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Irreversible regional cerebral ischemia: serial MR imaging and proton MR spectroscopy in a nonhuman primate model.

PURPOSE: To delineate the changes in proton MR spectroscopy and imaging that occur with acute, irreversible ischemia of the basal ganglia of a baboon. MATERIALS AND METHODS: The M1 segments of the middle cerebral arteries of six adult male baboons were occluded by endovascular means with microcatheters and N-butyl cyanoacrylate adhesive. Cerebral blood flow measurements were taken with positron emission tomography or radioactive microsphere techniques. Serial spatially localized proton MR spectroscopy of the basal ganglia and MR imaging of the brain were performed. The distribution of ischemic and infarcted tissue was demonstrated by histopathologic techniques or triphenyltetrazolium chloride staining. RESULTS: Radioactive microsphere or positron emission tomography measurements demonstrated no significant cerebral blood flow within the basal ganglia after occlusion of the middle cerebral artery. Proton MR spectroscopy of the basal ganglia demonstrated increasing cerebral lactate and decreasing N-acetyl aspartate within 30 minutes of middle cerebral artery occlusion. Changes in the MR imaging signal intensity of the basal ganglia were observed as early as 3.1 hours on T2-weighted, 3.3 hours on T1-weighted, and 6.1 hours on spin density-weighted images. The distribution of these changes correlated well with the histopathologic features of ischemia and infarction that were seen throughout the basal ganglia. CONCLUSION: Changes in MR imaging signal intensity corresponded to ischemia and infarction in our baboon model of acute irreversible ischemia of the basal ganglia. Increasing cerebral lactate and decreasing N-acetyl aspartate preceded changes in MR imaging signal intensity.

Animals↗

Egocenter location in children with strabismus: in the median plane and unchanged by surgery.

PURPOSE: Previous studies have shown that there are spatial localization shifts after horizontal strabismus surgery when a patient performs an open-loop pointing task. After monocular enucleation, an adult will also show a shift in the pointing response. Other studies have shown that in children who underwent enucleation, the egocenter location shifts toward the remaining eye. Is the pointing shift after surgery in children with strabismus the result of a shift in egocenter location? METHODS: Using a modified Roelofs' method for measuring the egocenter, eight children were tested before and after horizontal strabismus surgery to see if there were any shifts in egocenter location. One control group consisted of six children undergoing surgery for correction of vertical strabismus in which the horizontal muscles would be unaltered. RESULTS: Presurgery measurements of egocenter location in the people with strabismus were the same as those found in the other control group of 12 normal children. Postsurgical measurements of eye position showed horizontal rotations of 14.5 degrees for the horizontal group and 2.4 degrees for the vertical group. Egocenter measurements showed no postoperative shift for either strabismus group. CONCLUSIONS: Thus, the pointing shift seen in the previous studies is not from a shifting egocenter location but from a change in the registered position of the eye in the orbit.

Child↗

Isolation and interaction of ON and OFF pathways in human vision: pattern--polarity effects on contrast discrimination.

To activate selectively cortical ON and OFF pathways, I measured pattern contrast discrimination functions and manipulated contrast polarity (positive and negative) of base contrast (C) and added contrast (delta C). C was a large, long-duration cosine mask and delta C was a brief, localized, spatially narrow-band "D6" pattern. For same polarity C and delta C, contrast discrimination followed a "dipper" pattern: threshold facilitation at low C and a power relation (exponent < 1.0) at high C. The facilitation is predicted from the low-contrast response of cortical neurons and seems to represent isolation of an ON or OFF pathway. Opposite polarity C and delta C give a monotonic function. delta C increases at low base C and remaining higher than the same-polarity function at higher C values. This represents interaction between ON and OFF pathways. Pathway isolation also occurs: a positive test is detected as a contrast increment if masked by negative contrast and a negative test is detected as a contrast decrement if masked by positive contrast. Quantitative aspects of the data suggest a subtractive interaction at low C values and a divisive interaction between pathways at high C values. Test contrast thresholds upon uniform fields of varying luminance show that both the dipper effect and most of the rise in delta C with C are mediated in pattern-selective pathways rather than at a site of luminance adaptation. The pattern-polarity effects on contrast discrimination rule out the "channel uncertainty" explanation for the facilitation dipper. My results suggest that parallel ON and OFF pathways evolved because stimulus-produced decreases in the response of a single pathway are potentially confounded with the effects of contrast adaptation. Thus transient decreases in response in either pathway are not processed and both decreases and increases in contrast are expressed as response increases in separate pathways.

