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PubMed2006

In vivo macular pigment measurements: a comparison of resonance Raman spectroscopy and heterochromatic flicker photometry.

AIM: To investigate whether two methods of measuring macular pigment-namely, heterochromatic flicker photometry (HFP) and resonance Raman spectroscopy (RRS)--yield comparable data. METHODS: Macular pigment was measured using HFP and RRS in the right eye of 107 participants aged 20-79 years. Correlations between methods were sought and regression models generated. RRS was recorded as Raman counts and HFP as macular pigment optical density (MPOD). The average of the top three of five Raman counts was compared with MPOD obtained at 0.5 degrees eccentricity, and an integrated measure (spatial profile; MPODsp) computed from four stimulus sizes on HFP. RESULTS: The coefficient of variation was 12.0% for MPODsp and 13.5% for Raman counts. MPODsp exhibited significant correlations with Raman counts (r = 0.260, p = 0.012), whereas MPOD at 0.5 degrees did not correlate significantly (r = 0.163, p = 0.118). MPODsp was not significantly correlated with age (p = 0.062), whereas MPOD at 0.5 degrees was positively correlated (p = 0.011). Raman counts showed a significant decrease with age (p = 0.002) and were significantly lower when pupil size was smaller (p = 0.015). CONCLUSIONS: Despite a statistically significant correlation, the correlations were weak, with those in excess of 90% of the variance between MPODsp and Raman counts remaining unexplained, meriting further research.

Adult↗
PubMed2002

The Hermann-Hering grid illusion demonstrates disruption of lateral inhibition processing in diabetes mellitus.

BACKGROUND/AIM: The Hermann-Hering grid illusion consists of dark illusory spots perceived at the intersections of horizontal and vertical white bars viewed against a dark background. The dark spots originate from lateral inhibition processing. This illusion was used to investigate the hypothesis that lateral inhibition may be disrupted in diabetes mellitus. METHOD: A computer monitor based psychophysical test was developed to measure the threshold of perception of the illusion for different bar widths. The contrast threshold for illusion perception at seven bar widths (range 0.09 degrees to 0.60 degrees) was measured using a randomly interleaved double staircase. Convolution of Hermann-Hering grids with difference of Gaussian receptive fields was used to generate model sensitivity functions. The method of least squares was used to fit these to the experimental data. 14 diabetic patients and 12 control subjects of similar ages performed the test. RESULTS: The sensitivity to the illusion was significantly reduced in the diabetic group for bar widths 0.22 degrees, 0.28 degrees, and 0.35 degrees (p = 0.01). The mean centre:surround ratio for the controls was 1:9.1 (SD 1.6) with a mean correlation coefficient of R(2) = 0.80 (SD 0.16). In the diabetic group, two subjects were unable to perceive the illusion. The mean centre:surround ratio for the 12 remaining diabetic patients was 1:8.6 (SD 2.1). However, the correlation coefficients were poor with a mean of R(2) = 0.54 (SD 0.27), p = 0.04 in comparison with the control group. CONCLUSIONS: A difference of Gaussian receptive field model fits the experimental data well for the controls but does not fit the data obtained for the diabetics. This indicates dysfunction of the lateral inhibition processes in the post-receptoral pathway.

Diabetic Retinopathy↗
PubMed1995

Three-dimensional myocardial deformations: calculation with displacement field fitting to tagged MR images.

PURPOSE: To reconstruct three-dimensional (3D) myocardial deformations from orthogonal sets of parallel-tagged magnetic resonance (MR) images. MATERIALS AND METHODS: Displacement information in the direction normal to the undeformed tag planes was obtained at points along tag lines. Three independent sets of one-dimensional displacement data were used to fit an analytical series expression to describe 3D displacement as a function of deformed position. The technique was demonstrated with computer-generated models of the deformed left ventricle with data from healthy human volunteers. RESULTS: Model deformations were reconstructed with a 3D tracking error of less than 0.3 mm. Error between estimated and observed one-dimensional displacements along the tags in 10 human subjects was 0.00 mm +/- 0.36 (mean +/- standard deviation). Robustness to noise in the tag displacement data was demonstrated by using a Monte Carlo simulation. CONCLUSION: The combination of rapidly acquired parallel-tagged MR images and field-fitting analysis is a valuable tool in cardiac mechanics research and in the clinical assessment of cardiac mechanical function.

