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PubMed1990

Cell interactions and regeneration control.

This paper is a review of the main findings of our laboratory on the control of regeneration by cell interactions. These include results related to the role of both cell contact and local soluble factors in regeneration of the legs of insects and newts and of the parapodia and segments of nereis. The pattern of these structures is considered to be defined by positional information distributed as longitudinal and transverse positional value sequences carried by epidermal (insect) or mesenchymal (newt) cells. By associating tissues to create transverse and longitudinal discontinuities in these sequences, single or multiple regenerating structures were obtained. These structures are formed by the intercalation of cells characterized by intermediate positional values which fill the gap between the tissues in contact. Positional information may also be changed during regeneration by the nerve cord in nereis and retinoids in the newts. We describe additional cases where morphogenesis occurs without any overt discontinuity in positional information, such as from a locally injured or non-injured insect trochanter, or after deflection of nerves in nereis and newt. Regeneration following an amputation may be considered as a special case of intercalary regeneration, the first stage being the juxtaposition of normally non-contiguous cells resulting in a longitudinal or/and a transverse gap. We also report studies on local factors produced by nerves and the blastema during newt limb regeneration. The nerve factor is necessary for the division of blastemal cells. After denervation, mesenchyme differentiates in an abnormal way. The mitogenic signal from the nerves is mediated by the PKC pathway. Its production is enhanced by regeneration of cut nerve fibers. The blastema also produces growth factors. We show that the epidermal cap and mesenchyme contain acidic FGF-like factor, and that the proliferating mesenchyme stimulates nerve fibers to regrow into the blastema.

Amphibians↗
PubMed2003

Anticipatory cortico-cortical interactions: switching the task configuration between effectors.

Cognitive regulation enables a subject to plan actions according to context and to respond in a flexible manner to environmental conditions. This implies that foreknowledge about a change in system configuration will trigger preparatory activity in anticipation of the impending transformation. In the present study, we evaluate a unimanual task under two performance conditions that affected the cognitive context, and examine modulations in cortico-cortical interactions as determined by EEG coherence. The right hand movement was performed in an experimental paradigm that necessitated in some trials a voluntary and predictable switch towards a left hand movement, whereas in other trials no switch was required and movement of the right hand continued. The data showed that execution of the right hand movement was associated with an increased degree of task-related coherence in the alpha frequency band (8-12 Hz) in the switching as compared to the no switching condition, and this was most apparent for fronto-parietal connections of the movement-driving (left) as well as for the primed (right) hemisphere. For the primed hemisphere, we observed that the information flow was driven from the F4 electrode overlying the prefrontal area, which suggests that anticipatory preplanning occurred. These data indicate that higher-order cognitive operations bias cortico-cortical interactions in respect of an upcoming switch of the task settings between effectors by recruiting neural resources proactively. Dynamic adjustments in the alpha band suggest that low frequency activity is a characteristic of distributed information processing related to movement planning.

Adult↗
PubMed1986

Innovative blood pressure measurements yield information not reflected by sitting measurements.

A study of 873 healthy adults and children from Utah kindreds was performed to identify redundant and unique information contained in multiple diverse blood pressure determinations. Systolic blood pressure, fourth-phase and fifth-phase diastolic blood pressures, and simultaneous heart rates were measured in subjects sitting, standing, supine, and tilting, during half-maximal handgrip exercise, and just before blood drawing. A correlation matrix of 57 blood pressure and pulse variables in 618 healthy adults was analyzed. Factor analysis of the correlation matrix showed that all systolic blood pressures loaded as a single factor, accounting for 44% of the total variance of the observed variables. All heart rates also loaded together as a single factor. Diastolic blood pressures showed much more heterogeneity of information distributed among five separate factors. The same basic factors were found in young adults (age, 18-35 years) and older adults (age, 36 + years). Children under 12 years of age showed very different factor patterns, and youths 12 to 17 years of age showed patterns intermediate between those of adults and children. In light of recent clinical trials, better definitions are being sought for hypertension. Information from blood pressures other than sitting determinations may improve the definition of hypertension or better predict which patients have the highest risk of hypertension and its cardiovascular complications.

