Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation.

Methylation of DNA at the dinucleotide CpG is essential for mammalian development and is correlated with stable transcriptional silencing. This transcriptional silencing has recently been linked at a molecular level to histone deacetylation through the demonstration of a physical association between histone deacetylases and the methyl CpG-binding protein MeCP2 (refs 4,5). We previously purified a histone deacetylase complex from Xenopus laevis egg extracts that consists of six subunits, including an Rpd3-like deacetylase, the RbA p48/p46 histone-binding protein and the nucleosome-stimulated ATPase Mi-2 (ref. 6). Similar species were subsequently isolated from human cell lines, implying functional conservation across evolution. This complex represents the most abundant form of deacetylase in amphibian eggs and cultured mammalian cells. Here we identify the remaining three subunits of this enzyme complex. One of them binds specifically to methylated DNA in vitro and molecular cloning reveals a similarity to a known methyl CpG-binding protein. Our data substantiate the mechanistic link between DNA methylation, histone deacetylation and transcriptional silencing.

Comparison of BOLD, diffusion-weighted fMRI and ADC-fMRI for stimulation of the primary visual system with a block paradigm.

The blood oxygen level-dependent (BOLD) effect is extensively used for functional MRI (fMRI) but presents some limitations. Diffusion-weighted fMRI (DfMRI) has been proposed as a method more tightly linked to neuronal activity. This work proposes a protocol of DfMRI acquired for several b-values and diffusion directions that is compared to gradient-echo BOLD (GE-BOLD) and to repeated spin-echo BOLD (SE-BOLD, acquisitions performed with b=0s/mm2), which was also used to ensure the reproducibility of the response. A block stimulation paradigm of the primary visual system (V1) was performed in 12 healthy subjects with checkerboard alternations (2Hz frequency). DfMRI was performed at 3T with 5 b-values (b=1500, 1000, 500, 250, 0s/mm2) with TR/TE=1004/93ms, Δ/δ=45.4ms/30ms, and 6 spatial directions for diffusion measures. GE-BOLD was performed with a similar block stimulation design timing. Apparent Diffusion Coefficient (ADC)-fMRI was computed with all b-values used. An identical Z-score level was used for all fMRI modalities for the comparison of volumes of activation. ADC-fMRI and SE-BOLD fMRI activation locations were compared in a voxel-based analysis to a cytoarchitectural probability map of V1. SE-BOLD activation volumes represented only 55% of the GE-BOLD activation volumes (P<0.0001). DfMRI activation volumes averaged for all b-values acquired represented only 12% of GE-BOLD (P<0.0001) and only 22% of SE-BOLD activation volumes (P<0.005). Compared to SE-BOLD-fMRI, ADC-fMRI activations showed fewer pixels outside of V1 and a higher average probability of belonging to V1. DfMRI and ADC-fMRI acquisition at 3T could be easily post-processed with common neuro-imaging software. DfMRI and ADC-fMRI activation volumes were significantly smaller than those obtained with SE-BOLD. ADC-fMRI activations were more precisely localized in V1 than those of SE-BOLD-fMRI. This validated the increased capability of ADC-fMRI compared to BOLD to enhance the precision of localizing an fMRI activation in the cyto-architectural zone V1, thereby justifying the use of ADC-fMRI for neuro-scientific studies.

Chromosomal localization and expression pattern of the RNase L inhibitor gene.

2-5A-Dependent RNase (RNase L), an important component of the 2-5A pathway, is directly implicated in the molecular mechanism of interferon action. We have cloned and sequenced following immunoscreening, a full-length cDNA that encodes the RNase L inhibitor (RLI). Northern blot analysis from a variety of human tissues revealed that two transcript forms (3.8 kb and 2.4 kb) are ubiquitously expressed but differences in levels of expression suggest a tissue-specific regulation. The RLI gene was localized to locus 4q31 by in situ hybridization indicating that this gene and other enzymes of the 2-5A pathway are not organized in cluster in the human genome.

Expression and regulation of the CXC-chemokines, GRO/KC and IP-10/mob-1 in rat seminiferous tubules.

