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A noncyclopean diagram of binocular vision in strabismology.

Most diagrams concerning binocular vision and squint contain the cyclopean eye, which is a vestige of the 2000-year-old projection theory. The author's previously published diagram is based on a motor theory of spatial localization which has been formulated by Descartes, Lotze, and Roelofs.

Eye↗

Quantitative assessment of the microstructure of rat behavior: I, f(d), the extension of the scaling hypothesis.

Previous studies demonstrated that drug effects on the movement sequences of rats in unconditioned motor activity paradigms can be quantified by scaling measures that describe the average relationship between a variable of interest and an experimental parameter. However, rats engage in a wide variety of geometrically distinct movements that can be influenced differentially by drugs. In this investigation, the extended scaling approach is presented to capture quantitatively the relative contributions of geometrically distinct movement sequences to the overall path structure. The calculation of the spectrum of local spatial scaling exponents, f(d), is based on ensemble methods used in statistical physics. Results of the f(d) analysis confirm that the amount of motor activity is not correlated with the geometrical structure of movement sequences. Changes in the average spatial scaling exponent, d, correspond to shifting the entire f(d) function, and indicate overall changes in path structure. With the extended scaling approach, straight movement sequences are assessed independently from highly circumscribed movements. Thus, the f(d) function identifies drug effects on particular ranges of movement sequences as defined by the geometrical structure of movements. More generally, the f(d) function quantifies the relationship between microscopically recorded variables, in this paradigm consecutive (x,y) locations, and the macroscopic behavioral patterns that constitute the animal's response topography.

Animals↗

Comparison of line and space bisection in evaluation of normal and amblyopic spatial vision.

BACKGROUND: Partitioning experiments have been used historically and in the recent past to evaluate space perception in visually normal and disturbed individuals. Specifically, amblyopic patients display notably distorted and/or uncertain spatial localization when assessed by either line or space bisection. METHODS: This investigation was concerned with the comparison of line bisection with space bisection. Normal and amblyopic subjects bisected horizontal lines and spaces extending 1, 2, 3 and 15 deg arc monocularly on a computer screen. Results of the two procedures were compared. RESULTS: Visually normal subjects bisected both lines and spaces without reproducible distortion, within uncertainties approximating 1-3% of their length. No differences were observed between the two procedures. Strabismic amblyopes bisected without constant distortion to either side of the geometrical mean, irrespective of direction or extent of the deviation; their uncertainty at bisecting ranged from 2% to 12%. Again, no distinction between line and space bisection could be made. CONCLUSION: We conclude that the two procedures yield comparable results.

Adolescent↗

Positron emission tomography for detecting iodine-131 nonvisualized metastasis of well-differentiated thyroid carcinoma: two case reports.

To investigate the usefulness of positron emission tomography (PET) in detecting I-131 nonvisualized metastatic foci of well-differentiated thyroid carcinoma (WDTC), 2 patients with papillary and follicular thyroid carcinoma respectively, were studied with I-131 total body scan, thallium-201 scan, Tc99m bone scan and [18F]-2-deoxy-2-fluoro-D-glucose (FDG) PET. Case 1 showed no metastatic lesion in I-131 (up to 150 mCi) total body scan, 1 anterior mass in thallium-201 scan, none in Tc99m bone scan and 7 including the main anterior mediastinal mass in FDG-PET. Case 2 showed 2 metastatic lesions in I-131 (150 mCi) total body scan, 11 bony metastatic lesions in Tc99m bone scan and 13 in FDG-PET. However, lower extremities were not scanned in FDG-PET. Tumor/background ratio of 1.5 or above is needed to be visualized grossly. The FDG-PET tumor/background ratios are higher than those of thallium-201 except in one site. In conclusion, I-131 scintigraphy is still the first line method to use in detecting WDTC recurrence and metastasis, as I-131 has the advantage of being both a therapeutic and imaging agent. For I-131 nonvisualized metastasis of WDTC, thallium scintigraphy and FDG-PET may be considered. Even though FDG-PET has better sensitivity, resolution imaging and spatial localization, this has to be balanced with its higher cost when compared with thallium scintigraphy.

