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International audience; The literature focusing on the transverse mechanical properties of single fibers is very sparse compared to those related to longitudinal properties. An original characterization method is proposed herein, relying on a micro mechatronics device to implement a transverse compression test which is monitored using 2D full-field measurements. This is shown to allow for the identification of the transverse elastic properties of a single fiber. The method is used, at first, on a bio-based polymer monofilament (PA11) which is assumed to have regular and controlled dimensions and geometry. The transverse elastic modulus is identified to be equal to approximately 1500 MPa and the longitudinal modulus 2150 MPa. The proposed method is then used to investigate the transverse compressive behavior of contrasted natural fibers, such as beard hair (protein-based) and sisal fibers (polysaccharides-based) which have more complex shape and/or internal structure. This paper gives for the first time the compressive force displacement curves as well as the monitoring of the shape of the cross-section during the loading.

International audience; Real-time 3-D ultrasound imaging with matrix arrays remains a challenge in Non-Destructive Testing (NDT) due to the time-consuming reconstruction algorithms based on delay-and-sum operations. Other algorithms operating in the Fourier domain have lower algorithmic complexities and therefore higher frame rates at the cost requiring more storage space, which may limit the number of reconstruction points. In this paper, we present a 3-D real-time implementation of the Total Focusing Method (TFM) and the Plane Wave Imaging (PWI), as well as of their Fourier-domain counterparts, referred to as k-TFM and k-PWI. For both acquisition types, the Fourier-domain algorithms are used to increase frame rates, and they are compared to the time-domain TFM and PWI in terms of image quality, frame rates and memory requirements. In order to greatly reduce their memory requirements, a new implementations of k-TFM and k-PWI are proposed. The four imaging methods are then evaluated in real time on a block of stainless steel made by additive layer manufacturing using a laser powder bed fusion process and containing a 3-D network of spherical porosities.

Introduction Le score de Wells n’a jamais ete valide en milieu hospitalier. Or les patients hospitalises presentent des caracteristiques bien differentes, avec une incidence elevee de situations prothrombogenes (chirurgie, infection, immobilisation…) ou une prescription frequente d’un traitement anticoagulant. Nous avons donc realise une etude pour evaluer la pertinence du score de Wells chez les malades hospitalises sous anticoagulation (preventive ou curative). Methodes Etude monocentrique, prospective realisee au CHU de Nimes sur une periode de 9 mois, incluant tout patient hospitalise adresse pour recherche de thrombose veineuse profonde (TVP), sur prescription d’un medecin hospitalier avec calcul du score de Wells modifie. Le score de Wells etait reevalue par un medecin vasculaire lors de l’arrivee dans le service, au maximum 24 h apres la demande d’examen. Resultats Deux cent trente-deux patients ont ete inclus. La prevalence de TVP dans les categories de risque faible, intermediaire et haute etaient de 3,8 %, 7,4 % et 46,4 % (p 72 h ou curatif au long cours, le taux de TVP variait de 7,2 vs 27,3 % (p Discussion Le score de Wells ne semble pas adapte pour evaluer de maniere satisfaisante la stratification du risque de TVP chez les patients hospitalises. Les 3 categories de risque (faible, intermediaire et elevee) presentent des prevalences de TVP inferieures a celles observees dans un contexte ambulatoire. De plus, notre etude montre une tres faible concordance inter-observateurs entre medecin specialiste et medecin prescripteur. Seuls les items du score faisant appel au dossier medical du patient (cancer actif et antecedent thrombo-embolique) semblent conserver une bonne correlation. Conclusion Le score de Wells modifie ne devrait pas etre utilise en l’etat dans un contexte hospitalier et necessite une modification adaptee aux caracteristiques des patients hospitalises.

Position measurement at nanoscale currently raises issues such as making significant compromise between range and resolution or as the difficulty to measure several directions with a single sensor. This paper presents a novel visual method to measure displacements at nanometric scale along two axes. This method allows subpixelic measurement of position by using a pseudo-periodic pattern observed by a regular visual setup. This micrometric pattern corresponds to the intertwining of two perpendicular copies of a single-axis pattern made of two frequency carriers with slightly different periods. It was realized in clean room by photolythography of aluminium on glass. The algorithm is based on a twin-scale principle, itself based on direct phase measurement of periodic grids. Experiments are performed at video rate (30 fps) and show a linearity below 0.16% and a repeatability below 14 nm over an unambiguous range of 221 μm. A resolution below 0.5 nm is demonstrated by the use of 2000 images. The method can be adjusted to different ranges, according to the needs.

Introduction La valorisation des sejours en unite de surveillance continue (USC) comprend le versement de supplements journaliers. Mais certains sejours n’en beneficient pas, l’enjeu pour les etablissements etant de limiter leur proportion. Notre travail aux Hopitaux universitaires Paris-Sud (HUPS) etait d’identifier les facteurs pouvant expliquer ce non-versement pour proposer des actions correctrices et reduire la part des sejours non valorises. Methodes Le retour au dossier patient permettait de modifier eventuellement les diagnostics et/ou les actes CCAM pour chaque sejour en USC adulte sans supplement. La nature des corrections et leurs impacts sur la recuperation du supplement ont permis d’elaborer des recommandations ciblees de codage et de construire un algorithme de selection des sejours en USC a controler prioritairement au departement d’information medicale (DIM). Resultats Aux HUPS, entre le 01/01/2018 et le 30/09/2018, 477/2100 sejours en USC adultes n’avaient aucun supplement. Pour 231/477 sejours, des corrections - notamment ajouts ou precisions de diagnostics de traumatologie et ajouts d’actes de transfusion sanguine - ont ete apportes et 351 supplements recuperes pour 33 sejours. Compte tenu des caracteristiques de ces sejours, un algorithme de ciblage a ete construit, base sur l’Indice de gravite simplifie II (IGS II) des patients - compris entre 7 et 14 apres deduction des points generes par l’âge - et une duree de sejour en USC > 2 jours. Les bonnes performances de cet algorithme - specificite de 90 % et valeur predictive negative de 97 % - permettaient d’optimiser les controle sur un nombre restreint de sejours - 89 sejours cibles/477 - tout en n’affectant qu’a la marge le montant total des supplements recuperes. Discussion/Conclusion Un plan d’actions combinant recommandations de codage des sejours - necessite d’un codage exhaustif et de qualite de la traumatologie et des transfusions sanguines - et controle cible au DIM permettrait de limiter le non-versement des supplements journaliers en USC aux HUPS. Une reflexion devrait etre engagee plus largement sur l’evolution des modalites de financement des USC, de nombreux sejours restants sans supplement meme apres recodage.

