SEARCH · PubMed Health

Results for “spatial dependency”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources

PubMed2006

Selective spatial upregulation of intratumoral stromal aromatase in breast cancer patients: evidence for imbalance of local estrogen metabolism.

The suppression of local estrogens levels is of key importance in the treatment of ER-positive breast cancer. Essentially all endocrine strategies act by either suppressing estrogen formation or competitively inhibiting receptor-binding in tumor cells. Nevertheless, little is still known about the local expression of aromatase and sulfotransferase which are the key modulators of intra-tumoral estrogen levels. We have performed immunohistochemostry to investigate the expression of aromatase and sulfotransferase in 42 samples obtained directly from malignant breast tumors, and compared it to biopsies obtained from uninvolved tissue in the vicinity of the invasion front, and to distant breast tissue. We found that aromatase was equally detectable in both tumor epithelial and stroma, but was mostly epithelial in non-malignant tissues (P=0.00008, Fisher's exact test). Also, aromatase protein expression was significantly more common in tumoral stroma when compared with peritumoral and distant breast stroma (P=0.00005, and P<0.00001 respectively). With the notable exception of cystosarcoma phylloides, sulfotransferase protein was detectable only in epithelial tissues, regardless of the location within the diseased breast. However, epithelial sulfotransferase was correlated with epithelial aromatase (r=0.35461, P=0.0009, Spearman's rho test) and with the epithelial ER status (r=0.29313, P=0.005). We have demonstrated a differential aromatase and sulfotransferase protein expression pattern that is dependent on the spatial relation to a malignant breast tumor. Our results indicate a net increase in intratumoral active estrogen levels through increased stromal aromatization, while physiological local inactivation by sulfotransferase activity remains essentially unchanged.

Aromatase↗

PubMed1995

Spatial distribution of cardiac transmembrane potentials around an extracellular electrode: dependence on fiber orientation.

Recent theoretical models of cardiac electrical stimulation or defibrillation predict a complex spatial pattern of transmembrane potential (Vm) around a stimulating electrode, resulting from the formation of virtual electrodes of reversed polarity. The pattern of membrane polarization has been attributed to the anisotropic structure of the tissue. To verify such model predictions experimentally, an optical technique using a fluorescent voltage-sensitive dye was used to map the spatial distribution of Vm around a 150-microns-radius extracellular unipolar electrode. An S1-S2 stimulation protocol was used, and vm was measured during an S2 pulse having an intensity equal to 10x the cathodal diastolic threshold of excitation. The recordings were obtained on the endocardial surface of bullfrog atrium in directions parallel and perpendicular to the cardiac fibers. In the longitudinal fiber direction, the membrane depolarized for cathodal pulses (and hyperpolarized for anodal pulses) but only in a region within 445 +/- 112 microns (and 616 +/- 78 microns for anodal pulses) from the center of the electrode (n = 9). Outside this region, vm reversed polarity and reached a local maximum at 922 +/- 136 microns (and 988 +/- 117 microns for anodal pulses) (n = 9). Beyond this point vm decayed to zero over a distance of 1.5-2 mm. In the transverse fiber direction, the membrane depolarized for cathodal pulses (and hyperpolarized for anodal pulses) at all distances from the electrode. The amplitude of the response decreased with distance from the electrode with an exponential decay constant of 343 +/- 110 microns for cathodal pulses and 253 +/- 91 microns for anodal pulses (n = 7). The results were qualitatively similar in both fiber directions when the atrium was bathed in a solution containing ionic channel blockers. A two-dimensional computer model was formulated for the case of highly anisotropic cardiac tissue and qualitatively accounts for nearly all the observed spatial and temporal behavior of vm in the two fiber directions. The relationships between vm and both the "activating function" and extracellular potential gradient are discussed.

Animals↗

PubMed2004

On flow effects in balanced steady-state free precession imaging: pictorial description, parameter dependence, and clinical implications.

