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Immunohistochemical localization of gamma-aminobutyric acid in the rat pituitary gland and related hypothalamic regions.

The distribution of gamma-aminobutyric acid (GABA) containing neurons in the rat pituitary gland and related hypothalamic areas was immunohistochemically investigated using antibodies raised against GABA conjugated to bovine serum albumin by glutaraldehyde. A dense network of GABA-like immunoreactive fine varicose nerve fibers was observed within the posterior and intermediate lobes of the pituitary gland, surrounding endocrine cells and capillaries, but not in the anterior lobe. In the pituitary stalk, the dense varicose fibers ran along the anterior wall of the posterior lobe into the posterior and intermediate lobes. A small number of GABA-like immunoreactive cell bodies were evident in the intermediate lobe. GABA-like immunoreactive fibers occurred at low to high density in most parts of the hypothalamus. GABA-like immunoreactive neurons were observed in some regions related to the pituitary gland (such as periventricular nucleus, paraventricular nucleus, arcuate nucleus and accessory magnocellular nucleus). These results provide morphological evidence for the presence of GABAergic neurons in the rat hypothalamo-pituitary system.

Animals↗

Nerve fibres of the endolymphatic sac: electronmicroscopic findings in the Mongolian gerbil.

The presence of separate bundles of nerve fibres in the gerbilline endolymphatic sac (ES) is described, paying particular attention to their ultrastructure and localization. One bundle, localized in the area of the subepithelium which separates the sigmoid sinus from the ES, is composed only of myelinated fascicles which, moreover, seem to have an isolated contact with the ES area. Other two single nerve fibres, much smaller in caliber, are localized in the ES subepithelium and laterally to the ES area, still close to the sigmoid sinus. These fibres, composed of myelinated and unmyelinated fascicles, seem to have a rather longitudinal orientation and, moreover, contract close relationships with the rich vascular network of the ES subepithelial tissue. As far as the course is concerned, the serial sectioning technique would suggest that the nerve fibres get very close to the ES epithelial cell layer, going proximal to distal. Speculations on the origin of this nerve contingent in the ES are proposed and discussed in view of possible new theories for pathogenesis and therapy of some inner ear diseases.

Animals↗

Visual areas involved in the perception of human movement from dynamic form analysis.

The perception of biological motion combines the analysis of form and motion. However, patient observations by Vaina et al. and psychophysical experiments by Beintema and Lappe showed that humans could perceive human movements (a walker) without local image motion information. Here, we examine the specificity of brain regions responsive to a biological motion stimulus without local image motion, using functional magnetic resonance imaging. We used the stimulus from Beintema and Lappe and compared the brain activity with a point-light display that does contain local motion information and was often used in previous studies. Recent imaging studies have identified areas sensitive to biological motion in both the motion-processing and the form-processing pathways of the visual system. We find a similar neuronal network engaged in biological motion perception, but more strongly manifested in form-processing than in motion-processing areas, namely, fusiform-/occipital face area and extrastriate body area.

Adult↗

Regional interactions between thermosensitive neurons in diencephalic slices.

Rat brain slices were used to investigate regional interactions between thermosensitive neurons in different diencephalic regions. Horizontal tissue slices rested over three thermodes. This permitted independent thermal stimulation of rostral, middle, and caudal regions. Thermocouples measured tissue temperatures in these three locations, and extracellular recordings measured neuronal responses to temperature changes both locally (at the site of the recorded neuron) and in remote regions of the slice. Many of the neurons that were sensitive to remote temperatures were located near the lateral border of the diencephalic nuclei, especially in the perifornical area. All neurons displaying remote thermosensitivity also displayed local thermosensitivity. These neurons usually showed opposite responses to remote and local temperatures; i.e., most of these neurons were locally warm sensitive but showed cold sensitivity to remote temperatures. These findings indicate that thermosensitive synaptic networks extend throughout the diencephalon and may explain the effect of temperature on a variety of homeostatic systems.

Animals↗

Correlated discharges among putative pyramidal neurons and interneurons in the primate prefrontal cortex.