Introduction La prevalence de l’angiœdeme hereditaire de types 1 et 2 (AOH 1 et 2) en France n’est pas connue. Nous rapportons les resultats d’une etude transversale visant a estimer la prevalence des cas d’AOH 1 et 2 a Paris et en France en 2016. Patients et methodes Les cas prevalents d’AOH 1 et 2 en 2016 parmi les habitants de la ville de Paris ont ete identifies par une enquete basee sur les 5 sources d’information suivantes : – enquete postale envoyee a 2 reprises aux 3123 medecins generalistes, allergologues, dermatologues, gastro-enterologues, medecins internistes et pediatres en activite liberale a Paris ; – enquete par courrier electronique adressee aux 1136 medecins des services de medecine interne, dermatologie, gastro-enterologie, pediatrie et immunologie clinique de 22 hopitaux parisiens et de la banlieue parisienne proche et enquete telephonique aupres de 4 services hospitaliers experts de l’AOH a Paris ; – enquete aupres des 2 laboratoires prives dosant le C1 inhibiteur ; – adherents de l’Association des malades souffrant d’angiœdemes (AMSAO) ; – beneficiaires d’un statut d’affection de longue duree pour un deficit du complement (code D84.1 de la CIM 10). Pour tous les cas signales, les donnees cliniques et biologiques ont ete relevees des dossiers medicaux par un seul investigateur (S.G.C.). Les cas etaient retenus s’ils repondaient aux « criteres de Longhurst et Cicardi » [1] et s’ils etaient domicilies a Paris en 2016. La prevalence etait calculee en divisant le nombre de cas retenus par le nombre d’habitants a Paris en 2016 puis standardisee en prenant la population francaise metropolitaine comme reference. L’intervalle de confiance (IC) a 95 % a ete calcule en utilisant une distribution de Poisson. L’exhaustivite dans l’identification des cas a ete estimee par une analyse de capture-recapture (ACR) avec un modele log-lineaire a 5 sources. Resultats Parmi les 287 cas signales par les 5 sources d’information interrogees, 57 cas (dont 54 AOH de type 1) repondaient aux criteres d’inclusion. Le signalement provenait de centres hospitaliers experts de l’AOH dans 98 % des cas retenus. Les hommes representaient 56 % des cas. L’âge median aux premiers symptomes etait de 11 ans (extremes : 2–52 ans) (8 valeurs manquantes), l’âge median au diagnostic etait de 19 ans (extremes : 1–67 ans) (10 valeurs manquantes). La prevalence brute et standardisee de l’AOH 1 et 2 a Paris en 2016 (pour 100 000 habitants) est estimee a 2,60 (IC95 % : 1,97–3,37) et 2,42 (IC95 % : 1,78–3,07), respectivement. L’ACR estime l’exhaustivite dans l’identification des cas a 98,6 % (IC95 % : 94,5–100 %). L’extrapolation du taux standardise estime le nombre de personnes avec AOH 1 et 2 en France metropolitaine a 1565. Conclusion Cette premiere estimation de la prevalence de l’AOH 1 ou 2 pour une population francaise montre une frequence legerement superieure a celles rapportees par des etudes realisees dans d’autres pays. Cette maladie rare semble etre suivie presque exclusivement dans les centres experts. Le long delai diagnostique reflete possiblement une meconnaissance de l’AOH, notamment lorsqu’il n’y a pas d’antecedent familial connu.

Modularity and self-healing are two interesting properties that could help to design more flexible conveyors of micro-objects. In the Smart Blocks project, we propose to design a 2D modular and self-reconfigurable robot composed of centimeter-scale sliding blocks that embed their own actuators and control electronics. This article presents a proof-of-concept of the linkage and of the traveling system as well as an algorithm able to reconfigure a set of blocks from a spatial configuration to another one. Prototype blocks have been realized using electro-permanent magnets which show a good motion speed while saving power consumption during the linkage. Our reconfiguration algorithm is implemented in a simulator software showing in real-time the reconfiguration of the robot.

We have compared the effects of different sterilization techniques on the properties of Bombyx mori silk fibroin thin films with the view to subsequent use for corneal tissue engineering. The transparency, tensile properties, corneal epithelial cell attachment and degradation of the films were used to evaluate the suitability of certain sterilization techniques including gamma-irradiation (in air or nitrogen), steam treatment and immersion in aqueous ethanol. The investigations showed that gamma-irradiation, performed either in air or in a nitrogen atmosphere, did not significantly alter the properties of films. The films sterilized by gamma-irradiation or by immersion in ethanol had a transparency greater than 98% and tensile properties comparable to human cornea and amniotic membrane, the materials of choice in the reconstruction of ocular surface. Although steam-sterilization produced stronger, stiffer films, they were less transparent, and cell attachment was affected by the variable topography of these films. It was concluded that gamma-irradiation should be considered to be the most suitable method for the sterilization of silk fibroin films, however, the treatment with ethanol is also an acceptable method.

Resume ASTEC est un projet de recherche dont l’objectif est d’augmenter le taux d’inclusion des patients dans les essais cliniques de cancerologie grâce a l’exploitation automatique des donnees contenues dans le dossier medical informatise. Le projet ASTEC explore deux enjeux scientifiques majeurs dans le champ de l’informatique medicale : 1) l’interoperabilite syntactique et semantique entre systemes d’information. Il s’agit ici de faire interoperer un dossier structure informatise avec un outil d’aide a la decision. Le projet ASTEC propose un cadre syntaxico-semantique d’interoperabilite, base sur des standards internationaux. Sont developpees des methodes generiques de mediation semantique basees sur les ontologies pour adapter l’information issue des dossiers aux criteres d’inclusion/exclusion des etudes cliniques ; 2) l’aide a decision : developper des methodes d’inference sur les dossiers patients en utilisant un formalisme de representation adapte aussi bien a la structuration des donnees cliniques qu’a celle des criteres d’inclusion et d’exclusion des essais cliniques. Nous exposons ici les choix proceduraux et technologiques retenus dans le cadre de ce projet. Il est, par ailleurs, prevu que durant le projet ASTEC, nous implementerons et evaluerons le systeme en conditions reelles d’utilisation. L’hypothese est que ce systeme permettra d’augmenter de facon significative le nombre de patients eligibles a l’inclusion dans les etudes cliniques de cancerologie.