PURPOSE: To present a pictorial description of the origin of flow effects in balanced steady-state free precession (SSFP) imaging that can result in considerable frequency offset-dependent signal changes originating from outflow of spins that can still contribute to the total SSFP signal (out-of-slice contributions), to analyze the parameter dependence and slice broadening associated with outflow effects, and to illustrate clinical implications such as frequency offset-dependent flow artifacts and spatial misencoding. MATERIALS AND METHODS: Computer simulations were used to create a pictorial description of flow effects that illustrates the origin and parameter dependence of the observed signal changes and links their frequency dependency to the phase distribution of spins flowing in and out of the imaging slice. Slice broadening associated with out-of-slice contributions and flow-related signal enhancement was characterized by an effective slice thickness, which depends on flow rate, the T2* decay of signal magnitude from spins that have left the imaging slice, and the ratio of the net out-of-slice magnetization relative to the thickness of the imaging slice. RESULTS: Both simulated SSFP signal intensities and effective slice broadening vary with flip angle and demonstrate a nonlinear dependence on inflow. Simulations with bloodlike T1 and T2 show that the effective slice thickness can be as large as 15 times the prescribed slice thickness. These effects can have significant clinical implications such as large frequency offset-dependent signal enhancement, pulsatile flow artifacts, and spatial misrepresentation of blood signal that has already left the imaging slice. CONCLUSION: Flow-related signal changes in SSFP imaging exhibit highly complex parameter dependence, which predominantly has to be associated with frequency offset-dependent outflow effects and a resulting broadening of the slice thickness.

Artifacts↗

PubMed2005

Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory.

Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1.2) gene in the hippocampus and neocortex (Cav1.2(HCKO)). This model shows (1) a selective loss of protein synthesis-dependent NMDAR-independent Schaffer collateral/CA1 late-phase LTP (L-LTP), (2) a severe impairment of hippocampus-dependent spatial memory, and (3) decreased activation of the mitogen-activated protein kinase (MAPK) pathway and reduced cAMP response element (CRE)-dependent transcription in CA1 pyramidal neurons. Our results provide strong evidence for a role of L-type Ca2+ channel-dependent, NMDAR-independent hippocampal L-LTP in the formation of spatial memory in the behaving animal and for a function of the MAPK/CREB (CRE-binding protein) signaling cascade in linking Cav1.2 channel-mediated Ca2+ influx to either process.

2-Amino-5-phosphonovalerate↗

PubMed1988

[Normally functioning mitral prosthesis: visualization and characterization of the trans-valvular flow using color-coded Doppler].

Color flow imaging (CFI) allows real time visualization of intracardiac and transvalvular blood flow, superimposed on two-dimensional echocardiographic images. Therefore it can be useful in the identification and characterization of spatial configuration of jets through valve prosthesis. The aim of this study was to define the transvalvular flow pattern of jet in 54 patients (pts) with mitral valve prosthesis which were functioning well. Thirty-six of these pts were females and 18 males; their ages ranged from 40 to 73 years, mean age: 58. Prosthetic mitral inflow was evaluated utilizing the parasternal long axis, apical long axis and apical 4 chamber views; in addition ("off axis") intermediate sections were used when needed. Adequate CFI for detailed frame by frame analysis was obtained in 50 pts (92%). Fourteen pts had biological prosthesis (9 Hancock, 4 Carpentier-Edwards, 1 Ionescu-Shiley). Thirty-six pts had mechanical prosthesis: 13 Björk-Shiley, 8 Starr-Edwards, 9 Sorin, 5 Lillehey-Kaster, 1 Smeloff-Cutter. Variable jet configurations were identified, which were related to the type of prosthetic valve. Bioprosthetic valve characteristically had a wide, homogeneous transvalvular flow, directed towards the interventricular septum. Björk-Shiley prosthesis presented typically a jet with two components. Trans-prosthetic flow was dependent on the spatial position of the prosthesis and on the orientation of the tilting disc. Thus, the main jet, coming from the major orifice, could be directed towards the apex, flowing parallel to the left ventricular postero-lateral wall while the jet coming from the minor orifice was thin and directed towards the interventricular septum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2002

Auditory-visual interactions subserving goal-directed saccades in a complex scene.