Adenocarcinoma, Follicular↗

[New imaging methods in the diagnosis of mitral regurgitation].

Conventional Doppler echocardiographic methods still are limited when being used for evaluation of morphology and function of a regurgitant mitral valve. Methods based on two-dimensional image planes may be insufficient to demonstrate exact spatial localization of pathologic structures due to the need for mental reconstruction of the three-dimensional valve anatomy by the examiner. The determination of severity of mitral regurgitation is based either on the estimation of regurgitation jet size or on geometric assumptions on its shape which often are not correct and reduce the accuracy of the method.New echocardiographic techniques such as 3-D echocardiography provide a comprehensive visualization and assessment of valvular pathomorphology which especially in complex situations will increase sensitivity and diagnostic accuracy when compared to conventional methods. The combination of 3-D echo with three-dimensional Doppler data will allow an even more reliable and precise determination of lesion severity. Other imaging modalities such as magnetic resonance imaging will be a promising alternative due to their three-dimensional data acquisition and the enormous potential for the measurement of intracardiac flow.

Echocardiography, Three-Dimensional↗

The time and space of lexicality: a neuromagnetic view.

Illuminating the neural mechanisms subserving lexico-semantic processing is requisite to further understanding the neurophysiological basis of the dyslexias. Yet, despite numerous functional neuroimaging experiments, the location and temporal behavior of brain regions mediating word-level language processing remain an area of debate. Such investigations typically utilize the word/pseudoword contrast within hemodynamic measurements, and report several left hemisphere regions that respond more strongly to pseudowords but fail to replicate neural areas unique to real word processing. The present experiment addressed this problem from a different perspective. Mainly, we hypothesized that the time course, but not the neuroanatomy, would show within-subject across-condition disparities. For that purpose, we applied dipole-modeling techniques to high-density magnetoencephalographic recordings of healthy subjects, and utilized excellent spatiotemporal accuracy to demonstrate significant across-condition differences in the time domain, along with indistinguishable neural correlates within-subject. In all participants, both words and pseudowords elicited activity in left perisylvian language areas, with words consistently activating these regions approximately 100 ms earlier than pseudowords. Considerable functional heterogeneity was also observed, and this might underlie the inconsistencies among previous studies. We conclude that the neural distinction in word/pseudoword processing is not in spatial localization, but is better conceptualized as a dynamic difference in processing time.

Adolescent↗

Reaction times of manual responses to a visual stimulus at the goal of a planned memory-guided saccade in the monkey.

Monkeys demonstrate improved contrast sensitivity at the goal of a planned memory-guided saccade (Science 299:81-86, 2003). Such perceptual improvements have been ascribed to an endogenous attentional advantage induced by the saccade plan. Speeded reaction times have also been used as evidence for attention. We therefore asked whether the attentional advantage at the goal of a planned memory-guided saccade led to speeded manual reaction times following probes presented at the saccade goal in a simple detection task. We found that monkeys showed slower manual reaction times when the probe appeared at the memorized goal of the planned saccade when compared to manual reaction times following a probe that appeared opposite the saccade goal. Flashing a distractor at the saccade goal after target presentation appeared to slow reaction times further. Our data, combined with prior results, suggest that a spatially localized inhibition operates on the neural representation of the saccade goal. This inhibition may be closely related or identical to the processes underlying inhibition-of-return. We also found that if the same detection task was interleaved with a difficult perceptual discrimination task, manual reaction times became faster when the probe was at the saccade goal. We interpret these results as being an effect of task difficulty; the more difficult interleaved task may have engaged endogenous attentional resources more effectively, allowing it to override the inhibition at the saccade goal. We construct and discuss a simple working hypothesis for the relationship between the effects of prior attention on neural activity in salience maps and on performance in detection and discrimination tasks.

Animals↗

Reach-to-grasp movements during obstacle avoidance.