Testicular inflammation is classically observed in the pathogenesis of viral and bacterial infection or tumoral invasion. In these situations, leukocyte infiltration is generally encountered. GRO/KC (growth-related oncogene) and IP-10/mob-1 (IFN-gamma-inducible protein) are two CXC-chemokines which attract neutrophils and activated T lymphocytes, respectively, have been studied for their ability to participate to testicular inflammation (orchitis). In the present work, using Northern blot and immunocytochemistry, we aimed to investigate whether GRO/KC and IP-10/mob-1 are produced within the seminiferous tubules of the testis and if these chemokines are induced by a number of pro-inflammatory cytokines and lipopolysaccharides (LPS). Our results show that GRO/KC and IP-10/mob-1 mRNAs were never found in germ cells, whether they were stimulated or not. In contrast, GRO/KC mRNA was expressed by isolated peritubular cells when stimulated by interleukin-1 alpha and beta (IL-1 alpha and IL-1 beta) or LPS and to a lesser extent by tumor necrosis factor-alpha (TNF-alpha) and by Sertoli cells when the latter were stimulated by rIL-alpha and rIL-1 beta and to a lesser extent by TNF-alpha and LPS. Moreover, IP10/mob-1 transcripts were strongly induced in peritubular cells by interferon-alpha (IFN-alpha) and IFN-gamma, whereas, in isolated Sertoli cells, INF-alpha and TNF-alpha were the only potent inducers. The kinetics of GRO/KC and IP-10/mob-1 mRNA expression by peritubular and Sertoli cells (significant stimulation as early as 1 hour and 4 hours post-exposure to the stimuli, respectively) are compatible with the hypothesis of a rapid mobilisation of these cells in an inflammatory process. Moreover, the dose-dependent effects of pro-inflammatory cytokines to induce a chemokine response were compatible with a high sensitivity of peritubular and Sertoli cells in orchitis. In conclusion, this present study shows that 2 CXC-chemokines, GRO/KC and IP10/mob-1, are produced by testicular somatic cells of seminiferous tubules, strongly indicating a likely role of these chemokines in the accumulation of neutrophils and T lymphocytes during orchitis of various origins.

Standardization in the field of medical image management: the contribution of the MIMOSA model.

This paper deals with the development of standards in the field of medical imaging and picture archiving and communication systems (PACS's), and notably concerning the interworking between PACS's and hospital information systems (HIS). It explains, in detail, how a conceptual model of the management of medical images, such as the medical image management in an open system architecture (MIMOSA) model, can contribute to the development of standards for medical image management and PACS's. This contribution is twofold: 1) Since the model lists and structures the concepts and resources involved to make the images available to the users when and where they are required, and describes the interactions between PACS components and HIS, the MIMOSA work helps by defining a reference architecture which includes an external description of the various components of a PACS, and a logical structure for assembling them. 2) The model and the implementation of a demonstrator based on this model allow the relevance of the Digital Imaging and Communications in Medicine (DICOM) standard with respect to image management issues to be assessed, highlighting some current limitations of this standard and proposing extensions. Such a twofold action is necessary in order both to bring solutions, even partial, in the short term, and to allow for the convergence, in the long term, of the standards developed by independent standardization groups in medical informatics (e.g., those within Technical Committee 251 of CEN: Comité Européen de Normalisation).

[Use of tomographic scintigraphy with radio-labelled monoclonal antibodies for detecting human digestive cancers and medullary cancers of the thyroid]. / Utilisation en tomoscintigraphie d'anticorps monoclonaux radio-marqués pour la détection chez l'homme des cancers digestifs et des cancers médullaires de la thyroïde.

Two 131-Iodine radiolabelled monoclonal antibodies were used to perform tomoscintigraphy in 42 patients: 11 patients bearing medullary thyroid cancers and 19 patients bearing gastrointestinal cancers received an antibody directed against carcino-embryonic antigen; 12 patients bearing gastro-intestinal cancers received an antibody directed against a non circulating antigen expressed by human colorectal cancers cell lines. Tomoscintigraphy is particularly useful for analysing the complex biodistribution of radiolabelled antibodies and the low contrast images encountered in immunoscintigraphy; the problems related to the true positive rate and to the clinical specificity of the method are discussed.

A medical image object-oriented database with image processing and automatic reorganization capabilities.

