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At least 1,063 records · Page 59Linked to original sources
PubMed1995

Cellular adaptation to chronic cadmium exposure: intracellular localization of metallothionein protein in human trophoblast cells (JAr).

Trophoblast cells are the first embryonic cells that modulate the transfer of a variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal to the fetal circulation in the human placenta. Human placental exposure to the toxic metal, cadmium (Cd) results in a decrease in the production of human chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to adapt to exposure to the toxic metal Cd has been considered crucial. In this study, the expression and intracellular localization of metallothionein (MT), a small molecular weight, metal binding protein, was examined in trophoblast cells (JAr) grown in normal media and in cells exposed chronically (6 months) to 2 microM CdCl2. Conventional and confocal fluorescence microscopy were used to examine the intracellular localization of MT protein in control cells and cells grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily perinuclear with low level, punctate expression in the cytosol. Following both chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3-fold in both chronic and acute exposures) and the protein was now concentrated inside the nucleus with a lacy, cytoskeletal pattern of expression in the cytosol. To determine if the nuclear accumulation of MT protein was dependent on new protein synthesis, control cells were exposed to CdCl2 (2 microM) and cycloheximide (2 micrograms/. ml) for 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cadmium↗
PubMed2005

Opioid receptor-like 1 (NOP) receptors in the rat dorsal raphe nucleus: evidence for localization on serotoninergic neurons and functional adaptation after 5,7-dihydroxytryptamine lesion.

A high density of opioid receptor-like 1 (ORL1) receptor (also referred to as NOP receptor) is found in limbic areas and in regions containing monoamines, which are implicated in emotional activity and physiopathology of depression and anxiety. We aimed at defining precisely the localization of ORL1 receptors in dorsal raphe nucleus, by means of a lesion strategy and autoradiographic studies. In control rats, [3H]nociceptin and nociceptin-stimulated [35S]GTPgammaS bindings were found to be correlated in several brain regions. We performed in rats a selective destruction of serotoninergic neurons by surgical stereotaxic injection of 5,7-dihydroxytryptamine (5,7-DHT) in dorsal raphe nucleus. This led to a marked decrease in serotonin contents in striata and frontal cortices (about -60%) and in autoradiographic [3H]citalopram binding in posterior regions. In dorsal raphe nucleus, [3H]nociceptin binding was decreased to the same extent as [3H]citalopram binding, whereas it was unchanged in the other regions studied. Nevertheless, in the dorsal raphe, nociceptin-stimulated [35S]GTPgammaS binding was decreased to a lesser extent than [3H]nociceptin binding in 5,7-DHT-lesioned rats. The ratio between nociceptin-stimulated [35S]GTPgammaS binding and [3H]nociceptin binding was significantly increased in 5,7-DHT-lesioned rats compared with controls in this region. These data demonstrate 1) that ORL1 receptors are located on serotoninergic neurons in the dorsal raphe nucleus and 2) that, after a lesion, the functionality of remaining ORL1 receptors appears to be up-regulated, which could correspond to a compensatory mechanism.

5,7-Dihydroxytryptamine↗
PubMed2005

Introduction of standardised emergency department paediatric asthma clinical guidelines into a general metropolitan hospital.

'Aiming for Asthma Improvement in Children' is a South East Sydney Area Health Service (SESAHS) initiative. It is funded by the Commonwealth Government, under the Chronic & Complex Care Programmes, which is linked to New South Wales (NSW) Government Action Plan. One specific objective of the programme is to implement standardised paediatric asthma guidelines across the Emergency Departments of an area tertiary and local area hospitals. This paper will focus on the process of piloting, implementing and evaluating the guidelines into one local area hospital within SESAHS. SESAHS includes Sydney Children's Hospital, Randwick, a major paediatric referral and tertiary teaching hospital in Sydney. The paediatric asthma clinical practice guidelines (CPG) were developed, piloted and disseminated from Sydney Children's Hospital, Randwick, for local implementation and adaptation. The successful introduction of these guidelines at the local hospital promoted evidence-based practice and reduced the admission rate for children with asthma.