The transport and grip components are two controlled components of a prehensile movement. These components are coordinated so that objects of varying size and shape resting in diverse locations can be grasped easily. It has been suggested that the timing between these two components is a specified parameter, although the origin of such timing is unknown. The present study examines the interdependency of the reach and grasp components when the transport component is modified by placing an obstacle of varying height (9 cm and 11 cm) in the hand path between the starting position and the target object location. Subjects were asked to reach over a Plexiglas barrier and grasp a 2-cm dowel. To reach the object, the subject had to elevate the hand. At issue in this experiment is whether changes in hand path trajectory caused by obstacle avoidance produce corresponding changes in the kinematics of grip aperture. The findings showed that reaching in the presence of an obstacle resulted in the prolongation of most transport component time parameters except peak acceleration and a few amplitude parameters. Changes in the transport component also produced systematic prolongation in all time parameters of grip kinematics, including grip closure time. Temporal prolongation was also reflected in a significant decrease in grip opening and closing velocity; only relative time-to-peak closing velocity was maintained. Closure distance and maximum grip aperture were smaller for the obstacle conditions. Together with the observed smaller variability for the distance to peak aperture, these findings suggest that spatial localization of the hand aperture is an important prehensile movement control feature. Parameterization processes for the grip component are closely linked to those of the transport component, and their organization appears to be interdependent.

Adult↗

Motor cortical potentials precede long-latency EMG activity evoked by imposed displacements of the human wrist.

Rapid angular displacements of the wrist evoke cerebral potentials that precede the onset of the long-latency electromyographic (EMG) activity generated in muscles stretched by the displacement. The initial segment of the long-latency EMG activity (termed the M2 response) is thought to be mediated by a transcortical reflex. We used dipole source analysis to examine the source generators of the early components of the cerebral potentials and their relationship to the timing and magnitude of the M2 response. Subjects (n=10) were presented with instructions to either actively flex or extend the wrist in response to a torque motor-imposed extensor displacement or allow the wrist to be passively extended. Electroencephalographic (EEG) recordings were obtained from 32 scalp-surface electrodes, and EMG was recorded from the wrist flexors and extensors. For all three tasks, the M2 response was preceded by cerebral potentials that could be explained by a three-dipole model. One source generator localised to deep within the cerebrum, and the other two localised to the region of the contralateral sensorimotor cortex. We used the P20-N20 dipole evoked by electrical stimulation of the median nerve at the wrist, corresponding to synaptic activity within cortical area 3b, as a local spatial reference to examine the contributions of the pre- and postcentral cortex. This analysis showed that one of the sensorimotor dipoles was consistently located anterior to the P20-N20 dipole at a displacement (average 11.5 mm) appropriate for a generator originating within the deep layers of area 4 on the anterior bank of the central sulcus. The orientation of this dipole was also consistent with a precentral generator and not a reversal of the potentials generated by input to area 3b. The time course of the area-4 dipole moment (onset =35 ms, peak =54 ms) was appropriate to reflect synaptic activity onto corticospinal neurons whose descending volleys mediate the M2 response. Comparisons across tasks showed that the magnitude of the M2 was modulated with task instruction, being largest with active and smallest with passive resistance. In contrast, the magnitude of the early evoked potentials (up to 75 ms) did not grade across tasks. We interpret these results as suggesting that instruction-dependent modulation of the M2 response occurs downstream from inputs to the primary motor cortex.

Adult↗

Functional MRI of the cervical spinal cord on 1.5 T with fingertapping: to what extent is it feasible?