The structure of forest stands is an important determinant of habitat use by songbirds, including species of conservation concern. In this paper, we investigate the combined long-term impacts of variable tree regeneration and timber management on stand structure, songbird occupancy probabilities, and timber production in northern hardwood forests. We develop species-specific relationships between bird species occupancy and forest stand structure for canopy-dependent black-throated green warbler (Dendroica virens), eastern wood-pewee (Contopus virens), least flycatcher (Empidonax minimus) and rose-breasted grosbeak (Pheucticus ludovicianus) from field data collected in northern hardwood forests of Michigan’s Upper Peninsula. We integrate these bird-forest structure relationships with a forest simulation model that couples a forest-gap tree regeneration submodel developed from our field data with the US Forest Service Forest Vegetation Simulator (Ontario variant). Our bird occupancy models are better than null models for all species, and indicate species-specific responses to management-related forest structure variables. When simulated over a century, higher overall tree regeneration densities and greater proportions of commercially high value, deer browse-preferred, canopy tree Acer saccharum (sugar maple) than low-value, browse-avoided subcanopy tree Ostrya virginiana (ironwood) ensure conditions allowing larger harvests of merchantable timber and had greater impacts on bird occupancy probability change. Compared to full regeneration, no regeneration over 100 years reduces merchantable timber volumes by up to 25% and drives differences in bird occupancy probability change of up to 30%. We also find that harvest prescriptions can be tailored to affect both timber removal volumes and bird occupancy probability simultaneously, but only when regeneration is adequate. When regeneration is poor (e.g., 25% or less of trees succeed in regenerating), timber harvest prescriptions have a greater relative influence on bird species occupancy probabilities than on the volume of merchantable timber harvested. However, regeneration density and composition, particularly the density of Acer saccharum regenerating, have the greatest long-term effects on canopy bird occupancy probability. Our results imply that forest and wildlife managers need to work together to ensure tree regeneration density and composition are adequate for both timber production and the maintenance of habitat for avian species over the long-term. Where tree regeneration is currently poor (e.g., due to deer herbivory), forest and wildlife managers should pay particularly close attention to the long-term impacts of timber harvest prescriptions on bird species.

Resume La dermatite atopique est souvent la premiere etape de la marche atopique conduisant a l’asthme. L’asthme succedant a la dermatite atopique sera d’autant plus frequent et plus severe que les manifestations cutanees seront severes et associees a une polysensibilisation IgE dependante. Les deficits en filaggrine renforcent cette tendance, surtout en cas d’allergie alimentaire. Il est indispensable de traiter la peau mais il n’est pas certain que cela suffise a prevenir la survenue d’asthme et/ou de rhinite allergiques.

Introduction Le dupilumab, anticorps anti-interleukine 4/13 recepteur, a obtenu l’AMM en Europe pour le traitement de la dermatite atopique (DA) de l’adulte moderee a severe. Les objectifs de cette etude prospective monocentrique etaient (1) d’evaluer l’efficacite du dupilumab en vie reelle, (2) de decrire les comorbidites atopiques des patients et leur evolution sous traitement et (3) de decrire les profils d’IgE specifiques et leur evolution sous traitement. Patients et methodes Le dupilumab etait prescrit dans le contexte d’une autorisation temporaire d’utilisation, nominative puis de cohorte. Les patients etaient evalues initialement (semaine 0, S0) et a 16 semaines (S16) par le SCORAD (SCORing Atopic Dermatitis), les echelles visuelles analogiques (EVA) prurit et sommeil, le DLQI (Dermatology Life Quality Index), le score ACT (Asthma Control Test), une mesure de la fraction expiree du monoxyde d’azote (FeNO), une spirometrie, un examen ophtalmologique et ORL ainsi que le dosage des IgE totales et specifiques (puce ImmunoCAP™ ISAC 112). Resultats Dix-neuf patients ont ete inclus (15 hommes, âge median : 38 ans). L’asthme etait la comorbidite atopique la plus frequente (79 %). Le profil de sensibilisation IgE montrait une majorite de patients (76–82 %) sensibilisee contre les phaneres d’animaux, les herbaces, les pollens d’arbres, les graminees et les acariens de poussiere ( Fig. 1 ). Le SCORAD median a S0 etait a 49 (Intervalle interquartile : 32,5–58,5). A S16, une diminution de 55 % du SCORAD median etait observee (p Fig. 2a ). Le DLQI et les EVA pour le prurit et le sommeil diminuaient de maniere significative ( Fig. 2b–d ). La FeNO diminuait de maniere significative a S16 (p Discussion Le dupilumab confirme en vie reelle son efficacite dans la DA sur la severite globale de la maladie, le prurit, la perte de sommeil et la qualite de vie. Les comorbidites atopiques semblent egalement s’ameliorer sous traitement en dehors de la conjonctivite qui constitue un effet indesirable potentiellement invalidant chez 40 % des patients. Conclusion Le dupilumab ameliore les patients atteints de DA en vie reelle. Son impact sur le profil de sensibilisation IgE des patients montre une reduction importante des IgE totales et specifiques, independante de l’effet sur la DA.

Introduction Dans le cadre de la prise en charge des Accidents vasculaires cerebraux (AVC) ischemiques, un reperage et un suivi par les agences regionales de sante des activites de thrombolyse ont ete mis en place. Au CHU de Bicetre, le decompte des thrombolyses est effectue par confrontation d’un fichier produit par la pharmacie a usage interieur (PUI) avec les donnees du Programme de medicalisation des systemes d’information (PMSI). L’objectif etait de decrire cette methode permettant de fiabiliser le decompte des thrombolyses. Methodes Une etude retrospective a ete menee sur les thrombolyses realisees dans l’unite de soins intensifs neurovasculaire (USINV) de l’hopital de Bicetre au premier semestre 2017. Nous avons croise les donnees des sejours avec dispensation d’un agent thrombolytique (Actilyse®) – identifiees dans le fichier de la PUI – avec celles des sejours ayant un codage de thrombolyse–identifiees a partir du PMSI. Pour les sejours communs aux deux fichiers, la thrombolyse etait automatiquement comptabilisee. Dans les autres cas, la thrombolyse etait validee au cas par cas apres retour au dossier patient. Resultats Au premier semestre 2017, 54 thrombolyses ont ete identifiees dans le fichier de la PUI et 60 dans celui du PMSI. A partir de notre methode, 58 thrombolyses ont ete comptabilisees. Quarante-six correspondaient a des sejours communs aux deux fichiers et 12 ont ete validees par retour au dossier. La sensibilite et la specificite pour la detection des thrombolyses etaient respectivement de 86 % IC 95 % [75–93] et 98 % IC 95 % [96–99] pour le PMSI, et de 93 % IC 95 % [83–97] et 100 % IC 95 % [99–100] pour le fichier de la PUI. Discussion/Conclusion Notre methode permet de fiabiliser le decompte des thrombolyses a l’hopital de Bicetre par rapport a la seule utilisation d’une des deux sources de donnees qui souffrent d’un manque d’exhaustivite. Un accompagnement des acteurs est propose dans le but d’ameliorer la qualite des fichiers de donnees. Les chiffres des dernieres annees montrent une amelioration de la qualite des donnees.