Neurophysiological recordings have revealed that the discharges of nearby cortical cells are positively correlated in time scales that range from millisecond synchronization of action potentials to much slower firing rate co-variations, evident in rates averaged over hundreds of milliseconds. The presence of correlated firing can offer insights into the patterns of connectivity between neurons; however, few models of population coding have taken account of the neuronal diversity present in cerebral cortex, notably a distinction between inhibitory and excitatory cells. We addressed this question in the monkey dorsolateral prefrontal cortex by recording neuronal activity from multiple micro-electrodes, typically spaced 0.2-0.3 mm apart. Putative excitatory and inhibitory neurons were distinguished based on their action potential waveform and baseline discharge rate. We tested each pair of simultaneously recorded neurons for presence of significant cross-correlation peaks and measured the correlation of their averaged firing rates in successive trials. When observed, cross-correlation peaks were centered at time 0, indicating synchronous firing consistent with two neurons receiving common input. Discharges in pairs of putative inhibitory interneurons were found to be significantly more strongly correlated than in pairs of putative excitatory cells. The degree of correlated firing was also higher for neurons with similar spatial receptive fields and neurons active in the same epochs of the behavioral task. These factors were important in predicting the strength of both short time scale (<5 ms) correlations and of trial-to-trial discharge rate covariations. Correlated firing was only marginally accounted for by motor and behavioral variations between trials. Our findings suggest that nearby inhibitory neurons are more tightly synchronized than excitatory ones and account for much of the correlated discharges commonly observed in undifferentiated cortical networks. In contrast, the discharge of pyramidal neurons, the sole projection cells of the cerebral cortex, appears largely independent, suggesting that correlated firing may be a property confined within local circuits and only to a lesser degree propagated to distant cortical areas and modules.

Animals↗

[Neural pathways--neural networks].

During the past two decades, the introduction of several modern neuroanatomical approaches resulted in a rapidly growing body of informations about neuronal pathways in the central nervous system. Several new neuronal connections between brain areas have been discovered, and the chemical nature (neurotransmitter content) of pathways has been determined by using highly specific neurochemical and immunohistochemical techniques. On the basis of these new informations, our knowledge and attitude to the general organization of neuronal connections have been changed substantially: 1. Neuronal pathways are multi-neuronal networks rather than simple chain of neurons, wherein informations are forwarded between two brain areas bidirectionally, meanwhile several additional brain regions are inter-connected by axon-collaterals. 2. A single neuronal cell may synthesize several neuropeptides which co-localized in and released from nerve terminals, and depending on the target sites they may act as neurotransmitters or neurohormones. In certain conditions, neuropeptides may also function as nerve growth factors by supporting the survival or the restitution of neuronal cells. 3. By the introduction of molecular imaging in neuroscience (visualization of oncogenes, specific mRNA's, etc), topographical studies on neuronal pathways are more and more completed by functional informations.

Brain↗

Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth factor-stimulated PC12 cells.

Neurite outgrowth is an important process in the formation of neuronal networks. Rac1 and Cdc42, members of the Rho-family GTPases, positively regulate neurite extension through reorganization of the actin cytoskeleton. Here, we examine the dynamic linkage between Rac1/Cdc42 and phosphatidylinositol 3-kinase (PI3-kinase) during nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Activity imaging using fluorescence resonance energy transfer probes showed that PI3-kinase as well as Rac1/Cdc42 was transiently activated in broad areas of the cell periphery immediately after NGF addition. Subsequently, local and repetitive activation of PI3-kinase and Rac1/Cdc42 was observed at the protruding sites. Depletion of Vav2 and Vav3 by RNA interference significantly inhibited both Rac1/Cdc42 activation and the formation of short processes leading to neurite outgrowth. At the NGF-induced protrusions, local phosphatidylinositol 3,4,5-trisphosphate accumulation recruited Vav2 and Vav3 to activate Rac1 and Cdc42, and conversely, Vav2 and Vav3 were required for the local activation of PI3-kinase. These observations demonstrated for the first time that Vav2 and Vav3 are essential constituents of the positive feedback loop that is comprised of PI3-kinase and Rac1/Cdc42 and cycles locally with morphological changes.

Animals↗

The evolutionary origin of the language areas in the human brain. A neuroanatomical perspective.