This study addresses the integration of auditory and visual stimuli subserving the generation of saccades in a complex scene. Previous studies have shown that saccadic reaction times (SRTs) to combined auditory-visual stimuli are reduced when compared with SRTs to either stimulus alone. However, these results have been typically obtained with high-intensity stimuli distributed over a limited number of positions in the horizontal plane. It is less clear how auditory-visual interactions influence saccades under more complex but arguably more natural conditions, when low-intensity stimuli are embedded in complex backgrounds and distributed throughout two-dimensional (2-D) space. To study this problem, human subjects made saccades to visual-only (V-saccades), auditory-only (A-saccades), or spatially coincident auditory-visual (AV-saccades) targets. In each trial, the low-intensity target was embedded within a complex auditory-visual background, and subjects were allowed over 3 s to search for and foveate the target at 1 of 24 possible locations within the 2-D oculomotor range. We varied systematically the onset times of the targets and the intensity of the auditory target relative to background [i.e., the signal-to-noise (S/N) ratio] to examine their effects on both SRT and saccadic accuracy. Subjects were often able to localize the target within one or two saccades, but in about 15% of the trials they generated scanning patterns that consisted of many saccades. The present study reports only the SRT and accuracy of the first saccade in each trial. In all subjects, A-saccades had shorter SRTs than V-saccades, but were more inaccurate than V-saccades when generated to auditory targets presented at low S/N ratios. AV-saccades were at least as accurate as V-saccades but were generated at SRTs typical of A-saccades. The properties of AV-saccades depended systematically on both stimulus timing and S/N ratio of the auditory target. Compared with unimodal A- and V-saccades, the improvements in SRT and accuracy of AV-saccades were greatest when the visual target was synchronous with or leading the auditory target, and when the S/N ratio of the auditory target was lowest. Further, the improvements in saccade accuracy were greater in elevation than in azimuth. A control experiment demonstrated that a portion of the improvements in SRT could be attributable to a warning-cue mechanism, but that the improvements in saccade accuracy depended on the spatial register of the stimuli. These results agree well with earlier electrophysiological results obtained from the midbrain superior colliculus (SC) of anesthetized preparations, and we argue that they demonstrate multisensory integration of auditory and visual signals in a complex, quasi-natural environment. A conceptual model incorporating the SC is presented to explain the observed data.

Acoustic Stimulation↗

PubMed2004

The Invs gene encodes a microtubule-associated protein.

Microtubule networks are important for many vital processes such as mitosis, cell polarity, and differentiation. Ciliary architecture and function closely depend on the microtubule cytoskeleton, and recent studies suggest a role of apical cilia of renal epithelia in the pathogenesis of polycystic kidney disease. This study evaluates the localization, potential interacting partners, and functional aspects of the Invs gene product inversin. Only recently, INVS has been identified as the gene that is mutated in nephronophthisis type 2, an autosomal recessive polycystic kidney disease. Using immunoprecipitation and co-pelleting assays, we show that the Invs gene product inversin forms a stable complex with tubulin in cultured renal epithelial cells. Inversin localizes to several components of the cytoskeleton including ciliary, random, and polarized microtubule pools. During cell divison, inversin is recruited to mitotic spindle fibers. After microtubule depolymerization using colcemid inversin and tubulin staining is no longer characterized by a network pattern but by homogeneous, diffuse distribution. Inversin does not coprecipitate with tubulin after addition of colcemid. After removal of colcemid, inversin immunofluorescence reappears together with tubulin in centrioles. Treatment with the microtubule stabilizing agent paclitaxel leads to severe alteration of the microtubule cytoskeleton with bundling and formation of long spindles of tubulin and inversin. In conclusion, inversin is closely associated with the microtubule cytoskeleton, and its spatial distribution is dependent on tubulin polymerization. Hence, altered inversin-tubulin interaction may impair ciliary function and thereby contribute to cyst development in nephronophthisis.

Animals↗

PubMed2004

Differential trafficking of transforming growth factor-beta receptors and ligand in polarized epithelial cells.

Epithelial cells in vivo form tight cell-cell associations that spatially separate distinct apical and basolateral domains. These domains provide discrete cellular processes essential for proper tissue and organ development. Using confocal imaging and selective plasma membrane domain activation, the type I and type II transforming growth factor-beta (TGFbeta) receptors were found to be localized specifically at the basolateral surfaces of polarized Madin-Darby canine kidney (MDCK) cells. Receptors concentrated predominantly at the lateral sites of cell-cell contact, adjacent to the gap junctional complex. Cytoplasmic domain truncations for each receptor resulted in the loss of specific lateral domain targeting and dispersion to both the apical and basal domains. Whereas receptors concentrate basolaterally in regions of direct cell-cell contact in nonpolarized MDCK cell monolayers, receptor staining was absent from areas of noncell contact. In contrast to the defined basolateral polarity observed for the TGFbeta receptor complex, TGFbeta ligand secretion was found to be from the apical surfaces. Confocal imaging of MDCK cells with an antibody to TGFbeta1 confirmed a predominant apical localization, with a stark absence at the basal membrane. These findings indicate that cell adhesion regulates the localization of TGFbeta receptors in polarized epithelial cultures and that the response to TGFbeta is dependent upon the spatial distribution and secretion of TGFbeta receptors and ligand, respectively.