Los deficit de inhibidor de C1 son la causa de enfermedades peculiares por sus manifestaciones clinicas, que consisten en edemas subcutaneos o submucosos repetitivos. Su gravedad depende de la localizacion digestiva responsable de oclusion por el obstaculo que producen en la luz y, sobre todo, de la localizacion glotica, que puede comprometer el pronostico vital. Son enfermedades poco frecuentes (menos de 500 casos en Francia, por ejemplo), con una incidencia estimada de 1/50.000 y con 240 casos inscritos en el registro frances fundado en 1988. Los deficit hereditarios (de transmision autosomica dominante) se deben a una anomalia en el gen del inhibidor de C1 que produce un deficit cuantitativo o cualitativo de la proteina (angioedema hereditario [AEH] de tipo I y II). Se han identificado mas de 200 anomalias de este gen (mutaciones de terminacion o de aminoacido, deleciones e inserciones) y alrededor del 25% de los casos corresponde a formas de novo (sin antecedentes familiares, pero transmisibles). Los deficit adquiridos de inhibidor de C1 son infrecuentes y en muchos casos se asocian a un sindrome linfoproliferativo (de tipo gammapatia monoclonal de significado incierto, mieloma o linfoma). Estas formas tienen en comun la perdida de funcion del inhibidor de C1. Ante la mas minima sospecha de este deficit hay que hacer determinaciones de las fracciones del complemento (CH50, C3, C4, determinacion antigenica y funcional de inhibidor de C1) para poder confirmar el diagnostico con rapidez. El tratamiento preventivo y curativo consiste en medidas terapeuticas especificas cada vez mejor protocolizadas (danazol, que es un esteroide anabolizante, y acido tranexamico, que es un antifibrinolitico). Siempre hay que establecer un seguimiento clinico y analitico periodico para adaptar la posologia del tratamiento preventivo, con el que se ha logrado reducir de manera considerable la frecuencia de las crisis. En el momento actual se dispone de inhibidor de C1 purificado a partir del plasma humano, que se utiliza en pacientes en quienes las crisis comprometen el pronostico vital.

Complex spatial heterogeneity of ecological systems is difficult to capture and interpret using global models alone. For this reason, recent attention has been paid to local spatial modeling techniques. We used one local modeling approach, geographically weighted regression (GWR), to investigate the effects of local spatial heterogeneity on multivariate relationships of white-tailed deer distribution using land cover patch metrics and climate factors. The results of these analyses quantify differences in the contributions of model parameters to estimates of deer density over space. A GWR model with local kernel bandwidth was compared to a GWR model with global kernel bandwidth and an ordinary least-squares regression (OLS) model with the same parameters to evaluate their relative abilities in modeling deer distributions. The results indicated that the GWR models predicted deer density better than the traditional ordinary least-squares model and also provided useful information regarding local environmental processes affecting deer distribution. GWR model comparisons showed that the local kernel bandwidth GWR model was more realistic than the global kernel bandwidth GWR model, as the latter exaggerated local spatial variation. The parameter estimates and model statistics (e.g., model R 2 ) of the GWR models were mapped using geographic information systems (GIS) to illustrate local spatial variation in the regression relationship and to identify causes of large-scale model misspecifications and low estimation efficiencies. © 2005 Elsevier B.V. All rights reserved.

The deposition of fibrin is an integral part of the tissue repair process, but its persistence is also associated with a number of fibrotic conditions. This study addressed the hypothesis that reduced fibrinolysis and fibrin persistence are associated with an enhanced accumulation of collagen and the development of skin fibrosis. Decreased fibrinolysis was confirmed in fibrin gel cultures that contained human dermal fibroblasts plus the specific plasmin inhibitor alpha(2)-antiplasmin or dermal fibroblasts isolated from plasminogen activator (PA)-deficient mice. Collagen accumulation was significantly increased in the presence of inhibitor and in tPA-deficient, but not uPA-deficient, fibroblasts compared with controls. These findings were also confirmed using a skin fibrosis model in which multiple injections of fibrin were given subcutaneously to PA-deficient mice. Injection sites from tPA-deficient mice displayed significantly increased collagen levels compared with uPA-deficient mice and wild-type controls. Up-regulation of fibroblast procollagen gene expression and reduced activation of pro-MMP-1 appeared to mediate the increase in collagen by human dermal fibroblasts in the presence of alpha2-antiplasmin. These findings suggest that persistent fibrin is associated with enhanced collagen accumulation that may result in the development of fibrotic skin disorders in which reduced fibrinolysis is a feature.

Hereditary angioneurotic edema is a dominant autosomal disease (incidence 1/150,000), whose diagnosis is crucial as this condition can lead to fatal asphyxia within minutes. We report the case of a three-year-old girl, misdiagnosed as allergic asthma. Recognition of the syndrome led to adapted care restoring normal family and school life. Pathogenic cascades involved and therapeutic principles of this disease are reviewed.