Contrast Sensitivity↗

The processing of first- and second-order motion in human visual cortex assessed by functional magnetic resonance imaging (fMRI).

We have examined the activity levels produced in various areas of the human occipital cortex in response to various motion stimuli using functional magnetic resonance imaging (fMRI) methods. In addition to standard luminance-defined (first-order) motion, three types of second-order motion were used. The areas examined were the motion area V5 (MT) and the following areas that were delineated using retinotopic mapping procedures: V1, V2, V3, VP, V3A, and a new area that we refer to as V3B. Area V5 is strongly activated by second-order as well as by first-order motion. This activation is highly motion-specific. Areas V1 and V2 give good responses to all motion stimuli, but the activity seems to be related primarily to the local spatial and temporal structure in the image rather than to motion processing. Area V3 and its ventral counterpart VP also respond well to all our stimuli and show a slightly greater degree of motion specificity than do V1 and V2. Unlike V1 and V2, the response in V3 and VP is significantly greater for second-order motion than for first-order motion. This trend is evident, but less marked, in V3A and V3B and absent in V5. The results are consistent with the hypothesis that first-order motion sensitivity arises in V1, that second-order motion is first represented explicitly in V3 and VP, and that V5 (and perhaps also V3A and V3B) is involved in further processing of motion information, including the integration of motion signals of the two types.

Brain Mapping↗

[SPIC: a training simulator for coelioscopic interventions with gynecologic purpose].

There is much demand for laparoscopy training. We have developed a training simulator for initial training in gynecological laparoscopy. The simulator includes a mannequin with 3 located trocars, a PC and software for managing the graphical part of the training protocol. The objective is to learn how to achieve spatial localization and handle tools within the abdominal cavity. A series of exercises are proposed with increasing degree of difficulty. The simulator can be customized to simulate many different scenarios. The trainer must be present to provide an ultimate assessment of the trainee's experience. This new training tool cannot replace traditional surgical training but can help make it more efficient. The simulator is now being used by residents. Further technical developments are in progress to add further indispensable mechanical interactions (force feed back) to visualize the organ deformations and organ dissections within the abdominal cavity.

Computer Simulation↗

Tissue factor on cells.

Tissue factor (TF), a cell surface glycoprotein, serves as the cellular receptor for either activated or non-activated factor VII [FVII(a)] and it is the formation of TF-FVII(a) complexes on cell surfaces which triggers the coagulation cascade in vivo. TF procoagulant functional expression on cell surfaces can be regulated by at least three distinct major mechanisms: (1) transcriptional regulation of TF gene expression; (2) cell membrane alterations in cells expressing TF; and (3) neutralization of TF-activated factor VII (FVIIa) activity by plasma inhibitors. The TF gene, which is not normally expressed in vascular cell types, can be induced by several pathophysiological stimuli, particularly those elaborated upon in inflammation and cancer. However, some of the stimuli elaborated in these pathological processes, e.g. basic fibroblast growth factor, suppress the induced expression of TF in endothelium. Not all TF molecules expressed on cell surfaces are functional even though they have the ability to bind to FVII(a). The availability of anionic phospholipids on cell membranes in the vicinity of TF and the spatial localization of TF within the cell membrane influence the functional activity of TF. Once TF-FVII(a) complexes are assembled on cell surfaces, at least two plasma inhibitors, TF pathway inhibitor and antithrombin III play an important role in regulating the TF-FVII(a) functional activity by inhibiting the activation of factor VII bound to TF and by inhibiting the catalytic activity of TF-FVIIa complexes. The availability of heparan sulphate proteoglycans with anticoagulant activity on cell surfaces plays an important role in enhancing the activity of the inhibitors. This manuscript summarizes the mechanisms by which TF functional expression on cells is regulated with a particular emphasis on the recent findings of the authors and their collaborators.

