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PubMed1990

Time resolved 3-dimensional recording of redox ratio during spreading depression in gerbil brain.

Optical fluorescence and reflectance measurements have been used to map the distribution of metabolic states in three dimensions in the gerbil brain with a spatial resolution of 200 microns an a time resolution of 4-6 s. In Mongolian gerbils anesthetized with pentobarbital, the redox states of the nicotinamide adenine dinucleotide (NADH) and flavoprotein components of the electron transport chain exhibit two distinct phases during the wave of spreading depression: (1) a transient period of oxidation and (2) a prolonged period of reduction, during which the cytochromes are reduced, and the hemoglobin is predominantly in the deoxy form. These data are interpreted as indicating that the energy demand placed on the gerbil brain during such spreading depression wave is sufficient to drive the brain temporarily hypoxic.

Animals↗
PubMed2005

The endocytic pathway and formation of the Wingless morphogen gradient.

Controlling the spread of morphogens is crucial for pattern formation during development. In the Drosophila wing disc, Wingless secreted at the dorsal-ventral compartment boundary forms a concentration gradient in receiving tissue, where it activates short- and long-range target genes. The glypican Dally-like promotes Wingless spreading by unknown mechanisms, while Dynamin-dependent endocytosis is thought to restrict Wingless spread. We have utilized short-term expression of dominant negative Rab proteins to examine the polarity of endocytic trafficking of Wingless and its receptors and to determine the relative contributions of endocytosis, degradation and recycling to the establishment of the Wingless gradient. Our results show that Wingless is internalized via two spatially distinct routes: one on the apical, and one on the basal, side of the disc. Both restrict the spread of Wingless, with little contribution from subsequent degradation or recycling. As previously shown for Frizzled receptors, depleting Arrow does not prevent Wingless from entering endosomes. We find that both Frizzled and Arrow are internalized mainly from the apical membrane. Thus, the basal Wingless internalization route must be independent of these proteins. We find that Dally-like is not required for Wingless spread when endocytosis is blocked, and propose that Dally-like promotes the spread of Wingless by directing it to lateral membranes, where its endocytosis is less efficient. Thus, subcellular localization of Wingless along the apical-basal axis of receiving cells may be instrumental in shaping the Wingless gradient.

Animals↗
PubMed1989

Forward masking patterns produced by intracochlear electrical stimulation of one and two electrode pairs in the human cochlea.

Three psychophysical forward masking studies were conducted on a multichannel cochlear implant patient. The first study investigated the masking pattern produced by a bipolar electrode pair at different stimulus currents. It was found that the masking pattern for a single-masker bipolar electrode pair had a maximum located at an electrode position where the masker and probe coincided. The spread of the masking pattern was not symmetrical about the maximum. The amount of masking decreased very rapidly toward the apical direction and less rapidly toward the basal direction from the position of the maximum. As the stimulus current increased, the amount of masking at the maximum increased and the masking pattern broadened toward the base. The second study investigated the masking pattern produced by the activation of single bipolar electrode pairs with different spatial extents. The spatial extent of a bipolar electrode pair is defined as the distance between the apical and basal electrode members of the bipolar pair. With a small spatial extent (1.5 mm), the more basal electrode pairs (higher threshold and smaller dynamic range) produced broader masking patterns than the more apical electrode pairs (lower threshold and wider dynamic range), suggesting that there was more current spread at the basal region. With a larger spatial extent (4.5 mm), an additional secondary masking maximum was observed in the vicinity of the apical electrode member of the masker; this was observed only when the apical electrode member lay within the low-threshold apical region. The third study investigated the masking patterns produced by two loudness balanced bipolar masker electrode pairs activated within a stimulus period (inverse of the pulse repetition rate). The biphasic current pulses delivered to the two electrode pairs were nonoverlapping in time. It was found that, at any probe electrode position, the amount of masking produced by the two combined bipolar electrode pairs approximately followed the greater of the two maskings produced respectively by the two individual bipolar masker electrode pairs.

Cochlea↗
PubMed1994

[The superior and inferior venae cavae: angiography by TOF 2D magnetic resonance versus spin-echo sequences].

