France consists of 60mg/m

Antiglomerular basement membrane glomerulonephritis is a rare autoimmune disease characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage (Goodpasture syndrome). The disease is caused by autoantibodies (classically IgGs) directed against the α3 subunit of type IV collagen. This is a rare disease in the adult population and extremely rare in children, with a reported cumulative annual incidence at 1/10

Numerous parameters have to be tested to identify optimal conditions for prepubertal testicular tissue banking. Our study evaluated 19 different cryopreservation conditions for immature testicular tissue using a rapid screening method. Immature mice testes were cryopreserved using either 1,2-propanediol (PROH) or dimethyl sulfoxide (DMSO) at a concentration of 0.75 or 1.5 M using a controlled slow-cooling rate protocol with (S+) or without seeding (S+). Equilibration was performed either at room temperature or at 4°C for 15 or 30 minutes. Seminiferous cord cryodamage was determined by scoring morphologic alterations. Cell proliferation ability was evaluated using a proliferating cell nuclear antigen (PCNA) antibody. Testes cryopreserved with optimal conditions were grafted into immunodeficient mice. The highest proportions of PCNA-positive nuclei and lowest morphologic alterations were observed with 1.5 M DMSO. Tissues were more altered with 0.75 M DMSO or PROH. Complete germ cell maturation was observed after allografting of testicular pieces previously frozen with 1.5 M DMSO, S+, 30 minutes. The 1.5 M DMSO, S+ or S+ protocol preserved prepubertal mice testicular tissue architecture and germ cell and Sertoli cell proliferation potential. Allografting of thawed testis fragments into immunodeficient mice confirmed that the 1.5 M DMSO, S+, 30 minutes protocol maintained testicular somatic and germ cell functions. Postthaw histologic evaluation and PCNA immunostaining are useful to rapidly test numerous freeze-thaw parameters. They may also be efficient tools to control human prepubertal frozen testis quality, within the context of a clinical application.

Summary Background To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. Objectives The aims of the present study were: (i) to assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. Methods The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed. Results Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud’s phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. Conclusions Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit ‘mechanic’s hands’, Raynaud’s phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

International audience; This prospective study concerning the perception of audio virtual surfaces (AVSs) was inspired by two different research fields: sensory substitution and haptic and touch perception. We define Audio Virtual Surfaces as regions of space that trigger sounds when the user touches it or moves into it. First, we describe an example of interactive setup using an AVS to simulate a sonic interaction with a virtual water tank. Then, we present an experiment designed to investigate the ability of blindfolded adults to discriminate between concave and convex auditory virtual surfaces using only the gesture-sound interaction. Two groups received different sound feedback, a static one indicating presence in the AVS, and a static+dynamic one (related to the component of the hand velocity tangential to the surface). In order to demonstrate that curvature direction was correctly perceived, we estimated their discrimination thresholds with a psychophysical staircase procedure. Results show that most of the participants were able to learn the task. The best results were obtained with the additional dynamic feedback. Gestural patterns emerged from the interaction, suggesting the use of auditory representation of the virtual object. This work proposes a contribution to the introduction in virtual reality of sonic interactions with auditory virtual objects. The setups we present raise new questions, at both experimental (sensory substitution) and application levels (design of gesture-sound interaction for virtual reality).

International audience; The Modular Musical Objects (MO) are an ensemble of tangible interfaces and software modules for creating novel musical instruments or for augmenting objects with sound. In particular, the MOs allow for designing action-sound relationships and behaviors based on the interaction with tangible objects or free body movements. Such interaction scenarios can be inspired by the affordances of particular objects (e.g. a ball, a table), by interaction metaphors based on the playing techniques of musical instruments or games. We describe specific examples of action-sound relationships that are made possible by the MO software modules and which take advantage of machine learning techniques.

International audience; Studies of the nature of the neural mechanisms involved in goal-directed movements tend to concentrate on the role of vision. We present here an attempt to address the mechanisms whereby an auditory input is transformed into a motor command. The spatial and temporal organization of hand movements were studied in normal human subjects as they pointed toward unseen auditory targets located in a horizontal plane in front of them. Positions and movements of the hand were measured by a six infrared camera tracking system. In one condition, we assessed the role of auditory information about target position in correcting the trajectory of the hand. To accomplish this, the duration of the target presentation was varied. In another condition, subjects received continuous auditory feedback of their hand movement while pointing to the auditory targets. Online auditory control of the direction of pointing movements was assessed by evaluating how subjects reacted to shifts in heard hand position. Localization errors were exacerbated by short duration of target presentation but not modified by auditory feedback of hand position. Long duration of target presentation gave rise to a higher level of accuracy and was accompanied by early automatic head orienting movements consistently related to target direction. These results highlight the efficiency of auditory feedback processing in online motor control and suggest that the auditory system takes advantages of dynamic changes of the acoustic cues due to changes in head orientation in order to process online motor control. How to design an informative acoustic feedback needs to be carefully studied to demonstrate that auditory feedback of the hand could assist the monitoring of movements directed at objects in auditory space.