We investigated the potential of using unclassified spectral data for predicting the distribution of three bird species over a ¨400,000 ha region of Michigan’s Upper Peninsula using Landsat ETM+ imagery and 433 locations sampled for birds through point count surveys. These species, Black-throated Green Warbler, Nashville Warbler, and Ovenbird, were known to be associated with forest understory features during breeding. We examined the influences of varying two spatially explicit classification parameters on prediction accuracy: 1) the window size used to average spectral values in signature creation and 2) the threshold distance required for bird detections to be counted as present. Two accuracy measurements, proportion correctly classified (PCC) and Kappa, of maps predicting species’ occurrences were calculated with ground data not used during classification. Maps were validated for all three species with Kappa values >0.3 and PCC >0.6. However, PCC provided little information other than a summary of sample plot frequencies used to classify species’ presence and absence. Comparisons with rule-based maps created using the approach of Gap Analysis showed that spectral information predicted the occurrence of these species that use forest subcanopy components better than could be done using known land cover associations (Kappa values 0.1 to 0.3 higher than Gap Analysis maps). Accuracy statistics for each species were affected in different ways by the detection distance of point count surveys used to stratify plots into presence and absence classes. Moderate-to-large detection distances (100 m and 180 m) best classified maps of Blackthroated Green Warbler and Nashville Warbler occurrences, while moderate detection distances (50 m and 100 m), which ignored remote observations, provided the best source of information for classification of Ovenbird occurrence. Window sizes used in signature creation also influenced accuracy statistics but to a lesser extent. Highest Kappa values of majority maps were typically obtained using moderate window sizes of 9 to 13 pixels (0.8 to 1.2 ha), which are representative of the study species territory sizes. The accuracy of wildlife occurrence maps classified from spectral data will therefore differ given the species of interest, the spatial precision of occurrence records used as ground references and the number of pixels included in spectral signatures. For these reasons, a quantitative examination is warranted to determine how subjective decisions made during image classifications affect prediction accuracies.

Activation of the coagulation cascade is commonly observed in the lungs of patients with both acute and chronic inflammatory and fibrotic lung disorders, as well as in animal models of these disorders. The aim of this study was to examine the contribution of the major thrombin receptor, proteinase-activated receptor-1 (PAR-1), during the acute inflammatory and chronic fibrotic phases of lung injury induced by intratracheal instillation of bleomycin in mice. Inflammatory cell recruitment and increases in bronchoalveolar lavage fluid (BALF) protein were attenuated by 56 +/- 10% (P0.05) and 53 +/- 12% (P0.05), respectively, in PAR-1-deficient (PAR-1-/-) mice compared with wild-type (WT) mice. PAR-1-/- mice were also protected from bleomycin-induced pulmonary fibrosis with total lung collagen accumulation reduced by 59 +/- 5% (P0.05). The protection afforded by PAR-1 deficiency was accompanied by significant reductions in pulmonary levels of the potent PAR-1-inducible proinflammatory and profibrotic mediators, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta-1 (TGF-beta1), and connective tissue growth factor/fibroblast-inducible secreted protein-12 (CTGF/FISP12). In addition, PAR-1 was highly expressed in inflammatory and fibroproliferative lesions in lung sections obtained from patients with fibrotic lung disease. These data show for the first time that PAR-1 signaling plays a key role in experimentally induced lung injury, and they further identify PAR-1 as one of the critical receptors involved in orchestrating the interplay between coagulation, inflammation, and remodeling in response to tissue injury.

International audience; Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR1). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR1-deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR1-specific agonists and inhibitors were used to demonstrate that PAR1 mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR1 and not PAR2. These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis.

Pulmonary fibrosis occurs in a heterogenous group of disorders and is characterised by excessive deposition of extracellular matrix proteins within the pulmonary interstitium, leading to impaired gas transfer and a loss of lung function. This review examines some models used to investigate the pathogenesis and treatment of idiopathic pulmonary fibrosis. Although no single model accurately mimics all the characteristic features of this disease most, including bleomycin, reproduce important features of the disease and provide an important tool to investigate the pathogenesis of pulmonary fibrosis.

Levels of prostaglandin E(2) (PGE(2)), a potent inhibitor of fibroblast function, are decreased in the lungs of patients with pulmonary fibrosis, which has been shown to be because of limited expression of cyclooxygenase-2 (COX-2). To further investigate the relative importance of COX-2 and PGE(2) in the development of fibrosis we have used a selective COX-2 inhibitor and COX-2-deficient ((-/-) and (+/-)) mice in studies of bleomycin-induced lung fibrosis. We demonstrate in wild-type mice that bleomycin-induced lung PGE(2) production is predominantly COX-2 mediated. Furthermore, COX-2(+/-) mice show limited induction of PGE(2) and an enhanced fibrotic response with increased lung collagen content compared with wild-type mice after bleomycin injury (P0.001). In contrast, COX-2(-/-) mice show increased levels of lung PGE(2), compared with wild-type mice after injury (P0.05), because of compensatory up-regulation of COX-1, which appears to be associated with macrophage/monocytes but not fibroblasts derived from these mice. COX-2(-/-) mice show an enhanced and persistent inflammatory response to bleomycin, however the fibrotic response to injury was unaltered compared with wild-type animals. These data provide further direct evidence for the importance of up-regulating COX-2 and PGE(2) expression in protecting against the development of fibrosis after lung injury.

Proteinase-activated receptors (PARs) are novel G-protein-coupled receptors activated by serine and other proteinases to induce changes in cellular function. There is extensive evidence that PARs are expressed in the airways in a variety of cell types that are relevant to inflammatory lung diseases, and that activation of these receptors might be linked to significant pathological changes. Thus, PARs are exciting new targets in lung disease research. However, much of the data to date has come from in vitro studies using limited pharmacological tools, and considerably more needs to be known about the functions of this family of receptors in the lung before their potential as drug targets can be established.

The induction of fibroblast apoptosis and their clearance by phagocytes is essential for normal wound healing and prevention of scarring. However, little is known about the clearance of apoptotic fibroblasts and whether apoptotic cells are active participants in the recruitment and activation of phagocytes. In this study, we provide the first evidence that apoptotic fibroblasts actively release increased amounts of thrombospondin (TSP1) to actively recruit macrophages. Expression of TSP1 and its receptor CD36 was increased on the surface of apoptotic fibroblasts. By chemical cross-linking and immunoprecipitation we show that TSP1 and CD36 were directly associated. This was confirmed by confocal microscopy. Blockade of either CD36 or TSP1 on apoptotic fibroblasts inhibited phagocytosis. Blockade of alpha v beta 3 integrins as well as CD36 and TSP1 on macrophages inhibited phagocytosis. In contrast, phosphatidylserine or lectins were not involved. These findings suggest that apoptotic fibroblasts release TSP1 as a signal to recruit macrophages while the up-regulated expression of the CD36/TSP1 complex on their cell surface may form a ligand bridging the fibroblast to a complex consisting of alpha v beta 3/CD36/TSP1 on macrophages. These results establish fundamental mechanisms for the clearance of apoptotic fibroblasts and may provide insights into the processes involved in normal wound repair.