Computer Simulation↗
PubMed1991

Osmotic properties of cells: a computer laboratory.

A computer laboratory has been designed to teach the osmotic properties of cells. One program, CELL.BA, is for the teacher to enter values for the volume of cell water and osmotically inactive material, the concentration of impermeant solute in the cell, and the permeability of the plasma membrane to water and a nonelectrolyte. When the program is protected, students use it as a cell with unknown osmotic properties. They run experiments on the computer with different concentrations of impermeant or permeant solutes or combinations of the two. Changes in cell volume or solute concentration are collected as data and analyzed with the program, PERMEABILITY LAB.BA. This program provides a parameter list, and students try to fit the data that are graphed on the screen by choosing values for the unknown cell parameters and generating model curves. Programs are written for the Macintosh computer.

Animals↗
PubMed2006

Sleep-related neural activity in a premotor and a basal-ganglia pathway of the songbird.

During singing, neurons in premotor nucleus RA (robust nucleus of the arcopallium) of the zebra finch produce complex temporal sequences of bursts that are recapitulated during sleep. RA receives input from nucleus HVC via the premotor pathway, and also from the lateral magnocellular nucleus of the anterior nidopallium (LMAN), part of a basal ganglia-related circuit essential for vocal learning. We explore the propagation of sleep-related spike patterns in these two pathways and their influences on RA activity. We promote sleep in head-fixed birds by injections of melatonin and make single-neuron recordings from the three major classes of neurons in HVC: RA-projecting neurons, Area X-projecting neurons, and interneurons. We also record LMAN neurons that project to RA. In paired recordings, spike trains from identified HVC neuron types are strongly coherent with spike trains in RA neurons, whereas LMAN projection neurons on average exhibit only a weak coherency with neurons in HVC and RA. We further examine the relative roles of HVC and LMAN in generating RA burst sequences with reversible inactivation. Lidocaine inactivation of HVC completely abolishes bursting in RA, whereas inactivation of LMAN has no effect on burst rates in RA. In combination, our data suggest that in adult birds, RA burst sequences in sleep are driven via the premotor pathway from HVC. We present a simple generative model of spike trains in HVC, RA, and LMAN neurons that is able to qualitatively reproduce observed coherency functions. We propose that commonly observed coherency peaks at positive and negative time lags are caused by sequentially correlated HVC activity.

Algorithms↗
PubMed2002

Fibronectin splice variants--prognostic markers for the stage of renal interstitial fibrosis in the rat.

BACKGROUND/AIMS: Renal interstitial fibrosis (RIF) is the main cause for progressive renal failure, but its pathogenic factors are not well known. In animal models of renal fibrogenesis done thus far an increase of total fibronectin (FN) mRNA has been proved. Recent studies have pointed to a key role of the splice variant EIIIA(+)-FN and EIIIB(+)-FN for the development of organ fibrosis. However, a broader knowledge of the distribution of these different FN mRNA isoforms is still lacking. Our aim was to study the particular expression of the EIIIA(+)-FN and EIIIB(+)-FN during the process of fibrogenesis in two rat models and to evaluate the FN isoforms as diagnostic/prognostic marker for the stage of interstitial damage in rat kidneys. METHODS: Kidneys of unilateral ureteral obstruction (UUO) and control rats were removed in intervals of 5, 14 or 21 days after surgery. For the investigation of kidney damage due to uranyl nitrate (UN), rats obtained a single i.p. dose of 5 mg/kg body weight UN and were killed 2, 10 and 20 weeks thereafter. The quantitative RT-PCR method was used to estimate the total FN, EIIIA(+)-FN and EIIIB(+)-FN transcription rate. RESULTS: In the UUO model, a significant augmentation of both isoforms was obtained in the kidneys in the first 5-day interval, which was more pronounced at the 21-day interval. In the UN-treated kidneys there appeared only a continuous increase of EIIIA(+)-FN and the splice variant EIIIB(+)-FN failed to show a shift in these animals as compared to the controls. CONCLUSION: Both animal models generated fibrogenic damages of the tubulointerstitium, whereas only the UUO resulted in progressive fibrosis. Absence of EIIIB(+)-FN seems to enhance the progression of fibrogenesis.