Cell Membrane↗

Using EC and ES cell culture to study early development: recent observations on Indian hedgehog and Bmps.

Despite great technological advances in the study of mammalian development in the past two decades, certain problems in early development, such as how the extraembryonic lineages are established, have remained intractable. We suggest that teratocarcinoma (EC) and embryonic stem cells (ES) remain useful in vitro tools for studying some of these problems. We present a continuation of our studies on the role of IHH-based signaling in early development and demonstrate that the IHH N-peptide is expressed in the outer visceral endoderm cells of both the EC and ES-derived embryoid body. We also show that Bmp2 is upregulated and Bmp4 downregulated during the differentiation of F9 EC cells into embryoid bodies, whereas both genes are upregulated when J7 ES cells differentiate into embryoid bodies. We also examine the spatial localization of Ihh, Bmp2, and Bmp4 in day 6.5-7.0 and 7.5-8.0 embryos by in situ hybridization analysis. These data support the EC temporal expression data in that all 3 genes are expressed in visceral endoderm. Bmp4 expression appears to be limited to extraembryonic regions, where mesoderm as well as visceral endoderm are stained. Ihh and Bmp2 are expressed in extraembryonic tissues and the embryo proper. Functional roles for the observed expression patterns are discussed.

Animals↗

[Innervation of grouped lymphoid nodules (Peyer's patches) by the enteric nervous system and the topography of their interior neural elements in the rat].

Using the complex of histological methods (staining with toluidine blue, silver nitrate impregnation and application of retrograde fluorescent dye primulin) the data on the neural elements spatial localization within Peyer patches of the small intestine and their connections with the rest of enteric metasympathetic nervous system in rat was obtained. Submucosal plexus that is significantly developed within this lymphoid organ and is divided into internal and external plexuses was found to be most essential to the innervation of rat Peyers patches. These plexuses innervate all Peyers patch areas:nodules, cupula and internodular zones and the nodule-associated epithelium. Moreover, it was shown that within Peyers patch the plexuses form an integral part with the rest of the enteric nervous system and possess close connections with ganglia that are distant from the patch and are related both to submucosal and myenteric nervous plexuses. Direct inputs into Peyers patch nervous plexuses from extramural ganglia are present as well. These data was considered as a morphological basis for functional interaction of nervous and immune systems within the enteric immune organ and for possible enteric nervous system regulation of immune functions.

Animals↗

Spatial profiles of local and nonlocal effects upon contrast detection/discrimination from classification images.

We used classification images (A. J. Ahumada, Jr., & J. Lovell, 1971) to estimate the perceptual filter in a task designed to assess both local and nonlocal effects upon contrast detection/discrimination. Three observers performed a yes/no detection or discrimination task of a uniform circular decrement (radius = 0.68 deg) near threshold presented for 100 to 400 ms. Stimuli were presented in ring image noise that either covered the signal and an annular surrounding area (out to 1.36 deg), or only the surrounding annular area (out to 1.36 deg). Both the signal and the annular surround appeared on a uniform background. With ring noise over both the signal and surround, the amplitudes of the classification images in the signal area decreased as radial distance increased from the signal/surround border, and no effect of the surround was found. With ring noise only in the surround, classification images indicated noncontiguous effects at both the signal/surround border (local) and the surround/background border (nonlocal). The spatial extents of the nonlocal effects (< 0.07 deg) were smaller than local effects (0.25 deg), whereas the peak amplitudes of the local and nonlocal effects were comparable. These results suggest that the nonlocal effects were smaller than the local effects, and that the smaller effects would be due to smaller effective areas, as opposed to smaller amplitudes over the same area. Little or no change was found in the classification images across stimulus duration, suggesting that both the local and nonlocal processes found in this study were completed within 100 ms.