This work was aimed at assessing the usefulness of magnetic resonance angiography (MRA) in the investigation and diagnosis of vena cava conditions. Forty-five subjects that is 20 volunteers and 25 patients, were examined with MRA using a 1.5 T superconductive system (SE and angiography pulse sequences). In the 25 patients, 8 cases of thrombosis were diagnosed, together with 4 cases of suspected tumor spread into either the superior or the inferior vena cava, 2 cases of inferior vena cava agenesis, 5 cases of retroaortic left renal vein and 5 cases of abdominal aortic aneurysm. MRA was performed with the 2D time-of-flight (TOF) technique (FA 18 degrees, TR 30-40 ms, TE 10 ms); the images were acquired on the coronal, sagittal and axial planes with and without presaturation pulse and rotated in the post-processing according to the maximum intensity projection. In all volunteers MRA identified jugular veins, subclavian veins, anonymous veins, superior vena cava, inferior vena cava and common iliac veins. The main limitation of MRA was its spatial resolution. MRA proved to be less accurate than SE sequences in the assessment of tumor spread. As for thrombotic conditions, MRA provided useful additional information and is therefore considered a complementary technique to SE MRI. As for venous anomalies (double inferior vena cava, vena cava agenesis and retroaortic left renal vein) and in the study of the relationships with abdominal aortic aneurysms, MRA proved to be the more accurate of the two techniques.

Adult↗
PubMed2000

Performance of a PSPMT based detector for scintimammography.

In breast scintigraphy, compact detectors with high intrinsic spatial resolution and small inactive peripheries can provide improvements in extrinsic spatial resolution, efficiency and contrast for small lesions relative to larger conventional cameras. We are developing a pixelated small field-of-view gamma camera for scintimammography. Extensive measurements of the imaging properties of a prototype system have been made, including spatial resolution, sensitivity, uniformity of response, geometric linearity and energy resolution. An anthropomorphic torso phantom providing a realistic breast exit gamma spectrum has been used in a qualitative study of lesion detectability. A new type of breast imaging system that combines scintimammography and digital mammography in a single upright unit has also been developed. The system provides automatic co-registration between the scintigram and the digital mammogram, obtained with the breast in a single configuration. Intrinsic spatial resolution was evaluated via calculation of the phase-dependent modulation transfer function (MTF). Measurements of extrinsic spatial resolution, sensitivity and uniformity of response were made for two types of parallel hole collimator using NEMA (National Electrical Manufacturers Association) protocols. Geometric linearity was quantified using a line input and least squares analysis of the measured line shape. Energy resolution was measured for seven different crystal types, and the effectiveness of optical grease coupling was assessed. Exit gamma spectra were obtained using a cadmium zinc telluride based spectrometer. These were used to identify appropriate radioisotope concentrations for the various regions of an anthropomorphic torso phantom, such that realistic scatter conditions could be obtained during phantom measurements. For prone scintimammography, a special imaging table was constructed that permits simultaneous imaging of both breasts, as well as craniocaudal views. A dedicated breast imaging system was also developed that permits simultaneous acquisition and superposition of planar gamma images and digital x-ray images. The intrinsic MTF is nonstationary, and is dependent on the phase relationship between the signal and the crystal array matrix. Averaged over all phases, the MTF is approximately 0.75, 0.57 and 0.40 at spatial frequencies of 1.0, 1.5 and 2.0 cycles per cm, respectively. The phase averaged line spread function (LSF) has a FWHM value of 2.6 mm. Following uniformity corrections, the RMS deviations in flood images are only slightly greater than is predicted from counting statistics. Across an 80 mm section of the active area, the differential linearity is 0.83 mm and the absolute linearity 2.0 mm. Using an anthropomorphic torso phantom with detachable breasts, scatter radiation similar to that observed exiting the breast of scintimammography patients was observed. It was observed that scattered gamma rays can constitute the majority of the radiation incident on the detector, but that the scatter-to-primary ratio varies significantly across the field of view, being greatest in the caudal portion of the breast, where scatter from the liver is high. Using a lesion-to-breast concentration ratio of 6:1, a 1.0 cm3 simulated breast lesion was detectable in lateral images obtained with both the developmental camera and with a clinical camera, while a 0.35 cm3 lesion was detectable in neither. Utilization of the dual x-ray transmission, gamma emission breast imaging system greatly increases the conspicuity of scintimammographic lesions relative to prone imaging, as well as greatly facilitating the localization and identification of structures in the gamma image. The prototype imaging gamma detector exhibits spatial resolution superior to that of conventional cameras, and comparable uniformity of response and geometric linearity. Because of light losses in the crystals, the energy resolution is inferior to that of single crystal NaI(Tl) came