Alternative Splicing↗
PubMedDate not supplied

Spontaneous intracerebral hemorrhage in northeast Malaysian patients: a four-year study.

The aim of this study was to compare nonsurgical versus stereotactic aspiration of intracerebral hematomas in relation to clinical aspects, computed tomographic imaging features of the brain, laboratory parameters and specific risk factors that may influence the outcome in southeast Asian Malay patients. Fifty-five of the patients with intracerebral hemorrhage (ICH) underwent stereotactic aspiration and 57 did not. Analysis was done on risk factors, locations and treatments of ICH, and the final outcomes measured by the Glasgow Outcome Scale. A total of 112 patients were evaluated. Mean age was 52 years with ages ranging from 12 to 80 years. Hypertension was seen in 60.7% of patients with ICH. The mortality rate was 25% by 3 months. 58.9% had a poor final outcome, while 41.1% had a good outcome. The selected variables were incorporated into models generated by multiple logistic regression method analysis to define the significant predictors of outcome. Significant predictors of outcome were the Glasgow Coma Scale score on admission, the duration of surgery and the total volume of the hematoma. Significant predictors of mortality were high total white blood cell differential count, low plasma protein, and high plasma lactate dehydrogenase and brain edema. The study suggests that stereotactic aspiration of patients with ICH does not offer any definite advantage over conservative treatment.

Adolescent↗
PubMed2006

Stereotactic accuracy of a compact intraoperative MRI system.

OBJECTIVE: To analyze the stereotactic accuracy of the PoleStar N-20, a compact intraoperative magnetic resonance imaging (iMRI) system, based on a 0.15-Tesla (T) magnet. METHODS: An MRI-compatible phantom was scanned after being positioned in both the center of the magnetic field (COF) and the periphery of the field (POF) of the PoleStar N-20 magnet. Scans were acquired at various slice thicknesses in 3 sequences: T(1) weighted, T(2) weighted and Esteady (reversed fast imaging with steady-state precession, also known as 'PSIF'). The distance between the actual location of the probe tip in space and the location of the target on the image was measured on the axial, coronal, and sagittal planes for 9 points on each image. Each measurement was repeated 3 times. We also compared the structural features of the PoleStar N-20 to those of its predecessor. RESULTS: T(1)-weighted scans yielded the most accurate measurements. There was no statistically significant difference between scans acquired at thicknesses of 2, 3, 4 and 8 mm; all were accurate for clinical purposes. Comparison of COF with POF measurements using T(1)-weighted scans did not demonstrate a statistically significant difference in accuracy. CONCLUSIONS: The PoleStar N-20 0.15-T iMRI system provides surgical navigation that is at least as accurate as the first generation model of this system, which employed a 0.12-T magnet. Further analysis of stereotactic accuracy on clinical cases using the PoleStar N-20 is needed to confirm that these results will bear out in surgical reality.

Equipment Design↗
PubMed1997

Stereotactic craniotomy with the exoscope.