Adolescent↗
PubMed2000

A novel adapter protein employs a phosphotyrosine binding domain and exceptionally basic N-terminal domains to capture and localize an atypical protein kinase C: characterization of Caenorhabditis elegans C kinase adapter 1, a protein that avidly binds protein kinase C3.

Atypical protein kinase C isoforms (aPKCs) transmit regulatory signals to effector proteins located in the cytoplasm, nucleus, cytoskeleton, and membranes. Mechanisms by which aPKCs encounter and control effector proteins in various microenvironments are poorly understood. By using a protein interaction screen, we discovered two novel proteins that adapt a Caenorhabditis elegans aPKC (PKC3) for specialized (localized) functions; protein kinase C adapter 1 (CKA1, 593 amino acids) and CKA1S (549 amino acids) are derived from a unique mRNA by alternative utilization of two translation initiation codons. CKA1S and CKA1 are routed to the cell periphery by exceptionally basic N-terminal regions that include classical phosphorylation site domains (PSDs). Tethering of PKC3 is mediated by a segment of CKA1 that constitutes a phosphotyrosine binding (PTB) domain. Two aromatic amino acids (Phe(175) and Phe(221)) are indispensable for creation of a PKC3-binding surface and/or stabilization of CKA1.aPKC complexes. Patterns of CKA1 gene promoter activity and CKA1/CKA1S protein localization in vivo overlap with patterns established for PKC3 expression and distribution. Transfection experiments demonstrated that CKA1/CKA1S sequesters PKC3 in intact cells. Structural information in CKA1/CKA1S enables delivery of adapters to the lateral plasma membrane surface (near tight junctions) in polarized epithelial cells. Thus, a PTB domain and PSDs collaborate in a novel fashion in CKA1/CKA1S to enable tethering and targeting of PKC3. Avid ligation of a PKC isoform is a previously unappreciated function for a PTB module.

Adaptor Proteins, Signal Transducing↗
PubMed1995

A model for practice guideline adaptation and implementation: empowerment of the physician.

The Medical Center model of practice guideline adaptation and implementation uses local clinical leaders to evaluate nationally endorsed guidelines, adapt those guidelines for use in the local setting, work with support staff to develop and apply methods for guideline implementation, and assist the evaluation of clinical practice and outcomes data. The model described here combines the guideline dissemination techniques of clinical leadership, implementation, and data support and feedback. This model overcomes the failures of previous models by incorporating local physician involvement during every step of practice guideline selection, adaptation, implementation, and evaluation, and by supporting the physician leaders with quality data, resources to support guideline implementation, and outcomes assessment and feedback.

Feedback↗
PubMed1951

Localization of adrenocorticotropic hormone by histochemical and immunochemical methods.

The fluorescent antibody technique was adapted to the localization of native protein antigens in cells and tissues. This method was applied specifically to the localization of adrenocorticotropic hormone in the pituitary gland. An antiserum to hog ACTH was produced in an adrenalectomized rabbit. The gamma(2)-globulin fraction of the serum was conjugated with fluorescein. After purification, the fluorescent antibody solution stained selectively the cytoplasm of basophil cells of the hog pituitary. No cells of sheep or beef pituitary or of hog kidney were stained. A fluorescent globulin solution prepared from normal rabbit serum gave no selective staining in any of these tissues. Immunochemical tests showed that the fluorescent antibody gave a precipitin reaction with a highly active ACTH preparation of low molecular weight. The supernatant solution from this reaction showed a loss of hormone activity.

Adrenocorticotropic Hormone↗
PubMed1980

Uptake of horseradish peroxidase of sensory terminals of lamellated corpuscles in mouse foot pads.