Adherens Junctions↗

PubMed2005

Assessment of display performance for medical imaging systems: executive summary of AAPM TG18 report.

Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance testing and quality control of medical display devices. This paper is an executive summary of the TG18 report. TG18 guidelines include visual, quantitative, and advanced testing methodologies for primary and secondary class display devices. The characteristics, tested in conjunction with specially designed test patterns (i.e., TG18 patterns), include reflection, geometric distortion, luminance, the spatial and angular dependencies of luminance, resolution, noise, glare, chromaticity, and display artifacts. Geometric distortions are evaluated by linear measurements of the TG18-QC test pattern, which should render distortion coefficients less than 2%/5% for primary/secondary displays, respectively. Reflection measurements include specular and diffuse reflection coefficients from which the maximum allowable ambient lighting is determined such that contrast degradation due to display reflection remains below a 20% limit and the level of ambient luminance (Lamb) does not unduly compromise luminance ratio (LR) and contrast at low luminance levels. Luminance evaluation relies on visual assessment of low contrast features in the TG18-CT and TG18-MP test patterns, or quantitative measurements at 18 distinct luminance levels of the TG18-LN test patterns. The major acceptable criteria for primary/ secondary displays are maximum luminance of greater than 170/100 cd/m2, LR of greater than 250/100, and contrast conformance to that of the grayscale standard display function (GSDF) of better than 10%/20%, respectively. The angular response is tested to ascertain the viewing cone within which contrast conformance to the GSDF is better than 30%/60% and LR is greater than 175/70 for primary/secondary displays, or alternatively, within which the on-axis contrast thresholds of the TG18-CT test pattern remain discernible. The evaluation of luminance spatial uniformity at two distinct luminance levels across the display faceplate using TG18-UNL test patterns should yield nonuniformity coefficients smaller than 30%. The resolution evaluation includes the visual scoring of the CX test target in the TG18-QC or TG18-CX test patterns, which should yield scores greater than 4/6 for primary/secondary displays. Noise evaluation includes visual evaluation of the contrast threshold in the TG18-AFC test pattern, which should yield a minimum of 3/2 targets visible for primary/secondary displays. The guidelines also include methodologies for more quantitative resolution and noise measurements based on MTF and NPS analyses. The display glare test, based on the visibility of the low-contrast targets of the TG18-GV test pattern or the measurement of the glare ratio (GR), is expected to yield scores greater than 3/1 and GRs greater than 400/150 for primary/secondary displays. Chromaticity, measured across a display faceplate or between two display devices, is expected to render a u',v' color separation of less than 0.01 for primary displays. The report offers further descriptions of prior standardization efforts, current display technologies, testing prerequisites, streamlined procedures and timelines, and TG18 test patterns.

Computer Graphics↗

PubMedDate not supplied

Blood flow distribution in necrotic versus nonnecrotic rabbit hearts.

The spatial myocardial blood flow heterogeneity of the normal heart was previously investigated by means of the standard microsphere-defined regional myocardial blood flow in nonischemic hearts. We determined the probability density functions of coronary blood flows in the rabbit heart at selected macroautoradiographic 20-microns cross-sections of the left ventricle in nonischemic as well as infarcted hearts. Macroautoradiography gave us spatial resolutions of 0.1-0.2 mm. As a tracer we used 14C-iodoantipyrine given into the root of the aorta. We report here for the first time a systematic study of the shape of the flow probability density functions during acute regional myocardial necrosis. As the hearts became progressively and extensively necrotic, the distribution of flows changed its characteristics showing two independent components. The first component was the peak representing the nonischemic regions in the hearts subjected to acute ischemia. The second component was a monotonically decreasing component associated with very low flows and necrosis in the severely hypoperfused portion of the hearts. This monotonically decreasing component became larger as the extent of ischemia increased and was well separated from the peak attributable to the nonischemic regions. We could not demonstrate a leftward shift of the nonischemic central peak in the ischemic hearts. Our research shows that in transaxial radionuclide cardiac sections, such as those that might be obtained and analyzed in clinical SPECT and clinical PET, variable amounts of myocardial necrosis will result in a composite curve of myocardial blood flow heterogeneities. One portion of the curve will indicate the distribution of flows in the nonischemic zones. The other portion will vary in magnitude with the extent of ischemia, exhibit the shape of monotonically decreasing curve. Depending upon the spatial resolution of the radionuclide imaging technique utilized, a border zone will exist representing the interface between normally perfused and occluded vascular beds. In our investigation, it was found that the border zone determined statistically was consistently and significantly smaller than the border zone determined visually.