Adult↗

Spatial and temporal localization of transforming growth factor-beta1, bone morphogenetic protein-2, and platelet-derived growth factor-A in healing tooth extraction sockets in a rabbit model.

PURPOSE: The purpose of this study was to test the hypothesis that spatial and temporal localization of growth factors transforming growth factor (TGF)-beta1, bone morphogenetic protein (BMP)-2, and platelet derived growth factor (PDGF)-A in a rabbit tooth extraction model correlate with the histologic events contributing toward healing. MATERIALS AND METHODS: Twenty-four male New Zealand White rabbits were used in the study. Incisor teeth were extracted from both jaws, and the healing extraction socket with the surrounding jaw bone was harvested at 48 hours, 4 days, and 1, 2, 4, 8, 12, and 16 weeks. Tissues were fixed, decalcified, and processed for hematoxylin and eosin and immunohistochemical staining. The sections were stained to detect TGF-beta1, BMP-2, and PDGF-A. Stained sections were then imaged, and an automated computer program was used to detect the brown 3,3'-diaminobenzidine regions representing the location of growth factors of interest. The data were collected in terms of percentage area and intensity of stain, and an analysis of variance was conducted (Tukey-Kramer and Scheffe's test) for statistical comparison between different time points, jaws, and growth factors. These results were also compared with hematoxylin and eosin-stained histologic specimens obtained at similar time points. RESULTS: Spatial and temporal differences in localization of TGF-beta1, BMP-2, and PDGF-A were observed across all time frames in both jaws. Statistically significant differences in percentage area and intensity of brown diaminobenzidine stain were detected temporally between TGF-beta1, BMP-2, and PDGF-A (P < or =.0001). CONCLUSION: The results of this study showed positive correlation between histologic events and the spatial and temporal localization of TGF-beta1, BMP-2, and PDGF-A in a rabbit tooth extraction model.

3,3'-Diaminobenzidine↗

Apparent contrast and spatial frequency of local texture elements.

We measured the apparent contrast and spatial frequency of a parafoveal Gabor signal located at the center of an array of Gabor signals as a function of both element density and the direction of contrast and spatial frequency of the surrounding elements. The target Gabor appeared lower in contrast and higher in spatial frequency when the elements were in close proximity, regardless of the direction of contrast and spatial frequency of the surrounding elements. Overall, the evidence suggests that the appearance of a parafoveal target is strongly affected by its visual context. These findings provide additional support for the existence of spatial interactions among neurons implicated in textural processing.

Contrast Sensitivity↗

Comparison of the spatial-frequency selectivity of local and global motion detectors.

Convergent physiological and behavioral evidence indicates that the initial receptive fields responsible for motion detection are spatially localized. Consequently, the perception of global patterns of movement (such as expansion) requires that the output of these local mechanisms be integrated across visual space. We have differentiated local and global motion processes, with mixtures of coherent and incoherent moving patterns composed of bandpass filtered dots, and have measured their spatial-frequency selectivity. We report that local motion detectors show narrow-band spatial-frequency tuning (i.e., they respond only to a narrow range of spatial frequencies) but that global motion detectors show broadband spatial-frequency tuning (i.e., they integrate across a broad range of spatial frequencies), with a preference for low spatial frequencies.

Humans↗

Trophoblast-specific beta 1-glycoprotein: its spatial structure and localization of antigenic determinants.