Uptake of horseradish peroxidase (HRP) by sensory axon terminals was studied in lamellated corpuscles of mouse plantar foot pads after i.v. and local s.c. HRP injections. The corpuscles, considered to be rapidly adapting mechanoreceptors, are localized in dermal papillae and have discoid axon terminals enclosed in 1-5 lamellae of lamellar cells. The injected HRP diffused into interlamellar and adaxonal clefts and was taken up by sensory terminals, being incorporated in coated pits and coated vesicles formed by the axolemma. The tracer further appeared in the axoplasm in smooth vesicles, multivesicular bodies, and vacuoles. Similar incorporation of HRP into vesicles, inclusion bodies, and vacuoles was observed in the lamellae and perinuclear cytoplasm of lamellar cells. Vibratory stimulation considered to be adequate for this type of mechanoreceptors did not result in any perceptible increase in HRP uptake by sensory terminals. It is suggested that endocytosis by sensory terminals may serve for incorporation of regulatory macromolecules that presumably mediate information to the perikaryon about conditions of the distant terminals and their microenvironment.

Animals↗
PubMed2000

Global motion adaptation.

Image motion is initially detected locally. Local motion signals are then integrated across space in order to specify the global motion of objects or surfaces. It is well known that prolonged exposure to motion causes adaptation at the local motion level. We have investigated whether adaptation also occurs at the global motion level. We have devised a global motion stimulus (a random dot kinematogram) which has equal motion energy in opposite directions but nonetheless gives rise to global motion perception. At the local motion level, adaptation to this stimulus should cause equal adaptation in both directions and should not give rise to an aftereffect. Any aftereffect seen must therefore be attributable to adaptation at the global motion level. We find that following adaptation to this stimulus, judgements of the perceived direction of a test pattern are systematically biased towards the direction opposite to the adapting direction, suggesting that adaptation does occur at a level of visual processing at which global motion is represented.

Adaptation, Physiological↗
PubMed1981

[Local cerebral consumption of glucose in the mouse. Adaptation of the 14C deoxyglucose method to free-moving small mammals].

Local cerebral glucose utilisation (LCGU) was measured with the [14C] deoxyglucose ([14C] DG) method in the awake, free moving Mouse. Values vary from 112 mumoles. 100 g-1. min.-1 in the superior colliculus, the most active structure, to 22 mumoles. 100 g-1. min.-1 in the internal capsule. Glucose consumption is high in fasciculus retroflexus, a result peculiar to the Mouse when compared to the other Mammals were studied so far with this method. The modifications in plasma sampling proposed in this paper should facilitate the use of the [14C] DG method in free moving animals as small as the Mouse, and allow for study of the effects of behavior on local cerebral energy consumption.

Animals↗
PubMed1986

Ultrastructural localization of laminin in rat sensory ganglia.

We adapted immunocytochemical methods for localization of laminin to examine its disposition in neural tissue at the ultrastructural level. In dorsal root ganglia, laminin was found in basal laminae of the satellite and Schwann cells ensheathing neuronal perikarya and nerve fibers, respectively, and around blood vessels. Within the basal lamina, the immunostain was found in the lamina lucida and lamina densa. Occasional immunostained coated pits were identified in satellite and Schwann cells, but virtually no intracellular label was seen even in freeze-thawed/detergent-permeabilized specimens. In the perineurium, only the basal lamina of the inward-facing surface of the inner-most cell layer was usually stained.

Animals↗
PubMed2006

Locally weighted interpolating growing neural gas.

In this paper, we propose a new approach to function approximation based on a growing neural gas (GNG), a self-organizing map (SOM) which is able to adapt to the local dimension of a possible high-dimensional input distribution. Local models are built interpolating between values associated with the map's neurons. These models are combined using a weighted sum to yield the final approximation value. The values, the positions, and the "local ranges" of the neurons are adapted to improve the approximation quality. The method is able to adapt to changing target functions and to follow nonstationary input distributions. The new approach is compared to the radial basis function (RBF) extension of the growing neural gas and to locally weighted projection regression (LWPR), a state-of-the-art algorithm for incremental nonlinear function approximation.

Algorithms↗
PubMed2006

Automated localization of magnetoencephalographic interictal spikes by adaptive spatial filtering.