Animals↗

PubMed1999

Lack of protection of monoamine oxidase B-deficient mice from age-related spatial learning deficits in the Morris water maze.

Monoamine oxidase B (MAO-B) increases in brain in response to aging and neurodegeneration. Whether such increases represent a risk factor to further neuronal damage or simply represent epiphenomena remains unclear. L-deprenyl, an inhibitor of MAO-B, has been shown to improve learning in aged rodents. However, recent data suggests this may occur through mechanisms independent of its enzymatic inhibition. This study investigates visualspatial learning of MAO-B deficient mice and examines what effects absence of MAO-B has on age-related cognitive decline. Learning was tested in the Morris Water Maze in male transgenic MAO-B knockout mice (KO) ages 2 months (n = 9), 7 months (n = 7), and 17 months (n = 8). Performance was compared to that of wild type (WT) littermates. Animals were given four 60 second trials per day with the submerged platform in the "North" position. Animals received 7 days of learning in which they were introduced into the pool facing the wall, alternating between the "East" and "West" positions. A single probe trial followed on day 8, followed by continuation of the original learning paradigm on days 9 and 10. Subsequently, the platform position was changed to the diagonally opposite quadrant and learning continued on days 11-13, followed by a cue phase in which the platform was made visible. Total distance traveled and latency to the platform was increased in 7- and 17- month old mice, most significantly at the beginning of the acquisition phase. This effect reappeared again in 17- month old mice during the reversal phase. No predominant genotypic differences in latency or distance were observed during any phase of the experiment. Our results show that presence or absence of MAO-B does not appear to alter performance in the Morris water maze. Furthermore, presence or absence of MAO-B does not provide protection from the age-dependent deficits in spatial learning.

Aging↗

PubMed2026

Impact of spatial distribution of M2 macrophages on prognosis and neoadjuvant chemotherapy resistance in gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a crucial treatment for locally advanced gastric cancer; however, approximately 30-40% of patients experience primary resistance, the mechanisms of which urgently require elucidation. The tumor microenvironment exhibits a high degree of spatial heterogeneity. M2 macrophages, as critical immune cells within this environment, are typically associated with poor prognosis. Yet, whether their spatial distribution impacts chemotherapy efficacy remains unclear. This study aims to investigate the relationship between the in situ spatial distribution characteristics of M2 macrophages and chemoresistance in gastric cancer. METHODS: Based on The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, the association between M2 markers (CD163, MRC1) and histological grade as well as overall survival (OS) was evaluated. Spearman correlation and functional enrichment analyses were conducted to explore the mechanistic link between M2 macrophages and stromal barrier construction. Multiplex immunofluorescence (mIF) and digital pathology image analysis were utilized to calculate the areal density of M2 macrophages in the intratumoral core and the peritumoral stroma, respectively. The tumor-to-peritumoral ratio (TPR) was constructed, followed by a rank correlation analysis between TPR and the tumor regression grade (TRG). RESULTS: TCGA-STAD results confirmed that patients with high expression of M2 markers had worse OS (P=0.03), and the expression levels of M2 markers increased with histological grade. MRC1 was highly significantly and positively correlated with the pro-fibrotic factor TGFB1 (rho=0.447, P<0.001), with the gene set significantly enriched in pathways such as positive regulation of cytokine production and myeloid leukocyte activation. Histological examination revealed that in chemoresistant patients (TRG 3), M2 macrophages were primarily retained in the peritumoral stroma, with a median TPR of 0.50; in chemosensitive patients (TRG 1-2), a massive influx of M2 macrophages into the tumor core was observed, with a median TPR of 6.67. TPR was negatively correlated with TRG (rs=-0.65, P=0.043). CONCLUSIONS: The clinical impact of M2 macrophages in the gastric cancer microenvironment is highly dependent on their spatial distribution. The peritumoral-enriched pattern (TPR <1) mediates primary chemoresistance, whereas high infiltration in the core objectively reflects the pathological footprint following effective chemotherapy. The TPR serves as a novel tool for assessing neoadjuvant chemosensitivity in gastric cancer.