Equipment Design↗
PubMed1999

Optimal gradient waveform design for projection imaging and projection reconstruction echoplanar spectroscopic imaging.

The use of modulated B0 projection gradient waveforms is proposed for magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) to shape the k-space sampling density function to match the profile of an applied reconstruction window function. This allows for a time-efficient means of maximizing the signal-to-noise ratio when, for example, a low-pass spatial filter, designed to reduce k-space truncation artifacts and corresponding point-spread function sidelobe energies, is implemented. Both the two-dimensional (2D) and 3D cases are investigated. To create the projection gradient waveforms, a design method is developed that uses nonlinear constrained optimization (NLCO) to minimize the variance of the reconstruction noise. The design is subject to both equality and inequality constraints, which include the maximum gradient magnitude and slew rate. It is shown that NLCO can also be applied to twisting the projection trajectories for purposes of reducing the data acquisition time while still maintaining the desired sampling density. Applications to 1H MRSI are investigated via simulations. Advantages and limitations of the new sampling schemes are discussed.

Brain Chemistry↗
PubMed2005

Preoperative staging of rectal cancer: the MERCURY research project.

The development of a surgical technique that removes the tumour and all local draining nodes in an intact package, namely total mesorectal excision (TME) surgery, has provided the impetus for a more selective approach to the administration of preoperative therapy. One of the most important factors that governs the success of TME surgery is the relationship of tumour to the circumferential resection margin (CRM). Tumour involves the CRM in up to 20% of patients undergoing TME surgery, and results in both poor survival and local recurrence. It is therefore clear that the importance of the decision regarding the use of pre-operative therapy lies with the relationship of the tumour to the mesorectal fascia. In addition, a high-spatial-resolution MRI technique will identify tumours exhibiting other poor prognostic features, namely, extramural spread >5 mm, extramural venous invasion by tumour, nodal involvement, and peritoneal infiltration. The potential benefits of a selective approach using MRI-based selection criteria are evident. That is, over 50% of patients can be treated successfully with primary surgery alone without significant risk of local recurrence or systemic failure. Of the remainder, potentially dramatic improvements may be achieved through the use of intensive and targeted preoperative therapy aimed not only at reducing the size of the primary tumour and rendering potentially irresectable tumour resectable with tumour-free circumferential margins, but also at enabling patients at high risk of systemic failure to benefit from intensive combined modality therapy aimed at eliminating micrometastatic disease.

Endosonography↗
PubMed1990

Spatial interval discrimination with blurred lines: black and white are separate but not equal at multiple spatial scales.

We used Gaussian blurred lines of same- and opposite-polarity to measure the effects of blur on 3-line spatial interval discrimination (bisection). The results of our experiments can be summarized as follows. Spatial interval discrimination (3-line bisection) thresholds are proportional to the separation of the lines (i.e. Weber's law). At the optimal separation, spatial interval discrimination thresholds for same-polarity lines represent a "hyperacuity" as small as 2 sec arc. For same-polarity Gaussian blurred lines, over a wide range of the blur standard deviations (sigma), the optimal threshold occurs when the separation is approx. 2 sigma, and the optimal threshold is about 0.02 sigma, or a Weber fraction (delta s/s) of 0.01. For opposite-polarity lines, under conditions where same-polarity stimuli yield the best thresholds (at a separation approximately 2 sigma), spatial interval thresholds are an order of magnitude worse than that for same-polarity lines, suggesting that the localization of stimili of opposite-polarity is much worse than that of same-polarity stimuli over a wide range of spatial scales. At large separations, greater than about 5 sigma, spatial interval discrimination thresholds are more or less independent of both contrast and polarity. While hyperacuity is generally thought of in terms of the tiny spatial thresholds which are obtained at small separations with stimuli comprised of thin lines, the present results, and those of others, suggest that for same-polarity stimuli, hyperacuity thresholds are a general property of the visual system, occurring at many spatial scales. The present results also suggest that the poor localization of opposite-polarity lines occurs at multiple spatial scales, when the line separation is less than about five times the stimulus spread. We consider several models which can account for particular features of our data.