To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody.The aims of the present study were: (i) to assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody.The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed.Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud's phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents.Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit 'mechanic's hands', Raynaud's phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

Necrotizing autoimmune myopathy (NAM) is a group of severe acquired myopathies, characterized by prominent myofiber necrosis with little or no muscle inflammation. They can be misdiagnosed as muscular dystrophies, preventing initiation of appropriate therapy. Specific auto-antibody anti-Signal recognition protein is observed in 16% of cases. Recently, auto-antibodies against 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) were identified in NAM patients by one group, especially in statin exposed patients. Here we report the first European series of patients. We detected and quantified anti-HMGCR auto-antibodies using addressable laser bead immunoassay that we developed. Patients (n = 38) were 44 ± 19 years old (3 pediatric cases) and sex ratio male: female was 0.22. Statin exposure was recorded in 40% of patients. Patients suffered from myalgia (44%), and had a muscular deficit (92%). Subacute onset (less than 6 months) was noted for most of them (n = 18), nevertheless 10 patients had a slow progressive muscular deficit (10 months to years). Severe proximal weakness was observed (72%) and three patients were bedridden at the diagnosis. All patients had increase CK level (6630 ± 5990 UI/L). CK level correlated with muscular strength (r2 = −0.64, p = 0.005) and to anti-HMGR titer (r2 = −0.5, p = 0.04). None patients presented signs of pulmonary involvement. Mean duration of treatments (steroids, immunosupressant and/or IgIV) was 30.1 ± 36.1 [3–42] months, and to date it was not possible to stop the treatment for any patient. This the first study confirming the observation and the description of anti-HMGCR NAM. The majority of patients we detected was statin-naive, had a severe weakness and need prolonged treatments. Anti-HMGCR auto-antibodies testing may be warranted in dystrophic like patients. Anti-HMGR titer correlates with CK level suggesting their role in physiopathogenesis.

SUMMARYIn this study, we investigated the cytokine profiles of 14 treatment-naive HIV-infected patients on the initiation of highly active antiretroviral therapy (HAART). At baseline, plasma levels of TNF-α and its mRNA in peripheral blood mononuclear cells (PBMC) were highest in the most severely immunocompromised patients (

Recently, the NASA Lewis Research Center modified its Lear High Altitude Test Facility to fly two prototype ENTECH minidome Fresnel lens photovoltaic concentrator elements. The tests were highly successful, and the results verified the ability of the Lear High Altitude Facility to measure the optical performance of individual concentrator lens elements and concentrator/cell combinations at near AM0 insolation conditions. The two concentrator lenses flown achieved optical efficiencies, based on a gallium arsenide concentrator cell response, of 89.8% and 90.0%. The flights demonstrated the ability of the aircraft, to maintain the pointing accuracy required to obtain useful data. With proper alignment of the collimating tube and the pilot's sunsight, this facility could easily maintain a pointing accuracy of +or-0.5 degrees for a sufficiently long time to obtain accurate, reproducible results. >

Objectifs Analyser les facteurs predictifs de recidive des prostatites aigues bacteriennes. Methodes Une base de donnees prospectrice d’un reseau de soin a ete analysee et 254 prostatites aigues bacteriennes ont ete identifiees. Tous les malades ont ete contactes afin de mettre en evidence des recidives d’episodes de prostatites. Les donnees de 158 malades ont ete disponibles. Les facteurs predictifs de recidive ont ete analyses par methode uni- et multivariee. Resultats Quarante malades ont recidive soit 25,3 % dont 75 % plus de 6 mois apres le 1er episode. Seulement 5,1 % des prises en charge initiale avaient necessite une hospitalisation dont 2 pour dilatation des cavites renales. En analyse univariee, les facteurs predictifs retrouves etaient l’antecedent de prostatite (p = 0,034) et le traitement antibiotique autre qu’une quinolone lors du premier episode (p = 0,004). L’analyse multivariee retrouvait que le traitement antibiotique autre qu’une quinolone lors du premier episode (OR 3,152 ; IC 95 % [1,195–8,312], p = 0,0203) etait le seul facteur predictif de recidive. Conclusion Le traitement par fluoroquinolone reste le traitement de choix des prostatites aigues bacteriennes malgre une incidence de resistance en augmentation. En cas d’utilisation d’une autre molecule, le risque de recidive est augmente.