The paper presents the medical image database developed for use in the methodological research environment and in the laboratory clinical environment, designed to be capable of being interfaced to an image processing system. This database is intended to solve the numerous problems due to the complexity-multidimensionality and multimodality-of medical images. These problems are posed in terms of management, archiving, structuring and accessing of this archive, and specification of the interfaces with users and with image processing system Solving these problems involves making a formal description of the image and the data associated with the image, while taking into account the specifics of medical imaging. The kernel which contains this description allows the physical architecture of the management and archiving system to be decoupled from its logical architecture. This decoupling is essential in order to automate the recording of new data, the automatic reorganization of the system scheme in the event of change in the system environment, and to help in consulting the database.

Can plankton communities be considered as bio-indicators of water quality in the Lagoon of Venice?

This study examines whether plankton of the Lagoon of Venice could be considered as a bio-indicator of areas subjected to various anthropogenic influences. This study was a two year hydrochemical and biological survey in five areas of the Lagoon of Venice, each with different environmental conditions due to pollution from urban, industrial, thermal and agricultural wastes. Phytoplankton associations did not show any promising species. In the different lagoonal areas, this community was differentiated into its major groups. In contrast, the copepod Acartia tonsa Dana could be considered as a target species in highly eutrophic areas.

Air pollution and health in three urban communities.

A health study was conducted in three communities in the greater Montreal region; the first two were characterized by relatively high particulate and sulfur dioxide levels, respectively, and a third community without major industrial pollution. In each community, 300 men and women 45 to 64 yr of age were studied. Residents of the two more polluted communities exhibited a higher prevalence of respiratory symptoms and mean lung function evaluated by various tests was lower than in residents of the less polluted community. When intercity differences in age and smoking were accounted for, no statistically significant intercity differences in health status could be shown. Given the limitations of this study, the results provide no evidence to suggest that current Canadian standards for sulfur dioxide adequately protect human health as measured by the indices used in the study, for adults in the age range of 45 to 64 yr.

[Management and transmission of medical images. Main standards and norms]. / Gestion et transmission des images médicales. Principaux standards et normes.

Use of digital images is growing in medical imaging. To be efficient, up-to-date concepts such as distributed informatics and client/server architecture must be used. Interoperability and networks adapted to the data involved in medical imaging are prerequisites to the implementation of such concepts. This necessitates official and de facto standards. Users of medical imaging should be aware of these standards and insist on the implementation of such standards on imaging equipment. This paper presents a survey of the main standards suitable for medical image management and transmission. Particular attention is focused on DICOM which is becoming the worldwide recognized standard in the field of medical imaging.

Mimos: a description framework for exchanging medical image processing results.

Image processing plays increasingly important role in using medical images, both for routine as for research purposes, due to the growing interest in functional studies (PET, MR, etc.). Unfortunately, there exist nearly as many formats for data and results coding as image processing procedures. If Dicom presently supports a kind of structured reporting of image studies, it does not take into account the semantics of the image handling domain. This can impede the exchange and the interpretation of processing results. In order to facilitate the use of image processing results, we have designed a framework for representing image processing results. This framework, whose principle is called an "ontology" in the literature, extends the formalism, which we have used in our previous work on image databases. It permits a systematic representation of the entities and information involved in the processing, that is not only input data, command parameters, output data, but also software and hardware descriptions, and relationships between these different parameters. Consequently, this framework allows the building of standardized documents, which can be exchanged amongst various users. As the framework is based on a formal grammar, documents can be encoded using XML. They are thus compatible with Internet / Intranet technology. In this paper, the main characteristics of the framework are presented and illustrated. We also discuss implementation issues in order to be able to integrate documents, and correlated images, handling these with a classical Web browser.

[Anti-beta 2 glycoprotein 1 antibodies in idiopathic livedo reticularis]. / Les anticorps anti-Bêta 2 glycoprotéine 1 dans le livedo reticularis idiopathique.

