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.

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.

The immunohistochemical expression pattern of Chk2, p53, p19INK4d, MAGE-A4 and other selected antigens provides new evidence for the premeiotic origin of spermatocytic seminoma.

AIMS: Spermatocytic seminoma is a rare germ cell derived tumour of the testis that occurs mainly in older men. We analysed the expression of recently discovered markers for germ cell differentiation and the mitosis-meiosis transition in order to define the antigen profile for diagnostic purposes and to clarify the biology and histogenesis of spermatocytic seminoma. METHODS AND RESULTS: Twenty-five spermatocytic seminomas were examined for immunohistochemical expression of germ cell-specific onco-fetal antigens and proteins involved in regulation of germ cell division, DNA repair and differentiation. The panel included Chk2, p19INK4d, p53, MAGE-A4, KIT, TRA-1-60, neurone-specific enolase and placental-like alkaline phosphatase. Four of these proteins/antigens have never before been investigated in spermatocytic seminoma. Proteins highly expressed in gonocytes and spermatogonia, such as Chk2, MAGE-A4 and neurone-specific enolase, were consistently present in spermatocytic seminoma. Antigens expressed in embryonic germ cells but not in the normal adult testis, e.g. TRA-1-60, were undetectable, with the exception of p53 protein, which was demonstrated in 80% of cases. A proto-oncogene p19INK4d, which is involved in the transition from mitotic to meiotic division in germ cells, was not detected in spermatocytic seminoma. CONCLUSIONS: The investigation provided new information concerning the expression of Chk2, MAGE-A4, neurone-specific enolase and p19INK4d in spermatocytic seminoma. The pattern of expression is highly consistent with the origin of spermatocytic seminoma from a premeiotic germ cell, which has lost embryonic traits and has committed to spermatogenic lineage but has not yet passed the meiotic checkpoint, most probably from the spermatogonium of the adult testis.

MAGE-A4, a germ cell specific marker, is expressed differentially in testicular tumors.

BACKGROUND: Testicular germ cell tumors are the most common malignancy in young males, and the frequency of these tumors has risen dramatically over the last century. Because it is known that the MAGE genes are expressed in a wide variety of tumors but are expressed only in the mitotic spermatogonia (germ cells) and in the primary spermatocytes in the normal testis, the authors screened the expression of MAGE-A4 in a panel of testicular germ cell tumors. METHODS: Monoclonal antibody 57B raised against MAGE-A4 was tested immunohistochemically on 12 classical seminomas, 5 anaplastic seminomas, 10 various specimens of nonseminomatous germ cell tumors (NSGCTs), 2 combined tumors containing seminoma components, 1 Sertoli cell tumor, 2 Leydig cell tumors, and 15 carcinomas in situ (CIS). In addition, monoclonal antibody 57B was tested on embryonic gonad (age 8 weeks) and fetal gonads (ages 15 weeks, 17 weeks, and 28 weeks). RESULTS: Classical seminomas uniformly and specifically expressed MAGE-A4 compared with anaplastic seminomas and NSGCTs, which were negative for this antigen. Specific expression of MAGE-A4 also was seen in subpopulations of CIS cells, providing additional evidence for heterogeneity of the phenotype of these cells, in which it is believed that differentiation and proliferation generate seminomas and NSGCTs. Finally, MAGE-A4 was expressed in the fetal precursors of the stem germ cells from 17 weeks of gestation onward, in accordance the fact that CIS can arise from prespermatogonia in the fetus. CONCLUSIONS: MAGE-A4 can be considered a potential specific marker for normal premeiotic germ cells and germ cell tumors and can be used to characterize classical seminomas.

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.

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.

[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.

Expression and regulation of the CC-chemokine monocyte chemoattractant protein-1 in rat testicular cells in primary culture.