Adolescent↗
PubMed2003

[IHE (Integrating the Healthcare Enterprise): a new approach for the improvement of digital communication in healthcare].

Parallel to the introduction of diagnosis related groups (DRGs) for the reimbursement of hospitals, a marked reduction of financial means within the healthcare system is taking place. Healthcare enterprise information systems will play an increasing role to accommodate the new working conditions by developing reliable and efficient workflow solutions. Interfacing the systems currently in use can meet considerable obstacles. By offering high connectivity, IHE (Integrating the Healthcare Enterprise), which was initiated by concerted actions of users and vendors, ensures improved health care delivery and, furthermore, assists in acquiring new information systems in the future. IHE is not a standard but makes extensive use of existing international standards, such as HL7 and DICOM. National IHE demonstrations confirmed the power of this approach and presented its mission to large groups of users and vendors. The concept continues to grow and for the first time provides groups of various interests cooperative solutions to the problems encountered in collecting and distributing information.

Computer Systems↗
PubMedDate not supplied

Internet patient records: new techniques.

BACKGROUND: The ease by which the Internet is able to distribute information to geographically-distant users on a wide variety of computers makes it an obvious candidate for a technological solution for electronic patient record systems. Indeed, second-generation Internet technologies such as the ones described in this article--XML (eXtensible Markup Language), XSL (eXtensible Style Language), DOM (Document Object Model), CSS (Cascading Style Sheet), JavaScript, and JavaBeans--may significantly reduce the complexity of the development of distributed healthcare systems. OBJECTIVE: The demonstration of an experimental Electronic Patient Record (EPR) system built from those technologies that can support viewing of medical imaging exams and graphically-rich clinical reporting tools, while conforming to the newly emerging XML standard for digital documents. In particular, we aim to promote rapid prototyping of new reports by clinical specialists. METHODS: We have built a prototype EPR client, InfoDOM, that runs in both the popular web browsers. In this second version it receives each EPR as an XML record served via the secure SSL (Secure Socket Layer) protocol. JavaBean software components manipulate the XML to store it and then to transform it into a variety of useful clinical views. First a web page summary for the patient is produced. From that web page other JavaBeans can be launched. In particular, we have developed a medical imaging exam Viewer and a clinical Reporter bean parameterized appropriately for the particular patient and exam in question. Both present particular views of the XML data. The Viewer reads image sequences from a patient-specified network URL on a PACS (Picture Archiving and Communications System) server and presents them in a user-controllable animated sequence, while the Reporter provides a configurable anatomical map of the site of the pathology, from which individual "reportlets" can be launched. The specification of these reportlets is achieved using standard HTML forms and thus may conceivably be authored by clinical specialists. A generic JavaScript library has been written that allows the seamless incorporation of such contributions into the InfoDOM client. In conjunction with another JavaBean, that library renders graphically-enhanced reporting tools that read and write content to and from the XML data-structure, ready for resubmission to the EPR server. RESULTS: We demonstrate the InfoDOM experimental EPR system that is currently being adapted for test-bed use in three hospitals in Cagliari, Italy. For this we are working with specialists in neurology, radiology, and epilepsy. CONCLUSIONS: Early indications are that the rapid prototyping of reports afforded by our EPR system can assist communication between clinical specialists and our system developers. We are now experimenting with new technologies that may provide services to the kind of XML EPR client described here.

Internet↗
PubMed2004

Homecare: the need for cooperative information systems.

Assuming responsibility of patients at home (Homecare) is organized around a complex cooperation of partners: health care actors, relatives and helpers, all of whom intervene in the patient's home and who spark off the setting up of cooperative information systems. We present our work relating to such systems within the context of home care. Such activity is based on the collaboration of multiple mobile actors, obtaining information in a multimodal fashion, while taking the job profiles and professional grades of the users into account. Information is obtained from heterogeneous systems. The quality of management of the activity of the various health care actors and of the feedback on information handled at the time of the homecare process will determine how easy it may be to set up homecare as well as the quality of care. In this paper we outline the main stages of our work: grasping the context of homecare and studying co-operative activity from a fundamental point of view but also as applied to homecare. We describe the system proposed for accessing distributed information and for organizing the supervision of the 2 fundamental processes: (1) the LOGISTICAL process (to manage the organization), (2) and the CARE Process (to follow-up the medical or nursing status of the patient), and then we enhance the contribution of mobile technologies in this context.