Control of antidonor activated T cells involved in allograft rejection while preserving immunocompetence is a challenging goal in transplantation. Engineered T cells expressing a viral thymidine kinase (TK) suicide gene metabolize the nontoxic prodrug ganciclovir (GCV) into a metabolite toxic only to dividing cells. We evaluated this suicide gene strategy for inducing transplantation tolerance in mice.Transgenic mice expressing TK in mature T cells were analyzed for (i) specific T-cell depletion under GCV treatment upon various stimulations; (ii) outcome of allogeneic nonvascularized skin or heart allografts under a short 14-day GCV treatment initiated at the time of transplantation; and (iii) the capacities of T cells from such allotransplanted mice to proliferate in mixed lymphocyte reactions and to induce graft-versus-host disease in irradiated recipients with the genetic background of the donor allograft.Upon in vitro or in vivo GCV treatment, only activated dividing TK T cells but not B cells were efficiently depleted. Acute rejection of allogeneic grafts was prevented and a significant prolongation of graft survival was obtained, although associated with signs of chronic rejection. Prolonged skin graft survival correlated with decreased in vitro and in vivo T-cell reactivities against donor alloantigens, whereas overall immunocompetence was preserved.Efficient and specific depletion of alloreactive TK T cells can be achieved by administrating GCV. These results open new perspectives for the control of allogeneic graft rejection using suicide gene therapy.

Dividing cells expressing the Herpes simplex type 1 thymidine kinase (TK) can be killed upon ganciclovir treatment. Likewise, conditional cell knock-out can be obtained in transgenic mice expressing a TK gene placed under the control of tissue-specific regulatory sequences. Such animals provide powerful experimental systems for assessing the functional role of specific cell populations through their time-controlled ablation. However, whatever the regulatory sequences used, a leaky toxic overexpression of TK in testis renders male TK-transgenic mice sterile and prevents the generation of homozygous TK-expressing animals. To solve this problem, we designed a truncated TK variant (delta TK) not expressed in the testis. We generated transgenic mice expressing delta TK under the control of lymphocyte-specific regulatory sequences derived from the CD4 gene. The delta TK protein expressed in T-lymphocytes allowed the conditional ablation of activated T-cells in vitro and in vivo. Importantly, for one transgenic line we could generate fertile homozygous mice harboring a functional delta TK transgene. delta TK should thus dramatically facilitate the development of transgenic mice expressing a conditional suicide gene.

Despite extensive surgery for glioblastoma, residual tumor cells always lead to relapse. Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which specifically sensitizes dividing cells to ganciclovir (GCV) toxicity, may help eradicate such cells. During glioblastoma surgery, HSV-1 TK retroviral vector-producing cells (M11) were injected into the surgical cavity margins after tumor debulking. After a 7-day transduction period, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival. Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV. Quality of life was not negatively influenced by this treatment. Overall median survival was 206 days, with 25% of the patients surviving longer than 12 months. At 4 months after treatment, 4 of 12 patients had no recurrence; their median overall survival was 528 days, compared with 194 days for patients with recurrence (p=0.03 by the log rank test). One patient is still free of detectable recurrence, steroid free and independent, 2.8 years after treatment. Thus, brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses. These results warrant further development of this therapeutic strategy in brain tumor, including recurrent glioblastoma.

We performed a dose-escalating phase I/II study of retrovirus-mediated herpes simplex virus type 1 thymidine kinase (HSV-1-TK) suicide gene therapy for metastatic melanoma. HSV-1 TK expression, which specifically sensitizes transduced and bystander cancer cells to ganciclovir (GCV) toxicity, was mediated by one (four patients, first dose step) to three (four patients, second dose step) injections of "M11" retrovirus vector-producing cells in melanoma cutaneous nodules. After a 7-day period allowed for cancer cell transduction, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by tumor measurements and histology. M11 doses ranged from 76 to 1247 x 10(6) cells. Treatment-related adverse events were mild and transient, limited to inflammatory skin reactions at injection and fever on repeated injections. Plasma GCV was in the active range (0.2 microg/ml); transgene was detected by polymerase chain reaction in three of six patients; treated tumor size was moderately affected under GCV as compared with untreated tumors, although 2 weeks after GCV administration important (50%) treated-tumor necrosis was evidenced on histology in three of eight patients. All patients showed disease progression on long-term follow-up. Thus, M11-mediated HSV-1 TK gene therapy was well tolerated over a wide dose range. The limited tumor response is likely to be related to poor gene transfer efficiency. However, necrosis following GCV administration in transduced tumors indicates a potential for treatment efficacy.