During normal developmental tissue growth and in a number of diseases of the cardiopulmonary system, adventitial and interstitial fibroblasts are subjected to increased mechanical strain. This leads to fibroblast activation and enhanced collagen synthesis, but the underlying mechanisms involved remain poorly understood. In this study, we have begun to identify and characterize mechanical strain-responsive elements in the rat procollagen alpha 1(I) (COL1A1) gene and show that the activity of COL1A1 promoter constructs, transiently transfected into cardiac fibroblasts, was increased between 2- and 4-fold by continuous cyclic mechanical strain. This was accompanied by an approximately 3-fold increase in the levels of total active transforming growth factor-beta (TGF-beta) released into the medium. Inclusion of a pan-specific TGF-beta neutralizing antibody inhibited strain-induced COL1A1 promoter activation. Deletion analysis revealed the presence of two potential strain response regions within the proximal promoter, one of which contains an inverted CCAAT-box overlapping a GC-rich element. Both mechanical strain and exogenously added TGF-beta1 enhanced the binding activity of CCAAT-binding factor, CBF/NF-Y, at this site. Moreover, this element was sufficient to confer strain-responsiveness to an otherwise unresponsive SV40 promoter. In summary, this study demonstrates that strain-induced COL1A1 promoter activation in cardiac fibroblasts is TGF-beta-dependent and involves increased binding of CCAAT-binding factor at the proximal promoter. Furthermore, these findings suggest a novel and potentially important TGF-beta response element in the rat COL1A1 gene.

Prostaglandin E(2) (PGE(2)) inhibits fibroblast proliferation and collagen production. Its synthesis by fibroblasts is induced by profibrotic mediators including transforming growth factor (TGF)-beta(1). However, in patients with pulmonary fibrosis, PGE(2) levels are decreased. In this study we examined the effect of TGF-beta(1) on PGE(2) synthesis, proliferation, collagen production, and cyclooxygenase (COX) mRNA levels in fibroblasts derived from fibrotic and nonfibrotic human lung. In addition, we examined the effect of bleomycin-induced pulmonary fibrosis in COX-2-deficient mice. We demonstrate that basal and TGF-beta(1)-induced PGE(2) synthesis is limited in fibroblasts from fibrotic lung. Functionally, this correlates with a loss of the anti-proliferative response to TGF-beta(1). This failure to induce PGE(2) synthesis is because of an inability to up-regulate COX-2 mRNA levels in these fibroblasts. Furthermore, mice deficient in COX-2 exhibit an enhanced response to bleomycin. We conclude that a decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis in the presence of increasing levels of profibrotic mediators such as TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis and contribute to the pathogenesis of pulmonary fibrosis.

The coagulation protease thrombin plays a critical role in hemostasis and exerts pro-inflammatory and pro-fibrotic effects via proteolytic activation of the major thrombin receptor, protease-activated receptor-1 (PAR-1). Connective tissue growth factor (CTGF) is a novel fibroblast mitogen and also promotes extracellular matrix protein production. It is selectively induced by transforming growth factor beta (TGF-beta) and is thought to be the autocrine agent responsible for mediating its pro-fibrotic effects. CTGF is up-regulated during tissue repair and in fibrotic conditions associated with activation of the coagulation cascade. We therefore hypothesized that coagulation proteases promote the production of CTGF by cells at sites of tissue injury. To begin to address this hypothesis, we assessed the effect of coagulation proteases on fibroblast CTGF expression in vitro, and we show that thrombin, at physiological concentrations, up-regulated CTGF mRNA levels 5-fold relative to base line (p0.01) in fetal fibroblasts and 7-fold in primary adult fibroblasts (p0.01). These effects were cycloheximide-insensitive and were not blocked with a pan-specific TGF-beta-neutralizing antibody. They were further paralleled by a concomitant increase in CTGF protein production and could be mimicked with selective PAR-1 agonists. In addition, fibroblasts derived from PAR-1 knockout mice were unresponsive to thrombin but responded normally to TGF-beta(1). Finally, factor Xa, which is responsible for activating prothrombin during blood coagulation, exerted similar stimulatory effects. We propose that coagulation proteases and PAR-1 may play a role in promoting connective tissue formation during normal tissue repair and the development of fibrosis by up-regulating fibroblast CTGF expression.

Background: Few data are available on the comparative performance of different types of sphincterotome. The aim of this study was to compare the efficacy of endoscopic sphincterotomy performed with either a reusable, single-lumen sphincterotome or a disposable triple-lumen instrument. Methods: Seventy-seven consecutive adults requiring endoscopic sphincterotomy were prospectively and randomly assigned treatment with either a standard reusable single-lumen sphincterotome (group A, n = 38) or a disposable triple-lumen sphincterotome with a guidewire (group B, n = 39). The success rate, complications, and cost of the procedure per patient were compared. Results: Deep cannulation was successful in 87% of cases in each group and sphincterotomy was achieved in 76% and 84% of cases in group A and B, respectively (NS). In the endoscopists' opinion the two instruments performed almost equally well. Twelve procedure-related complications occurred: 5 (all hemorrhages) in group A and 7 (1 hemorrhage, 4 cases of pancreatitis and 2 of cholangitis) in group B (NS). Eight reusable sphincterotomes were used with a cost of $61 per patient, compared with 39 disposable sphincterotomes with a cost of $241 per patient (p = 0.02). Conclusions: A standard reusable sphincterotome is satisfactory for most endoscopic sphincterotomies, and yields a substantial cost savings without compromising the success or safety of the procedure. (Gastrointest Endosc 2000;51:704-7)

Resume Nul ne peut ignorer aujourd'hui l'importance de la pollinose des arbres qui requiert de demeurer attentif a notre environnement et aux variations climatiques quotidiennes. Les especes impliquees different d'une region a l'autre de notre pays et les pollens produits subissent alors l'influence de la pollution, de la circulation automobile et de la pluviosite, tres variables elles aussi selon le lieu de vie. Des calendriers polliniques peuvent ainsi etre etablis dans chaque region apres evaluation clinique de la repercussion de la pluie pollinique sur les muqueuses respiratoires et oculaires des malades. La standardisation de certains extraits allergeniques de pollens d'arbres a ameliore nos moyens diagnostiques et therapeutiques mais nous sommes impatients de pouvoir disposer d'extraits issus de recombinants d'allergenes majeurs dont la modification des epitopes B pourrait rendre encore plus efficaces.