INTRODUCTION: Idiopathic livedo reticularis can be a sign of systemic disease since certain complications are frequently associated: cerebral thrombotic events in Sneddon's syndrome, necrotic ulcerations of the lower limbs. Antiphospholipid antibodies have been found in 0 to 85 p. 100 of patients with Sneddon's syndrome and anti-beta 2-glycoprotein 1 antibodies in 65 p. 100 of a series of 20 cases with Sneddon's syndrome. The aim of our study was to determine the prevalence of anti-beta 2-glycoprotein 1 antibodies in idiopathic livedo reticularis. PATIENTS AND METHODS: Twelve patients in a series of 17 with idiopathic livedo reticularis seen between 1981 and 1992 were studied progressively. All underwent a clinical examination and simple laboratory tests with search for anticardiolipin antibodies, lupus type circulating anticoagulant and anti-beta 2-glycoprotein 1 antibodies. RESULTS: Eight of our 12 patients (60 p. 100) were positive for anti-beta 2-glycoprotein 1 antibodies, 3 of whom also had episodes of thrombosis similar to those described in antiphospholipid syndrome. Only one of the 8 patients also had anticardiolipin antibodies and no chronic manifestation of thrombosis. DISCUSSION: beta 2-glycoprotein 1 is a cofactor which increases anticardiolipin antibody adhesion to cardiolipin in ELISA. Anti-beta 2-glycoprotein 1 antibodies are associated with thrombosis and antiphospholipid antibodies with lupus. Our results would suggest that the prevalence of anti-beta 2-glycoprotein 1 antibodies is high in idiopathic livedo, but, due to the small number of patients, do not allow confirmation that anti-beta 2-glycoprotein 1 antibodies are associated with thrombosis. Anti-beta 2-glycoprotein 1 antibody assay would be justified in routine evaluation of patients with livedo and at follow-up examinations.

[Towards the integration of the digital medical image folder within the computerized patient folder: PACS and image networks]. / Vers l'intégration du dossier d'imagerie au dossier patient informatisé : PACS et réseaux d'images.

Medical Images are components of the so-called "Medical Imaging Folder". This folder is a subset of the so-called "Medical Folder", part of the "Patient Folder. The G8 promotes the concept of a "Global Information Society for Health. Within this society, the Patient Folder is seen either from a healthcare organization, from a country or from an international point of view. The Global Patient Folder (Healthcare Folder) is composed of the different Patient Folder instances. Presently, Pacs and Telemedicine are no longer concerned only by storage and transmission issues. The medical images have only meaning associated with their context, the patient healthcare status. This context is rich in information provided by various information systems or healthcare professionals. The different data are linked and time dependant. Therefore, the expert community in the field of patient records argues that the approach must be the integration of Medical Images within the patient folder. It appears clearly that the complete deployment of such an "International Healthcare Folder" needs time and will proceed in several steps. Due to the increase of the people's mobility this deployment is inescapable. Infrastructure must be sized up taking into account the Digital Medical Image spreading and its large data volume which necessitates a large bandwith. In this paper, we detail the Medical Image Folder concept and its position within the Patient Folder and the Healthcare Folder. Then we present PACS, networking and Telemedicine concepts as well as the needs in standards.

Risk factors of squamous cell carcinoma of the skin. A case-control study in the Montreal region.

A matched case-control study was undertaken to assess the relative risk associated with known and suspected risk factors of squamous cell carcinoma of the skin among patients in the Montreal region. Three hundred eleven cases histologically diagnosed in 1977 and 1978 in 12 hospitals and meeting strict definition criteria were identified. With the exception of six cases, two controls were matched to each case for sex, age, and hospital of diagnosis. A logistic regression analysis was done. The known host risk factors (eye and hair color, complexion, descent) and nonoccupational sunlight exposure were found to be operative in the Montreal region. After adjusting for these factors, occupational sunlight exposure appeared to be a risk factor. An association was then observed between the risk of squamous cell carcinoma of the skin and tobacco smoking and the use of a sunlamp. Relative risks associated with the above-mentioned factors were estimated.

A database manager of biomedical images.

In order to allow an efficient archiving and retrieval of biomedical images, PACS would include an image DBMS. As biomedical images have complex structures we developed a specific DBMS over a relational one. The medical image database manager ensures a data description that takes into account data semantics so that consistency or existential constraints may be verified. It provides a unique language to retrieve images no matter what their storage format. It encompasses the queries of the user which constitute a filter over associated data. The manager can handle changes in the environment of the image. We implemented a manager prototype to show the validity of logical access possibilities. The user need no longer know the structure of the image database to access data. The logical access allows retrieval of images, whatever the architecture of the base. An automatic query construction consists of three functional levels including the interfaces towards the external environment which ensure a logical independence from the database, a query generator which creates the correspondence between the user's query and physical access queries, a dictionary which contains the structure of the image data and consistency constraints.