A three-dimensional computer graphic program has been developed to guide the surgeon through the resection of a brain tumor. It consists of a video camera mounted on a stereotactic frame which visualizes the operative field in real time. Superimposed on the video monitor is a computer generated model of the tumor or other resection target mass. The mass can be displayed in several modes. The computer image of the mass is adjusted to correspond to the surgeon's eye view, with appropriate settings for the stereotactic apparatus indicated. Prior to incision, the image of the mass is superimposed on the scalp to guide placement and size of the scalp and bone flaps. As the resection proceeds, a cross-section of the mass is illustrated on the video picture of the operative field. The distance from the camera to the surface is measured, and the cross-section at that depth is displayed. A small window indicates the surgeon's eye view and the tangential view of the mass with an indication of the cross-section currently being displayed. As resection proceeds, the distance to the bottom of the resection cavity is measured repeatedly. The image is updated to indicate only that level of the tumor under resection. As the far side of the tumor is encountered, the mass disappears from the monitor, signaling completion of the resection.

Brain Mapping↗
PubMed1982

Swedish prosody. Summary of a project.

The paper summarizes project work on Swedish accents and intonation. One major goal was the development of a generative model for intonation. The input of the model is a text with markings for word and sentence prosody and dialect. The output is a realistic intonation contour. The model was first set up for statement intonation in isolated sentences from five prototype dialects. It was later applied to interrogative intonation, to transitional forms between the prototype dialects, to Greek and French intonation and to prosodic transfer in a foreign accent.

Humans↗
PubMed2006

Inflammatory response to acute myocardial infarction augments neointimal hyperplasia after vascular injury in a remote artery.

OBJECTIVE: Percutaneous coronary intervention (PCI) is currently the most widely accepted treatment for acute myocardial infarction (AMI). It remains unclear, however, whether post-AMI conditions might exacerbate neointimal hyperplasia and restenosis following PCI. Given that both a medial smooth muscle cell lineage and a bone marrow (BM)-derived hematopoietic stem cell lineage are now thought to contribute to neointima formation, the primary aims of the present study were to determine whether AMI augments neointimal hyperplasia at sites of arterial injury, and whether BM-derived cells contribute to that process. METHODS AND RESULTS: We simultaneously generated models of AMI and arterial injury in the same mice, some of which had received BM transplantation. We found that AMI augments neointimal hyperplasia at sites of femoral artery injury by approximately 35% (P<0.05), but that while BM-derived cells contributed to neointimal hyperplasia, they did not contribute to the AMI-related augmentation. Expression of interleukin (IL)-6 mRNA was approximately 7-fold higher in the neointimas of mice subjected to both AMI and arterial injury than in those of mice subjected to arterial injury alone. In addition, we observed increased synthesis of tumor necrosis factor (TNF)-alpha within infarcted hearts and TNF-alpha receptor type 1 (TNFR1) within injured arteries. Chronic treatment with pentoxifylline, which mainly inhibits TNF-alpha synthesis, reduced levels of circulating TNF-alpha and attenuated neointimal hyperplasia after AMI. CONCLUSIONS: Conditions after AMI could exacerbate postangioplasty restenosis, not by increasing mobilization of BM-derived cells, but by stimulating signaling via TNF-alpha, TNFR1 and IL-6.

Animals↗
PubMed2004

Proangiogenic action of thyroid hormone is fibroblast growth factor-dependent and is initiated at the cell surface.

The effects of thyroid hormone analogues on modulation of angiogenesis have been studied in the chick chorioallantoic membrane model. Generation of new blood vessels from existing vessels was increased 3-fold by either l-thyroxine (T4; 10(-7) mol/L) or 3,5,3'-triiodo-l-thyronine (10(-9) mol/L). T4-agarose reproduced the effects of T4, and tetraiodothyroacetic acid (tetrac) inhibited the effects of both T4 and T4-agarose. Tetrac itself was inactive and is known to block actions of T4 on signal transduction that are initiated at the plasma membrane. T4 and basic fibroblast growth factor (FGF2) were comparably effective as inducers of angiogenesis. Low concentrations of FGF2 combined with submaximal concentrations of T4 produced an additive angiogenic response. Anti-FGF2 inhibited the angiogenic effect of T4. The proangiogenic effects of T4 and FGF2 were blocked by PD 98059, a mitogen-activated protein kinase (MAPK) pathway inhibitor. Endothelial cells (ECV304) treated with T4 or FGF2 for 15 minutes demonstrated activation of MAPK, an effect inhibited by PD 98059 and the protein kinase C inhibitor CGP41251. Reverse transcription-polymerase chain reaction of RNA extracted from endothelial cells treated with T4 revealed increased abundance of FGF2 transcript at 6 to 48 hours, and after 72 hours, the medium of treated cells showed increased FGF2 content, an effect inhibited by PD 98059. Thus, thyroid hormone is shown to be a proangiogenic factor. This action, initiated at the plasma membrane, is MAPK dependent and mediated by FGF2.