INTRODUCTION: Until recently, functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) contrast, was mainly used to study brain physiology. The activation signal measured with fMRI is based upon the changes in the concentration of deoxyhaemoglobin that arise from an increase in blood flow in the vicinity of neuronal firing. Technical limitations have impeded such research in the human cervical spinal cord. The purpose of this investigation was to determine whether a reliable fMRI signal can be elicited from the cervical spinal cord during fingertapping, a complex motor activity. Furthermore, we wanted to determine whether the fMRI signal could be spatially localized to the particular neuroanatomical location specific for this task. METHODS: A group of 12 right-handed healthy volunteers performed the complex motor task of fingertapping with their right hand. T2*-weighted gradient-echo echo-planar imaging on a 1.5-T clinical unit was used to image the cervical spinal cord. Motion correction was applied. Cord activation was measured in the transverse imaging plane, between the spinal cord levels C5 and T1. RESULTS: In all subjects spinal cord responses were found, and in most of them on the left and the right side. The distribution of the activation response showed important variations between the subjects. While regions of activation were distributed throughout the spinal cord, concentrated activity was found at the anatomical location of expected motor innervation, namely nerve root C8, in 6 of the 12 subjects. CONCLUSION: fMRI of the human cervical spinal cord on an 1.5-T unit detects neuronal activity related to a complex motor task. The location of the neuronal activation (spinal cord segment C5 through T1 with a peak on C8) corresponds to the craniocaudal anatomical location of the neurons that activate the muscles in use.

Adolescent↗

Aggregates of resident bacteria facilitate survival of immigrant bacteria on leaf surfaces.

The fate of immigrant bacterial cells on leaves under stressful conditions was determined as a function of the anatomical features and the local spatial density of resident cells at their landing site. Pantoea agglomerans 299R was established on bean leaves and the survival of immigrant cells of Pseudomonas fluorescens A506 and Pseudomonas syringae B728a, as well as P. agglomerans itself, was determined by epifluorescence microscopy following subsequent exposure of plants to desiccation stress. Resident and immigrant bacterial strains constitutively expressed the cyan and the green fluorescent protein, respectively, and the viability of individual cells was assessed directly on leaf surfaces following propidium iodide staining. Although only a small fraction of the immigrant cells landed on established bacterial aggregates, their fate was usually strongly influenced by the presence of indigenous bacteria at the site at which they landed. Immigrants of P. agglomerans 299R or P. fluorescens A506 that arrived as solitary cells had about double the probability of survival when landing on aggregates formed by P. agglomerans 299R than when landing on uncolonized areas of the leaf surface. In contrast, the survival of P. syringae B728a was similar irrespective of whether it landed on colonized or uncolonized parts of a leaf. The nature of plant anatomical features at which immigrant bacteria landed also strongly influenced the fate of immigrant bacteria. The fraction of immigrant cells of each species tested that landed on veins, glandular trichomes, or epidermal cells altered by P. agglomerans that died was always less than when they landed on normal epidermal cells or at the base of hooked trichomes. Depending on the process by which immigrants arrive at a leaf, only a small fraction of cells may be deposited on existing bacterial aggregates. Although uncolonized sites differed greatly in their ability to influence the survival of immigrant cells, the fate of an immigrant bacterium will depend on the nature of the leaf structure on which it is deposited, and apparently indirectly on the amount of nutrients and water available at that site to support the development of bacterial aggregates.

Micronutrients↗

Combining anatomy and function: the path to true image fusion.

Modern imaging technologies visualize different aspects of disease in a non-invasive way. Considerable progress has been made in the fusion of images from different imaging modalities using software approaches. One goal of fusion software is to align anatomical and functional images and allow improved spatial localization of abnormalities. The resulting correlation of the anatomical and functional images may clarify the nature of the abnormality and help diagnose or stage the underlying disease. Whereas successful image fusion software has been developed for the brain, only limited success has been achieved for image alignment in other parts of the body. The development and current status of alternative approaches are presented. Dual-modality imaging is described with devices where two modalities are combined and mounted in a single gantry. The use of existing scanner technology ensures that no compromises are made in the clinical efficacy of either the anatomical or functional imaging modality. A combined positron emission tomography (PET) and computed tomography (CT) scanner has been developed and is undergoing clinical evaluation. Combining PET with MR is technologically more challenging because of the strong magnetic fields restricting the use of certain electronic components. An overview of the current status and future prospects of dual-modality imaging devices is presented.

Diagnostic Imaging↗

[Some aspects of the current controversy about the treatment of amblyopia].