Contrast Sensitivity↗
PubMed2001

Thermal compression and characterization of three-dimensional nonwoven PET matrices as tissue engineering scaffolds.

Nonwoven fibrous matrices have been widely used as scaffolds in tissue engineering, and modification of microstructure of these matrices is needed to organize cells in three-dimensional space with spatially balanced proliferation and differentiation required for functional tissue development. The method of thermal compression of nonwoven polyethylene terephthalate (PET) fabrics was developed and key parameters of temperature, pressure, and compression duration were evaluated in this study. The permanent deformation was obtained at elevated temperature under pressure and the viscoelastic compressional behaviors were observed, characterized by a distinct apparent modulus change in glass transition temperature region. A liquid extrusion method was further employed to analyze both pore size and its distribution for matrices with porosity ranging from 84 to 93%. It is also found that a more uniformly distributed pore size was resulted from thermal compression and the isotropic nature of nonwoven fabrics was preserved because of the proportional reduction of the pore by compression. The thermally compressed fabric matrices with two different pore sizes (15 and 20 microm in pore radius) were used to culture human trophoblast ED27 and NIH 3T3 cells. It was found that cells cultured in the different pore-size PET matrices had different cell spatial organization and proliferation rates. The smaller pores in the matrix allowed cells to spread better and proliferate faster, while cells in the larger pores tended to form large aggregates and had lower proliferation rate. The thermal compression technique also can be applied to other synthetic fibrous matrices including biodegradable polymers used in tissue engineering to modify the microstructure according to their viscoelastic properties.

3T3 Cells↗
PubMed2001

High bubble concentrations produced by ultrasounds in binary mixtures.

It was discovered that simultaneous insonification and air blowing of different aqueous binary solutions such as water/sodium-dodecyl-sulphate (SDS), water/methanol or water/potassium-sulphate yields a very concentrated bubble cloud invading the whole vessel in a few seconds. After the end of insonification, this cloudiness remained in the solution for about 1 min. The phenomenon was investigated by computer-treatment of solution pictures recorded every second after the end of insonification. Turbidity appeared to increase with ultrasound power, and also with SDS concentration. During the disappearance of the cloud, a turbidity front appeared rising and spreading upward. This front was studied in the characteristic plane and interpreted as a spatial segregation of different bubble sizes rising with different terminal velocities. The bubble sizes involved were estimated to about 10 microns. Adsorption of surface active species are invoked to explain the cloud formation and its abnormally slow disappearance, but the occurrence of the phenomenon for potassium-sulphate salt remains unexplained.

Journal Article↗
PubMed2001

Risk factors associated with an outbreak of dengue fever in a favela in Fortaleza, north-east Brazil.

To increase the effectiveness of ongoing anti-dengue control measures, we conducted a case-control study in a favela in Fortaleza (north-east Brazil) during an outbreak of dengue fever. Cases were defined according to the national guidelines for dengue control as well as based on the detection of IgM-dengue antibodies, and 34 cases and 34 controls were investigated. Significant risk factors were: living in a street perpendicular to the beach on which the favela is situated (P < 0.0001), an interval > 30 days since the last visit of the vector control agent (P=0.001), receptacles in the garden or courtyard (P=0.001), plants with temporary water pools on the property, gutter to collect rainwater, uncovered water storage container (all P=0.02), and no waste collection (P=0.03). Socio-economic variables were not associated with dengue fever. The probable starting point of the epidemic was an uncovered water tank on the roof of the house adjacent to the index case. From there, the outbreak spread uphill parallel to the prevailing direction of the wind. Thus, the chronological and spatial evolution of the epidemic could have been forecast after the first cases had occurred. This example of investigative epidemiology in an operational setting shows that targeted intervention leading to increased effectiveness of control measures is possible.