Animals↗
PubMed2004

Bayesian computation in recurrent neural circuits.

A large number of human psychophysical results have been successfully explained in recent years using Bayesian models. However, the neural implementation of such models remains largely unclear. In this article, we show that a network architecture commonly used to model the cerebral cortex can implement Bayesian inference for an arbitrary hidden Markov model. We illustrate the approach using an orientation discrimination task and a visual motion detection task. In the case of orientation discrimination, we show that the model network can infer the posterior distribution over orientations and correctly estimate stimulus orientation in the presence of significant noise. In the case of motion detection, we show that the resulting model network exhibits direction selectivity and correctly computes the posterior probabilities over motion direction and position. When used to solve the well-known random dots motion discrimination task, the model generates responses that mimic the activities of evidence-accumulating neurons in cortical areas LIP and FEF. The framework we introduce posits a new interpretation of cortical activities in terms of log posterior probabilities of stimuli occurring in the natural world.

Action Potentials↗
PubMed1987

Transplantation of preneoplastic rat hepatocytes by intraportal injection.

Hepatocyte suspensions prepared from inbred male Wistar-Kyoto rats were transplanted to the livers of syngeneic recipients by injection into the portal venous system immediately after partial hepatectomy. Donor cells were labelled with 51Cr in vitro before transplantation. Animals were sacrificed 1 hr, 10 hr, 48 hr, or 1 week later and the liver radioactivity was measured in a gamma counter. Total liver radioactivity declined rapidly during the first 10 hr after transplantation, and then stabilized. After 1 week, 15-20% of the injected radioactivity still remained, indicating that this fraction of the injected cells was retained by the liver. The percentage was unaffected by the number of cells injected. In another experiment, 10(6) hepatocytes from a carcinogen-treated rat were transplanted to syngeneic rats fed 0.05% phenobarbital in the diet. Recipients developed liver carcinomas from 7 weeks after transplantation, and at 5 months 4 out of 5 animals showed severe debility and had large hepatocellular carcinomas. This model generates tumors considerably faster than those previously described, and is well suited for the study of the tumorigenic potential of subclasses of cells in liver carcinogenesis.

Animals↗
PubMed1999

Modeling circadian rhythm generation in the suprachiasmatic nucleus with locally coupled self-sustained oscillators: phase shifts and phase response curves.

Circadian rhythm generation in the suprachiasmatic nucleus was modeled by locally coupled self-sustained oscillators. The model is composed of 10,000 oscillators, arranged in a square array. Coupling between oscillators and standard deviation of (randomly determined) intrinsic oscillator periods were varied. A stable overall rhythm emerged. The model behavior was investigated for phase shifts of a 24-h zeitgeber cycle. Prolongation of either the dark or the light phase resulted in a lengthening of the period, whereas shortening of the dark or the light phase shortened the period. The model's response to shifts in the light-dark cycle was dependent only on the extent of the shift and was insensitive to changes in parameters. Phase response curves (PRC) and amplitude response curves were determined for single and triple 5-h light pulses (1000 lux). Single pulses lead to type 1 PRCs with larger phase shifts for weak coupling. Triple pulses generally evoked type 1 PRCs with the exception of weak coupling, where a type 0 PRC was observed.

Algorithms↗
PubMed2000

How do general practitioners choose their practice? Preferences for practice and job characteristics.