The capacity to learn syntactic rules is a hallmark of the human species, but whether this has been acquired by the process of natural selection has been the subject of controversy. Furthermore, the cortical localization of linguistic capacities has prompted some authors to suggest a modular representation of language in the brain. In this paper, we rather propose that the neural device involved in language is embedded into a large-scale neurocognitive network comprising widespread connections between the temporal, parietal and frontal (especially prefrontal) cortices. This network is involved in the temporal organization of behavior and motor sequences, and in working (active) memory, a sort of short-term memory that participates in immediate cognitive processing. In human evolution, a precondition for language was the establishment of strong cortico-cortical interactions in the postrolandic cortex that enabled the development of multimodal associations. Wernicke's area originated as a converging place in which such associations (concepts) acquired a phonological correlate. We postulate that these phonological representations projected into inferoparietal areas, which were connected to the incipient Broca's area, thus forming a working memory circuit for processing and learning complex vocalizations. As a result of selective pressure for learning capacity and memory storage, this device yielded a sophisticated system able to generate complicated utterances (precursors of syntax) as it became increasingly connected with other brain regions, especially in the prefrontal cortex. This view argues for a gradual origin of the neural substrate for language as required by natural selection.

Animals↗

Differentiation between nodules and end-on vessels using a convolution neural network architecture.

In recent years, many computer-aided diagnosis schemes have been proposed to assist radiologists in detecting lung nodules. The research efforts have been aimed at increasing the sensitivity while decreasing the false-positive detections on digital chest radiographs. Among the problems of reducing the number of false positives, the differentiation between nodules and end-on vessels is one of the most challenging tasks performed by computer. Most investigators have used a conventional two-stage pattern recognition approach, ie, feature extraction followed by feature classification. The performance of this approach depends totally on good feature definition in the feature extraction stage. Unfortunately, suitable feature definition and corresponding extraction implementation algorithms proved to be very difficult to define and specify. A convolution neural network (CNN) architecture, trained by direct connection to the raw image is proposed to tackle the problem. The CNN, which uses locally responsive activation function, is directly and locally connected to the raw image. The performance of the CNN is evaluated in comparison to an expert radiologist. We used the receiver operating characteristics (ROC) method with area under the curve (Az) as the performance index to evaluate all the simulation results. The CNN showed superior performance (Az = 0.99) to the radiologist's (Az = 0.83). The CNN approach can potentially be applied to other applications, such as the differentiation of film defects and microcalcifications in mammography, in which the image features are difficult to define or not known a priori.

Algorithms↗

How to enhance the efficacy of health network growth.

In almost every American metropolitan area, health executives are busily enhancing the efficacy of their health networks by corporately restructuring so that their organization can become a fiscally and politically powerful oligopoly or a regulated monopoly. When the formation of these alliances are initially announced by the local media, they are reported to be vehicles to enhance access, social equity and quality of care, and to reduce costs. Since an increasing number of these health networks are currently experiencing fiscal, cultural and other difficulties, it is critical to study: (a) what factors should be considered when developing an effective and efficient health network?; (b) what are the practical issues in their strategic formation and management so they eventually achieve their full potential?; and (c) why will some divestitures among these health networks occur and how will these corporate 'spin offs' impact on consumers, providers, insurers and governmental agencies? Within the next decade the United States will face some inevitable economic difficulties. At that time, enhancing access and reducing costs will become more critical issues for health networks. These alliances may then need to become more responsive to consumer pressures as the Americans shift their political proclivities from the current quasi-competitive to a more quasi-regulatory position. In this context, the use of global budgetary targets is discussed as a possible option in the United States to constrain costs, an approach used in almost all other western industrialized nations.

Budgets↗

Intranuclear distribution of DNA topoisomerase II and chromatin.

Domain-specific anti-Drosophila DNA topoisomerase II antibodies were generated, affinity purified and used for confocal laser scanning immunofluorescence microscopy. Except for the nucleolus, DNA topoisomerase II is distributed throughout interphase nuclei. In adult accessory glands as well as third instar larval neural ganglion and imaginal disk nuclei, DNA topoisomerase II shows areas of co-localization with chromatin adjacent to areas of extrachromosomal distribution. These observations made in a variety of tissues under different fixation conditions and with a number of molecular probes support the notion that DNA topoisomerase II is a component of a substantially extrachromosomal network that functions to organize interphase chromatin within nuclei.