Gastric cancer (GC)↗

PubMed2002

Multisensory integration for spatial orientation in trait anxiety subjects: absence of visual dependence.

Studies suggest a greater reliance on visual information for maintaining balance in anxious subjects. Nevertheless, links between this supposed preferred visual processing and spatial orientation have not yet been evaluated. Two groups of subjects differing in their level of trait anxiety were formed. Equipped with a head-mounted visual display, they learned a virtual corridor using passive translation but active rotation, both with normal and with two different conflicting sensory conditions. After two visual navigation trials in the corridor, they were blindfolded and asked to reproduce the same trajectory from memory. In addition, subjects drew a map of the remembered corridor. Anxious subjects were comparable to non-anxious subjects when asked to reproduce the trajectory from memory, but exhibited a deficit when drawing a map of the corridor they were in. The results do not support the hypothesis that anxious subjects use preferentially one type of sensory cue over another for spatial orientation, but instead manifest difficulties in constructing more global representations of space.

Adult↗

PubMed2002

A psychophysical correlate of contrast dependent changes in receptive field properties.

Recent physiological investigations have demonstrated that a neuron's area of spatial summation can vary depending on stimulus contrast. Specifically, when the same stimulus is presented to a neuron at a low contrast, the area of summation (or neuron's receptive field) can increase by at least a factor of two, compared to that estimated with a high contrast stimulus. We sought to examine this phenomenon psychophysically by using an orientation discrimination task carried out in the presence of contextual stimuli. We have found previously that orientation discrimination thresholds for a sine-wave grating are elevated by the presence of a surround pattern of similar orientation (with an offset) and spatial frequency. However, when these patterns were separated by a gap of mean luminance exceeding roughly 1 deg, thresholds dropped to the level measured using the center pattern alone. Here, we examined the surround pattern's effect on orientation thresholds as a function of the contrast of the center and surround. We find that when both are presented at a low contrast, the detrimental influence of the surround on orientation thresholds is maintained over larger gap separations. We also find that the spatial frequency and orientation selectivity of the surround's masking effect on orientation thresholds is broader at low contrast than at high contrast. Although the results support the idea of a spatial reorganization of the mechanisms involved in the task at low contrast, these changes are insufficient, in and of themselves, to account for the data. We suggest that additional influences possibly reflecting image segmentation also affect performance.

Contrast Sensitivity↗

PubMed2005

Stimulus requirements for the decoding of myopic and hyperopic defocus under single and competing defocus conditions in the chicken.

PURPOSE: The bidirectional nature of emmetropization, as observed in young chicks, implies that eyes are able to distinguish between myopic and hyperopic focusing errors. In the current study the spatial frequency and contrast dependence of this process were investigated in an experimental paradigm that allowed strict control over both parameters of the retinal image. Also investigated was the influence of accommodation. METHODS: Defocusing stimuli were presented through lens-cone devices with attached targets. These devices were monocularly applied to 5-day-old chickens for 4 days. Defocus conditions included: (1) 7 D of myopic defocus, (2) 7 D of hyperopic defocus, and (3) a combination of the two. Two high contrast target designs, a spatially rich, striped Maltese cross (target 1) and a standard Maltese cross (target 2) were used, except in some experiments where target contrast or spatial frequency content was further manipulated. To test the role of accommodation, the treated eye of some chicks underwent ciliary nerve section before attachment of the device. Refractive error (RE) was measured by retinoscopy and axial ocular dimensions measured by A-scan ultrasonography, both in chicks under anesthesia. RESULTS: With imposed myopic defocus and high contrast, target 1 elicited significantly better compensation than did target 2. With imposed hyperopic defocus, both targets elicited near normal compensatory responses. Reducing image contrast to 32% for target 2 and to 16% for target 1 precluded compensation for myopic defocus, inducing myopia instead. The low-pass-filtered target also induced myopia, irrespective of the sign of imposed defocus. With competing defocus and intact accommodation, target 1 induced a transient hyperopic growth response, whereas myopia was consistently observed with target 2. When accommodation was rendered inactive, both targets induced myopia under these competitive conditions. CONCLUSIONS: Compensation to myopic defocus is critically dependent on the inclusion of middle to high spatial frequencies in the stimulus and has a spatial frequency-dependent threshold contrast requirement. With competing myopic and hyperopic defocus, the former transiently dominates the latter as a determinant of ocular growth, provided that the stimulus conditions include sufficient middle to high spatial frequency information and that accommodation cues are available.