Cell Phone↗
PubMed1998

GeneCards: a novel functional genomics compendium with automated data mining and query reformulation support.

MOTIVATION: Modern biology is shifting from the 'one gene one postdoc' approach to genomic analyses that include the simultaneous monitoring of thousands of genes. The importance of efficient access to concise and integrated biomedical information to support data analysis and decision making is therefore increasing rapidly, in both academic and industrial research. However, knowledge discovery in the widely scattered resources relevant for biomedical research is often a cumbersome and non-trivial task, one that requires a significant amount of training and effort. RESULTS: To develop a model for a new type of topic-specific overview resource that provides efficient access to distributed information, we designed a database called 'GeneCards'. It is a freely accessible Web resource that offers one hypertext 'card' for each of the more than 7000 human genes that currently have an approved gene symbol published by the HUGO/GDB nomenclature committee. The presented information aims at giving immediate insight into current knowledge about the respective gene, including a focus on its functions in health and disease. It is compiled by Perl scripts that automatically extract relevant information from several databases, including SWISS-PROT, OMIM, Genatlas and GDB. Analyses of the interactions of users with the Web interface of GeneCards triggered development of easy-to-scan displays optimized for human browsing. Also, we developed algorithms that offer 'ready-to-click' query reformulation support, to facilitate information retrieval and exploration. Many of the long-term users turn to GeneCards to quickly access information about the function of very large sets of genes, for example in the realm of large-scale expression studies using 'DNA chip' technology or two-dimensional protein electrophoresis. AVAILABILITY: Freely available at http://bioinformatics.weizmann.ac.il/cards/ CONTACT: cards@bioinformatics.weizmann.ac.il

Algorithms↗
PubMed1991

Use of a digital brain atlas to compare the distribution of NGF- and bFGF-protected cholinergic neurons.

The effectiveness of basic fibroblast growth factor and nerve growth factor in preventing the lesion-induced disappearance of septal cholinergic neurons was compared by using a computerized data-acquisition system and a digital brain atlas that yielded quantitative and distributional information. Adult rats were given unilateral partial transections of the fimbria and then received daily intraventricular injection of one of the growth factors for 15 days. Given the high degree of co-localization of nerve growth factor receptors with choline acetyltransferase in these areas, cholinergic neurons were identified by nerve growth factor receptor immunoreactivity. Their locations were plotted in the context of a three-dimensional brain atlas permitting the analysis of relative distributions of cholinergic neurons in control brains and those of animals treated with each growth factor. The cholinergic cell disappearance induced by the partial fimbrial transection was restricted to the medial septal nucleus and the vertical limb of the diagonal band of Broca. Within the affected areas cholinergic cell disappearance increased gradually in severity from anterior to posterior levels of the septal nucleus. Both growth factors prevented the disappearance of cholinergic cell bodies in medial septal nucleus and vertical limb of the diagonal band. In lesioned control animals the unilateral cell disappearance amounted to 53.5% of the number of cholinergic neurons of the unlesioned side. Nerve growth factor and basic fibroblast growth factor reduced this disappearance to 13% and 28%, respectively. The distribution of cholinergic cells was the same in animal treated with each growth factor, suggesting that the two growth factors protect the same population of cholinergic neurons.

Brain↗
PubMed1989

Reconstruction of the probe angular distribution from a series of electron spin resonance spectra of tilted oriented samples.

