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PubMed2002

Vascular patterning by Eph receptor tyrosine kinases and ephrins.

During vertebrate development, morphologically and functionally very different tissue types and organ systems need to be generated and organised in close coordination with each other. Blood vessels, which become critically required during early embryogenesis and remain indispensable throughout life, need to integrate into a great diversity of tissue types and adapt to both local and systemic requirements of the organism. Far from being randomly placed and uniformly shaped tubes, blood vessels form, with some degree of flexibility, a highly organised and precisely arranged network. Their differentiation, ultrastructure and physiology are well adapted to the requirements and functions of the surrounding tissues. How coordinated development and differentiation are achieved at a molecular level remains to be characterised. This review highlights the large family of Eph receptor tyrosine kinases and their ligands, called ephrins, which, because of their versatile functions in many cell and tissue types and their molecular complexity, might well provide one example of a control system integrating blood vessel and tissue morphogenesis.

Animals↗
PubMed1992

Chromatic adaptation to natural and incandescent illuminants.

A color CRT image display system was used to present adapting backgrounds that were spatially and temporally varied. Three observers adjusted the chromaticity of test stimuli to produce an achromatic appearance under a variety of adapting conditions. The achromatic-appearing chromaticities were used as measures of the observers' states of chromatic adaptation. The spatial configuration of the adapting background was varied to measure the spatial extent of the mechanisms responsible for chromatic adaptation. The temporal configuration of the adapting background was varied to measure the time-course of these mechanisms. The results show that chromatic adaptation is spatially localized with a time-course on the order of 10 sec. Since the mechanisms were shown to be spatially localized, the observed temporal integration across eye movements is required to allow these mechanisms to adjust to the spatially integrated scene chromaticity.

Adaptation, Ocular↗
PubMed1995

Chromosomal localization of the mouse Src-like adapter protein (Slap) gene and its putative human homolog SLA.

Molecules containing Src-homology 2 (SH2) and Src-homology 3 (SH3) domains are critical components of signal transduction pathways that serve to relay signals originating from the cell surface to the interior of the cell. Src-like adapter protein (SLAP) is a recently described adapter protein that binds activated the Eck receptor protein-tyrosine kinase. Although SLAP bears a striking homology to the SH3 and SH2 domains of the Src family of nonreceptor tyrosine kinases, it does not contain a tyrosine kinase catalytic domain. In this report, the Slap gene was mapped by linkage analysis to mouse chromosome 15, while its putative human homolog (SLA) was identified and mapped to human 8q22.3-qter using a panel of somatic cell hybrids.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Dynamic changes in electrogram morphology at functional lines of block in reentrant circuits during ventricular tachycardia in the infarcted canine heart: a new method to localize reentrant circuits from electrogram features using adaptive template matching.

INTRODUCTION: Fractionated, low-amplitude or long-duration electrograms have limited specificity for locating reentrant circuits causing ventricular tachycardia (VT). In this study a new method is described, adaptive template matching (ATM), based on the quantification of beat-to-beat changes in electrograms, for locating functional reentrant circuits that are relatively stable and cause monomorphic VT. METHODS AND RESULTS: Monomorphic VTs were induced in 4-day-old infarcted canine hearts by programmed stimulation and reentrant circuits mapped in the epicardial border zone with a 196 or 312 bipolar electrode array. For ATM analysis, a template electrogram from each electrode, during an early cycle, was matched with all subsequent (input) electrograms at the same site by weighting the inputs of amplitude, duration, average baseline, and phase lag. The mean square error (MSE) between template and input was the criterion used to adapt the weights, and was also a measure of changes in electrogram shape that occur from cycle to cycle. The variance of each of the weighting parameters at all electrode sites were plotted on a representation of the electrode array, and the location of the functional lines of block bounding the central common pathway of reentrant circuits with figure-of-eight characteristics, overlaid on the ATM map. Peaks of high variance were found to be coincident with functional lines of block during all tachycardia episodes. CONCLUSION: Specific beat-to-beat changes in electrograms occur at functional lines of block in reentrant circuits that can be quantified by ATM analysis, suggesting that these regions might be located without activation mapping. The method might be useful to guide ablation catheter position.

Animals↗
PubMed1986

Adaptation of fetal pulmonary blood flow to local infusion of tolazoline.