Accommodation, Ocular↗

PubMed2000

Laser-guided direct writing of living cells.

To perform their myriad functions, tissues use specific cell-cell interactions that depend on the spatial ordering of multiple cell types. Recapitulating this spatial order in vitro will facilitate our understanding of function and failure in native and engineered tissue. One approach to achieving such high placement precision is to use optical forces to deposit cells directly. Toward this end, recent work with optical forces has shown that a wide range of particulate materials can be guided and deposited on surfaces to form arbitrary spatial patterns. Here we report that, when we use the light from a near-infrared diode laser focused through a low numerical aperture lens, individual embryonic chick spinal cord cells can be guided through culture medium and deposited on a glass surface to form small clusters of cells. In addition, we found that the laser light could be coupled into hollow optical fibers and that the cells could be guided inside the fibers over millimeter distances. The demonstration of fiber-based guidance extends by 2 orders of magnitude the distance over which optical manipulation can be performed with living cells. Cells guided into the fiber remained viable, as evidenced by normal cell adhesion and neurite outgrowth after exposure to the laser light. The results indicate that this particle deposition process, which we call "laser-guided direct writing," can be used to construct patterned arrays of tens to hundreds of cells using arbitrary numbers of cell types placed at arbitrary positions with micrometer-scale precision.

Animals↗

PubMed1999

Regulation of exocytosis via release of Ca(2+) from intracellular stores.

The release of Ca(2+) from intracellular stores is an important trigger for secretion in many cell types. Depending on the spatial relationship between the intracellular Ca(2+) stores and the site of exocytosis, the Ca(2+) signal can be very local or spread throughout the entire cell. Here, we review how the release of Ca(2+) from inositol trisphospate (IP(3))-sensitive stores contributes differently to the stimulus-secretion coupling in three types of secretory cells (acinar cells of the pancreas, gonadotrophs, and corticotrophs of the anterior pituitary gland). We propose that in both pancreatic acinar cells and pituitary gonadotrophs the IP(3)-sensitive stores may be in close proximity to the sites of exocytosis such that the concentration of Ca(2+) at these sites are transiently much higher than the average cytosolic Ca(2+) concentration. In contrast, the local Ca(2+) gradient is less prominent in pituitary corticotrophs. Finally, some recent technical developments that may contribute significantly to future investigations of local Ca(2+) signals are discussed.

Adrenocorticotropic Hormone↗

PubMed1990

Role of receptor tyrosine kinases during Drosophila development.

In vertebrates, a tyrosine kinase activity has been identified as an integral component of growth factor receptors and the products of proto-oncogenes. Many of these receptor tyrosine kinases (RTKs) appear to play a key role in the regulation of cell growth. Recent analyses of several Drosophila genes encoding putative RTKs indicate that this class of proteins also plays an important role in decisions about cell fate that depend on cellular interactions during development. The sevenless RTK mediates the position-dependent specification of a particular photoreceptor cell type (R7) in the eye. The local specification of R7 cells requires a functional tyrosine kinase domain of the sevenless protein but does not depend on the spatially restricted expression of the sevenless gene. The Drosophila EGF receptor homologue serves multiple functions during development, some of which are clearly unrelated to regulation of cell growth. Finally, the torso gene encodes an RTK required for the specification of the terminal regions of the Drosophila larva. A number of other genes have been genetically identified that appear to function in the same developmental processes upstream or downstream of these three RTKs. These loci are excellent candidates for genes encoding other components of the signalling pathways, such as ligands or substrates of the RTKs.

Alleles↗