Thrombin is a multifunctional serine protease which plays a central role in haemostasis by regulating platelet aggregation and blood coagulation. It is formed from its precursor prothrombin following tissue injury and converts fibrinogen to fibrin in the final step of the clotting cascade. It also promotes numerous cellular effects including chemotaxis, proliferation, extracellular matrix turnover and release of cytokines. These actions of thrombin on cells have been implicated in tissue repair processes and in the pathogenesis of inflammatory and fibroproliferative disorders such as pulmonary fibrosis and atherosclerosis. Thrombin mediates its cellular effects by proteolytically activating cell surface receptors. Presently, two such receptors have been described and their roles in regulation of these functions are currently being investigated. The discovery of multiple thrombin receptors creates the possibility of selective receptor blockade of specific thrombin mediated events. New drugs with these actions should add to our current repertoire of thrombin inhibitors used to treat thrombotic diseases.

Resume Signalee des les premiers calendriers polliniques etablis pour Paris il y a 30 ans, la pollinose du frene apparait de plus en plus frequente a Paris. La pluie de ce pollen est relativement precoce, en mars en regle, de courte duree et responsable de manifestations respiratoires aigues comportant souvent de l'asthme. Le frene appartient, comme le troene, a la famille des oleacees ce qui peut fournir une explication des frequentes reactions croisees avec le pollen d'olivier. Nous avons teste avec le pollen de frene 140 malades porteurs de rhinite ou d'asthme a la fin de l'hiver ou au tout debut du printemps. Le test cutane fut positif dans 36 cas. Le RAST fut positif 11 fois et le test specifique de provocation nasale 19 fois sur 41 a des concentrations comprises entre le 1/1600 e et le 1/200 e . Chez vingt-trois de ces malades examines pendant les saisons polliniques suivantes, les manifestations cliniques ont pu etre rattachees a la pluie pollinique du frene. Bien que cet allergene ne soit pas encore disponible en extrait standardise, le test cutane et le test nasal specifique apparaissent de meilleure valeur predictive que le RAST dont la sensibilite est mediocre (0,44 dans cette serie). Toutefois, le RAST au pollen d'olivier peut lui etre prefere pour suspecter la sensibilite aux pollens des oleacees. Le pollen de frene doit etre teste a Paris en cas de manifestations respiratoires allergiques de debut de saison car les pollinoses precoces ne sont pas toutes liees aux betulacees. Une standardisation de l'extrait s'impose pour ameliorer l'outil diagnostique et permettre une meilleure utilisation de l'immunotherapie specifique.

Resume Introduction. L'effort est une cause rare d'anaphylaxie. Dans nombre de cas on peut retrouver le role pathogenique d'une sensibilisation alimentaire. Notre experience porte sur 51 cas dans lesquels l'hypothese d'une allergie alimentaire a ete systematiquement recherchee comme agent etiologique favorisant. Materiel et methodes. 51 sujets consecutifs ont presente des signes, pour la plupart severes, d'anaphylaxie survenant pendant ou juste apres un effort souvent intense. Les methodes diagnostiques de l'allergie alimentaire utilisent les tests cutanes, avec l'aliment frais lorsque les prick-tests aux allergenes commerciaux sont negatifs, et la recherche d'IgE specifiques. Resultats. Parmi les aliments responsables de sensibilisations, le plus souvent jusque-la inapparentes, on note une frequence elevee des cereales et en particulier de la farine de ble. Arachide et fruits secs sont des causes non exceptionnelles, mais de nombreux autres aliments ont aussi ete releves comme agents etiologiques d'episodes preoccupants. Aussi aucun aliment ne nous parait devoir etre neglige dans l'enquete etiologique. Dans les cas severes, le test d'effort est ethiquement difficile a proposer : il est alors conseille d'eviter un ou plusieurs aliments, en fonction de l'anamnese et des sensibilisations relevees, pendant les 5 heures precedant tout effort important. Chez la plupart des sujets, avec ces mesures d'eviction, des efforts physiques d'intensite comparable a ceux qui ont entraine des signes d'anaphylaxie ont pu etre repetes sans le moindre symptome attestant du role de l'alimentation dans l'induction de cette pathologie d'effort. C'est cette repetition au cours d'un suivi prolonge qui permet de porter un diagnostic etiologique dans 80 p. cent des cas. Conclusion. Au cours de l'anaphylaxie liee a l'effort, les investigations destinees a mettre en evidence une allergie alimentaire sont indispensables. C'est en particulier la recherche systematique du role des cereales et des fruits qui sont bien souvent contenus dans les preparations utilisees par les sportifs. L'exclusion pendant 5 heures des aliments pour lesquels une sensibilisation a ete mise en evidence permet l'effort sans symptome dans notre experience.

Resume Les angio-œdemes par deficit en C1 inhibiteur constituent une entite particuliere par son aspect clinique associant œdemes sous-cutanes ou sous muqueux iteratifs, sa pathogenie, de mieux en mieux connue, et par les therapeutiques singulieres, preventives et curatives, aujourd'hui efficaces. La suspicion de ce deficit doit conduire aux dosages des fractions du complement permettant d'etablir le diagnostic. Un suivi regulier est alors necessaire pour preciser les indications du traitement qui a fait disparaitre le risque vital lie a la topographie laryngee de l'angio-œdeme. Dans les formes familiales de transmission autosomique dominante, les etudes immunogenetiques ont fait progresser nos connaissances sur les anomalies du gene de structure du C1 inhibiteur situe sur le chromosome 11. Dans les formes acquises, la mise en evidence, de plus en plus frequente, d'anticorps anti-C1 inhibiteur permet de preciser le mecanisme du deficit et d'exclure une forme neoplasique ou infectieuse.

Resume Les manifestations allergiques par piqures d'hymenopteres sont habituellement cutanees et/ou muqueuses. Elles sont soit locales et benignes, soit a distance du point de piqure, systemiques, isolees ou associees a d'autres atteintes anaphylactiques, respiratoires ou cardio-vasculaires qui menacent alors le pronostic vital a court terme. Leur frequence et leur gravite potentielle doivent bien faire connaitre leur semiologie et les methodes diagnostiques qui precisent leur mecanisme IgE dependant. Les reactions cutanees retardees font discuter leur mecanisme immunologique. L'efficacite de l'immunotherapie specifique sur la prevention des rechutes systemiques lors d'une nouvelle piqure et sa bonne tolerance justifient une bonne connaissance de ses indications et de ses modalites.