Although tolazoline is the most commonly used drug in the treatment of neonatal pulmonary hypertension, its mode of action and efficacy remain incompletely understood. In order to study the effects of tolazoline on a high resistance pulmonary circulation and to better understand mechanisms that control pulmonary vascular tone and reactivity in the fetus, we infused tolazoline either continuously or as bolus into the left pulmonary artery of 15 chronically instrumented, normoxic fetal lambs during late gestation. The vasodilatory effects of bolus injections of tolazoline (2.5 mg) were inhibited by the prior administration of the histaminergic receptor blockers, cimetidine (56%), diphenhydramine (56%), or both (100%). During the continuous infusion of tolazoline (4.5 mg/h for 9 min), pulmonary blood flow to the left lung increased from 61 +/- 6 ml/min (mean +/- SE; control) to 100 +/- 10 (peak) at 30 min (p less than 0.001). However, following this initial vasodilatation, pulmonary blood flow steadily decreased toward control values by 90 min, despite the continued infusion of tolazoline (p less than 0.001). Although the calcium channel blocker, verapamil, and the alpha-adrenergic blocker, phentolamine, had little effect on fetal pulmonary blood flow when infused alone, both drugs increased the vasodilatory response to tolazoline (p less than 0.001). We conclude that tolazoline effects pulmonary vasodilatation by a histaminergic mechanism and that subsequent refractoriness to the drug is a calcium-dependent process which may be partially mediated by an alpha-adrenergic mechanism.

Animals↗
PubMed2004

Adaptation varies through space and time in a coevolving host-parasitoid interaction.

One of the central challenges of evolutionary biology is to understand how coevolution organizes biodiversity over complex geographic landscapes. Most species are collections of genetically differentiated populations, and these populations have the potential to become adapted to their local environments in different ways. The geographic mosaic theory of coevolution incorporates this idea by proposing that spatial variation in natural selection and gene flow across a landscape can shape local coevolutionary dynamics. These effects may be particularly strong when populations differ across productivity gradients, where gene flow will often be asymmetric among populations. Conclusive empirical tests of this theory have been particularly difficult to perform because they require knowledge of patterns of gene flow, historical population relationships and local selection pressures. We have tested these predictions empirically using a model community of bacteria and bacteriophage (viral parasitoids of bacteria). We show that gene flow across a spatially structured landscape alters coevolution of parasitoids and their hosts and that the resulting patterns of adaptation can fluctuate in both space and time.

Adaptation, Physiological↗
PubMed2004

Principal components analysis competitive learning.

We present a new neural model that extends the classical competitive learning by performing a principal components analysis (PCA) at each neuron. This model represents an improvement with respect to known local PCA methods, because it is not needed to present the entire data set to the network on each computing step. This allows a fast execution while retaining the dimensionality-reduction properties of the PCA. Furthermore, every neuron is able to modify its behavior to adapt to the local dimensionality of the input distribution. Hence, our model has a dimensionality estimation capability. The experimental results we present show the dimensionality-reduction capabilities of the model with multisensor images.

Algorithms↗
PubMed1995

Intestinal B-cell isotype response in relation to local bacterial load: evidence for immunoglobulin A subclass adaptation.

BACKGROUND & AIMS: In experimental animals, the indigenous microbiota modulates mucosal immunity. In humans, such direct evidence is scarce. The aim of this study was to examine the effect of intestinal bacteria on the local immunoglobulin (Ig) response. METHODS: The numbers of IgA-, IgM-, and IgG-producing immunocytes per defined mucosal length unit were determined, and the local IgA subclass response was studied using immunohistochemistry in jejunal segments from adults with bacterial overgrowth and in sterile ileal urinary conduits from children. RESULTS: The ileal bladder mucosa showed atrophy, but the number of immunocytes only tended to be decreased. The jejunal segments with bacterial overgrowth showed minor histological changes; the numbers of IgA and IgG immunocytes were fairly normal, whereas the number of IgM immunocytes was significantly reduced (P < 0.05) (12 cells/U) compared with control mucosa (24 cells/U). The number of IgA2 immunocytes was significantly decreased (P < 0.01) in ileal conduits (7 cells/U or 30% of total IgA) but increased (P < 0.05) in jejunal segments with bacterial overgrowth (42 cells/U or 43% of total IgA) compared with normal ileum (15 cells/U or 40% of total IgA) and jejunum (24 cells/U or 23% of total IgA). CONCLUSIONS: An association exists between bacterial load and IgA subclass production. An increase in IgA2 may enhance mucosal protection and probably reflects immunomodulation caused by lipopolysaccharides.

Adolescent↗
PubMed1999

Development and application of a generic methodology to assess the quality of clinical guidelines.