Occlusion has been used for centuries for treating amblyopia but in recent years an intensive debate about the treatment has arisen. The aim of this article is to summarize some of the new aspects of this discussion: on the one hand the effect of occlusion treatment during childhood is being questioned and on the other hand experimental approaches are being tested which are aimed at treating amblyopia in adults. Evidence from own experimental work is presented showing the influence of occlusion on the spatial localization of visual stimuli. A continuation of research on amblyopia and the effect of the therapy is urgently needed.

Adolescent↗

Ca2+ channels, Ca2+ sparks, and regulation of arterial smooth muscle function.

In cardiac, skeletal, and arterial muscle, transient, spatially localized elevations in [Ca2+]i, termed "Ca2+ sparks", have been observed using confocal laser scanning microscopy. Ca2+ sparks are thought to represent "elementary" Ca2+ release events, which arise from one or more ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In striated muscle, Ca2+ sparks are thought to be key elements of excitation-contraction coupling. In arterial smooth muscle, Ca2+ sparks have been suggested to oppose myogenic vasoconstriction and to influence vasorelaxation. Using a developmental model, we have investigated whether RyRs causing Ca2+ sparks and activation of Ca(2+)-activated K+ (KCa) channels (STOCs) function as "elementary" Ca2+ release units that regulate arterial myogenic tone. Whereas increases in the global [Ca2+]i induce sustained constriction of arterial smooth muscle, Ca2+ sparks induce vasodilation through the local activation of KCa channels. In cerebral arteries, the global bulk [Ca2+]i and a Ca2+ spark frequency < 10(-2) Hz/cell do not cause sufficient KCa channel activity to regulate membrane potential of smooth muscle cells and myogenic tone. The frequency of Ca2+ sparks and STOCs is regulated by agents that modulate protein kinase G and protein kinase A activity. Our findings suggest that "elementary" Ca2+ release units may represent novel, important therapeutic targets for regulating function of the intact arterial smooth muscle tissue.

Animals↗

Developmental appearance of dentin matrix protein 1 during the early dentinogenesis in rat molars as identified by high-resolution immunocytochemistry.

Dentin matrix protein 1 (DMP 1) is an acidic phosphoprotein that has been postulated to play an important role in mineralized tissue formation. We have examined rat molar tooth germs by applying a high-resolution immunocytochemical approach with the purpose to identify the temporal and spatial localization of DMP 1 at the onset of dentinogenesis. Upper molar tooth germs of 2- to 3-day-old Wistar rats were fixed in a cacodylate-buffered 0.1% glutaraldehyde + 4% formaldehyde fixative, left unosmicated and embedded in LR White resin. The sections were incubated with a polyclonal DMP 1 antibody for postembedding colloidal gold immunolabeling and examined in a Jeol 1010 transmission electron microscope. The earliest localization of DMP 1 was in the Golgi region as well as in the nucleus of differentiating odontoblasts. When mineralization spread from matrix vesicles to the surrounding matrix, DMP 1 was extracellularly detected around the mineralizing globules. In the regions of fully mineralized mantle dentin, it was present in the mineralized regions, mainly around the peritubular dentin. The appearance of DMP 1 during early dentinogenesis implies a direct role for this protein in both odontoblast differentiation and matrix mineralization.

Animals↗

Color genes in the orchid Oncidium Gower Ramsey: identification, expression, and potential genetic instability in an interspecific cross.

Orchids are one of the most unique and evolved of flowering plants, with many being valuable floricultural crops. Spatial localization of pigments within the flower of the commercially important bi-color Oncidium Gower Ramsey demonstrated a mixture of carotenoids and anthocyanins concentrated in the adaxial epidermis. Chromatography identified the predominant yellow pigment to be an equal mixture of all-trans and 9-cis isomers of violaxanthin, with esterification specific to the 9-cis isomer. Red ornamentation was comprised of the anthocyanins cyanidin and its methylated derivate, peonidin. Five key pigment biosynthesis genes encoding dihydroflavonol 4-reductase (DFR), phytoene synthase (PSY), phytoene desaturase, carotenoid isomerase, and the downstream 9-cis epoxycarotenoid dioxygenase were isolated and their expression profiles determined. Northern analyses showed both phytoene desaturase and carotenoid isomerase expression to be up-regulated in floral tissue relative to leaves whereas PSY was not. Three closely related DFR genes were isolated, including one with an insertion in the 3' coding region. DFR expression occurred throughout flower development in Oncidium, unlike in Dendrobium and Bromheadia orchids. A number of the isolated anthocyanin and carotenoid genes showed variations due to insertion events. These findings raise questions about the genetic stability in interspecific crosses in orchids, such as the tri-specific Oncidium Gower Ramsey.