Model-independent methods for the reconstruction of the nitroxide spin probe angular distribution of labeled oriented biological assemblies from electron spin resonance (ESR) spectra were investigated. We found that accurate probe angular distribution information could be obtained from the simultaneous consideration of a series of ESR spectra originating from a sample at differing tilt angles relative to the Zeeman magnetic field. Using simulated tilt series data sets, we developed a consistent criteria for judging the reliability of the simulated fit to the data as a function of the free spectral parameters and thereby have increased the significance of the model-independent reconstruction of the probe angular distribution derived from the fit. We have also enhanced the angular resolution measurable with the model-independent methodology by increasing the rank of the order parameters that we can reliably deduce from a spectrum. This enhancement allows us to accurately deduce higher resolution features of the spin probe distribution. Finally we investigated the usefulness of fitting the tilt series data in multiple data sets such that tilt series data from many identical sample preparations are fitted simultaneously. This method proved to be useful in rapidly reducing a large amount of data by eliminating any redundant computations in the application of the enhanced model-independent analysis to identical sets of tilt series data. We applied the methodology developed here to ESR spectra from probe labeled muscle fibers to study the orientation of myosin cross-bridges in fibers. This application is described in the accompanying paper.

Electron Spin Resonance Spectroscopy↗
PubMed2002

GeneNet: a database on structure and functional organisation of gene networks.

The GeneNet database is designed for accumulation of information on gene networks. Original technology applied in GeneNet enables description of not only a gene network structure and functional relationships between components, but also metabolic and signal transduction pathways. Specialised software, GeneNet Viewer, automatically displays the graphical diagram of gene networks described in the database. Current release 3.0 of GeneNet database contains descriptions of 25 gene networks, 945 proteins, 567 genes, 151 other substances and 1364 relationships between components of gene networks. Information distributed between 14 interlinked tables was obtained by annotating 968 scientific publications. The SRS-version of GeneNet database is freely available (http://wwwmgs.bionet.nsc.ru/mgs/systems/genenet/).

Animals↗
PubMed2006

Children use categories to maximize accuracy in estimation.

The present study tests a model of category effects upon stimulus estimation in children. Prior work with adults suggests that people inductively generalize distributional information about a category of stimuli and use this information to adjust their estimates of individual stimuli in a way that maximizes average accuracy in estimation (see Huttenlocher, Hedges & Vevea, 2000). However, little is known about the developmental origin of this cognitive process. In the present study, 5- and 7-year-old children viewed stimuli that varied in size and reproduced each from memory. Consistent with the predictions of a Bayesian model of category effects on estimation, responses were adjusted toward the central value of the stimulus distribution. Additionally, the dispersion of the stimulus distribution affected the pattern of bias and variability of responses in a way that is predicted by the model. The results suggest that, like adults, children use categories for increasing average accuracy in estimating inexact stimuli.

Age Factors↗
PubMed2003

How adolescents use technology for health information: implications for health professionals from focus group studies.

BACKGROUND: Adolescents present many challenges in providing them effective preventive services and health care. Yet, they are typically the early adopters of new technology (eg, the Internet). This creates important opportunities for engaging youths via eHealth. OBJECTIVE: To describe how adolescents use technology for their health-information needs, identify the challenges they face, and highlight some emerging roles of health professionals regarding eHealth services for adolescents. METHODS: Using an inductive qualitative research design, 27 focus groups were conducted in Ontario, Canada. The 210 participants (55% female, 45% male; median age 16 years) were selected to reflect diversity in age, sex, geographic location, cultural identity, and risk. An 8-person team analyzed and coded the data according to major themes. RESULTS: Study participants most-frequently sought or distributed information related to school (89%), interacting with friends (85%), social concerns (85%), specific medical conditions (67%), body image and nutrition (63%), violence and personal safety (59%), and sexual health (56%). Finding personally-relevant, high-quality information was a pivotal challenge that has ramifications on the depth and types of information that adolescents can find to answer their health questions. Privacy in accessing information technology was a second key challenge. Participants reported using technologies that clustered into 4 domains along a continuum from highly-interactive to fixed information sources: (1) personal communication: telephone, cell phone, and pager; (2) social communication: e-mail, instant messaging, chat, and bulletin boards; (3) interactive environments: Web sites, search engines, and computers; and (4) unidirectional sources: television, radio, and print. Three emerging roles for health professionals in eHealth include: (1) providing an interface for adolescents with technology and assisting them in finding pertinent information sources; (2) enhancing connection to youths by extending ways and times when practitioners are available; and (3) fostering critical appraisal skills among youths for evaluating the quality of health information. CONCLUSIONS: This study helps illuminate adolescent health-information needs, their use of information technologies, and emerging roles for health professionals. The findings can inform the design and more-effective use of eHealth applications for adolescent populations.