BACKGROUND: Despite clinical guidelines penetrating every aspect of clinical practice and health policy, doubts persist over their ability to improve patient care. We have designed and tested a generic critical appraisal instrument, that assesses whether developers have minimized the biases inherent in creating guidelines, and addressed the requirements for effective implementation. DESIGN: Thirty-seven items describing suggested predictors of guideline quality were grouped into three dimensions covering the rigour of development, clarity of presentation (including the context and content) and implementation issues. The ease of use, reliability and validity of the instrument was tested on a national sample of guidelines for the management of asthma, breast cancer, depression and coronary heart disease, with 120 appraisers. A numerical score was derived to allow comparison of guidelines within and between diseases. RESULTS: The instrument has acceptable reliability (Cronbach's alpha coefficient, 0.68-0.84; intra-class correlation coefficient, (0.82-0.90)). The results provided some evidence of validity (Pearson's correlation coefficient between appraisers' dimension scores and their global assessment was 0.49 for dimension one, 0.63 for dimension two and 0.40 for dimension three). The instrument could differentiate between national and local guidelines and was easy to apply. There was variation in the performance of guidelines with most not achieving a majority of criteria in each dimension. CONCLUSIONS: Use of this instrument should encourage developers to create guidelines that reflect relevant research evidence more accurately. Potential users or groups adapting guidelines for local use could apply the instrument to help decide which one to follow. The National Health Service Executive is using the instrument to assist in deciding which guidelines to recommend to the UK National Health Service. This methodology forms the basis of a common approach to assessing guideline quality in Europe.

Evaluation Studies as Topic↗
PubMed2000

The practice of community development approaches in heart health promotion.

There has been a recent shift in public health policy towards population-based approaches to the reduction of cardiovascular disease. This shift has been accompanied by a re-examination of strategies appropriate to the goal. Often, community development approaches, designed to affect socio-environmental change, are suggested as the most appropriate strategy for affecting community-wide change. Despite the fact that community development approaches have been used by several of the major community-based heart health initiatives, evidence of their use and usefulness remains sparse. This paper presents the findings of a qualitative study of the factors (i.e. community context, facilitators, barriers) affecting the use of community development approaches to heart health promotion in Ontario, Canada. Key informant interviews (n = 30) were conducted with stake-holders representing voluntary agencies, community health providers, boards of education and local coalitions in eight of the 42 health unit areas across Ontario. The qualitative analysis reveals (1) that the use of comprehensive community development approaches is limited and (2) that community agencies typically employ elements of community development approaches (e.g. community organization, community-based), often in combination and adapted to suit local conditions. The resulting landscape of community development approaches is characterized by a continuum of collaborative practices indicating that no one type of community approach is appropriate for all initiatives and in all communities. Therefore, from a programmatic perspective, it may not be realistic to advocate community development as the goal to which all communities should strive.

Attitude to Health↗
PubMed1975

Coronary arteries in infants up to the age of ten years. I. Chronology of adaptive intimal changes.

In the coronary arteries of old fetuses the presence of musculo-elastic and elastic hyperplastic layers was firstly detected in the branching pads of aortic ostia and the emergence of the left anterior descending branch. These layers appeared constantly more developed in the left than in the right coronary bed. During the first six months of the extrauterine life the coalescence of pads revealed a passage from localized to diffuse adaptive changes in the main branching sites and in their immediate vicinity. Then, in the first decade of life, a progressive extension of the musculo-elastic and elastic hyperplastic layers was observed, leading to the well known aspect of diffuse intimal thickening.

Age Factors↗
PubMed2006

Experimental evolution of resistance in Paramecium caudatum against the bacterial parasite Holospora undulata.

Host-parasite coevolution is often described as a process of reciprocal adaptation and counter adaptation, driven by frequency-dependent selection. This requires that different parasite genotypes perform differently on different host genotypes. Such genotype-by-genotype interactions arise if adaptation to one host (or parasite) genotype reduces performance on others. These direct costs of adaptation can maintain genetic polymorphism and generate geographic patterns of local host or parasite adaptation. Fixation of all-resistant (or all-infective) genotypes is further prevented if adaptation trades off with other host (or parasite) life-history traits. For the host, such indirect costs of resistance refer to reduced fitness of resistant genotypes in the absence of parasites. We studied (co)evolution in experimental microcosms of several clones of the freshwater protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. After two and a half years of culture, inoculation of evolved and naive (never exposed to the parasite) hosts with evolved and founder parasites revealed an increase in host resistance, but not in parasite infectivity. A cross-infection experiment showed significant host clone-by-parasite isolate interactions, and evolved hosts tended to be more resistant to their own (local) parasites than to parasites from other hosts. Compared to naive clones, evolved host clones had lower division rates in the absence of the parasite. Thus, our study indicates de novo evolution of host resistance, associated with both direct and indirect costs. This illustrates how interactions with parasites can lead to the genetic divergence of initially identical populations.

Animals↗
PubMed2003

Temporal and spatial variations of gyne production in the ant Formica exsecta.