OBJECTIVES: To investigate the strength of preferences for practice and job characteristics among recently appointed general practitioners (GPs) in south-east England. METHODS: Conjoint analysis based on a postal questionnaire survey of all 293 GPs who joined a new practice between April 1997 and March 1998 in London, Essex and Hertfordshire. GPs were presented with descriptions of practices in pairs, which varied systematically for key characteristics, and asked to indicate their preferred practice in each pair. RESULTS: The response rate was 58.7%. The most important influence on GPs' choice of practice was aversion to location in an area of high deprivation. They were more likely to choose a practice that: had an extended primary health care team; offered opportunities to develop outside interests; and offered them higher income, shorter working hours and smaller list sizes. The model generated estimates of the strength of these preferences. For example, GPs would require additional income of just over 5000 Pounds per annum to work in an area with a high proportion of deprived patients. CONCLUSIONS: Potential policy interventions to attract GPs to under-served areas include increasing their level of remuneration, providing opportunities to develop outside interests and ensuring that practices have a primary health care team.

Attitude of Health Personnel↗
PubMed2004

Effects of iron and phytic acid on production of extracellular radicals by Enterococcus faecalis.

Enterococcus faecalis is a human intestinal commensal that produces extracellular superoxide, hydrogen peroxide, and hydroxyl radical while colonizing the intestinal tract. To determine whether dietary factors implicated in colorectal cancer affect oxidant production by E. faecalis, radicals were measured in rats colonized with this microorganism while on diets supplemented with iron or phytic acid. Hydroxyl radical activity was measured by assaying for aromatic hydroxylation products of D-phenylalanine using reverse-phase high-performance liquid chromatography and electrochemical detection. In vitro, as expected, iron enhanced, and phytic acid decreased, hydroxyl radical formation by E. faecalis. For rats colonized with E. faecalis given supplemental dietary iron (740 mg elemental iron as ferric phosphate per kg diet) or phytic acid (1.2% w/w), no differences were found in concentrations of urinary ortho- or meta- isomers of D-phenylalanine compared to rats on a basal diet. Aqueous radicals in colonic contents were further assessed ex vivo by electron spin resonance using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. Mixtures of thiyl (sulfur-centered) and oxygen-centered radicals were detected across all diets. In vitro, similar spectra were observed when E. faecalis was incubated with hydrogen sulfide, air-oxidized cysteine, or an alkylsulfide, as typical sulfur-containing compounds that might occur in colonic contents. In conclusion, intestinal colonization with E. faecalis in a rat model generates both thiyl and oxygen-centered radicals in colonic contents. Radical formation, however, was not significantly altered by short-term dietary supplementation with iron or phytic acid.

Animals↗
PubMed2004

Wall shear stress gradient topography in the normal left coronary arterial tree: possible implications for atherogenesis.

OBJECTIVE: Wall shear stress gradient (WSSG) in vitro has shown its importance in atherogenesis, probably as a local modulator of endothelial gene expression. The purpose of this study is to numerically analyse the WSSG distribution over the normal human left coronary artery (LCA) tree. RESEARCH DESIGN AND METHODS: A three-dimensional computer generated model of the LCA tree, based on an averaged human data set extracted from angiographies, was adopted for finite-element analysis. The LCA tree includes the left main coronary artery (LMCA), the left anterior descending (LAD), the left circumflex artery (LCxA) and their major branches. RESULTS: In proximal LCA tree regions where at bifurcations in regions opposite the flow atherosclerosis frequently occurs, low WSSG appears. At distal segments, the WSSG increases substantially due to increased velocity resulting from increased vessel tapering. Low WSSG occurs dividers, which are anatomic sites predisposed for atherosclerotic development. CONCLUSIONS: This computational work determines, probably for the first time, the topography of the WSSG in the normal human LCA tree. Spatial WSSG differentiation indicates that low values of this parameter probably correlate to atherosclerosis localization. However, further studies are needed to clarify the role of WSSG in atherogenesis.

Blood Flow Velocity↗