Resume La diversite des travaux necessaires a l'elaboration d'un vin de qualite explique que le viticulteur puisse etre theoriquement soumis au risque de contacts allergeniques. Toutefois, les manifestations cliniques relevant de ce type de risque sont de fait rarement rapportees dans cette profession qui evolue toujours vers plus de technicite pour une meilleure qualite. Nous passons en revue les differentes etapes de production du vin et tentons d'etablir une liste, non exhaustive, des allergenes potentiels pour le viticulteur.

Interstitial fibrosis is seen in the lung in response to a variety of insults, and often appears stereotypical in terms of its clinical and pathological features. However, exposure to a known aetiological factor does not always lead to fibrosis. For example in bleomycin-induced pulmonary fibrosis, a wide variation in response is seen both in humans and in animal models, which is not completely accounted for by known risk factors. These observations and the existence of a number of familial forms of lung fibrosis suggest a genetic predisposition. Current hypotheses concerning the pathogenesis of pulmonary fibrosis propose an initial stage involving the influx of inflammatory cells into the interstitium. These cells, together with activated resident cells are then thought to release polypeptide mediators that stimulate the fibroblast proliferation and matrix protein synthesis typical of these disorders. Genetic influences could have an important role in regulating a number of these events, altering the immunological response to injury or modulating collagen metabolism in the lung. However, despite recent advances in molecular genetic techniques, there have been few human studies to date. Most have concentrated on genetic loci with a high degree of polymorphism such as the human leucocyte antigen (HLA) system and yield conflicting results. Others offer tantalising but as yet, incomplete insights into the mechanisms involved. Defining the genetic abnormalities underlying both the familial forms of pulmonary fibrosis and the variations seen in response to lung injury should enhance our understanding of the pathogenic processes and help to focus research in this area.

Resume Buts : Apprecier la frequence de la responsabilite des differentes especes d'animaux a poils dans les reactions d'hypersensibilite et rechercher chez ces malades l'existence de sensibilisations pour d'autres especes animales. Methodes : Etude prospective comprenant un interrogatoire planifie puis des tests cutanes avec une serie de squames d'animaux. Cent sept malades consecutifs vus a la consultation en 12 mois et se plaignant d'une allergie au contact d'un animal ont ete etudies. Resultats : Les animaux incrimines sont le chat 88 fois, le chien 51 fois, le cheval 31 fois, le lapin 12 fois, le hamster, la souris et les oiseaux 3 fois chacun. Soixante six malades decrivent une allergie multiple qui est apparue a intervalle court chez 22 d'entre eux. Un contact animal regulier avant l'âge d'un an est rapporte par 36 malades. Le test cutane est negatif pour au moins un des animaux responsables de signes cliniques chez 45 malades. Il est, par ailleurs, positif chez 49 autres patients pour un animal n'ayant jusqu'alors jamais provoque de manifestations pathologiques. Conclusion : Le chat est l'animal le plus souvent mis en cause. Pres d'un allergique sur deux a cependant un test cutane negatif vis-a-vis d'un ou des animaux incrimines. Une meme proportion de ces allergiques est sensibilisee pour un autre animal. Ces donnees incitent d'une part a ameliorer la qualite de certains extraits allergeniques et d'autre part a elargir desormais l'eventail de l'exploration par tests cutanes chez ces malades.

Resume Les difficultes diagnostiques sont le plus souvent grandes lorsqu'une allergie alimentaire est suspectee. Apres un interrogatoire precis et prolonge, l'examen clinique permet souvent d'authentifier la pathologie presentee et d'apprecier le role d'une eventuelle composante allergique. Les tests cutanes, pratiques suivant des regles precises, permettent de confirmer la sensibilisation et parfois d'orienter l'enquete puis d'indiquer eventuellement, en l'absence de tout obstacle ethique, le test de reintroduction specifique en double aveugle, seul capable d'affirmer la responsabilite de l'aliment. A defaut de cette certitude, une ou plusieurs evictions specifiques peuvent etre proposees avec discernement et sous surveillance clinique etroite. Elle doit conduire a une remission clinique durable pour etre poursuivie.

Resume Le complement contribue aux defenses innees de l'organisme contre les agents infectieux. Il est constitue de proteases capables, l'une apres l'autre, d'activer la fraction en aval et d'aboutir ainsi a la formation du complexe lytique terminal agissant sur la membrane cellulaire des micro-organismes. Le systeme du complement doit demeurer en memoire car certains deficits en l'une de ses fractions peuvent conduire a des tableaux cliniques proches de ceux rencontres lors d'une reaction d'hypersensibilite. De plus, des observations encore preliminaires laissent supposer l'implication du systeme du complement dans certaines reactions anaphylactiques authentiques.

The cultured fibroblast has been extensively used as a model system to study aging. However, few studies have examined the veracity of observations obtained in cultured fibroblasts aged in vitro to those made in animal tissues in vivo. This paper compares age-related alterations in collagen metabolism measured in cultured cells with previously reported results in the aging rat (Mays et al. (1991) Biochem. J. 276, 307–313). Age-related changes in collagen synthesis in rat skin fibroblasts in vitro over 30 population doublings were determined based on the production of hydroxy-[14C]proline. Degradation of newly synthesized collagen was based on the appearance of free hydroxy-[14C]proline in the culture system. Total protein synthesis rates were based on the incorporation of [14C]proline into proteins. In vitro rates of collagen synthesis decreased 5-fold over 30 population doublings (P < 0.05). Degradation of newly synthesized collagen increased from 33.0 ± 0.8% (n = 4, SEM) to 45.2 ± 1.1% (n = 4; P < 0.05) over the same period, with a maximum after 25 population doublings of 55.8 ± 1.1% (n = 4). Total protein synthesis rates decreased by one-half over 30 population doublings (P < 0.05). The results indicated that collagen production decreased as cells aged in vitro and that this was due to both changes in synthesis and degradation. The results demonstrate that age-related alterations in collagen and total protein metabolism of skin fibroblasts in culture were similar to those reported previously for skin in vivo, suggesting that for studies of these processes, fibroblasts in culture provide an appropriate model.