Social insects have become a general model for tests of sex allocation theory. However, despite tremendous interest in the topic, we still know remarkably little about the factors that cause dramatic differences in sex allocation among local populations. A number of studies have suggested that environmental factors may influence sex allocation in ant populations. In polygynous (multiple queens per nest) populations of the ant Formica exsecta, sex allocation is extremely male biased at the population level, with only a small proportion of nests producing any gynes (female reproductive brood). We analysed the proportion of gyne-producing nests in 12 F. exsecta populations during three successive breeding seasons and found considerable temporal and spatial variability in the proportion of gyne-producing nests. The populations differed in a number of characteristics, including elevation, nest density, size of the nest mound, and number of nests per population. However, the proportion of gyne-producing nests was not associated with any of these geographic and demographic variables. Moreover, differences between populations in the production of gynes were not consistent between years. Thus, the proportion of gyne-producing nests appears to vary stochastically, perhaps because of stochastic variations in environmental factors. For example, year-to-year variations in the proportion of gyne-producing nests were associated with differences in spring weather conditions between years. The finding that gyne production varies greatly between years suggests that it may not always be adaptive at a local scale.

Adaptation, Physiological↗
PubMed2006

Prolonged dark adaptation changes connexin expression in the mouse retina.

In the retina, ambient light levels influence the cell coupling provided by gap junction (GJ) channels, to compensate the visual function for various lighting conditions. However, the effects of ambient light levels on expression of connexins (Cx), the proteins that form the GJ channels, are poorly understood. In the present study, we first determined whether gene expression of specific Cx (Cx26, Cx31.1, Cx36, Cx37, Cx40, Cx43, Cx45, Cx50, and Cx57) was affected by prolonged dark adaptation. Cx mRNA relative levels were determined in mouse retinas dark adapted for 3 hr, 1 day, and 7 days by using quantitative real-time PCR. Transcript levels of some Cx were repressed after 3 hr (Cx57), 1 day (Cx45), or 7 days (Cx36 and Cx43) of dark adaptation; others were increased after 1 day (Cx50) or 7 days (Cx31.1 and Cx37); and two of them (Cx26 and Cx40) were not significantly altered. The second aim was to determine whether prolonged dark adaptation affects protein expression of two important Cx in retina: neuronal Cx36 and glial Cx43. We were able to demonstrate that important changes in protein distribution and expression also took place in retina during long-term dark adaptation. Given their localization, the specific alterations in Cx expression may reflect their distinct response to ambient light levels.

Animals↗
PubMed1987

Pathophysiology of intestinal uptake and absorption of antigens in food allergy.

An important adaptation of the gastrointestinal tract to the extrauterine environment is its development of a mucosal barrier against the penetration of proteins and protein fragments. To combat the potential danger of invasion across the mucosal barrier, the infant must develop within the lumen and on the luminal mucosal surface an elaborate system of defense mechanisms that act to control and maintain the epithelium as an impermeable barrier to the uptake of macromolecular antigens. These defenses include a unique local immunologic system adapted to function in the complicated milieu of the intestine as well as other nonimmunologic processes such as a gastric barrier, intestinal surface secretions, peristaltic movement, etc, all of which help to provide maximum protection for the intestinal surface. Unfortunately, during the immediate postpartum period, especially for premature and "small-for-date" infants, this elaborate local defense system is incompletely developed. As a result of the delay in the maturation of the mucosal barrier, newborn infants are particularly vulnerable to pathologic penetration by harmful intraluminal substances. The consequences of altered defense are susceptibility to infection and the potential for hypersensitivity reactions and the formation of immune complexes. With these reactions comes the potential for developing life-threatening diseases such as necrotizing enterocolitis, sepsis, and hepatitis. Fortunately, nature has provided a means for passively protecting the "vulnerable" newborn against the dangers of a deficient intestinal defense system: human milk. It is now increasingly apparent that human milk contains not only antibodies and viable leukocytes, but many other substances that can interfere with bacterial colonization and prevent antigen penetration.

Antigens↗
PubMed1998

[Treatment of urinary infections in children. Pharmaco-economic aspects].

The risk factors for urinary tract infections in children are the young age, the severe febrile symptoms, any obstruction or dilatation of the urinary tract, recurrent episodes of acute disease and delay in initiating effective treatment. Today a new risk factor lies in the increasing resistance of germs to usually used antibiotics. The treatment therefore must be adapted to the local patterns of bacterial sensitives. To lower cost of the therapy, different ways may be followed: 1. To try to reduce the time of the inpatient management by using day-care or outpatient management possibilities. 2. To try to switch from the initial, heavy parenteral drugs to antibiotics to which the germ is sensitive and even to an adapted oral medication, when the child is doing well, is well hydrated and can tolerate the treatment. The outpatient management requires more compliance from the child and may be a burden for the parents.

Acute Disease↗