Adolescent↗
PubMed2002

Predictors of residual venous obstruction after deep vein thrombosis of the lower limbs: a prospective cohort study.

INTRODUCTION: Delayed thrombus regression after deep vein thrombosis (DVT) of the lower limbs is associated with increased risk of DVT recurrence. Predictors of residual venous occlusion are unknown. We hypothesized that obesity, which causes reduced fibrinolytic activity, can predict delayed thrombus regression. MATERIALS AND METHODS: In a prospective cohort study, 98 patients with objective diagnosis of DVT underwent compression ultrasonography (CUS) after 6 and 12 months. Persistent occlusion was arbitrarily defined as a thrombus occupying, at maximal point of compressibility, more than 20% of the vein area in the absence of compression. The body mass index (BMI) and waist circumference were measured at baseline and at follow up to assess individual patterns of body fat distribution. Information on antithrombotic treatment, family history of varicose veins, cigarette smoking, concomitant disorders, the presence of known risk factors for DVT, the duration of anticoagulant treatment and the use of elastic stockings was collected. RESULTS: Post-thrombotic recanalization was documented in 34 patients (34.7%) at 6 months and in 44 patients (44.9%) at 12 months. There was no difference in the mean BMI (p=0.469 at 12 months), in the prevalence of obesity (p=0.479) and visceral pattern of body fat distribution (p=0.239) between patients who did and did not show thrombus regression. The presence of a permanent risk factor for DVT was the only predictor of delayed thrombus regression (OR 11.0, 95% CI 1.359-61.978). CONCLUSIONS: Despite consistent evidence of impaired fibrinolysis, obesity is not associated with persistent venous obstruction.

Body Mass Index↗
PubMedDate not supplied

The Internet's impact on EDI.

Explosive growth of the Internet in a number of industries has created an information distribution channel that is likely to alter and leverage every aspect of electronic commerce. With the levels of IS integration and technological innovations in development in healthcare today, it is not unreasonable to predict that this industry soon will be similarly driven.

Commerce↗
PubMed1999

A 'distributed degron' allows regulated entry into the ER degradation pathway.

Protein degradation is employed in both regulation and quality control. Regulated degradation of specific proteins is often mediated by discrete regions of primary sequence known as degrons, whereas protein quality control involves recognition of structural features common to damaged or misfolded proteins, rather than specific features of an individual protein. The yeast HMG-CoA reductase isozyme Hmg2p undergoes stringently regulated degradation by machinery that is also required for ER quality control. The 523 residue N-terminal transmembrane domain of Hmg2p is necessary and sufficient for regulated degradation. To understand how Hmg2p undergoes regulated degradation by the ER quality control pathway, we analyzed over 300 mutants of Hmg2p. Regulated degradation of Hmg2p requires information distributed over the entire transmembrane domain. Accordingly, we refer to this determinant as a 'distributed' degron, which has functional aspects consistent with both regulation and quality control. The Hmg2p degron functions in the specific, regulated degradation of Hmg2p and can impart regulated degradation to fusion proteins. However, its recognition is based on dispersed structural features rather than primary sequence motifs. This mode of targeting has important consequences both for the prediction of degradation substrates and as a potential therapeutic strategy for targeted protein degradation using endogenous degradation pathways.

Amino Acid Sequence↗
PubMed2001

Particle size and chemical species 'fingerprinting' of aerosols in primary nickel production industry workplaces.