Adolescent↗
PubMed2004

Statistical inference and model selection for the 1861 Hagelloch measles epidemic.

A stochastic epidemic model is proposed which incorporates heterogeneity in the spread of a disease through a population. In particular, three factors are considered: the spatial location of an individual's home and the household and school class to which the individual belongs. The model is applied to an extremely informative measles data set and the model is compared with nested models, which incorporate some, but not all, of the aforementioned factors. A reversible jump Markov chain Monte Carlo algorithm is then introduced which assists in selecting the most appropriate model to fit the data.

Adolescent↗
PubMed2006

Tissue resistivities determine the current flow in the cochlea.

PURPOSE OF REVIEW: In individuals with severe to profound hearing loss, cochlear implants bypass normal inner ear function by applying electrical current directly into the cochlea, thereby stimulating cochlear nerve fibers. Stimulating discrete populations of spiral ganglion cells in cochlear implant users' ears is similar to the encoding of small acoustic frequency bands in a normal-hearing person's ear. Thus, spiral ganglion cells stimulated by an electrode convey the information contained by a small acoustic frequency band. Problems that refer to the current spread and subsequent nonselective stimulation of spiral ganglion cells in the cochlea are reviewed. RECENT FINDINGS: Cochlear anatomy and tissue properties determine the current path in the cochlea. Current spreads largely via scala tympani and across turns. While most of the current leaves the cochlea via the modiolus, the facial canal and the round window constitute additional natural escape paths for the current from the cochlea. Moreover, degenerative processes change tissue resistivities and thus may affect current spread in the cochlea. SUMMARY: Electrode design and coding strategies may result in more spatial stimulation of spiral ganglion cells, resulting in a better performance of the electrode-tissue interface.

Cochlea↗
PubMed2006

Modelling the initial spread of foot-and-mouth disease through animal movements.

Livestock movements in Great Britain (GB) are well recorded and are a unique record of the network of connections among livestock-holding locations. These connections can be critical for disease spread, as in the 2001 epidemic of foot-and-mouth disease (FMD) in the UK. Here, the movement data are used to construct an individual-farm-based model of the initial spread of FMD in GB and determine the susceptibility of the GB livestock industry to future outbreaks under the current legislative requirements. Transmission through movements is modelled, with additional local spread unrelated to the known movements. Simulations show that movements can result in a large nationwide epidemic, but only if cattle are heavily involved, or the epidemic occurs in late summer or early autumn. Inclusion of random local spread can considerably increase epidemic size, but has only a small impact on the spatial extent of the disease. There is a geographical bias in the epidemic size reached, with larger epidemics originating in Scotland and the north of England than elsewhere.

Animals↗
PubMed2005

A segmental pattern of alkaline phosphatase activity within the notochord coincides with the initial formation of the vertebral bodies.

This study shows that segmental expression of alkaline phosphatase (ALP) activity by the notochord of the Atlantic salmon (Salmo salar L.) coincides with the initial mineralization of the vertebral body (chordacentrum), and precedes ALP expression by presumed somite-derived cells external to the notochordal sheath. The early expression of ALP indicates that the notochord plays an instructive role in the segmental patterning of the vertebral column. The chordacentra form segmentally as mineralized rings within the notochordal sheath, and ALP activity spreads within the chordoblast layer from ventral to dorsal, displaying the same progression and spatial distribution as the mineralization process. No ALP activity was observed in sclerotomal mesenchyme surrounding the notochordal sheath during initial formation of the chordacentra. Our results support previous findings indicating that the chordoblasts initiate a segmental differentiation of the notochordal sheath into chordacentra and intervertebral regions.

Alkaline Phosphatase↗
PubMed2000

Functional coupling between glycolysis and excitation-contraction coupling underlies alternans in cat heart cells.