Animals↗

Localization of laminin in nephritic glomeruli as revealed by a quick-freezing and deep-etching method with immunohistochemistry.

The three-dimensional localization of laminin in rat glomeruli at the chronic phase of Masugi nephritis was investigated by a quick-freezing and deep-etching method combined with immunohistochemistry. Light-microscopically, laminin was localized in increased mesangial matrix and thickened glomerular basement membrane. The quick-freezing and deep-etching method revealed that the increased mesangial matrix, which was newly formed in axial portions and areas of mesangial interposition, was composed of fine fibrillar networks. They were revealed with the 3,3'-diaminobenzidine tetrahydrochloride (DAB) reaction products of peroxidase-labelled secondary antibody following anti-laminin antibody. However, these reaction products were not uniformly distributed in the newly formed matrix. Although the fibrils organizing lamina densa were also immunostained with anti-laminin antibody, the fibrils connected to mesangial cells, podocytes and endothelial cells had smaller amounts of DAB reaction products for laminin. These results indicate that one of the components of fibrils in the mesangial matrix and lamina densa is laminin, which is heterogeneously distributed in the newly formed matrix.

3,3'-Diaminobenzidine↗

Dynamic reverberation. A unified mechanism for central and phantom pain.

Central and phantom pains remain unexplained by current pathophysiological hypotheses. Newer theories suggest that these may be the result of an altered processing inside a network of neurons extending throughout wide-spread areas of the brain, precluding neurosurgical treatment. On the basis of a literature review of cases with spontaneous resolution of the pain, it is argued that both central and phantom pain depend on a localized corticothalamic reverberatory loop, which is at the basis of the steady components of both. In this case, selective stereotactic lesions of the corona radiata deep to the frontoparietal sensorimotor strip may achieve a permanent cure. This theory refutes the neuromatrix hypothesis of phantom phenomena. It is speculated that electroconvulsive therapy might block the pathologic reverberation in both central and phantom pains.

Adult↗

Cross-regulatory role of interferon-gamma (IFN-gamma), IL-4 and IL-10 in schistosome egg granuloma formation: in vivo regulation of Th activity and inflammation.

This study examined the relationship of IL-4, IL-10 and IFN-gamma with regard to the local granuloma (GR) and draining lymph node (LN) response to Schistosoma mansoni eggs. Synchronized GR were induced in naive and schistosome-infected mice at the vigorous (8 weeks) and late chronic (20 weeks) stages. In LN cultures, IL-10 and IFN production peaked on day 4 and was greatest for 8 week-infected mice. All GR cultures contained IFN, but compared with naive mice IL-10 production was accelerated at 8 weeks and abrogated at 20 weeks, consistent with expansion and abatement of Th2 activity. Cytokine neutralization was performed in egg-challenged, naive mice that were adoptively sensitized with lymphoid cells from 8 week-infected donors. GR size, GR macrophage tumour necrosis factor (TNF) production and egg antigen-elicited IL-2, IL-4, IL-5, IL-10 and IFN were examined on day 4 of GR formation. Anti-IFN augmented GR area by 40%, increased local IL-4 and IL-10, but decreased IFN and TNF production. In corresponding LN cultures, IFN decreased by about 50%, while IL-2, IL-4, IL-10 and IL-5 increased by nearly two-, four-, five- and six-fold, respectively. Anti-IL-10 did not affect GR size or GR cytokines, but abrogated GR area by 40%, along with a reduction in local IL-4 and TNF production. In LN, IL-4 depletion reduced IL-4 and IL-5 by 60-70% and increased IFN levels. These results support the notion of a cross-regulatory network in which IFN inhibits Th2 and IL-10 inhibits Th1 cells. IL-4 fosters Th2 cells differentiation in LN, but also performs a critical recruitment function in the eosinophil-rich schistosome egg-induced GR, whereas IFN contributes to enhanced GR macrophage function.

Animals↗

Influence of fibroblast growth factor, insulin-like growth factor I, and transforming growth factor beta on satellite cell type I collagen expression and localization during differentiation.