A field study was conducted at a range of worksites at a number of plants, for two companies, in the primary nickel production industry. The aim of the field study was to provide direct measurements of the distributions of both particle size and relevant nickel species groups (soluble, sulfidic, metallic and oxidic). and to use the data to characterize health-relevant aerosol exposures of workers at the worksites in question. Since there was no commercially-available sampler that could provide samples of sufficient quantity to enable chemical speciation for the species fractions of interest, as well as particle size distribution information, new instrumentation was developed, based on a modified version of the Andersen cascade impactor, incorporating a porous foam media top stage that produced particle classification over the upper end of the inhalable range (Kerr, Vincent and Ramachandran, Annals of Occupational Hygiene, 2001, in the press). This modified-Andersen sampler was used in extensive field studies, along with other sampling instruments, including, in particular, the IOM personal inhalable aerosol sampler. The results of the field study provided results that could be represented succinctly in terms of the distributions of the four nickel species groups and the three health-related particle-size fractions: inhalable, thoracic and respirable. They showed that, for practical purposes, the distributions of the four nickel species groups were consistently uniform across the full range of particle-size distribution. For the purpose of characterizing the distribution of nickel species for each worksite, this finding enabled incorporation of additional data taken at those same sites using the IOM personal inhalable aerosol sampler. This yielded a data set sufficient to permit the development of exposure 'fingerprints' for each worksite. Such 'fingerprints' make it possible for the occupational hygienists at the plants in question to estimate workers' exposure to individual nickel species fractions based on measurement only of overall inhalable nickel. In addition, by reference to the differing threshold limit values (TLV) for the various nickel species, the 'fingerprints' also allow the individual worksites to be characterized by hazard indices (in the form of 'equivalent sulfidic fractions', or ESFs) that reflect the weightings of the risks experienced by workers at each worksite.

Aerosols↗
PubMed2026

Evaluating three alternative scenarios for the origin of a disjunct Arctium tomentosum population in the Pyrenees.

BACKGROUND: Disjunctions in species distributions offer natural experiments for investigating the mechanisms underlying distributional breaks, such as range contraction, long-distance pollen transport, or long-distance seed dispersal. Here, we document and characterise a floristic novelty in the Pyrenean and Iberian regions, and use it as a case study to investigate the processes underlying disjunct species distributions. Our analysis focuses on Arctium L. (burdocks), a genus native to Eurasia comprising several cosmopolitan weedy species. It is characterised by hooked capitula that facilitate epizoochorous dispersal. METHODS: To clarify the taxonomic identity of a previously undocumented Pyrenean population resembling A. tomentosum, we adopted an integrative approach, combining distribution information, morphology, genome size, repetitive DNA analysis and chloroplast data across the four known European species. Additionally, we conducted a comparative study of functional capitulum traits, predispersal fruit predation, and associated entomofauna for the newly discovered population and nearby A. minus populations. RESULTS: The discovered population constitutes a floristic novelty for the region and is identified as A. tomentosum, exhibiting signatures of past introgression from A. minus, as indicated by cytonuclear discordance. We evaluated three alternative scenarios to explain its origin: (i) persistence as a relict from a previously wider distribution, (ii) long-distance pollination by migrating insects, and (iii) long-distance seed dispersal from an A. tomentosum population with a history of past introgression. Of these, only the third is consistent with the available evidence. These results highlight the complexity of interpreting disjunct species distributions and underscore the value of integrative approaches for resolving population identity, origin, dispersal, and persistence across environments.

Arctium↗
PubMed1980

Correlation of the growth of Chinese hamster V279-17lb multicellular spheroids with cytokinetic parameters.

The volumes of Chinese hamster V279-17lb multicellular spheroids grown in spinner culture were measured and correlated to DNA distribution and cell volume distribution information. Spheroid growth curves were obtained over a 21-day period using both electronic cell volume measurements and microscope micrometer sizing. The spheroids were collected from the aperture tube after electronic sizing, and single cell suspensions were prepared via trypsinization. Saline-washed cells were then stained with mithramycin and analyzed as unfixed or ethanol-fixed cells for both cell volume and DNA fluorescence measurements. Spheroid growth was determined to have an initial 8- to 9-day rapid growth phase, and a slow phase from 10 to 21 days. The single cell volume distributions of cells obtained from spheroids were dependent on spheroid volume and the relative proportions of small volume noncycling cells to large volume cycling cells comprising the spheroids were also dependent on spheroid volume. DNA distribution data and dual parameter DNA distribution cell volume contour patterns obtained for single cells dissociated from spheroids were closely related to the measured spheroid volume and revealed that the fraction of small, hypoxic G0-like cells was greatest in old, large spheroids.

Animals↗