Alcohol Oxidoreductases↗

Distribution of ERK1/2 and ERK3 during normal rat fetal lung development.

The extracellular regulated kinases-1 and -2 (ERK1/2) are well-characterized mitogen-activated protein kinases (MAPK) that play critical roles in proliferation and differentiation, whereas the function(s) of MAPK ERK3 are currently unknown. To understand better the roles of these kinases in development, the temporal distribution of ERK1, -2, and -3 proteins were investigated in multiple tissues. The ERK3 protein, in contrast to ERK1/2 varied both between and within individual organs over time. To characterize this variability in greater detail, the temporal and spatial distributions of activated ERK1/2 and ERK3 during rat fetal lung development were investigated. The diphosphorylated (activated) forms of ERK1/2 (dp-ERK1/2), ERK3, and its phosphorylated form (P-ERK3) decreased from embryonic day 17 (E17) through E21 while both ERK1 and ERK2 total proteins remained unchanged, indicating that ERK1/2 and ERK3 proteins are expressed independently during fetal lung development. In addition, characterization of the distribution of these proteins by fluorescent immunohistochemistry indicated that phosphorylated ERK1/2 and total ERK1/2 were distributed throughout multiple cell types, with the phosphorylated ERK1/2 colocalizing with prophase mitotic cells. In contrast, ERK3 was restricted to the distal lung epithelium during the pseudoglandular phase (E17) but shifted to the proximal airways, particularly Clara cells during the saccular stage (E21). The P-ERK3 colocalized with the mitotic marker P-histone H3 in fetal lung and in NIH3T3 and HeLa cells, implicating a potential role for P-ERK3 in mitosis. Thus, expression of ERK1/2 and ERK3 and their phosphorylated forms are expressed independently and are temporally and spatially localized during fetal lung morphogenesis. These observations will facilitate detailed functional analysis of these kinases to assess their roles in pulmonary development and diseases.

Animals↗

Coordinate cell-surface expression of matrix metalloproteinases and their inhibitors on cancer-associated myofibroblasts from malignant ascites in patients with gastric carcinoma.

PURPOSE: The crucial role of tumor stroma in cancer cell invasion has been described in human carcinoma tissues. However, myofibroblastic invasion remains largely unexplored in malignant ascites. Purpose of this study is to investigate the spatial localization or regulation of matrix metalloproteinases (MMP-2, -7 -9, MT1-MMP) and their inhibitors (TIMP-2 and -4) on myofibroblasts from malignant ascites in 20 patients with gastric carcinoma. METHODS: The quantitative flow cytometric analysis of MMPs or TIMPs on myofibroblasts was based on the percentage of double positive cells defined by anti MMPs or anti TIMPs, and anti alpha-smooth muscle actin (alpha-SMA) antibodies. RESULT: The results clearly showed that the coordination of the high level of cell-surface expression of secreted MMPs and TIMPs was noted on the alpha-SMA+ myofibroblasts. The finding suggests the possible formation of ternary complex, MT1-MMP/TIMPs/MMPs on the cells. The events might be a cause and result of activation processing of MMPs on the cells. CONCLUSION: This study provides the presence of invasive myofibroblasts with activated MMPs in close association with MMPs+ and TIMPs+ cancer cells and tumor-infiltrating lymphocytes from malignant ascites, emphasizing the importance of molecular cross-talk in tumor-host microenvironment for cancer invasion, metastasis and progression.

Aged↗