OBJECTIVE: Automated adaptive spatial filtering techniques can be applied to magnetoencephalographic (MEG) data collected from people with epilepsy. Source waveforms estimated by these methods have higher signal-to-noise ratio (SNR) than spontaneous MEG data, allowing identification and location of interictal spikes. The software tool SAM(g(2)) provides an adaptive spatial filtering algorithm for MEG data that yields source images of excess kurtosis and provides source time-courses in voxels exhibiting high excess kurtosis. The sensitivity and specificity of SAM(g(2)) in epilepsy is unknown. METHODS: Interictal MEG data from 36 patients with intractable epilepsy were analyzed using SAM(g(2)), and results compared with equivalent current dipole (ECD) fit procedures. RESULTS: When SNR of interictal spikes was high (compared to background) with a clear single focus, in most cases there was good agreement between ECD and SAM(g(2)). With multiple foci, there was typically overlap but imperfect concordance between results of ECD and SAM(g(2)). CONCLUSIONS: SAM(g(2)) may in some cases be equivalent to manual ECD fit for localizing interictal spikes with single locus and good SNR. Further studies are required to validate SAM(g(2)) with multiple foci or poor SNR. SIGNIFICANCE: In some cases, SAM(g(2)) might eventually assist or replace manual ECD analysis of MEG data.

Algorithms↗
PubMed2000

Adaptive changes in M1 muscarinic receptors localized to specific rostral brain regions during and after morphine withdrawal.

Morphine-dependent rats were allowed to undergo withdrawal by abrupt discontinuation of the drug. The regional expression of brain M1 muscarinic receptors was measured directly by autoradiographic determination with [(3)H] pirenzepine, and indirectly by quantifying the relative levels of M1 mRNA encoding the receptor protein. Patterns of receptor changes after morphine treatment were in general agreement using the two methods. Frontal cortical samples derived from morphine-dependent rats exhibited a 28% increase in M1 receptor mRNA measured at the end of the infusion. At the peak of the withdrawal, M1 mRNA levels for dependent rats were much lower (33.4%) than those for control rats. Hippocampal samples derived from morphine-dependent rats exhibited no changes in M1 mRNA levels after the morphine infusion. During the peak of withdrawal, however, hippocampal M1 mRNA levels were reduced (57%) compared with levels for controls. The M1 mRNA levels remained at this reduced degree of expression even after withdrawal symptoms had subsided. Addition of diisopropylflurophophate (DFP) to the morphine infusion schedule inhibited the adaptive changes in M1 mRNA levels induced by morphine. During the peak period of withdrawal, M1 mRNA levels in the hippocampus declined by only 18% as compared with 57% for the morphine control group. The adaptive decrease in hippocampal M1 receptors after withdrawal subsided may reflect prolonged heightened cholinergic activity in an area where such cholinergic innervation plays an important role in memory.

Animals↗
PubMed2002

Bivectorial transparent stimuli simultaneously adapt mechanisms at different levels of the motion pathway.

The motion aftereffect (MAE) to drifting bivectorial stimuli, such as plaids, is usually univectorial and in a direction opposite to the pattern direction of the plaid. This is true for plaids that are perceived as coherent, but also for other plaids which are seen as transparent for most or all of the adaptation period. The underlying mechanisms of this MAE are still not well understood. In order to assess these mechanisms further, we measured static and dynamic MAEs and their interocular transfer (IOT). Adaptation stimuli were plaids with small (coherent) and large (transparent) angles between the directions of the component gratings and a horizontal grating, which were adjusted in spatial frequency and drift velocity so that the pattern speed and vertical periodicity remained constant. Test stimuli were horizontal static or counterphasing gratings with the same periodicity as the adaptation stimuli. MAE duration was measured for monocular, binocular and IOT conditions. All static MAEs were smallest for the transparent plaid and largest for the grating, while all dynamic MAEs were constant across adaptation stimuli. IOT was twice as big for dynamic MAEs as for static MAEs, and did not vary with the adaptation stimuli. Other adaptation stimuli were plaids that differed in intersection luminance, contrast or spatial frequency, resulting in different amounts of perceived coherence. MAEs and IOT did not vary with perceived coherence. The results suggest that the MAE for bivectorial stimuli consists of low-level adaptation (dependent on local component properties, small IOT), as well as high-level adaptation (dependent on global integrated pattern properties, large IOT), which can be measured independently with static and dynamic test stimuli.