Effects of temperature and pH on the spatial structures of trophoblast-specific beta 1-glycoprotein (TSG) and its various derivatives and fragments have been studied by circular dichroic spectroscopy. The spatial organization of the protein portion of TSG derivatives, as revealed by the spectroscopic evidence, has been discussed with respect to the antigenic activity of the species studied. We concluded that the TSG protein portion consists mainly of a beta-structural type. The antigenic determinants were shown to be topographic, and are preferentially localized in the protein portion; only about 15% of the TSG antigenic activity failed to bear a direct relation to the spatial structure. The antigenic determinants seemed to include a tryptophan residue.

Circular Dichroism↗

Spatial extension of local pacing capture in the lateral free wall of the right atrium during clinical chronic atrial fibrillation.

OBJECTIVES: The aims of our study were to define the spatial extension of local atrial pacing capture (LAPC) in the right lateral atrial wall and to verify the effects of antiarrhythmic drugs on capture extension. BACKGROUND: Recently, LAPC during spontaneous chronic atrial fibrillation (AF) has been demonstrated directly in humans, but no systematic attempt has been made to evaluate its spatial extension. METHODS: The study was conducted in 14 consecutive patients with chronic AF, nine of whom were taking antiarrhythmic drugs. A Franz catheter for pacing and monophasic action potential recording was positioned in the lateral right atrial wall. An octopolar recording lead was positioned about 10 mm apart. The presence of atrial capture and its extension (number of captured bipolar pairs) were evaluated during decremental pacing. RESULTS: Forty-eight atrial capture attempts were made. LAPC was achieved in all the performed attempts. The AF types immediately before capture were type 1 in 35 (73%) and type 2 in 13 (27%) episodes. In 32 episodes, the capture was lost within 15 seconds and in the remaining 16 pacing was stopped after 15 seconds of stable capture. In 26 episodes, capture extended radially up to 4 cm from the pacing site, in 18 up to 3 cm, in 3 up 1 cm and in 1 up 1 cm. The mean extension in patients being treated with antiarrhythmic drugs was significantly greater than what was seen in untreated patients (3.8 +/- 0.4 vs 2.9 +/- 0.7 cm, p < 0.00001). Capture loss was less frequently observed when all four of the bipolar recording sites had been captured (13/25, 52% vs 19/23, 82%, respectively, p = 0.05). CONCLUSIONS: LAPC in the lateral right atrial wall extends over a radius of 30-40 mm in the majority of capture episodes and is greater in patients treated with antiarrhythmic drugs. Our results suggest that, at least theoretically, simultaneous multisite pacing could be used to terminate AF. Moreover, a reduction in the atrial defibrillation threshold could be expected performing low-energy internal cardioversion during LPC.

Aged↗

Local processes and spatial pooling in texture and symmetry detection.

We examined the ability of human observers to detect three kinds of statistical structure in binary arrays: first-order statistics (luminance), local fourth-order statistics (isodipole textures), and long-range statistics (bilateral symmetry). Performance was closest to ideal on the luminance task and furthest from ideal on the symmetry task. For each kind of statistic, the dependence of performance on the degree of structure was well described by a model consisting of an initial stage of multiple independent detectors, followed by a pooling stage. For the luminance task and the isodipole task, performance was well-modeled by local processing followed by extensive spatial pooling. For the symmetry task, limitations at the local detection stage and a near-absence of spatial pooling were needed to model for performance.

Adult↗

Spatially resolved and localized real-time velocity distribution.

A technique is presented for collecting the spin velocity distribution as a function of position and time. It uses a multidimensional excitation pulse to select a cylinder, giving localization in two dimensions. Resolution in the third spatial dimension is achieved in the readout. During readout, an oscillating gradient encodes the acquired data in both one spatial dimension (x) and one velocity dimension (v). Two acquisitions (42 ms each) are needed to get a complete coverage of kx--kv space, which makes this technique real-time. The data is interpolated from the nonuniformly sampled kx--kv space to a Cartesian frame with a gridding scheme to take advantage of the Fast Fourier Transform. The technique was successfully applied to phantoms and normal volunteers, giving reasonable real-time measurements of velocity.