Microgravity research techniques have been established to achieve a greater understanding of the role of gravity in the fundamentals of a variety of physical phenomena and material processing. One technique in use at the NASA Lewis Research Center involves flying Keplarian trajectories with a modified Lear Jet and DC-9 aircraft to achieve a highly accurate Microgravity environment by neutralizing accelerations in all three axis of the aircraft. The Low Gravity Guidance System (LGGS) assists the pilot and copilot in flying the trajectories by displaying the aircraft acceleration data in a graphical display format. The Low Gravity Guidance System is a microprocessor based system that acquires and displays the aircraft acceleration information. This information is presented using an electroluminescent display mounted over the pilot's instrument panel. The pilot can select the Microgravity range that is required for a given research event. This paper describes the characteristics, design, calibration and testing of the Low Gravity Guidance System Phase 3, significant lessons from earlier systems and the developmental work on future systems.

Results from preliminary performance tests conducted in an aircraft low-G testbed for nonfree-floating experimental packages have identified several operational variables that directly influence the duration and quality of each trajectory. Flight test measurements were made to identify and quantify the presence of higher-frequency airborne and structureborne noise that may affect the correlation of research data with acceleration levels recorded on trajectory traces.

Objectif La therapie cellulaire basee sur l’utilisation de cellules progenitrices endotheliales (CPE) issues de la moelle osseuse ou du sang peripherique permet d’ameliorer la neovascularisation apres un infarctus du myocarde. Cependant, les cellules utilisees lors de telles therapies sont souvent heterogenes, et leur mecanisme d’action mal connu : reelle incorporation dans la paroi vasculaire ou effet paracrine promouvant l’angiogenese ? Ainsi, nous avons voulu identifier quelle sous-population de cellules mononucleees issues de la moelle osseuse de souris contenait le plus de CPE ayant la capacite de generer des cellules endotheliales matures en culture. Methodes Nous avons evalue differentes techniques de selection : la separation par gradient de densite qui permet d’obtenir des cellules mononucleees, les selections magnetiques « Lineage negative » (Lin-), Sca-1+, et c-kit+ ainsi que la selection c-kit+/VEGFR-2+. L’expression des marqueurs endotheliaux matures a ete etudiee par immunocytochimie, cytometrie en flux, et RT-PCR surles colonies obtenues. Resultats Les colonies apparaissaient au 8e jour de culture. Letri Lin- permettait d’obtenir le plus grand nombre de colonies par rapport aux autres tris. Les analyses immunocytochimiques et cytometriques montraient qu’a l’interieur des colonies Lin-, c-kit+ et de celles derivant des cellules mononucleees, une majorite de cellules etait LDL+, Lectine+, VEGFR-2+, CD31+ et CD144+, c’esta-dire a caractere endothelial mature. Cependant, les colonies derivees des cellules mononucleees semblaient egalement contenir des cellules fibroblastiques comme le montrait une expression plus importante du gene FSP-1. Par ailleurs, la cytometrie en flux a montre que les colonies Sca-1+ n’avaient majoritairement pas un phenotype endothelial (1 a 2 % de cellules VEGFR-2+ et CD31+), et que 35 % des cellules exprimaient le CD11b, correspondant a un phenotype monocytaire. Conclusion La population cellulaire Lin- issue de la moelle osseuse de souris est une source importante de CPE. En effet, la culture de cellules Lin- parait etre la plus adaptee pour generer des cellules endotheliales matures, si on la compare a la culture de cellules Sca-1+, c-kit+ ou de cellules mononucleees. La population Lin- constituerait donc une cible de choix pour la therapie cellulaire destinee a stimuler la vasculogenese.

Le premier systeme de gene suicide developpe pour un usage de therapie genique utilise la thymidine kinase du virus Herpes simplex de type 1 (HSV1-TK). Cette enzyme est capable de phosphoryler le ganciclovir, un analogue nucleosidique dont la forme triphosphate est fortement toxique pour les cellules en division. Dans ce systeme, la toxicite induite est conditionnelle, restreinte aux cellules en cycle et engendre un important effet de voisinage assurant la destruction de cellules tumorales non transduites. Cette approche a ete largement validee par des etudes precliniques chez l'animal et fait maintenant l'objet de nombreux essais cliniques. Les premiers resultats ont revele une excellente tolerance a la therapie genique par gene suicide. Toutefois, l'efficacite du traitement reste aujourd'hui limitee par l'efficacite du transfert de gene. L'amelioration des vecteurs, l'optimisation des methodologies de ciblage ainsi qu'une meilleure comprehension de l'effet de voisinage, et notamment sa composante immunologique, devraient maintenant permettre d'ameliorer l'efficacite therapeutique.

International audience