Adaptation, Ocular↗
PubMed1999

Spatial characteristics of the second-order visual pathway revealed by positional adaptation.

The visual system is thought to process luminance (first-order) and contrast (second-order) information by dedicated cortical streams. To explore the spatial characteristics of the second-order pathway, we examined the effect of adaptation on spatial localization in human subjects. We show that, unlike first-order adaptation, second-order positional adaptation via cortical mechanisms transfers across orientations but not across spatial frequencies. These results support physiological evidence that these two processing streams are distinct and suggest that the cortical mechanism mediating second-order positional adaptation maintains spatial frequency information but sums signals across orientations.

Adaptation, Ocular↗
PubMed1987

Towards a general theory of adaptive walks on rugged landscapes.

Adaptive evolution, to a large extent, is a complex combinatorial optimization process. In this article we take beginning steps towards developing a general theory of adaptive "walks" via fitter variants in such optimization processes. We introduce the basic idea of a space of entities, each a 1-mutant neighbor of many other entities in the space, and the idea of a fitness ascribed to each entity. Adaptive walks proceed from an initial entity, via fitter neighbors, to locally or globally optimal entities that are fitter than their neighbors. We develop a general theory for the number of local optima, lengths of adaptive walks, and the number of alternative local optima accessible from any given initial entity, for the baseline case of an uncorrelated fitness landscape. Most fitness landscapes are correlated, however. Therefore we develop parts of a universal theory of adaptation on correlated landscapes by adaptive processes that have sufficient numbers of mutations per individual to "jump beyond" the correlation lengths in the underlying landscape. In addition, we explore the statistical character of adaptive walks in two independent complex combinatorial optimization problems, that of evolving a specific cell type in model genetic networks, and that of finding good solutions to the traveling salesman problem. Surprisingly, both show similar statistical features, encouraging the hope that a general theory for adaptive walks on correlated and uncorrelated landscapes can be found. In the final section we explore two limits to the efficacy of selection. The first is new, and surprising: for a wide class of systems, as the complexity of the entities under selection increases, the local optima that are attainable fall progressively closer to the mean properties of the underlying space of entities. This may imply that complex biological systems, such as genetic regulatory systems, are "close" to the mean properties of the ensemble of genomic regulatory systems explored by evolution. The second limit shows that with increasing complexity and a fixed mutation rate, selection often becomes unable to pull an adapting population to those local optima to which connected adaptive walks via fitter variants exist. These beginning steps in theory development are applied to maturation of the immune response, and to the problem of radiation and stasis. Despite the limitations of the adaptive landscape metaphor, we believe that further development along the lines begun here will prove useful.

Adaptation, Biological↗
PubMed2005

Localization bias and spatial resolution of adaptive and non-adaptive spatial filters for MEG source reconstruction.

This paper discusses the location bias and the spatial resolution in the reconstruction of a single dipole source by various spatial filtering techniques used for neuromagnetic imaging. We first analyze the location bias for several representative adaptive and non-adaptive spatial filters using their resolution kernels. This analysis theoretically validates previously reported empirical findings that standardized low-resolution electromagnetic tomography (sLORETA) has no location bias. We also find that the minimum-variance spatial filter does exhibit bias in the reconstructed location of a single source, but that this bias is eliminated by using the normalized lead field. We then focus on the comparison of sLORETA and the lead-field normalized minimum-variance spatial filter, and analyze the effect of noise on source location bias. We find that the signal-to-noise ratio (SNR) in the measurements determines whether the sLORETA reconstruction has source location bias, while the lead-field normalized minimum-variance spatial filter has no location bias even in the presence of noise. Finally, we compare the spatial resolution for sLORETA and the minimum-variance filter, and show that the minimum-variance filter attains much higher resolution than sLORETA does. The results of these analyses are validated by numerical experiments as well as by reconstructions based on two sets of evoked magnetic responses.

Algorithms↗