Testicular inflammation is classically observed in pathogenesis caused by infectious agents, environmental toxins, trauma, or autoimmune reactions and can lead to transitory or even permanent sterility. In these situations, a leukocyte infiltration is generally encountered. Macrophage inflammatory proteins (MIP)-1alpha and -1beta and monocyte chemoattractant protein-1 (MCP-1) are CC-chemokines involved in macrophage and lymphocyte chemoattraction. In the present study, using reverse transcription-polymerase chain reaction, Northern blot, and a specific ELISA, we investigated whether or not these chemokines are present within the testis and whether they are induced by a number of proinflammatory cytokines and lipopolysaccharides (LPS). MIP-1alpha and MIP-1beta were not detected in Sertoli cells, germ cells, peritubular cells, or Leydig cells. In contrast, MCP-1 mRNA and protein were found to be expressed by control isolated peritubular cells, and expression was markedly stimulated by interleukin-1alpha and-1beta (IL-1alpha and IL-1beta), tumor necrosis factor alpha (TNF-alpha), interferon gamma, and LPS. Leydig cells expressed MCP-1 when stimulated by IL-1beta. In contrast, MCP-1 was not found to be produced by Sertoli cells or germ cells as established by Northern blot and ELISA techniques. The kinetics of MCP-1 production by peritubular cells, as demonstrated by expression as early as 8 h poststimulation, are compatible with there being a rapid mobilization of these cells and this chemokine in an inflammatory process. Moreover, MCP-1 production by peritubular cells after half-maximal stimulation by LPS, TNF-alpha, and IL-1beta (2 pg/ml-0.9 ng/ml) is also compatible with the physiologic concentrations of the proinflammatory cytokines generally found in an inflammatory site. It is concluded that MCP-1 is produced by Leydig cells and peritubular cells and that it could be involved in the mobilization and migration of leukocytes observed during testicular inflammation.

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.

Identification of a human 17p-located cDNA encoding a protein of the Snf2-like helicase family.

Following immunoscreening, we have cloned and sequenced a human cDNA encoding a novel member of the expanding helicase family. The deduced protein, designated hZFH (human zinc-finger helicase), contains the seven domains conserved among the helicase superfamily II and four potential zinc-fingers motifs. In particular, hZFH shows significant similarity to some proteins of the Snf2-like family, known to act as transcriptional regulators for multiples genes. Furthermore, hZFH has 68.5% identity to a human Mi-2 autoantigen to which autoantibodies are produced by a subgroup of patients affected by dermatomyositis. Northern-blot analyses have revealed several hZFH mRNAs with quantitative differences in various human tissues. One alternative splice site of hZFH mRNA was demonstrated and others were predicted. We also report the chromosomal localization of gene hZFH to locus 17p13-17p12 by in situ hybridization. Thus, this novel gene appears as a candidate for several malignant and genetic diseases associated with this region of the genome. The combination of these features suggests that hZFH plays an important role in gene regulation.

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).

[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.

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.

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.

[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.

Redistribution of nuclear antigens linked to cell proliferation and RNA processing in mouse oocytes and early embryos.

We have systematically analyzed by indirect immunofluorescence the subcellular distribution of nuclear antigens in relation to developmental stages of maturing mouse oocytes and developing embryos. Antigens were of two types: (1) a protein whose nuclear localization in interphase somatic cells depends on their proliferative state protein recognized by a monoclonal antibody 43B1N, and (2) snRNP polypeptides recognized by autoimmune sera of anti-Sm and anti-RNP type. The protein recognized by 43B1N was present in the germinal vesicle of oocytes from antral follicles, but absent from the nuclei during the first hours of embryonic life up to the middle to late 2-cell stage. Starting from this stage, it was always found in nuclei of interphase blastomeres, where its "speckles" co-localized with the speckles containing high concentrations of snRNP polypeptides. SnRNP polypeptides recognized by anti-Sm and anti-RNP sera were in turn found in nuclei of all developmental stages. When embryos were treated with aphidicolin or cytochalasin D to arrest cell division, the 43B1N reacting protein was again localized in the pronuclei at 42 hr post-hCG, i.e., slightly later than the onset of transcriptional activity. These results suggest a progressive building up of nuclei during embryonic development, which could influence gene expression.

MIMOSA: a functional model of the management of medical images.

The concept of picture archiving and communication system (PACS) appeared in 1982. Twelve years later most PACS prototypes still do not satisfy the medical community requirements: too much emphasis has been put on technical solutions and little effort devoted to the management of images itself. A common approach to this problem is needed more than ever to allow cost-effective systems to be developed. Modelling is a way to reach this objective, and the MIMOSA topic within the AIM/EurlPACS project aims at defining such a model of medical image management. This paper presents the MIMOSA approach with the three underlying constraints, i.e. genericity, implementation independence and performance. The MIMOSA group is building three interrelated models: a data model, a functional model and a dynamic model. However, in this report we focus only on the functional model, and explain how it was abstracted from various clinical scenarios in the first phase of the project. The availability level concept is introduced as a customizable and implementation independent solution to the problem of managing the delay of access to the information. The so-called contextual diagram and the acquisition of a new examination which are two representative parts of the model are detailed. The validation aspects and the relationships to projects working on the management of patient records are addressed as a conclusion.