Electromechanical alternans was characterized in single cat atrial and ventricular myocytes by simultaneous measurements of action potentials, membrane current, cell shortening and changes in intracellular Ca2+ concentration ([Ca2+]i). Using laser scanning confocal fluorescence microscopy, alternans of electrically evoked [Ca2+]i transients revealed marked differences between atrial and ventricular myocytes. In ventricular myocytes, electrically evoked [Ca2+]i transients during alternans were spatially homogeneous. In atrial cells Ca2+ release started at subsarcolemmal peripheral regions and subsequently spread toward the centre of the myocyte. In contrast to ventricular myocytes, in atrial cells propagation of Ca2+ release from the sarcoplasmic reticulum (SR) during the small-amplitude [Ca2+]i transient was incomplete, leading to failures of excitation-contraction (EC) coupling in central regions of the cell. The mechanism underlying alternans was explored by evaluating the trigger signal for SR Ca2+ release (voltage-gated L-type Ca2+ current, ICa,L) and SR Ca2+ load during alternans. Voltage-clamp experiments revealed that peak ICa,L was not affected during alternans when measured simultaneously with changes of cell shortening. The SR Ca2+ content, evaluated by application of caffeine pulses, was identical following the small-amplitude and the large-amplitude [Ca2+]i transient. These results suggest that the primary mechanism responsible for cardiac alternans does not reside in the trigger signal for Ca2+ release and SR Ca2+ load. beta-Adrenergic stimulation with isoproterenol (isoprenaline) reversed electromechanical alternans, suggesting that under conditions of positive cardiac inotropy and enhanced efficiency of EC coupling alternans is less likely to occur. The occurrence of electromechanical alternans could be elicited by impairment of glycolysis. Inhibition of glycolytic flux by application of pyruvate, iodoacetate or beta-hydroxybutyrate induced electromechanical and [Ca2+]i transient alternans in both atrial and ventricular myocytes. The data support the conclusion that in cardiac myocytes alternans is the result of periodic alterations in the gain of EC coupling, i. e. the efficacy of a given trigger signal to release Ca2+ from the SR. It is suggested that the efficiency of EC coupling is locally controlled in the microenvironment of the SR Ca2+ release sites by mechanisms utilizing ATP, produced by glycolytic enzymes closely associated with the release channel.

Action Potentials↗
PubMed1976

The relation between intercellular coupling and electrical noise in turtle photoreceptors.

1. Intracellular recordings from cones and rods in the retina of the turtle, Pseudemys scripta elegans, revealed that in darkness the cell voltage fluctuated spontaneously about its mean level. The fluctuations were reduced during bright steady illmination of the cell often to a level close to that obtained with the electrode outside the cell where the noise did not change significantly during illumination. 2. The magnitude of the intrinsic dark noise (voltage variance in darkness minus voltage variance in strong light) varied widely from cell to cell. In the noisiest cones it was about 0-4 mV2 while in quiet cones it was often as low as 0-01 mV2. The noise appeared radom and could be fitted by a Gaussian probability density function. 3. The spread of voltage in the network of coupled photoreceptors was estimated by measuring the spatial profile of the response to a brief flash of constant intensity moved across the retina. For a light stimulus in the form of a long narrow slit, the peak flash response usually decayed exponentially with displacement from the centred position. 4. For maximum responses less than about 5 mV in cones, the length constant of exponential decay, lambda, varied from less than 10 mum to greater than 35 mum, and the values obtained in opposite directions were often unequal. Background illumination did not significantly change lambda. In cells with extremely narrow spatial profiles, an exponential fit to the decay could not be made reliably. 5. Occasionally the spatial profiles had definite secondary peaks. In the most pronounced examples in a red-sensitive cone and in a rod the maxima were separated by about 20 and 50 mum respectively; for each, one peak was approximately as sharp as the optical stimulator while the second was broader. 6. Cones with short length constants displayed high dark noise while cones with long length constants were relatively quiet. 7. Three models of electrical coupling between cells were investigated: one based on a distributed network, one on a discrete square grid arrangement, and one on a discrete hexagonal array. Each model predicts a strong dependence of both noise and input resistance on length constant, and for tightly coupled cells each predicts that voltage variance is proportional to lambda-2. 8. The measured relationship between voltage variance and lambda in a large sample of cones was well described by both discrete models when the average cell spacing was taken to be approximately 15 mum. 9...

Animals↗
PubMed1998

Sex differences in patients with mesial temporal lobe epilepsy.

Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.

Adult↗