Blood Flow Velocity↗

Spatial and temporal localization of transforming growth factor-beta, fibroblast growth factor-2, and osteonectin, and identification of cells expressing alpha-smooth muscle actin in the injured anulus fibrosus: implications for extracellular matrix repair.

STUDY DESIGN: The spatial and temporal localization of fibroblast growth factor-2, transforming growth factor-beta, osteonectin, and alpha-smooth muscle cell actin in the injured anulus fibrosus was investigated. OBJECTIVE: To assess the involvement of fibroblast growth factor-2, transforming growth factor-beta, osteonectin, and alpha-smooth muscle cell actin in anulus fibrosus repair. SUMMARY OF BACKGROUND DATA: Fibroblast growth factor-2 and transforming growth factor-beta have been localized to disc herniation tissue, and alpha-smooth muscle cell actin has been identified in a number of mesenchymal cell types, but their roles have not been evaluated in repair processes in the experimentally injured anulus fibrosus. METHODS: For this study, 32 two adult merinos received a 4-mm deep standard annular incision in their L1L2 and L3L4 discs (lesion group). A similar number of sham-surgery animals served as control subjects. Osteonectin, fibroblast growth factor-2, transforming growth factor-beta, and alpha-smooth muscle cell actin were immunolocalized in sagittal disc sections 3, 6, 12, and 26 months after the operation. Selected specimens also were stained with hematoxylin and eosin, Masson-trichrome, toluidine blue, and picrosirius red. RESULTS: Early focal depletion of proteoglycan was evident in the anulus fibrosus and reorganization of outer annular lamellas 3 to 6 months after the operation. Blood vessel ingrowth and fibroblast infiltration from the outer anulus fibrosus along the plane of the annular defect were maximal 12 months after the operation. Focal upregulation in alpha-smooth muscle cell actin expression was evident with maximal staining in the 12-month lesion samples near infiltrating blood vessels at the lesion site, and also in cells well away from these vessels. Some of the anulus fibrosus cells of the sham sections also stained positively for alpha-smooth muscle cell actin, but this staining was significantly less than in the lesion samples. Staining for fibroblast growth factor-2, transforming growth factor-beta, and osteonectin was strongly localized to blood vessels and cells in the vicinity of the annular lesion. It was maximal 12 months after the operation and diminished by 26 months after the operation. Osteonectin expression also was significantly elevated in outer anulus fibrosus cells distant from the lesion site and its associated blood vessels. In the sham discs, immunoreactivity to fibroblast growth factor-2, transforming growth factor-beta, osteonectin, and alpha-smooth muscle cell actin was confined to sparsely distributed cells in the anulus fibrosus. No matrix staining was observed. CONCLUSIONS: Immunoreactivity for the noted agents was strongly associated with regions of the annular lesions undergoing matrix reorganization consistent with an active repair response. This response extended as far as the middle third of the anulus fibrosus, which also demarcated the extent of blood vessel ingrowth and cellular infiltration in this model. The alpha-smooth muscle cell actin expression suggested an active involvement of myofibroblasts in the anulus fibrosus repair processes.

Actins↗

Carcinoembryonic antigen, its spatial structure and localization of antigenic determinants.

The effects of temperature and pH on the spatial structure of carcinoembryonic antigen (CEA) and its various derivatives are studied by circular dichroic spectroscopy and differential UV spectroscopy. The spatial organization of the protein portion of CEA and its derivatives as revealed by spectroscopic evidence is discussed with respect to the antigenic activity of the species studied. We conclude that the protein portion of CEA consists mainly of a beta-structural type. Using the various modifications of the sugar moiety and the protein portion, antigenic determinants of CEA are shown to possess the main conformational character of the molecule while participation of the sugars in the formation and orientation of the carbohydrate chains relative to the protein core of the antigen appear to be important.

Carbohydrate Conformation↗