Expression, and temporal and spatial distribution of type I collagen were investigated in chicken satellite cell cultures during differentiation. There was no difference in the relative amounts of type I collagen after treatment with basic fibroblast growth factor (FGF), insulin-like growth factor-I (IGF-I), or transforming growth factor beta 1 (TGF-beta 1). However, myotube morphology was influenced by the presence of the growth factors. The temporal and spatial distribution of type I collagen was also modified. Control cultures maintained a predominant distribution of type I collagen surrounding the cellular area until approximately 48 h after the initiation of fusion whereas cultures with FGF or IGF-I maintained a cellular localization of type I collagen throughout the fusion process. TGF-beta 1 resulted in the early formation of an extracellular network of type I collagen preceding control cultures by approximately 24 h. These results suggest that type I collagen expression but not localization is independent of satellite cell proliferation and differentiation.

Animals↗

Java-based framework for the secure distribution of electronic medical records.

In this paper, we present a Java-based framework for the processing, storage and delivery of Electronic Medical Records (EMR). The choice of Java as a developmental and operational environment ensures operability over a wide-range of client-side platforms, with our on-going work emphasising migration towards Extensible Markup Language (XML) capable Web browser clients. Telemedicine in support of womb-to-tomb healthcare as articulated by the Multimedia Supercorridor (MSC) Telemedicine initiative--which motivated this project--will require high-volume data exchange over an insecure public-access Wide Area Network (WAN), thereby requiring a hybrid cryptosystem with both symmetric and asymmetric components. Our prototype framework features a pre-transaction authentication and key negotiation sequence which can be readily modified for client-side environments ranging from Web browsers without local storage capability to workstations with serial connectivity to a tamper-proof device, and also for point-to-multipoint transaction processes.

Computer Communication Networks↗

[Quality management in a Swiss hospital].

Although there are quite good examples of quality management in Swiss hospitals available (the guidelines of quality management in the Swiss hospital etc.), the distribution of measures of quality assurance in Swiss hospitals is insufficient and focuses more on Hotel services and technical equipment rather than on the care by physicians and nurses. Beginning with Jan. 1, 1998, contracts of quality assurance between health care providers and sponsors have to be presented according to the new health insurance act. These contracts are proofed periodically by a national office. This necessitates a country-wide introduction of statistics (ICD-codes) and computerization. This is currently only in the process of realization. Additionally, hospitals and medical practices already undertake a comprehensive quality control due to local and regional initiatives. The society of Swiss physicians FMH supports mainly three areas: compulsory continuing medical education (80 hours annually, including 50 hours in recognized meetings), the development of guidelines by medical societies, and data collection including the development of a network for measures of quality assurance. The ISO-standard 9000 was changed for health care as ordered by the NAQ (National workshop for quality assurance) and the FMH. It is supposed to be used mainly for the certification of facilities for continuing medical education, perhaps also for the certification of hospitals.

Education, Medical, Continuing↗

Crossmodal integration for perception and action.

The integration of information from different sensory modalities has many advantages for human observers, including increase of salience, resolution of perceptual ambiguities, and unified perception of objects and surroundings. Several behavioral, electrophysiological and neuroimaging data collected in various tasks, including localization and detection of spatial events, crossmodal perception of object properties and scene analysis are reviewed here. All the results highlight the multiple faces of crossmodal interactions and provide converging evidence that the brain takes advantages of spatial and temporal coincidence between spatial events in the crossmodal binding of spatial features gathered through different modalities. Furthermore, the elaboration of a multimodal percept appears to be based on an adaptive combination of the contribution of each modality, according to the intrinsic reliability of sensory cue, which itself depends on the task at hand and the kind of perceptual cues involved in sensory processing. Computational models based on bayesian sensory estimation provide valuable explanations of the way perceptual system could perform such crossmodal integration. Recent anatomical evidence suggest that crossmodal interactions affect early stages of sensory processing, and could be mediated through a dynamic recurrent network involving backprojections from multimodal areas as well as lateral connections that can modulate the activity of primary sensory cortices, though future behavioral and neurophysiological studies should allow a better understanding of the underlying mechanisms.

Animals↗